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  • 1. Bergmann, Astrid
    et al.
    Jovanovska, Elena
    Schilling, Thomas
    Hedenstierna, Göran
    Föllner, Sebastian
    Schreiber, Jens
    Hachenberg, Thomas
    Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers.2020In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 271, article id 103287Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Remote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol.

    RESULTS: 60 min after RIP capillary pO2 decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO2, variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups.

    CONCLUSION: Oxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.

  • 2.
    Bergmann, Astrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Schilling, Thomas
    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.
    Ahlgren, Kerstin M.
    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.
    Kretzschmar, Moritz
    Kozian, Alf
    Hachenberg, Thomas
    Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury.2018In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 259, p. 111-118Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: One-lung ventilation (OLV) may result in lung injury due to increased mechanical stress and tidal recruitment. As a result, a pulmonary inflammatory response is induced. The present randomized, controlled, animal experiment was undertaken to assess the effects of remote ischemic preconditioning (RIP) on diffuse alveolar damage and immune response after OLV.

    METHODS: Fourteen piglets (26 ± 2 kg) were randomized to control (n = 7) and RIP group (n = 7). For RIP, a blood pressure cuff at hind limb was inflated up to 200 mmHg for 5 min and deflated for another 5 min, this being done four times before OLV. Mechanical ventilation settings were constant throughout the experiment: VT = 10 ml/kg, FIO2 = 0.40, PEEP = 5cmH2O. OLV was performed by left-sided bronchial blockade. Number of cells was counted from BAL fluid; cytokines were assessed by immunoassays in lung tissue and serum samples. Lung tissue samples were obtained for histological analysis and assessment of diffuse alveolar damage (DAD) score.

    RESULTS: Hemodynamic and respiratory data were similar in both groups. Likewise, no differences in pulmonary tissue TNF-α and protein content were found, but fewer leukocytes were counted in the ventilated lung after RIP. DAD scores were high without any differences between controls and RIP. On the other hand, alveolar edema and microhemorrhage were significantly increased after RIP.

    CONCLUSIONS: OLV results in alveolar injury, possibly enhanced by RIP. On the other hand, RIP attenuates the immunological response and decreased alveolar leukocyte recruitment in a porcine model of OLV.

  • 3.
    Brander, Lukas
    et al.
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;Cantonal Hosp Lucerne, Dept Intens Care Med, CH-6000 Luzern, Switzerland..
    Moerer, Onnen
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;Univ Gottingen, Dept Anaesthesiol Emergency & Crit Care Med, Gottingen, Germany..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Beck, Jennifer
    Univ Toronto, Dept Pediat, Toronto, ON, Canada.;St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.;Ryerson Univ, Inst Biomed Engn & Sci Technol, Toronto, ON, Canada.;St Michaels Hosp, Toronto, ON, Canada..
    Takala, Jukka
    Univ Hosp Bern, Inselspital, Dept Intens Care Med, Bern, Switzerland.;Univ Bern, CH-3012 Bern, Switzerland..
    Slutsky, Arthur S.
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada..
    Sinderby, Christer
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.;Ryerson Univ, Inst Biomed Engn & Sci Technol, Toronto, ON, Canada.;St Michaels Hosp, Toronto, ON, Canada..
    Neural control of ventilation prevents both over-distension and de-recruitment of experimentally injured lungs2017In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 237, p. 57-67Article in journal (Refereed)
    Abstract [en]

    Background: Endogenous pulmonary reflexes may protect the lungs during mechanical ventilation. We aimed to assess integration of continuous neurally adjusted ventilatory assist (cNAVA), delivering assist in proportion to diaphragm's electrical activity during inspiration and expiration, and Hering-Breuer inflation and deflation reflexes on lung recruitment, distension, and aeration before and after acute lung injury (ALI).

    Methods: In 7 anesthetised rabbits with bilateral pneumothoraces, we identified adequate cNAVA level (cNAVA(AL)) at the plateau in peak ventilator pressure during titration procedures before (healthy lungs with endotracheal tube, [HLETT]) and after ALI (endotracheal tube [ALI(ETT)] and during non-invasive ventilation [ALI(NIV)]). Following titration, cNAVA(AL) was maintained for 5 min. In 2 rabbits, procedures were repeated after vagotomy (ALI(ETT+VAG)). In 3 rabbits delivery of assist was temporarily modulated to provide assist on inspiration only. Computed tomography was performed before intubation, before ALI, during cNAVA titration, and after maintenance at cNAVA(AL).

    Results: During ALI(ETT) and ALI(NIV), normally aerated lung-regions doubled and poorly aerated lung-regions decreased to less than a third (p < 0.05) compared to HLETT; no over-distension was observed. Tidal volumes were <5 ml/kg throughout. Removing assist during expiration resulted in lung de-recruitment during ALI(ETT) but not during ALI(NIV). During ALI(ETT+VAG) the expiratory portion of EAdi disappeared, resulting in cyclic lung collapse and recruitment.

