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  • 1.
    Bachmann, M. Consuelo
    et al.
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Morais, Caio
    Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Bugedo, Guillermo
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Bruhn, Alejandro
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Morales, Arturo
    Pontificia Univ Catolica Chile, Fac Med, Dept Enfermedades Resp, Santiago, Chile.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Costa, Eduardo
    Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Retamal, Jaime
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Electrical impedance tomography in acute respiratory distress syndrome2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, article id 263Article, review/survey (Refereed)
    Abstract [en]

    Acute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.

  • 2.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Sao Paulo, Sao Paulo, Brazil.
    The Plausibility of "Bronchiolotrauma"2018In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197, no 8, p. 1086-1087Article in journal (Refereed)
  • 3.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil.
    Amato, Marcelo B P
    Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    The Increasing Call for Protective Ventilation During Anesthesia2017In: JAMA Surgery, ISSN 2168-6254, E-ISSN 2168-6262, Vol. 152, no 9, p. 893-894Article in journal (Other academic)
  • 4.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Hosp Clin, Pulm Div Heart Inst InCor, Sao Paulo, Brazil..
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    The "normal" ventilated airspaces suffer the most damaging effects of mechanical ventilation2017In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 43, no 7, p. 1057-1058Article in journal (Other academic)
  • 5.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bergman, J. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Dussault, C.
    Armed Forces Biomed Res Inst, Bretigny Sur Orge, France..
    Amato, M. B. P.
    Univ Sao Paulo, Sch Med, Sao Paulo, Brazil..
    Montmerle-Borgdorff, S.
    Armed Forces Biomed Res Inst, Bretigny Sur Orge, France..
    First-Time Monitoring Of Simultaneous Effects Of Hypergravity On Heart And Lung By Electrical Impedance Tomography2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 6.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Santos, Arnoldo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lucchetta, L.
    Hosp San Matteo, Pavia, Italy..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Redistribution Of Regional Lung Perfusion During Mechanical Ventilation With An Open Lung Approach Impacts Pulmonary Vascular Mechanics2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, article id A3751Article in journal (Other academic)
  • 7.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L. V.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lucchetta, Luca
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Amato, Marcelo B. P.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 5, p. E123-E132Article in journal (Refereed)
    Abstract [en]

    Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

  • 8.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bergman, Jakob S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo B. P.
    Avenel, Jacques
    Montmerle-Borgdorff, Stephanie
    First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity2015In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, no 2, p. 353-363Article in journal (Refereed)
    Abstract [en]

    Aeroatelectasis can develop in aircrew flying the latest generation high-performance aircraft. Causes alleged are relative hyperoxia, increased gravity in the head-to-foot direction (+G(z)), and compression of legs and stomach by anti-G trousers (AGT). We aimed to assess, in real time, the effects of hyperoxia, +G(z) accelerations and AGT inflation on changes in regional lung volumes and breathing pattern evaluated in an axial plane by electrical impedance tomography (EIT). The protocol mimicked a routine peacetime flight in combat aircraft. Eight subjects wearing AGT were studied in a human centrifuge during 1 h 15 min exposure of +1 to +3.5G(z). They performed this sequence three times, breathing AIR, 44.5 % O-2 or 100 % O-2. Continuous recording of functional EIT enabled uninterrupted assessment of regional lung volumes at the 5th intercostal level. Breathing pattern was also monitored. EIT data showed that +3.5G(z), compared with any moment without hypergravity, caused an abrupt decrease in regional tidal volume (V-T) and regional end-expiratory lung volume (EELV) measured in the EIT slice, independently of inspired oxygen concentration. Breathing AIR or 44.5 % O-2, sub-regional EELV measured in the EIT slice decreased similarly in dorsal and ventral regions, but sub-regional V-T measured in the EIT slice decreased significantly more dorsally than ventrally. Breathing 100 % O-2, EELV and V-T decreased similarly in both regions. Inspired tidal volume increased in hyperoxia, whereas breathing frequency increased in hypergravity and hyperoxia. Our findings suggest that hypergravity and AGT inflation cause airway closure and air trapping in gravity-dependent lung regions, facilitating absorption atelectasis formation, in particular during hyperoxia.

  • 9.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation StrategyManuscript (preprint) (Other academic)
  • 10.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Regional Lung Kinetics of Ventilator-Induced Lung Injury and Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mechanical ventilation in itself can harm the lung and cause ventilator-induced lung injury (VILI), which can induce or aggravate acute respiratory distress syndrome (ARDS). Much debate remains over pivotal concepts regarding the pathophysiology of VILI, especially about the precise contribution, kinetics, and primary role of potential VILI mechanisms. Consequently, it remains largely unknown how best to design a well-timed and full-bodied mechanical ventilation strategy. Little is known also about small airways dysfunction in ARDS. Dynamic positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (18F-FDG) can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We studied the regional evolution of inflammation using dynamic PET/CT imaging of 18F-FDG in VILI and during different lung-protective mechanical ventilation strategies. By dynamic CT we investigated also the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction. Piglets were submitted to an experimental model of early ARDS combining repeated lung lavages and injurious mechanical ventilation. The animals were subsequently studied during sustained VILI, or submitted to distinct approaches of lung-protective mechanical ventilation: the one recommended by the ARDS Network (ARDSNet), or to one defined as open lung approach (OLA). The normally and poorly aerated regions - corresponding to intermediate gravitational zones - were the primary targets of the inflammatory process accompanying early VILI, which may be attributed to the small volume of the aerated lung that receives most of ventilation. The ARDSNet strategy did not attenuate global pulmonary inflammation during 27h and led to a concentration of inflammatory activity in the upper and poorly aerated lung regions. The OLA, in comparison with the ARDSNet approach, resulted in sustained and better gas exchange and lung mechanics. Moreover, the OLA strategy resulted in less global and regional inflammation. Dynamic CT data suggested that a significant amount of airway closure and related reabsorption atelectasis occurs in acute lung injury. Whether potential distal bronchioles injury (“bronchiolotrauma”) is a critical and decisive element in ventilator-associated lung injury is a matter for future studies.

