Effects of mean airway pressure and tidal excursion on lung injury inducedby mechanical ventilation in an isolated perfused rabbit lung model

Objective: To study the relative contributions of mean airway pressure (mPa w) and tidal excursion (V-T) to ventilator-induced lung injury under consta nt perfusion conditions. Design: Prospective, randomized study. Setting: Experimental animal laboratory. Subjects: Fifteen sets of isolated rabbit lungs. Interventions: Rabbit lungs were perfused (constant flow, 500 mL/min; capil lary pressure, 10 mm Hg) and randomized to be ventilated at identical peak transpulmonary pressure (pressure control ventilation [30 cm H2O and freque ncy of 20/min]) with three different ventilatory patterns that differed fro m each other by either mPaw or V-T: group A (low mPaw [13.4 +/- 0.2 cm H2O] /large V-T [55 +/- 8 mL], n = 5); group B thigh mPaw [21.2 +/- 0.2 cm H2O]/ small V-T [18 +/- 1 mL], n = 5); and group C thigh mPaw [21.8 +/- 0.5 cm H2 O]/large V-T [53 +/- 5 mt], n = 5), Measurements and Main Results: continuous weight gain (edema formation), ch ange in ultrafiltration coefficient (Delta K-f, vascular permeability index ), and histology (lung hemorrhage) were examined, In group A, Delta K-f (0. 08 +/- 0.08 g/min/cm H2O/100 g) was less than in group 8 (0.28 +/- 0.19 g/m in/cm H2O/100 g) or group C (0.41 +/- 0.29 g/min/cm H2O/100 g) (p = .05), G roup 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 simila r trend was observed for weight gain. In contrast to tidal excursion, mPaw was found to be a significant factor for lung hemorrhage and increased K-f (two-way analysis of variance; p < .05), Weight gain (r(2) = .54, p = .04) and lung hemorrhage (r(2) = .65, p = .01) correlated with the mean pulmonar y artery pressure changes that resulted from the implementation of the vent ilatory strategies. The difference between the changes in mPaw and mean pul monary artery pressure linearly predicted Delta K-f (p = .005 and .05, resp ectively, r(2) = 0.73), Conclusions: Under these experimental conditions, mPaw contributes more tha n tidal excursion to lung hemorrhage and permeability alterations induced b y mechanical ventilation.