    Conclusions: When using cNAVA in ALI, vagally mediated reflexes regulated lung recruitment preventing both lung over-distension and atelectasis. During non-invasive cNAVA the upper airway muscles play a role in preventing atelectasis. Future studies should be performed to compare these findings with conventional lung-protective approaches.

  • 4.
    Buehler, Sarah
    et al.
    Univ Med Ctr Freiburg, Dept Anesthesiol & Intens Care Med, Div Expt Anesthesiol, Freiburg, Germany..
    Schumann, Stefan
    Univ Med Ctr Freiburg, Dept Anesthesiol & Intens Care Med, Div Expt Anesthesiol, Freiburg, Germany..
    Vimlati, Laszlo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Guttmann, Josef
    Univ Med Ctr Freiburg, Dept Anesthesiol & Intens Care Med, Div Expt Anesthesiol, Freiburg, Germany..
    Simultaneous monitoring of intratidal compliance and resistance in mechanically ventilated piglets: A feasibility study in two different study groups2015In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 219, p. 36-42Article in journal (Refereed)
    Abstract [en]

    Compliance measures the force counteracting parenchymal lung distension. In mechanical ventilation, intratidal compliance-volume (C(V))-profiles therefore change depending on PEEP, tidal volume (V-T), and underlying mechanical lung properties. Resistance counteracts gas flow through the airways. Due to anatomical linking between parenchyma and airways, intratidal resistance-volume (R(V))-profiles are hypothesised to change in a non-linear way as well. We analysed respiratory system mechanics in fifteen piglets with lavage-induced lung injury and nine healthy piglets ventilated at different PEEP/V-T-settings. In healthy lungs, R(V)-profiles remained mostly constant and linear at all PEEP-settings whereas the shape of the C(V)-profiles showed an increase toward a maximum followed by a decrease (small PEEP) or volume-dependent decrease (large PEEP). In the lavage group, a large drop in resistance at small volumes and slow decrease toward larger volumes was found for small PEEP/V-T-settings where C(V)-profiles revealed a volume-dependent increase (small PEEP) or a decrease (large PEEP and large VT). R(V)-profiles depend characteristically on PEEP, V-T, and possibly whether lungs are healthy or not. Curved R(V)-profiles might indicate pathological changes in the underlying mechanical lung properties and/or might be a sign of derecruitment.

  • 5.
    Jonasson, Sofia
    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.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hjoberg, Josephine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Comparisons of effects of intravenous and inhaled methacholine on airway physiology in a murine asthma model2009In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 165, no 2-3, p. 229-236Article in journal (Refereed)
    Abstract [en]

    Airway responses to intravenous (i.v.) and inhaled (i.h.) delivery of methacholine (MCh) in BALB/c and C57BL/6 mouse strains have been compared with and without ovalbumin (OVA)-induced airway inflammation. Bronchial reactivity to MCh was assessed in anaesthetised and tracheostomised animals by using an animal ventilator (flexiVent). We partitioned the response of the lungs into airway and parenchymal components in order to compare the contributions of the airways with those of the lung parenchyma to the pulmonary mechanical responses resulting from different routes of MCh administration. Our results indicate disparate physiological responses. Intravenous MCh delivery induced a higher maximum lung resistance than i.h. MCh in OVA-treated BALB/c mice but not in C57BL/6 mice. Inhaled MCh delivery led to a significantly larger fall in lung compliance and a greater impact on peripheral airways than i.v. MCh in both strains. In conclusion, i.v. and i.h. MCh produced disparate effects in different murine strains and variant responses in inflamed airways and healthy controls. The two methods of MCh delivery have important advantages but also certain limitations with regard to measuring airway reactivity in a murine model of allergic asthma.

  • 6.
    Kretzschmar, Moritz
    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 Medical Sciences, Clinical Physiology.
    Kozian, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Baumgardner, James E
    Schreiber, Jens
    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.
    Hachenberg, Thomas
    Schilling, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model2016In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 220, p. 88-94Article in journal (Refereed)
    Abstract [en]

    Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (V̇A/Q̇) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100μg/ml, n=6) increased respiratory resistance, impaired V̇A/Q̇ distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5min vs. 1.1min, to P90: 4.0min vs. 14.8min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous V̇A/Q̇ distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.