    List of papers
    1. Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
    Open this publication in new window or tab >>Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
    Show others...
    2014 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, p. e279-e287Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: A university animal research laboratory.

    SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

    INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

    CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

    National Category
    Medical and Health Sciences
    Research subject
    Clinical Physiology
    Identifiers
    urn:nbn:se:uu:diva-223348 (URN)10.1097/CCM.0000000000000161 (DOI)000332839700003 ()24448197 (PubMedID)
    Available from: 2014-04-17 Created: 2014-04-17 Last updated: 2017-12-05Bibliographically approved
    2. Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
    Open this publication in new window or tab >>Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-230045 (URN)
    Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2018-11-12Bibliographically approved
    3. Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
    Open this publication in new window or tab >>Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-230046 (URN)
    Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2015-01-22Bibliographically approved
    4. Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
    Open this publication in new window or tab >>Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
    Show others...
    2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1464-1473Article in journal (Refereed) Published
    Abstract [en]

    Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

    Keywords
    small airways dysfunction, absorption atelectasis, acute respiratory distress syndrome
    National Category
    Medical and Health Sciences Physiology
    Identifiers
    urn:nbn:se:uu:diva-213823 (URN)10.1152/japplphysiol.00763.2013 (DOI)000327398600007 ()
    Available from: 2014-01-05 Created: 2014-01-04 Last updated: 2018-01-11Bibliographically approved
  • 11.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L V
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury2014In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, p. e279-e287Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: A university animal research laboratory.

    SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

    INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

    CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

  • 12.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eduardo, Costa LV
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, Luca
    Widström, Charles
    Maripuu, Enn
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Marcelo, Amato
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.Manuscript (preprint) (Other academic)
  • 13.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    The Rediscovery of Galligas REPLY2011In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 52, no 6, p. 1004-1004Article in journal (Refereed)
  • 14.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Altering the mechanical scenario to decrease the driving pressure2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 342Article in journal (Refereed)
    Abstract [en]

    Ventilator settings resulting in decreased driving pressure (ΔP) are positively associated with survival. How to further foster the potential beneficial mediator effect of a reduced ΔP? One possibility is promoting the active modification of the lung's "mechanical scenario" by means of lung recruitment and positive end-expiratory pressure selection. By taking into account the individual distribution of the threshold-opening airway pressures to achieve maximal recruitment, a redistribution of the tidal volume from overdistended to newly recruited lung occurs. The resulting more homogeneous distribution of transpulmonary pressures may induce a relief of overdistension in the upper regions. The gain in lung compliance after a successful recruitment rescales the size of the functional lung, potentially allowing for a further reduction in ΔP.

  • 15.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst Incor, BR-05508 Sao Paulo, Brazil..
    Porra, L.
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Pellegrini, M.
    Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Tannoia, A.
    Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Derosa, S.
    Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, S.
    Univ Picardie Jules Verne, CHU Amiens, INSERM, UMR1105, Amiens, France.;Univ Picardie Jules Verne, CHU Amiens, Pediat Lung Funct Lab, Amiens, France..
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Hedenstierna, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 7, p. 958-968Article in journal (Refereed)
    Abstract [en]

    BackgroundIt is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. MethodsIn a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV.). Heterogeneity of ventilation was calculated as the coefficient of variation in sV. (CVsV.). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH(2)O and F(I)O(2)1.0 (Open Lung-PEEP = OLP). ResultsThe mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV. and poor aeration at ZEEP-0.21 than at OLP: 12.9 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV. of the total imaged lung at PEEP 12 cmH(2)O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ConclusionZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.

  • 16.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ribeiro Carvalho, Carlos Roberto
    The Quest for the Holy Grail: A Dead Lock2010In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 182, no 4, p. 579-580Article in journal (Refereed)
  • 17.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Senturk, Mert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Open Lung in Lateral Decubitus With Differential Selective Positive End-Expiratory Pressure in an Experimental Model of Early Acute Respiratory Distress Syndrome2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 10, p. e404-e411Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: After lung recruitment, lateral decubitus and differential lung ventilation may enable the titration and application of optimum-selective positive end-expiratory pressure values for the dependent and nondependent lungs. We aimed at compare the effects of optimum-selective positive end-expiratory pressure with optimum global positive end-expiratory pressure on regional collapse and aeration distribution in an experimental model of acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: University animal research laboratory.

    SUBJECTS: Seven piglets.

