Vascular Remodeling Protects against Ventilator-induced Lung Injury in the In Vivo Rat

Abstract

The role of the pulmonary vasculature in the pathogenesis of ventilator-induced lung injury is not well established. In this study, the authors investigated the effect of vascular remodeling due to chronic pulmonary hypertension on susceptibility to ventilator-induced lung injury. The authors hypothesized that the enhanced vascular tensile strength associated with pulmonary vascular remodeling would protect against ventilator-induced lung injury. Chronic pulmonary arterial hypertension was induced in rats by exposure to hypoxia for 28 days and was confirmed by demonstration of right ventricular hypertrophy. Normotensive and hypertensive groups of rats (as well as a group in which pulmonary hypertension was acutely reversed with a Rho-kinase inhibitor, Y-27632) were exposed to injurious ventilation (respiratory rate 30 min, 30/0 cm H2O) for 90 min. Lung injury was assessed by change in lung mechanics, oxygenation, edema development, and cytokine levels. Electron microscopy was used to examine vascular structure in additional animals. Injurious ventilation caused significant lung injury (lung compliance, oxygenation, pulmonary edema) in the normotensive controls, but not in the presence of pulmonary hypertension; acute reversal of pulmonary hypertension did not alter the lessened susceptibility to ventilator-induced lung injury. Electron microscopy demonstrated capillary endothelial and epithelial breaks in injuriously ventilated normotensive controls that were not seen with pulmonary hypertension, whether or not the pulmonary hypertension was acutely reversed. Vascular remodeling induced by chronic pulmonary hypertension confers protection against the effects of injurious mechanical ventilation in vivo by a mechanism that may involve structural alterations rather than increased pulmonary artery pressure.