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  • 1. Ehrhardt, Harald
    et al.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rieger-Fackeldey, Esther
    Schaller, Peter
    Schulze, Andreas
    Sedin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology and Medical Biophysics.
    Effects of the inspiratory pressure waveform during patient-triggered ventilation on pulmonary stretch receptor and phrenic nerve activity in cats2001In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 29, no 6, p. 1207-1214Article in journal (Refereed)
    Abstract [en]

    Objective:

    To examine the effects of square wave, sinusoidal, and linear inspiratory pressure waveforms during pressure-controlled assist/control ventilation on the firing pattern of pulmonary stretch receptors and phrenic nerve activity.

    Design:

    Experimental, comparative study.

    Setting:

    Research laboratory at a university biomedical center.

    Subjects:

    Nine anesthetized, endotracheally intubated young cats (2.5–3.4 kg).

    Intervention:

    With interposed periods of continuous positive airway pressure (0.2 kPa), each cat was exposed to periods of assist/control ventilation with three different pressure waveforms, where the peak inspiratory pressure (0.74 ± 0.13 kPa), end-expiratory pressure (0.2 ± 0.02 kPa), and tidal volume (14.9 ± 5.22 mL/kg) were kept constant. Preset controlled ventilator rate was set below the rate of spontaneous breathing, and the mechanical inflation time equaled the inspiratory time during spontaneous breathing on continuous positive airway pressure.

    Measurements and Main Results:

    Respiratory rate and arterial blood gases did not change between the three pressure waveforms during assist/control ventilation. Peak pulmonary stretch receptor activity was lower and mean phrenic nerve activity higher during continuous positive airway pressure than during assist/control ventilation (p < .05). Peak inspiratory pulmonary stretch receptor activity was the same with all three pressure waveforms (82 ± 17 impulses·sec-1) but occurred earlier with square wave than with sinusoidal or linear pressure waveforms (p < .05). The total number of impulses in the phrenic nerve activity burst was smaller with square wave than with the other two pressure waveforms (0.21 ± 0.17 vs. 0.33 ± 0.27 and 0.42 ± 0.30 arbitrary units;p < .05), and the phrenic nerve activity burst duration was shorter with square wave (1.10 ± 0.45 vs. 1.54 ± 0.36 and 1.64 ± 0.25 secs;p < .05).

    Conclusion:

    Square wave pressure waveform during pressure-controlled assist/control ventilation strongly inhibits spontaneous inspiratory activity in cats. One mechanism for this inhibition is earlier and sustained peak pulmonary stretch receptor activity during inspiration. These findings show that differences in inspiratory pressure waveforms influence the spontaneous breathing effort during assist/control ventilation in cats.

  • 2. Ley, D
    et al.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kapitel 3: Neonatala cirkulationsstörningar inkluderande hypovolemi, hypotension och PDA2010In: Akut Pediatrik / [ed] Svante Norgren, Jonas F. Ludvigsson, Mikael Norman, Tomas Widlund, Stockholm: Liber , 2010, p. 37-44Chapter in book (Other academic)
  • 3.
    Munsters, Josanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wallström, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Norsted, Torgny
    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.
    Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age2012In: Early Human Development, ISSN 0378-3782, E-ISSN 1872-6232, Vol. 88, no 1, p. 21-26Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants >28 gestational age (GA) submitted to heel lancing.

    OBJECTIVE: To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA).

    METHODS: In six infants <28+0 GA and 4 infants ≥28+0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA.

    RESULTS: Baseline SC prior to intervention took longer time to stabilise and was higher in <28 than in ≥28+0 PNA. The combination of heel lancing and squeezing gave an increased SC in <28 PNA, whereas heel lancing alone gave the same SC response in ≥28+0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in <28 PNA. to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born <28 GA. SC seems to be able to differentiate between pain and discomfort.