    INTERVENTIONS: A one-hit injury acute respiratory distress syndrome model was established by repeated lung lavages. After replacing the tracheal tube by a double-lumen one, we initiated lateral decubitus and differential ventilation. After maximum-recruitment maneuver, decremental positive end-expiratory pressure titration was performed. The positive end-expiratory pressure corresponding to maximum dynamic compliance was defined globally (optimum global positive end-expiratory pressure) and for each individual lung (optimum-selective positive end-expiratory pressure). After new maximum-recruitment maneuver, two steps were performed in randomized order (15 min each): ventilation applying the optimum global positive end-expiratory pressure and the optimum-selective positive end-expiratory pressure. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: Aeration homogeneity was evaluated as a nondependent/dependent ratio (percent of total gas content in upper lung/percent of total gas content in lower lung) and tidal recruitment as the difference in the percent mass of nonaerated tissue between expiration and inspiration. At the end of the 15-minute optimum-selective positive end-expiratory pressure, compared with the optimum global positive end-expiratory pressure, resulted in 1) decrease in the percent mass of collapse in the lower lung at expiratory CT (19% ± 15% vs 4% ± 5%; p = 0.03); 2) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-expiratory-CT and optimum-selective positive end-expiratory pressure-expiratory-CT (3.7 ± 1.2 vs 0.8 ± 0.5; p = 0.01); 3) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-inspiratory-CT and optimum-selective positive end-expiratory pressure-inspiratory-CT (2.8 ± 1.1 vs 0.6 ± 0.3; p = 0.01); and 4) less tidal recruitment (p = 0.049).

    CONCLUSIONS: After maximum lung recruitment, lateral decubitus and differential lung ventilation enabled the titration of optimum-selective positive end-expiratory pressure values for the dependent and the nondependent lungs, made possible the application of an optimized regional open lung approach, promoted better aeration distribution, and minimized lung tissue inhomogeneities.

  • 18.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Costa, Eduardo L. V.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Comment on Borges et al. "Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse" Reply2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 12, p. 2128-2128Article in journal (Refereed)
  • 19.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H
    Tusman, Gerardo
    Melo, Alexandre
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Park, Marcelo
    Costa, Eduardo L V
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Regional Lung Perfusion estimated by Electrical Impedance Tomography in a piglet model of lung collapse2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 1, p. 225-236Article in journal (Refereed)
    Abstract [en]

    The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology which provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT) based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6 %, with a standard deviation of 2.9 %. This method outperformed the estimates of lung perfusion based on impedance-pulsatility. In conclusion, we describe a novel method based on Electrical Impedance Tomography for estimating regional lung perfusion at the bedside. In both, healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this paper has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.

  • 20.
    Broche, L.
    et al.
    ESRF, Grenoble, France.;Univ Bari, Bari, Italy..
    Tannoia, A.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Derosa, S.
    Sindaco, A.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Porra, L.
    Univ Helsinki, Helsinki, Finland..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bravin, A.
    ESRF, Grenoble, France..
    Perchiazzi, G.
    Wexler, A. S.
    Univ Calif Davis, Davis, CA 95616 USA..
    Verbanck, S.
    UZ Brussel, Brussels, Belgium..
    Bates, J. H. T.
    Univ Vermont, Burlington, VT USA..
    Bayat, S.
    Univ Picardie Med Sch CHU Amiens, Amiens, France..
    Role Of Parenchymal Interdependence In The Short-Term Dynamics Of Recruitment/derecruitment In Injured Lung: A Modelling Study2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191Article in journal (Other academic)
  • 21.
    Broche, Ludovic
    et al.
    Grenoble, France..
    Gaetano, Perchiazzi
    Univ Bari, Bari, Italy..
    Liisa, Porra
    Univ Helsinki, Helsinki, Finland..
    Angela, Tannoia
    Univ Bari, Bari, Italy..
    Mariangela, Pellegrini
    Univ Bari, Bari, Italy..
    Savino, Derosa
    Univ Bari, Bari, Italy..
    Alessandra, Sindaco
    Univ Bari, Bari, Italy..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Loic, Degrugilliers
    Univ Picardie Jules Verne, Amiens, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Anthony, Wexler
    Univ Calif Davis, Davis, CA 95616 USA..
    Alberto, Bravin
    ESRF, Grenoble, France..
    Sylvia, Verbanck
    Univ Hosp UZ Brussel, Brussels, Belgium..
    Bradford, J. Smith
    Univ Vermont, Burlington, VT USA..
    Jason, H. T. Bates
    Univ Vermont, Burlington, VT USA..
    Sam, Bayat
    Univ Picardie Jules Verne, Amiens, France..
    Dynamic mechanical interactions between neighboring airspaces determine cyclic opening and closure in injured lung2016In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, p. 141-141Article in journal (Other academic)
  • 22.
    Broche, Ludovic
    et al.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.;Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Porra, Liisa
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Tannoia, Angela
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Derosa, Savino
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Sindaco, Alessandra
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Degrugilliers, Loic
    Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Wexler, Anthony S.
    Univ Calif Davis, Dept Mech Engn, Davis, CA 95616 USA.;Univ Calif Davis, Environm Qual Lab, Davis, CA 95616 USA..
    Bravin, Alberto
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France..
    Verbanck, Sylvia
    Univ Hosp UZ Brussel, Div Resp, Brussels, Belgium..
    Smith, Bradford J.
    Univ Vermont, Dept Med, Burlington, VT USA. European Synchrotron Radiat Facil, Grenoble, France..
    Bates, Jason H. T.
    Univ Vermont, Dept Med, Burlington, VT USA. European Synchrotron Radiat Facil, Grenoble, France..
    Bayat, Sam
    Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 4, p. 687-694Article in journal (Refereed)
    Abstract [en]

    Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

  • 23.
    Broche, Ludovic
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Pisa, Pauline
    Univ Picardie Jules Verne, Fac Med, Amiens, France.
    Porra, Liisa
    Univ Helsinki, Dept Phys, Helsinki, Finland;Univ Helsinki, Cent Hosp, Med Imaging Ctr, Helsinki, Finland.
    Degrugilliers, Loic
    Amiens Univ Hosp, Dept Pediat Intens Care, Amiens, France.
    Bravin, Alberto
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, Sam
    Univ Grenoble Alpes, Grenoble, France;INSERM, UA7, STROBE Lab, Grenoble, France;Grenoble Univ Hosp, Dept Pulmonol & Physiol, Grenoble, France.
    Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung2019In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 47, no 9, p. E774-E781Article in journal (Refereed)
    Abstract [en]

    Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.

    Design: Laboratory animal investigation.

    Setting: European synchrotron radiation facility.

    Subjects: Six New-Zealand White rabbits.

    Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio(2), 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 x 47.5 x 47.5 mu m voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.

    Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.350.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 +/- 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).

    Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.

  • 24.
    Derosa, Savino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Segelsjö, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tannoia, Angela
    Pellegrini, Mariangela
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Perchiazzi, Gaetano
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1464-1473Article in journal (Refereed)
    Abstract [en]

    Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

  • 25.
    El-Dash, S. A.
    et al.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil.
    Costa, E. L. V.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil.;Hosp Sirio Libanes, Res & Educ Inst, Sao Paulo, Brazil..
    Tucci, M. R.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Ranzani, O. T.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Caramez, M. P.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Carvalho, C. R. R.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Amato, M. B. P.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    There is no cephalocaudal gradient of computed tomography densities or lung behavior in supine patients with acute respiratory distress syndrome2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 6, p. 767-779Article in journal (Refereed)
    Abstract [en]

    Background: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs.

    Methods: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH(2)O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2O every 4 min, and a semi-complete scan performed at the end of each PEEP step.

    Results: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (beta = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP.

    Conclusions: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non-dependent lung regions.

  • 26.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Kerstin M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Engström, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 331Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.

    METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.

    RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.

    CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

  • 27.
    Kretzschmar, Moritz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Kozian, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Baumgardner, James E
    Oscill LLC, Pittsburgh, PA USA; Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA USA.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Schilling, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane2017In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 127, no 5, p. 800-812Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model.

    METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique.

    RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min.

    CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

  • 28.
    Kretzschmar, Moritz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Schilling, Thomas
    Vogt, Andreas
    Rothen, Hans Ulrich
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hachenberg, Thomas
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Baumgardner, James E.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry-a comparison with reference gas chromatography2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 8, p. 1107-1118Article in journal (Refereed)
    Abstract [en]

    The mismatching of alveolar ventilation and perfusion (V-A/Q) is the major determinant of impaired gas exchange. The gold standard for measuring V-A/Q distributions is based on measurements of the elimination and retention of infused inert gases. Conventional multiple inert gas elimination technique (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures, which requires tonometry of blood samples with a gas that can then be injected into the chromatograph. The method is laborious and requires meticulous care. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) facilitates the handling of blood and gas samples and provides nearly real-time analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3 with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left lower lobe ventilation. The different protocols ensured a large range of normal and abnormal V-A/Q distributions. Eight inert gases (SF6, krypton, ethane, cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused; six of these gases were measured with MMIMS, and six were measured with GC. We found close agreement of retention and excretion of the gases and the constructed V-A/Q distributions between GC and MMIMS, and predicted Pa-O2 from both methods compared well with measured Pa-O2. V-A/Q by GC produced more widely dispersed modes than MMIMS, explained in part by differences in the algorithms used to calculate V-A/Q distributions. In conclusion, MMIMS enables faster measurement of V-A/Q, is less demanding than GC, and produces comparable results.

  • 29. Li, Y.
    et al.
    Tesselaar, E.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bohm, S. H.
    Sjoberg, F.
    Janerot-Sjoberg, B.
    Hyperoxia affects the regional pulmonary ventilation/perfusion ratio: an electrical impedance tomography study2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 6, p. 716-725Article in journal (Refereed)
    Abstract [en]

    Background The way in which hyperoxia affects pulmonary ventilation and perfusion is not fully understood. We investigated how an increase in oxygen partial pressure in healthy young volunteers affects pulmonary ventilation and perfusion measured by thoracic electrical impedance tomography (EIT). Methods Twelve semi-supine healthy male volunteers aged 21-36 years were studied while breathing room air and air-oxygen mixtures (FiO2) that resulted in predetermined transcutaneous oxygen partial pressures (tcPO2) of 20, 40 and 60kPa. The magnitude of ventilation (Zv) and perfusion (ZQ)-related changes in cyclic impedance variations, were determined using an EIT prototype equipped with 32 electrodes around the thorax. Regional changes in ventral and dorsal right lung ventilation (V) and perfusion (Q) were estimated, and V/Q ratios calculated. Results There were no significant changes in Zv with increasing tcPO2 levels. ZQ in the dorsal lung increased with increasing tcPO2 (P=0.01), whereas no such change was seen in the ventral lung. There was a simultaneous decrease in V/Q ratio in the dorsal region during hyperoxia (P=0.04). Two subjects did not reach a tcPO2 of 60kPa despite breathing 100% oxygen. Conclusion These results indicate that breathing increased concentrations of oxygen induces pulmonary vasodilatation in the dorsal lung even at small increases in FiO2. Ventilation remains unchanged. Local mismatch of ventilation and perfusion occurs in young healthy men, and the change in ventilation/perfusion ratio can be determined non-invasively by EIT.

