Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics

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Abstract
Introduction: Acute respiratory distress syndrome causes a heterogeneous lung injury, and without protective mechanical ventilation a secondary ventilator-induced lung injury can occur. To ventilate noncompliant lung regions, high inflation pressures are required to 'pop open' the injured alveoli. The temporal impact, however, of these elevated pressures on normal alveolar mechanics (that is, the dynamic change in alveolar size and shape during ventilation) is unknown. In the present study we found that ventilating the normal lung with high peak pressure (45 cmH20) and low positive end-expiratory pressure (PEEP of 3 cmH2O) did not initially result in altered alveolar mechanics, but alveolar instability developed over time. Methods: Anesthetized rats underwent tracheostomy, were placed on pressure control ventilation, and underwent sternotomy. Rats were then assigned to one of three ventilation strategies: control group (n = 3, Pcontrol = 14 cmH2O, PEEP = 3 cmH2O), high pressure/low PEEP group (n = 6, Pcontrol = 45 cmH2O, PEEP = 3 cmH2O), and high pressure/high PEEP group (n = 5, Pcontrol = 45 cmH2O, PEEP = 10 cmH2O). In vivo microscopic footage of subpleural alveolar stability (that is, recruitment/derecruitment) was taken at baseline and than every 15 minutes for 90 minutes following ventilator adjustments. Alveolar recruitment/derecruitment was determined by measuring the area of individual alveoli at peak inspiration (I) and end expiration (E) by computer image analysis. Alveolar recruitment/derecruitment was quantified by the percentage change in alveolar area during tidal ventilation (%I – EΔ). Results: Alveoli were stable in the control group for the entire experiment (low %I – EΔ). Alveoli in the high pressure/low PEEP group were initially stable (low %I – EΔ), but with time alveolar recruitment/derecruitment developed. The development of alveolar instability in the high pressure/low PEEP group was associated with histologic lung injury. Conclusion: A large change in lung volume with each breath will, in time, lead to unstable alveoli and pulmonary damage. Reducing the change in lung volume by increasing the PEEP, even with high inflation pressure, prevents alveolar instability and reduces injury. We speculate that ventilation with large changes in lung volume over time results in surfactant deactivation, which leads to alveolar instability.

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