  • 4. Nydert, Per
    et al.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Enteral läkemedelsadministrering till barn i nyföddhetsperioden2013In: Information från Läkemedelsverket, ISSN 1101-7104, Vol. 24, no 2, p. 46-49Article in journal (Refereed)
  • 5.
    Olsson, Karl Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    A High Ductal Flow Velocity is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22-27 Weeks Gestational Age2012In: Critical Care Research and Practice, ISSN 2090-1305, E-ISSN 2090-1313, p. 715265-Article in journal (Refereed)
    Abstract [en]

    Objective:

    To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22-27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors.

    Method:

    Infants born at 22-27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory and outcome parameters. Echocardiographic examinations during treatment were reviewed.

    Results:

    Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25+4 weeks vs. 24+3 weeks; P=0.047), and a higher pre-treatment left to right maximal ductal flow velocity (1.6 m/s vs. 1.1 m/s; P=0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at treatment start, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04, p=0.049).

    Conclusion:

    Maximal ductal flow velocity was independently associated with success of PDA treatment.

  • 6.
    Olsson, Karl Wilhelm
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Future Benefits of Sequential Echocardiography: Unmasking the Indications for Treatment of Patent Ductus Arteriosus in Extremely Preterm Infants2015In: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 108, no 2, p. 99-99Article in journal (Refereed)
  • 7.
    Rieger-Fackeldey, Esther
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Schulze, Andreas
    Sedin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Inhibition of breathing after Surfactant Depletion is Achieved at a Higher Arterial PCO2 during Ventilation with Liquid than with Gas2005In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 6, p. 24-Article in journal (Refereed)
    Abstract [en]

    Background

    Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.

    Objective

    To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.

    Methods

    Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (Vt), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.

    Results

    During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO2 during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.

    Conclusion

    Inhibition of inspiratory activity occurs at a higher PaCO2 during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.

  • 8.
    Rieger-Fackeldey, Esther
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Sindelar, Richard
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Jonzon, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Schulze, Andreas
    Sedin, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Pulmonary stretch receptor activity during Partial Liquid Ventilation in Cats with Healthy Lungs.2004In: Biol Neonate, ISSN 0006-3126, Vol. 86, no 2, p. 73-80Article in journal (Other scientific)
  • 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.
    Sindelar, R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Kapitel Neonatalperioden. Andningstörningar. Cirkulationsstörningar2007Other (Other scientific)
  • 11.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Läkemedelsadministrering via sond. Behandlingsrekommendation2013Report (Other academic)
  • 12.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Neonatal hypotension2013In: Terapikompendium i pediatrik, Uppsala: UAS , 2013, p. 1-3Chapter in book (Other academic)
  • 13.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Pulmonell hypertension hos nyfödda2013In: Terapikompendium i pediatrik, Uppsala: UAS , 2013, p. 1-2Chapter in book (Other academic)
  • 14.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Vård av extremt för tidigt födda barn: En vägledning för vården av barn födda före 28 fullbordade graviditetsveckor2014Report (Other academic)
  • 15.
    Sindelar, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kapitel 2. Andningsstörningar hos nyfödda2010In: Akut Pediatrik / [ed] Svante Norgren, Jonas F Ludvigsson, Mikael Norman, Tomas Widlund, Stockholm: Liber, 2010, p. 24-36Chapter in book (Other academic)
  • 16.
    Sindelar, Richard
    et al.
    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.
    Diafragmal pacing och kongenital centralt hypoventilationssyndrom2013In: Terapikompendium i pediatrik, Uppsala: UAS , 2013, p. 1-3Chapter in book (Other academic)
  • 17.
    Sindelar, Richard
    et al.
    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.
    PDA hos underburna barn2013In: Terapikompendium i pediatrik, Uppsala: UAS , 2013, p. 1-3Chapter in book (Other academic)
  • 18.
    Sindelar, Richard
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Jonzon, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Schulze, Andreas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Sedin, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Surfactant replacement partially restores the activity of pulmonary stretch receptors in surfactant-depleted cats.2006In: J Appl Physiol, ISSN 8750-7587, Vol. 100, no 2, p. 594-601Article in journal (Refereed)
  • 19.
    Sindelar, Richard
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Rieger-Fackeldey, Esther
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Jonzon, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Schaller, Peter
    Schulze, Andreas
    Sedin, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity.2006In: Respir Res, ISSN 1465-993X, Vol. 7, p. 38-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV). It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs) followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]). Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment. OBJECTIVE: To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP) early after surfactant instillation in relation to phrenic nerve activity (PNA) and the activity of PSRs. METHODS: Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2-0.5 kPa) before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil. RESULTS: Tidal volume and respiratory rate were higher with lower PaCO2 and higher PaO2 during PAV than during CPAP both before and after surfactant instillation (p < 0.05; both conditions). As an indicator of breathing effort, esophageal deflection pressure and PNA were lower during PAV than during CPAP in both conditions (p < 0.02). Peak PSR activity was higher and occurred earlier during PAV than during CPAP (p < 0.01), and correlated linearly with PNA duration in all conditions studied (p < 0.001). The inspiratory time decreased as tidal volume increased when CPAP was changed to PAV, with the highest correlation observed after surfactant instillation (r = -0.769). No apneic periods could be observed. CONCLUSION: PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.