  • 30.
    Morais, C. C. A.
    et al.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Plens, G.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Tucci, M. R.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Yoshida, T.
    Hosp Sick Children, Toronto, ON, Canada..
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ramos, O. P.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Pereira, S. M.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Lima, C. A. S.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Gomes, S.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Melo, M. Vidal
    Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA..
    Amato, M. B. P.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Costa, E. L. V.
    Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil..
    Higher Positive End-Expiratory Pressures Affect The Distribution Of Lung Inflammation During Spontaneous Breathing In An Experimental Model Of Severe Acute Respiratory Distress Syndrome2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, article id A7669Article in journal (Other academic)
  • 31.
    Morais, Caio C. A.
    et al.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Koyama, Yukiko
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan.
    Yoshida, Takeshi
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan;Univ Toronto, Hosp Sick Children, Dept Crit Care Med & Anesthesia, Translat Med, 686 Bay St, Toronto, ON M5G 0A4, Canada.
    Plens, Glauco M.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Gomes, Susimeire
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Lima, Cristhiano A. S.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Ramos, Ozires P. S.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Pereira, Sergio M.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Kawaguchi, Naomasa
    Osaka Univ, Sch Allied Hlth Sci, Dept Pathol, Grad Sch Med, Suita, Osaka, Japan.
    Yamamoto, Hirofumi
    Osaka Univ, Sch Allied Hlth Sci, Dept Pathol, Grad Sch Med, Suita, Osaka, Japan.
    Uchiyama, Akinori
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Melo, Marcos F. Vidal
    Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
    Tucci, Mauro R.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Amato, Marcelo B. P.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Kavanagh, Brian P.
    Univ Toronto, Hosp Sick Children, Dept Crit Care Med & Anesthesia, Translat Med, 686 Bay St, Toronto, ON M5G 0A4, Canada.
    Costa, Eduardo L. V.
    Univ Sao Paulo, Fac Med, Hosp Clin, Div Pneumol,Inst Coracao Incor, Sao Paulo, Brazil.
    Fujino, Yuji
    Osaka Univ Hosp, Intens Care Unit, Suita, Osaka, Japan.
    High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious2018In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197, no 10, p. 1285-1296Article in journal (Refereed)
    Abstract [en]

    Rationale: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious.

    Objectives: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP).

    Methods: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS.

    Measurements and Main Results: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients).

    Conclusions: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

  • 32.
    Reinius, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Laboratório de Pneumologia LIM–09, Disciplina de Pneumologia, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Engström, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Fredén, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Optimal PEEP during one-lung ventilation with capnothorax: An experimental study2019In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, no 2, p. 222-231Article in journal (Refereed)
    Abstract [en]

    Background: One‐lung ventilation (OLV) with induced capnothorax carries the risk of severely impaired ventilation and circulation. Optimal PEEP may mitigate the physiological perturbations during these conditions.

    Methods: Right‐sided OLV with capnothorax (16 cm H2O) on the left side was initiated in eight anesthetized, muscle‐relaxed piglets. A recruitment maneuver and a decremental PEEP titration from PEEP 20 cm H2O to zero end‐expiratory pressure (ZEEP) was performed. Regional ventilation and perfusion were studied with electrical impedance tomography and computer tomography of the chest was used. End‐expiratory lung volume and hemodynamics were recorded and.

    Results: PaO2 peaked at PEEP 12 cm H2O (49 ± 14 kPa) and decreased to 11 ± 5 kPa at ZEEP (P < 0.001). PaCO2 was 9.5 ± 1.3 kPa at 20 cm H2O PEEP and did not change when PEEP step‐wise was reduced to 12 cm H2O PaCO2. At lower PEEP, PaCO2 increased markedly. The ventilatory driving pressure was lowest at PEEP 14 cm H2O (19.6 ± 5.8 cm H2O) and increased to 38.3 ± 6.1 cm H2O at ZEEP (P < 0.001). When reducing PEEP below 12‐14 cm H2O ventilation shifted from the dependent to the nondependent regions of the ventilated lung (P = 0.003), and perfusion shifted from the ventilated to the nonventilated lung (P = 0.02).

    Conclusion: Optimal PEEP was 12‐18 cm H2O and probably relates to capnothorax insufflation pressure. With suboptimal PEEP, ventilation/perfusion mismatch in the ventilated lung and redistribution of blood flow to the nonventilated lung occurred.

  • 33.
    Reinius, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Fredén, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jideus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Camargo, E. D. L. B.
    Amato, M. B. P.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax2015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 3, p. 354-368Article in journal (Refereed)
    Abstract [en]

    Background: Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.

