ObjectiveTo study the relative contributions of mean airway pressure (mPaw) and tidal excursion (VT) to ventilator-induced lung injury under constant perfusion conditions.DesignProspective, randomized study.SettingExperimental animal laboratory.SubjectsFifteen sets of isolated rabbit lungs.InterventionsRabbit lungs were perfused (constant flow, 500 mL/min; capillary pressure, 10 mm Hg) and randomized to be ventilated at identical peak transpulmonary pressure (pressure control ventilation [30 cm H2O and frequency of 20/min]) with three different ventilatory patterns that differed from each other by either mPaw or VT: group A (low mPaw [13.4 +/- 0.2 cm H2O]/large VT[55 +/- 8 mL], n = 5); group B (high mPaw [21.2 +/- 0.2 cm H2O]/small VT[18 +/- 1 mL], n = 5); and group C (high mPaw [21.8 +/- 0.5 cm H2O]/large VT[53 +/- 5 mL], n = 5).Measurements and Main ResultsContinuous weight gain (edema formation), change in ultrafiltration coefficient (Delta Kf, vascular permeability index), and histology (lung hemorrhage) were examined. In group A, Delta Kf(0.08 +/- 0.08 g/min/cm H2O/100 g) was less than in group B (0.28 +/- 0.19 g/min/cm H2O/100 g) or group C (0.41 +/- 0.29 g/min/cm H2O/100 g) (p = .05). Group A experienced significantly less hemorrhage (histologic score, 5.4 +/- 2.2) than groups B (10.3 +/- 2.1) and C (11.1 +/- 3.0) (p < .05). A similar trend was observed for weight gain. In contrast to tidal excursion, mPaw was found to be a significant factor for lung hemorrhage and increased Kf(two-way analysis of variance; p < .05). Weight gain (r2= .54, p = .04) and lung hemorrhage (r2= .65, p = .01) correlated with the mean pulmonary artery pressure changes that resulted from the implementation of the ventilatory strategies. The difference between the changes in mPaw and mean pulmonary artery pressure linearly predicted Delta Kf(p = .005 and .05, respectively, r2= 0.73).ConclusionsUnder these experimental conditions, mPaw contributes more than tidal excursion to lung hemorrhage and permeability alterations induced by mechanical ventilation. (Crit Care Med 1999; 27:1533-1541)