  • 20.
    Sindelar, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wallström, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Neonatala andningsstörningar2013In: Terapikompendium i pediatrik, Uppsala: UAS , 2013, p. 1-6Chapter in book (Other academic)
  • 21.
    Sindelar, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wallström, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Neonatala andningsstörningar2013In: Terapikompendium pediatrik / [ed] Tryggve Nevéus, Johan Ågren, Uppsala: Uppsala Akademiska barnsjukhus , 2013, , p. 6p. 71-76Chapter in book (Other academic)
  • 22.
    Stålhammar, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Douhan Håkansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Under Agarose Migration Assay: a Method to Study Graded Chemotactic Activity of Leukocytes in Newborn Infants2010In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 68, no suppl. 1, p. 427-427Article in journal (Refereed)
  • 23.
    Stålhammar, Maria E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Douhan Håkansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bacterial N-formyl Peptides Reduce PMA and Escherichia coli-Induced Neutrophil Respiratory Burst in Term Neonates and Adults2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 85, no 5, p. 365-371Article in journal (Refereed)
    Abstract [en]

    Neutrophil migration and respiratory burst is the prerequisite for efficient first line defense against invading microorganisms. However, migration and respiratory burst can be compromised in adults and especially in newborn infants, where sustained neutrophil accumulation, uncontrolled burst and reduced scavenging of ROS might cause inadvertent tissue damage due to uncontrolled inflammation. The aim of this study was to investigate the modulatory effect of the chemoattractants formyl-methionyl-leucyl-phenylalanine (fMLP) and IL-8 on respiratory burst in neutrophils from term newborn infants and adults. Whole blood from the umbilical cord of 17 healthy term newborn infants delivered by caesarean section and from 17 healthy adults as reference was preincubated with fMLP or IL-8 and stimulated with PMA or E.coli bacteria. Respiratory burst was quantified by flow cytometry analysis of dihydrorhodamine 123 fluorescence. fMLP reduced the PMA-induced respiratory burst of neutrophils from newborn infants and adults by 12% and 21% respectively (p<0.05). E.coli-induced burst was also reduced by fMLP in neutrophils from newborn infants (10%; p<0.01) and adults (6%; p<0.05). No such changes were observed with IL-8. Similar respiratory burst in response to single stimulus with PMA or E.coli were observed in both newborn infants and adults. fMLP reduced PMA- and E.coli-induced respiratory burst of neutrophils in whole blood from term newborn infants as well as in adults. The reduced respiratory burst by fMLP might be a mechanism to reduce the detrimental effects of uncontrolled inflammation during neutrophil migration

  • 24.
    Stålhammar, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Håkansson, Lena Douhan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonzon, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sindelar, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Differential Neutrophil Chemotactic Response towards IL-8 and Bacterial N-formyl Peptides in Term Newborn Infants2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A prerequisite for an effective innate immunity is the migrative ability of neutrophils to respond to inflammatory and infectious agents such as the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic capacity of neutrophils from newborn infants and adults in response to IL-8 and the bacterial peptide fMLP.

