Protective effects of inhaled nitric oxide and gabexate mesilate in lung reperfusion injury after transplantation from non-heart-beat donors.

BACKGROUND: The use of lung grafts from non-heart-beat donors (NHBDs) is one way of solving the critical donor organ shortage. Inhaled nitric oxide (NO) and gabexate mesilate (FOY), a protease inhibitor, can attenuate some types of neutrophil-mediated tissue injury. Using an isolated lung ventilation and perfusion model, we studied the effects of these agents on reperfusion injury following lung transplantation from NHBDs.

METHODS: Five groups of minipigs were studied. In group 1(n = 6), the lungs were flushed and harvested after cardiac arrest, and were reperfused for 2 hours after 2 hours of cold ischemia. In group 2 (n = 6), the lungs were harvested after 2 hours of in situ warm ischemia, followed by 2 hours of cold ischemia and 2 hours of reperfusion. In groups 3 (n = 7), 4 (n = 7), and 5 (n = 6), the procedure was the same as in group 2, except in group 3, NO was inhaled before and after ischemia, in group 4, FOY was given intravenously, and in group 5, a combination of inhaled NO and intravenous FOY were administered.

RESULTS: Compared with group 1, group 2 had higher mean pulmonary arterial pressure, vascular resistance, and lower arterial blood oxygen tension. Furthermore, these negative effects of warm ischemia were also reflected in the contents of bronchoalveolar lavage fluid, tissue myeloperoxidase (MPO) activity, histology, and permeability change. Either FOY or NO administration (groups 3 or 4) ameliorated the associated injury. A combination of FOY and NO use (group5) decreased the parameters of lung reperfusion injury measurement to a larger degree than either agent individually.

CONCLUSIONS: The inhaled NO and FOY can protect NHBD lung grafts at an early reperfusion period. Their use in combination has an additive protective effect that might be applied to the protection of NHBD grafts from preservation and reperfusion injury.