  • 7.
    Pellegrini, Mariangela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Derosa, Savino
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Tannoia, Angela
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Rylander, Christian
    Sahlgrens Univ Hosp, Dept Anaesthesia & Intens Care Med, Gothenburg, Sweden..
    Fiore, Tommaso
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    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.
    Perchiazzi, Gaetano
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Effects of superimposed tissue weight on regional compliance of injured lungs2016In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 228, p. 16-24Article in journal (Refereed)
    Abstract [en]

    Computed tomography (CT), together with image analysis technologies, enable the construction of regional volume (V-REG) and local transpulmonary pressure (P-TP,P-REG) maps of the lung. Purpose of this study is to assess the distribution of V-REG vs P-TP,P-REG along the gravitational axis in healthy (HL) and experimental acute lung injury conditions (eALI) at various positive end-expiratory pressures (PEEPS) and inflation volumes. Mechanically ventilated pigs underwent inspiratory hold maneuvers at increasing volumes simultaneously with lung CT scans. eALI was induced via the iv administration of oleic acid. We computed voxel-level V-REG vs P-TP,P-REG curves into eleven isogravitational planes by applying polynomial regressions. Via F-test, we determined that V-REG vs P-TP,P-REG curves derived from different anatomical planes (p-values < 1.4E-3), exposed to different PEEPs (p-values < 1.5E-5) or subtending different lung status (p-values < 3E-3) were statistically different (except for two cases of adjacent planes). Lung parenchyma exhibits different elastic behaviors based on its position and the density of superimposed tissue which can increase during lung injury.

  • 8.
    Perchiazzi, Gaetano
    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, Hedenstierna laboratory.
    Rylander, Christian
    Derosa, Savino
    Pellegrini, Mariangela
    Pitagora, Loredana
    Polieri, Debora
    Vena, Antonio
    Tannoia, Angela
    Fiore, Tommaso
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Regional distribution of lung compliance by image analysis of computed tomograms2014In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 201, p. 60-70Article in journal (Refereed)
    Abstract [en]

    Computed tomography (CT) can yield quantitative information about volume distribution in the lung. By combining information provided by CT and respiratory mechanics, this study aims at quantifying regional lung compliance (CL) and its distribution and homogeneity in mechanically ventilated pigs. The animals underwent inspiratory hold maneuvers at 12 lung volumes with simultaneous CT exposure at two end-expiratory pressure levels and before and after acute lung injury (ALI) by oleic acid administration. CL and the sum of positive voxel compliances from CT were linearly correlated; negative compliance areas were found. A remarkably heterogeneous distribution of voxel compliance was found in the injured lungs. As the lung inflation increased, the homogeneity increased in healthy lungs but decreased in injured lungs. Image analysis brought novel findings regarding spatial homogeneity of compliance, which increases in ALI but not in healthy lungs by applying PEEP after a recruitment maneuver.

  • 9.
    Rieger-Fackeldey, Esther
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sedin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bronchopulmonary C-fibers modulate the breathing pattern in surfactant-depleted juvenile cats2008In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 160, no 3, p. 341-349Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the influence of nonmyelinated C-fibers on the breathing pattern by cooling the vagal nerves to temperatures at which myelinated nerve transmission from pulmonary stretch receptors is blocked (+7 degrees C) and further at which nonmyelinated fiber input is blocked (0 degrees C), in anaesthetized spontaneously breathing juvenile cats with normal (L(N)), surfactant-depleted (L(D)) and surfactant-treated (L(T)) lungs. In L(N), vagal cooling from +7 to 0 degrees C decreased respiratory frequency (f(R); -8%; p < 0.01), and increased tidal volume (V(T); +40%; p < 0.01). In the presence of shallow fast breathing in L(D), f(R) decreased (+38 to +7 degrees C: -26%; p < 0.015 and +7 to 0 degrees C: -24%; p < 0.001) and V(T) increased (+37%; p < 0.049 and +88%; p < 0.016). In L(T), f(R) decreased (+7 to 0 degrees C: -21%; p < 0.001), whereas V(T) remained the same at 0 degrees C (+12%; NS). These findings show for the first time that the activity of bronchopulmonary C-fibers have a prominent role in modulating the breathing pattern in juvenile cats with surfactant-depleted lungs.

  • 10.
    Rostami, Elham
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rocksen, David
    Ekberg, Neda R.
    Goiny, Michel
    Ungerstedt, Urban
    Brain metabolism and oxygenation in healthy pigs receiving hypoventilation and hyperoxia2013In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 189, no 3, p. 537-542Article in journal (Refereed)
    Abstract [en]

    Modulation in ventilatory settings is one of the approaches and interventions used to treat and prevent secondary brain damage after traumatic brain injury (TBI). Here we investigate the effect of hyperoxia in combination with hypoventilation on brain oxygenation, metabolism and intracranial pressure. Twelve pigs were divided into three groups; groupl-100% hyperoxia (n=4), group 2-100% hyperoxia and 20% decrease in minute volume (MV) (n=4) and group 3-100% hyperoxia and 50% decrease in MV (n=4). Neither of the ventilator settings affected the lactate/pyruvate ratio significantly. However, there was a significant decrease of brain lactate (2.6+/-1.7 to 1.8+/-1.6 mM) and a rapid and marked increase in brain oxygenation (7.9+/-0.7 to 61.3+/-17.6 mmHg) in group 3. Intracranial pressure (ICP) was not significantly affected in this group, however, the ICP increased significantly in group 2 with 100% hyperoxia plus 20% reduction in minute volume. We conclude that hyperoxia in combination with 50% decrease in MV showed pronounced increase in partial brain oxygen tension (pbrO(2)) and decrease in brain lactate. The ventilatory modification, used in this study should be considered for further investigation as a possible therapeutic intervention for TBI patients.