    Methods: Five anesthetized, muscle-relaxed piglets were subjected to first right and then left capnothorax with an intra-pleural pressure of 19cm H2O. The contra-lateral lung was mechanically ventilated with a double-lumen tube at positive end-expiratory pressure 5 and subsequently 10cm H2O. Regional lung perfusion and ventilation were assessed by EIT. Hemodynamics, cerebral tissue oxygenation and lung gas exchange were also measured.

    Results: During right-sided capnothorax, mixed venous oxygen saturation (P=0.018), as well as a tissue oxygenation index (P=0.038) decreased. There was also an increase in central venous pressure (P=0.006), and a decrease in mean arterial pressure (P=0.045) and cardiac output (P=0.017). During the left-sided capnothorax, the hemodynamic impairment was less than during the right side. EIT revealed that during the first period of OLV/capnothorax, no or very minor ventilation on the right side could be seen (33% vs. 97 +/- 3%, right vs. left, P=0.007), perfusion decreased in the non-ventilated and increased in the ventilated lung (18 +/- 2% vs. 82 +/- 2%, right vs. left, P=0.03). During the second OLV/capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 +/- 4% vs. 16 +/- 4%, right vs. left).

    Conclusion: EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.

  • 34. Reske, Andreas W.
    et al.
    Costa, Eduardo L. V.
    Reske, Alexander P.
    Rau, Anna
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Beraldo, Marcelo A.
    Gottschaldt, Udo
    Seiwerts, Matthias
    Schreiter, Dierk
    Petroff, David
    Kaisers, Udo X.
    Wrigge, Hermann
    Amato, Marcelo B. P.
    Bedside Estimation of Nonaerated Lung Tissue Using Blood Gas Analysis2013In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 41, no 3, p. 732-743Article in journal (Refereed)
    Abstract [en]

    Objectives: Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. Design: Prospective observational clinical and laboratory animal investigations. Setting: ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of Sao Paulo, Brazil). Patients, Subjects and Interventions: Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different FIO2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/FIO2 to change this nonlinear relationship into a linear regression problem. Measurements and Main Results: We observed strong linear correlations between Riley's approximation of physiological shunt and CT shunt (R-2 = 0.84) and between logarithmically transformed PaO2/FIO2 and CT shunt (R-2 = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R-2 = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/FIO2 during pure oxygen ventilation, use of logarithmically transformed PaO2/FIO2 instead of the "raw" PaO2/FIO2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [-200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. Conclusion: During pure oxygen ventilation, logarithmically transformed PaO2/FIO2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [-200 and +100] Hounsfield Units.

  • 35.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bergamini, Bruno
    Carvalho, Alysson R
    Bozza, Fernando A
    Borzone, Gisella
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bugedo, Guillermo
    Bruhn, Alejandro
    Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 5, p. 505-Article in journal (Refereed)
    Abstract [en]

    Introduction

    When alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.

    Methods

    A total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.

    Results

    Atelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.

    Conclusions

    The present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.

  • 36.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bruhn, A
    Cao, Xiaofang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Feinstein, R
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Johansson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 1, p. 79-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium.

    METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated.

    RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR.

    CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

  • 37.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Hurtado, Daniel
    Villarroel, Nicolás
    Bruhn, Alejandro
    Bugedo, Guillermo
    Amato, Marcelo Britto Passos
    Costa, Eduardo Leite Vieira
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Pulmonary Division, Heart Institute (InCor), Hospital das Clinicas, University of São Paulo, São Paulo, Brazil.
    Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation?: An Experimental Porcine Study2018In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, no 6, p. e591-e599Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome.

    DESIGN: Retrospective analysis of CT images and positron emission tomography images using [18F]fluoro-2-deoxy-D-glucose.

    SETTING: University animal research laboratory.

    SUBJECTS: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls.

    INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal.

    MEASUREMENTS AND MAIN RESULTS: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [18F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R2 = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals.

    CONCLUSION: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

  • 38.
    Retamal, Jaime
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Departament de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spai.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Pulmonary Divison, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
    Feinstein, Ricardo
    The Swedish National Veterinary Institute, Sweden.
    Jalkanen, Sirpa
    MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Roivainen, Anne
    Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Turku Center for Disease Modelling, University of Turku, Furku, Finland.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Feasibility of 68Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome2016In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 1, p. 18-31Article in journal (Refereed)
    Abstract [en]

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.

  • 39.
    Retamal Montes, Jamie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bruhn, A.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Open Lung Approach Impedes Pulmonary Edema Accumulation Secondary To High Respiratory Rate In An Experimental Model Of Acute Lung Injury2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191Article in journal (Other academic)
  • 40.
    Retamal Montes, Jamie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hurtado, D. E.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Villarroel, N.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Bruhn, A.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Image-Based Estimation Of Regional Lung Strain During Ventilator-Induced Lung Injury2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191Article in journal (Other academic)
  • 41.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. CIBER Enfermedades Resp CIBERES, Madrid, Spain.; CNIC, Ctr Nacl Invest Cardiovasc Carlos 3, Madrid, Spain.
    Gomez-Peñalver, Eva
    Hosp Gen Villalba, Intens Care Unit, Villalba, Spain.
    Monge-Garcia, M Ignacio
    Hosp SAS, Intens Care Unit, Jerez de la Frontera, Spain.
    Retamal, Jaime
    Pontificia Univ Catolica Chile, Dept Med Intens, Santiago, Chile.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Sao Paulo, Heart Inst InCor, Hosp Clin, Div Pulm, Sao Paulo, Brazil.
    Tusman, Gerardo
    Department of Anesthesia, Hospital Privado de Comunidad, Mar del Plata, Argentina.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain..
    Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 11, p. e1157-e1164Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome.

