L-arginine and pentoxifylline attenuate endothelial dysfunction after lung reperfusion injury in the rabbit. The Paris-Sud University Lung Transplant Group.

Abstract

Among the factors involved in the early complications of lung transplantation is the ischemia-reperfusion syndrome related to a warm reperfusion in ischemic lungs. Using an isolated rabbit lung preparation perfused with whole blood, we studied the effects of cold ischemia followed by a warm reperfusion on pulmonary vascular responses to reproduce experimentally the conditions encountered during lung transplantation. Pulmonary vascular responses to acetylcholine were rapidly altered by warm ischemia (relaxation of 7% versus 60% in controls). Conversely, relaxation was maintained even after a prolonged cold ischemic storage (maximal relaxation of 57% at 48 hours). Warm reperfusion in ischemic lungs induced major alteration of endothelium-dependent relaxation (maximal relaxation of 13% at 4 hours). The addition of L-arginine or pentoxifylline during reperfusion prevented the pulmonary endothelial alteration resulting from warm reperfusion. These data suggest that treatments aimed at maintaining intact functional endothelium reduce ischemia-reperfusion injury in transplanted lungs.