    METHODS: In the under-agarose cell migration assay, isolated leukocytes from healthy adults and from cord blood of healthy term newborn infants were studied with dose responses towards IL-8 and fMLP. The same number of leukocytes (1 × 10(5) cells), with the same distribution of neutrophils and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil pattern of migration, i.e. the migration distance and the number of migrating neutrophils per distance, was evaluated.

    RESULTS: In comparison to adults, fewer neutrophils from newborn infants migrated towards IL-8 and for a shorter distance (P < .01, respectively). The number of neutrophils migrating to different gradients of fMLP, the distance they migrated, and the correlation between the number and the distance were the same for neonates and adults. Random migration did not differ in any instance.

    CONCLUSION: Chemotaxis of neutrophils from newborn infants was as co-ordinated as neutrophils from adults in response to fMLP, whereas the response to IL-8 was reduced. The differential response of neutrophils from neonates to intermediate and end-target chemoattractants could indicate a reduced infectious response.

  • 25.
    Stålhammar, Maria
    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.
    Douhan Håkansson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Neutrophil Receptor Response to Bacterial N-formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL-82016In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 84, no 6, p. 332-337Article in journal (Refereed)
    Abstract [en]

    We have previously observed that neutrophils from neonates exhibit different migratory responses to intermediate and end-target chemoattractants compared to adults. The aim of the present study was to investigate the effect of the chemoattractants IL-8 (intermediate) and formyl-methionine-leucyl-phenylalanine (fMLP; end-target) on cell surface receptor expression involved in adhesion, migration and granule release of neutrophils from term newborn infants and adults. Heparinized cord blood from 16 healthy term infants delivered by caesarean section and peripheral blood from 17 healthy adults were incubated with 1 μM IL-8 or 0.01 μM fMLP, previously defined as optimal inducers of neutrophil migration. The leukocytes were labelled with antibodies to cell surface receptors (CD11b, CD15S, CD18, CD35, CD44, CD64, CD65, CD88, CD162, CD181 and CD182). Receptor expression was quantified by flow cytometry analysis. Up regulation of CD11b and down regulation of CD88 and CD182 after stimulation with IL-8, was more pronounced in adults than in neonates (p<0.05, p<0.05 and p≤0.001 respectively), whereas fMLP induced changes in receptor expression that were of the same magnitude in neutrophils from neonates as from adults. We observed similar expression of receptors that mediate adhesion, migration, granule activation, and phagocytosis induced by fMLP in neutrophils from neonates and adults. In contrast, differences between neonates and adults, induced by IL-8, suggest that the neutrophil response to intermediate chemoattractants might lead to a compromised infectious response in newborn infants.

  • 26.
    van Kaam, Anton H
    et al.
    Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands.
    De Jaegere, Anne P
    Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands.
    Borensztajn, Dorine
    Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands.
    Rimensberger, Peter C
    Pediatric and Neonatal Intensive Care, Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland.
    Surfactant replacement therapy in preterm infants: a European survey2011In: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 100, no 1, p. 71-77Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exogenous surfactant is an undisputed treatment for neonatal respiratory distress syndrome but its efficacy is highly dependent on the treatment strategy. International guidelines have published recommendations on the optimal surfactant replacement strategy.

    OBJECTIVE: To determine how evidence-based guidelines on surfactant replacement therapy are implemented in daily clinical practice.

    METHODS: Data on surfactant replacement therapy, including preparation, dosing and timing, were collected in 173 European neonatal intensive care units (NICUs) by questionnaire and in a cohort of preterm infants mechanically ventilated on two separate predefined dates in these units.