    DESIGN: Experimental study.

    SETTING: University animal research laboratory.

    SUBJECTS: Twelve pigs (30.8 ± 2.5 kg).

    INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected.

    MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005).

    CONCLUSIONS: In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  • 42.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, Luca
    Monge-Garcia, M Ignacio
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Tusman, Gerardo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 3, p. e298-e305Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome.

    DESIGN: Experimental study.

    SETTING: Animal research laboratory.

    SUBJECTS: Ten pigs, 35 ± 5.2 kg.

    INTERVENTIONS: Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves.

    MEASUREMENTS AND MAIN RESULTS: After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p < 0.001), vascular compliance decreased (from 2.76 ± 0.86 to 1.48 ± 0.32 mL/mm Hg; p = 0.003), and reflected waves arrived earlier (0.23 ± 0.07 vs 0.14 ± 0.05, arbitrary unit; p = 0.002) compared with baseline. Comparing the three positive end-expiratory pressure levels, open lung approach resulted in the lowest: 1) Z0 (297 ± 83 vs 378 ± 79 dyn.s.cm, p = 0.033, and vs 450 ± 119 dyn.s.cm, p = 0.002); 2) effective arterial elastance (0.37 ± 0.08 vs 0.50 ± 0.15 mm Hg/mL, p = 0.04, and vs 0.61 ± 0.12 mm Hg/mL, p < 0.001), and 3) reflection coefficient (0.35 ± 0.17 vs 0.48 ± 0.10, p = 0.024, and vs 0.53 ± 0.19, p = 0.005), comparisons with hyperinflation and collapse, respectively.

    CONCLUSIONS: In this experimental setting, positive end-expiratory pressure consistent with the open lung approach resulted in the best pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressure settings.

  • 43.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Monge-Garcia, I
    Gomez Peñalver, E
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, L
    Retamal, Jaime
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Tusman, G
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    ARDS Decreases Pulmonary Artery Compliance in a Porcine Model2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 93, article id A7917Article in journal (Refereed)
    Abstract [en]

    Rationale: Importance of pulmonary hemodynamic disarrangements in ARDS has been remarked recently. In this study we describe the effect of ARDS on pulmonary artery compliance and the related effect on pulmonary hemodynamics. In this way we highlight the importance of pulsatile hemodynamic evaluation beyond the classic evaluation based only on resistance.

    Methods: 17 anesthetized and muscle relaxed pigs were monitored with a transonic flow probe and high fidelity micro-tip pressure sensor placed in the pulmonary artery through a small thoracotomy. An experimental model of ARDS was induced in these animals by means of lung saline lavages followed by two hours of injurious mechanical ventilation. Pulmonary artery compliance was measured as the stroke volume divided by the pulse pressure. Waveform analysis of pulmonary artery pressure and flow signal was applied to calculate the following variables: first harmonic impedance magnitude (inversely related with arterial compliance), characteristic impedance, wave reflections (which are affected by arterial compliance) magnitude and peak and foot arrival time (normalized to cardiac period). These variables are related to the pulmonary vessels efficiency to transmit pressure and flow produced by the right ventricle. In addition, pulmonary vascular resistance was evaluated as usual. Variables were evaluated before (Baseline) and after (ARDS) development of the model.

    Results: Comparing with Baseline, ARDS provoked a decrease in pulmonary artery compliance (3.03±0.99 vs 1.53±0.41 ml/mmHg, p<0.001), and in the wave reflections arrival time of foot (0.18±0.09 vs 0.11±0.05, p<0.001) and peak (0.50±0.12 vs 0.39±0.10, p< 0.001) and an increase in the impedance magnitude of the first harmonic (80±29 vs 145±38 dyn.s.cm-5, p<0.001) and in the pulmonary vascular resistance (230±79 vs 504±129 dyn.s.cm-5, p<0.001). Characteristic impedance and wave reflections magnitude showed no differences.

    Conclusions: In this porcine model, ARDS provoked a decrease in pulmonary artery compliance. This effect was followed by a deterioration of pulmonary vascular efficiency. Our findings can be relevant for the pathophysiology of right ventricle failure during ARDS. This abstract is funded by: European Society of Intensive Care Medicine (ESICM), Basic Science Award 2012, the Swedish Heart and Lung foundation and the Swedish Research Council (K2015-99X-22731-01-4)

