Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung

Abstract

Both ventilator pattern and neutrophil activation influence lung injury in adult respiratory distress syndrome (ARDS). We therefore questioned whether ventilator pattern independently affects neutrophil accumulation and function in early ARDS. Thirty-five New Zealand White rabbits were anesthetized, paralyzed, and prepared using sterile techniques. Fifteen surfactant-depleted animals were randomized and ventilated for 4 h using high-frequency oscillatory ventilation (HFO) at 15 Hz with an inspired O2 fraction = 1.0 and arterial PO2 (PaO2) > 400 Torr (a pattern known to reverse atelectasis) or conventional mechanical ventilation (CMV) with PaO2 = 80-100 Torr (a pattern with some atelectasis despite positive end-expiratory pressure). Eight normal animals on CMV with PaO2 > 400 Torr served as a reference group (NorCMV). NorCMV animals progressively increased circulating polymorphonuclear neutrophil (PMN) numbers and had minor pressure-volume curve alterations but no other significant changes. Lavaged CMV animals developed the characteristic gas exchange and marked pressure-volume curve abnormalities of ARDS. Circulating PMNs remained constant but developed decreased chemotactic activity, whereas lung neutrophil numbers increased significantly (P = 0.0002) and had substantially enhanced chemiluminescence (P = 0.0003 vs. NorCMV animals). Although lavaged HFO animals accumulated an intermediate number of lung neutrophils (lung myeloperoxidase > NorCMV animals; P = 0.003), the chemiluminescence and chemotaxis of these PMNs were the same as in cells from NorCMV animals. We concluded that both the degree of neutrophil activation and lung injury can be minimized by preventing cyclic alveolar/airway expansion and collapse in the surfactant-deficient lung by use of appropriate ventilator patterns.