    RESULTS: All NICUs used animal-derived surfactant in the treatment of respiratory distress syndrome, with Poractant being most widely used (86%). The most frequently used first dose was 100 mg/kg (58%) and 200 mg/kg (39%) and all NICUs allowed for repeat dosing. 39% of the NICUs claimed to use prophylactic treatment (<15 min of life). Data on surfactant treatment were collected in 338 infants, with a median gestational age of 27 weeks and a birth weight of 860 g. All infants were treated with animal-derived surfactant. The median first dose was 168 mg/kg in the Poractant group compared with 100 mg/kg in the Beractant and Bovactant groups. Prophylactic treatment was used in 23% of the infants and 28% of the infants received surfactant >2 h after birth. 43% of the infants received multiple doses.

    CONCLUSIONS: With the exception of surfactant timing, guidelines on surfactant replacement therapy seem to be implemented in daily clinical practice in European NICUs.

  • 27. van Kaam, Anton H
    et al.
    De Jaegere, Anne P
    Rimensberger, Peter C
    Incidence of hypo- and hyper-capnia in a cross-sectional European cohort of ventilated newborn infants.2013In: Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN 1359-2998, E-ISSN 1468-2052, Vol. 98, no 4, p. F323-6Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the incidence of hypo- and hyper-capnia in a European cohort of ventilated newborn infants.

    DESIGN AND SETTING: Two-point cross-sectional prospective study in 173 European neonatal intensive care units.

    PATIENTS AND METHODS: Patient characteristics, ventilator settings and measurements, and blood gas analyses were collected for endotracheally ventilated newborn infants on two separate dates.

    RESULTS: A total of 1569 blood gas analyses were performed in 508 included patients with a mean±SD Pco2 of 48±12 mm Hg or 6.4±1.6 kPa (range 17-104 mm Hg or 2.3-13.9 kPa). Hypocapnia (Pco2<30 mm Hg or 4 kPa) and hypercapnia (Pco2>52 mm Hg or 7 kPa) was present in, respectively, 69 (4%) and 492 (31%) of the blood gases. Hypocapnia was most common in the first 3 days of life (7.3%) and hypercapnia after the first week of life (42.6%). Pco2 was significantly higher in preterm infants (49 mm Hg or 6.5 kPa) than term infants (43 mm Hg or 5.7 kPa) and significantly lower during pressure-limited ventilation (47 mm Hg or 6.3±1.6 kPa) compared with volume-targeted ventilation (51 mm Hg or 6.8±1.7 kPa) and high-frequency ventilation (50 mm Hg or 6.7±1.7 kPa).

    CONCLUSIONS: This study shows that hypocapnia is a relatively uncommon finding during neonatal ventilation. The higher incidence of hypercapnia may suggest that permissive hypercapnia has found its way into daily clinical practice.

  • 28. van Kaam, Anton H
    et al.
    Rimensberger, Peter C
    Borensztajn, Dorine
    De Jaegere, Anne P
    Ventilation practices in the neonatal intensive care unit: a cross-sectional study2010In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 157, no 5, p. 767-U101Article in journal (Refereed)
    Abstract [en]

    Objective To assess current ventilation practices in newborn infants. 

    Study design We conducted a 2-point cross-sectional study in 173 European neonatal intensive care units, including 535 infants (mean gestational age 28 weeks and birth weight 1024 g). Patient characteristics, ventilator settings, and measurements were collected bedside from endotracheally ventilated infants. 

    Results A total of 457 (85%) patients were conventionally ventilated. Time cycled pressure-limited ventilation was used in 59% of these patients, most often combined with synchronized intermittent mandatory ventilation (51%). Newer conventional ventilation modes like volume targeted and pressure support ventilation were used in, respectively, 9% and 7% of the patients. The mean tidal volume, measured in 84% of the conventionally ventilated patients, was 5.7 +/- 2.3 ml/kg. The mean positive end-expiratory pressure was 4.5 +/- 1.1 cmH(2)O and rarely exceeded 7 cmH(2)O. 

    Conclusions Time cycled pressure-limited ventilation is the most commonly used mode in neonatal ventilation. Tidal volumes are usually targeted between 4 to 7 mL/kg and positive end-expiratory pressure between 4 to 6 cmH(2)O. Newer ventilation modes are only used in a minority of patients. (J Pediatr 2010; 157:767-71).

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