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Preemptive Application of Airway Pressure Release Ventilation Prevents Development of Acute Respiratory Distress Syndrome in a Rat Traumatic Hemorrhagic Shock Model

ABSTRACT Background: Once established, the acute respiratory distress syndrome (ARDS) is highly resistant to treatment and retains a high mortality. We hypothesized that preemptive application of airway pressure release ventilation (APRV) in a rat model of trauma/hemorrhagic shock (T/HS) would prevent ARDS. Methods: Rats were anesthetized, instrumented for hemodynamic monitoring, subjected to T/HS, and randomized into two groups: (a) volume cycled ventilation (VC) (n = 5, tidal volume 10 mL/kg; positive end-expiratory pressure 0.5 cmH2O) or (b) APRV (n = 4, Phigh = 15–20 cmH2O; Thigh = 1.3–1.5 s to achieve 90% of the total cycle time; Tlow = 0.11–0.14 s, which was set to 75% of the peak expiratory flow rate; Plow = 0 cmH2O). Study duration was 6 h. Results: Airway pressure release ventilation prevented lung injury as measured by PaO2/FIO2 (VC 143.3 ± 42.4 vs. APRV 426.8 ± 26.9, P < 0.05), which correlated with a significant decrease in histopathology as compared with the VC group. In addition, APRV resulted in a significant decrease in bronchoalveolar lavage fluid total protein, increased surfactant protein B concentration, and an increase in epithelial cadherin tissue expression. In vivo microscopy demonstrated that APRV significantly improved alveolar patency and stability as compared with the VC group. Conclusions: Our findings demonstrate that preemptive mechanical ventilation with APRV attenuates the clinical and histologic lung injury associated with T/HS. The mechanism of injury prevention is related to preservation of alveolar epithelial and endothelial integrity. These data support our hypothesis that preemptive APRV, applied using published guidelines, can prevent the development of ARDS.