  • 11. Schumann, S.
    et al.
    Kessler, V.
    Joerges, S.
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Guttmann, J.
    Respiratory system inertance corresponds to extravascular lung water in surfactant-deficient piglets2008In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 160, no 3, p. 313-9Article in journal (Refereed)
    Abstract [en]

    In various cardio-pulmonary diseases lung mass is considerably increased due to intrapulmonary fluid accumulation, i.e. extravascular lung water (EVLW). Generally, inertance is a physical system parameter that is mass-dependent. We hypothesized that changes in lung mass influence the inertive behavior of the respiratory system. EVLW and intrathoracic blood volume (ITBV) were compared with respiratory system inertance (I(rs)) in four piglets before and after broncho-alveolar lavage (BAL) that induced surfactant deficiency with interstitial edema. EVLW and ITBV were determined using the double-indicator dilution technique, I(rs) by multiple linear regression analysis. Measurements were taken before, and 1 and 2 h after BAL. EVLW increased threefold (from 6.2+/-0.8 mL/kg at baseline to 17.7+/-0.9 mL/kg (p < 0.001) after BAL). I(rs) increased by 35% (from 0.17+/-0.02 to 0.23+/-0.04 cmH(2)O s(2)/L (p = 0.036) after BAL) and was tightly correlated to EVLW (r(2) = 0.95, p < 0.023). ITBV did not change significantly after BAL. We conclude that I(rs) reflects actual changes in lung mass and thus hints at fluid accumulation within the lung.

  • 12. Schumann, Stefan
    et al.
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Haberthuer, Christoph
    Stahl, Claudius A.
    Moeller, Knut
    Guttmann, Josef
    Detection of partial endotracheal tube obstruction by forced pressure oscillations2007In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 155, no 3, p. 227-233Article in journal (Refereed)
    Abstract [en]

    Rapid airway occlusions during mechanical ventilation are followed immediately by high-frequency pressure oscillations. To answer the question if the frequency of forced pressure oscillations is an indicator for partial obstruction of the endotracheal tube (ETT) we performed mathematical simulations and studies in a ventilated physical lung model. Model-derived predictions were evaluated in seven healthy volunteers. Partial ETT obstruction was mimicked by decreasing the inner diameter (ID) of the ETT. In the physical model ETTs of different ID were used. In spontaneously breathing volunteers viscous fluid was applied into the ETT's lumen. According to the predictions derived from mathematical simulations, narrowing of the ETT's ID from 9.0 to 7.0 mm decreased the frequency of the pressure oscillations by 11% while changes of the respiratory system's compliance had no effect. In volunteers, a similar reduction (10.9%) was found when 5 ml fluid were applied. We conclude that analysis of pressure oscillations after flow interruption offers a tool for non-invasive detection of partial ETT obstruction.

  • 13.
    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. 

  • 14. Tusman, Gerardo
    et al.
    Suarez-Sipmann, Fernando
    Peces-Barba, Germán
    Climente, Carlos
    Areta, Martín
    Arenas, Paloma Gonzalez
    Bohm, Stephan H
    Pulmonary blood flow generates cardiogenic oscillations2009In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 167, no 3, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Cardiogenic oscillations are small waves produced by heartbeats, which are superimposed on the pressure and flow signals at the airway opening. The aim of this study was to investigate the role of the two main factors believed to generate these oscillations: (1) contact between heart and lungs and (2) pulmonary blood flow. We studied 15 heart surgery patients on cardiopulmonary bypass so both factors could be manipulated independently.

    At minimal heart–lung contact pressure and flow oscillations were larger than during maximal contact (1.20 ± 0.17 cmH2O and 2.36 ± 0.08 L min−1 vs 0.92 ± 0.15 cmH2O and 1.78 ± 0.26 L min−1, mean ± SD, p < 0.05). Cardiogenic oscillations for pressure and flow were smaller at 50% compared to 100% pulmonary blood flow (0.80 ± 0.12 cmH2O and 1.56 ± 0.34 L min−1 vs 1.19 ± 0.14 cmH2O and 2.38 ± 0.19 L min−1). We conclude that the amount of pulmonary blood flow and not the contact between heart and lungs is the main factor determining the amplitude of cardiogenic oscillations.

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