Nitroglycerin reperfusion reduces ischemia-reperfusion injury in non-heart-beating donor lungs

Background: Lung transplantation is severely limited by an inadequate supply of lungs from brain-dead donors. A potential solution is use of lungs from non-heart-beating donors (NHBDs) with retrieval at intervals after circulatory arrest and death. A warm ischemic period with concomitant reperfusion injury is a major limiting factor in the transplantation of lungs retrieved from NHBDs. We hypothesized that the administration of the nitric oxide-donor nitroglycerin to lungs from NHBI)s would reduce ischemia-reperfusion injury by activation of guanylate cyclase to form guanosine 3',5'-cyclic monophosphate (cGMP.). Methods: An in situ isolated perfused rat lung model was used. Lungs were retrieved from rats-at varying intervals after circulatory arrest and death. Lungs were either ventilated with 0, in situ or not ventilated. Lungs were reperfused at intervals after death with Earle's solution with or without nitroglycerin (0.1 mg/ml). Lung ischernia-reperfusion injury was assessed by capillary filtration coefficient, wet-to-dry lung weight ratio, and pulmonary hemodynamics. Tissue levels of adenine nucleotides and cG.MP concentrations were measured by high-performance liquid chromatography and enzyme immunoassay, respectively. Results: Reperfusion with nitroglycerin decreased capillary filtration coefficient compared with reperfusion without nitroglycerin at all post-mortem ischemic times, irrespective of pre-harvest ventilation. cGMP levels increased significantly with nitroglycerin-reperfusion and attenuated decreases in high-energy adenine nucleotides. Conclusions: Reperfusion of lungs with nitroglycerin may facilitate safe lung transplantation from NHBDs by reducing capillary leak after reperfusion. J Heart Lung Transplant 2006;25:110-19. Copyright (c) 2006 by the International Society for Heart and Lung Transplantation.