Nutrition of preterm infants in relation to bronchopulmonary dysplasia

<p/> <p>Background</p> <p>The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial. In addition to prenatal inflammation, postnatal malnutrition also affects lung development.</p> <p>Methods</p> <p>A retrospective study was performed to analyse during the first two weeks of life the total, enteral and parenteral nutrition of premature infants (<31 weeks, birth weight ≤1500 g) born between 08/04 and 12/06.</p> <p>Results</p> <p>Ninety-five premature infants were analysed: 26 with BPD (27 ± 1 weeks) and 69 without BPD (28 ± 1 weeks). There was no statistical significant difference in the total intake of fluids, calories, glucose or protein and weight gain per day in both groups. The risk of developing BPD was slightly increased in infants with cumulative caloric intake below the minimal requirement of 1230 kcal/kg and a cumulative protein intake below 43.5 g/kg. Furthermore, the risk of developing BPD was significantly higher when infants had a cumulative fluid intake above the recommended 1840 ml/kg. In infants who developed BPD, the enteral nutrition was significantly lower than in non-BPD infants [456 ml/kg (IQR 744, 235) vs. 685 (IQR 987, 511)]. Infants who did not develop BPD reached 50% of total enteral feeding significantly faster [9.6 days vs. 11.5].</p> <p>Conclusions</p> <p>Preterm infants developing BPD received less enteral feeding, even though it was well compensated by the parenteral nutrient supply. Data suggest that a critical minimal amount of enteral feeding is required to prevent development of BPD; however, a large prospective clinical study is needed to prove this assumption.</p

Continuous Noninvasive Monitoring of Lung Recruitment during High-Frequency Oscillatory Ventilation by Electrical Impedance Measurement: An Animal Study

Background: Ventilatory pressures should target the range between the upper and lower inflection point of the pressure volume curve in order to avoid atelecto- and volutrauma. During high-frequency oscillatory ventilation (HFOV), this range is difficult to determine. Quadrant impedance measurement (QIM) has recently been shown to allow accurate and precise measurement of lung volume changes during conventional mechanical ventilation. Objectives: To investigate if QIM can be used to determine a static pressure-residual impedance curve during a recruitment-derecruitment manoeuvre on HFOV and to monitor the time course of alveolar recruitment after changing mean airway pressure (MAP). Methods: An incremental and decremental MAP trial (6 cm H₂O to 27 cm H₂O) was conducted in five surfactantdepleted newborn piglets during HFOV. Ventilatory, gas exchange and haemodynamic parameters were recorded. Continuous measurement of thoracic impedance change was performed. Results: Mean residual impedance (RI) increased with each stepwise increase of MAP resulting in a total mean increase of +26.5% (±4.0) at the highest MAP (27 cm H₂O) compared to baseline ventilation at 6 cm H₂O. Upon decreasing MAP levels, RI fell more slowly compared to its ascent; 83.4% (±19.1) and 84.8% (±16.4) of impedance changes occurred in the first 5 min after an increase or decrease in airway pressure, respectively. Conclusions: QIM could be used for continuous monitoring of thoracic impedance and determination of the pressure-RI curve during HFOV. The method could prove to be a promising bedside method for the monitoring of lung recruitment during HFOV in the future

Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells

<p>Abstract</p> <p>Background</p> <p>In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair.</p> <p>Objective</p> <p>The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis.</p> <p>Methods</p> <p>Curosurf^®and Alveofact^®were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation.</p> <p>Results</p> <p>Curosurf^®resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact^®exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models.</p> <p>Conclusion</p> <p>This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.</p

Tolerability of inhaled N-chlorotaurine in the pig model

<p>Abstract</p> <p>Background</p> <p>N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.</p> <p>Methods</p> <p>Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH₄Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO₂) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH₄Cl led to significantly lower PaO₂values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO₂) (p = 0.004). Interestingly, AaDO₂was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH₄Cl (p = 0.05).</p> <p>Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells <it>in vitro </it>was similar to that known from other body cells (0.25–0.5 mM).</p> <p>Conclusion</p> <p>The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.</p

Wachstum von respiratorischen Epithelzellen unter Einfluss von porcinem Surfactant in vitro

Beim Atemnotsyndrom des Frühgeborenen (RDS) werden über zehnfach höhere Mengen an exogenem Surfactant verabreicht, als sich bei einem reifen, gesunden Neugebornen nachweisen lassen. Diese Studie wurde durchgeführt mit dem Ziel den Einfluss von exogenem Surfactant auf das Wachstum von respiratorischen Epithelzellen in vitro zu untersuchen. Der Proliferationstest erfolgte per Messung des BrdU-Einbaus. Surfactant führte zur signifikanten Hemmung der Zellproliferation. Auch die Zellkonzentration beeinflusst das Zellwachstum signifikant. Bei Erhöhung der Zellzahl verminderte sich das Zellwachstum unter Surfactantinkubation. Diese Studie zeigt eine Beeinflussung des Zellwachstums durch exogenes Surfactant. Dies könnte ein Hinweis sein für eine bedeutende Rolle von Surfactant in der Entstehung von chronischen Lungenerkrankungen, wie der Bronchopulmonalen Dysplasie

Pulmonary surfactant prevents exocytosis that is induced by PolymyxinB.

<p>Fluorescence (lyso tracker green) scattergram of alveolar type II cells after 5 h incubation with mixtures of modified porcine surfactant (SF) and/or Polymyxin B (PxB), 30 min after staining of lamellar bodies, compared to controls (DMEM). Fluorescence in cells exposed to PxB is significantly reduced compared to DMEM, SF or in mixture with SF. Bars show mean ± SD, n = 14–16. *: p<0.01 vs. DMEM, SF and SF plus PxB.</p

Polymyxin B induces exocytosis of alveolar type II cells.

<p>Initial lyso tracker green fluorescence of alveolar type II cells 30 min after staining, comparing cells incubated with Polymyxin B (PxB) to controls (DMEM). The fluorescence in cells exposed to PxB decreases in a time-dependent manner, whereas it remains stable in controls. Bars are mean+SD, n = 14–16. *: p<0.01 vs. DMEM.</p