Zusammenfassung
The poorly understood tolerance toward high tidal volume (V-T) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V-T with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion, leading to improved lung ...
Zusammenfassung
The poorly understood tolerance toward high tidal volume (V-T) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V-T with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion, leading to improved lung function, and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Rats (14 days old) were allocated to five groups: nonventilated controls, PEEP 5 cm H2O with V-T of 8, 16, and 24 mL/kg, and PEEP 1 cmH(2)O with V-T 24 mL/kg. Following 6 h of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy. High V-T (24 mL/kg) with PEEP of 5 cm H2O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with V-T 24 mL/kg and PEEP 1 cm H2O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (V-T 24 mL/kg, PEEP 1 cm H2O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats toward high V-T-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.
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