  • 44.
    Santos, Arnoldo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Monge-Garcia, M.
    Hosp SAS, Jerez de la Frontera, Spain..
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gomez-Penalver, E.
    Hosp Gen Villalba, Villalba, Spain..
    Retamal, J.
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Lucchetta, L.
    Hosp San Matteo, Pavia, Italy..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Pulmonary Vascular Efficiency Worsening And Cardiac Energy Wasting During Early Stages Of Experimental Acute Respiratory Distress Syndrome2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, no D27, article id A7698Article in journal (Other academic)
  • 45.
    Scaramuzzo, Gaetano
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Ferrara, Dept Morphol Surg & Expt Med, Ferrara, Italy.
    Broche, Ludovic
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. European Synchrotron Radiat Facil, Grenoble, France;Grenoble Alpes Univ, Synchrotron Radiat Biomed STROBE Lab, INSERM UA7, Amiens, France.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Porra, Liisa
    Univ Helsinki, Fac Math & Nat Sci, Dept Phys, Helsinki, Finland;Univ Helsinki, Cent Hosp, Helsinki, Finland.
    Derosa, Savino
    Univ Bari Aldo Moro, Dept Emergency & Organ Transplant, Bari, Italy.
    Tannoia, Angela Principia
    Univ Bari Aldo Moro, Dept Emergency & Organ Transplant, Bari, Italy.
    Marzullo, Andrea
    Univ Bari Aldo Moro, Dept Emergency & Organ Transplant, Bari, Italy.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Kings Coll London, Fac Sci & Med, Ctr Human & Appl Physiol Sci, London, England.
    Bayat, Sam
    Grenoble Alpes Univ, Synchrotron Radiat Biomed STROBE Lab, INSERM UA7, Amiens, France.
    Bravin, Alberto
    European Synchrotron Radiat Facil, Grenoble, France.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Regional Behavior of Airspaces During Positive Pressure Reduction Assessed by Synchrotron Radiation Computed Tomography2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 719Article in journal (Refereed)
    Abstract [en]

    Introduction: The mechanisms of lung inflation and deflation are only partially known. Ventilatory strategies to support lung function rely upon the idea that lung alveoli are isotropic balloons that progressively inflate or deflate and that lung pressure/volume curves derive only by the interplay of critical opening pressures, critical closing pressures, lung history, and position of alveoli inside the lung. This notion has been recently challenged by subpleural microscopy, magnetic resonance, and computed tomography (CT). Phase-contrast synchrotron radiation CT (PC-SRCT) can yield in vivo images at resolutions higher than conventional CT.

    Objectives: We aimed to assess the numerosity (ASden) and the extension of the surface of airspaces (ASext) in healthy conditions at different volumes, during stepwise lung deflation, in concentric regions of the lung. Methods: The study was conducted in seven anesthetized New Zealand rabbits. They underwent PC-SRCT scans (resolution of 47.7 mu m) of the lung at five decreasing positive end expiratory pressure (PEEP) levels of 12, 9, 6, 3, and 0 cmH(2)O during end-expiratory holds. Three concentric regions of interest (ROIs) of the lung were studied: subpleural, mantellar, and core. The images were enhanced by phase contrast algorithms. ASden and ASext were computed by using the Image Processing Toolbox for MatLab. Statistical tests were used to assess any significant difference determined by PEEP or ROI on ASden and ASext.

    Results: When reducing PEEP, in each ROI the ASden significantly decreased. Conversely, ASext variation was not significant except for the core ROI. In the latter, the angular coefficient of the regression line was significantly low.

    Conclusion: The main mechanism behind the decrease in lung volume at PEEP reduction is derecruitment. In our study involving lung regions laying on isogravitational planes and thus equally influenced by gravitational forces, airspace numerosity and extension of surface depend on the local mechanical properties of the lung.

  • 46.
    Suarez-Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    How We Stretch the Lung Matters2013In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 41, no 4, p. 1153-1155Article in journal (Other academic)
  • 47.
    Suarez-Sipmann, Fernando
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Santos, Arnoldo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Boehm, Stephan H.
    Borges, Joao Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Tusman, Gerardo
    Corrections of Enghoffs dead space formula for shunt effects still overestimate Bohr's dead space2013In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 189, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Dead space ratio is determined using Enghoffs modification (VDB-E/V-T) of Bohr's formula (V-DBohr/V-T) in which arterial is used as a surrogate of alveolar PCO2. In presence of intrapulmonary shunt Enghoffs approach overestimates dead space. In 40 lung-lavaged pigs we evaluated the Kuwabara's and Niklason's algorithms to correct for shunt effects and hypothesized that corrected VDB-E/V-T should provide similar values as V-DBohr/V-T. We analyzed 396 volumetric capnograms and arterial and mixed-venous blood samples to calculate V-DBohr/V-T and VDB-E/V-T. Thereafter, we corrected the latter for shunt effects using Kuwabara's (K) VDB-E/V-T and Niklason's (N) VDB-E/V-T algorithms. Uncorrected VDB-E/V-T (mean +/- SD of 0.70 +/- 0.10) overestimated V-DBohr/V-T (0.59 +/- 0.12) (p < 0.05), over the entire range of shunts. Mean (K) VDB-E/V-T was significantly higher than V-DBor/V-T (0.67 +/- 0.08, bias 0.085, limits of agreement 0.232 to 0.085; p< 0.05) whereas (N)VDB-E/V-T showed a better correction for shunt effects (0.64 +/- 0.09, bias 0.048, limits of agreement -0.168 to 0.072; p < 0.05). Neither Kuwabara's nor Niklason's algorithms were able to correct EnghofFs dead space formula for shunt effects. 

  • 48.
    Velikyan, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Berhane, T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    One pot preparation of Ga-68-labelled macroaggregated albumin for PET-imaging of acute pulmonary embolism and myocardial perfusion quantification2012In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 39, no S2, p. S410-S411Article in journal (Other academic)
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