ENHANCED PRESERVATION OF ORTHOTOPICALLY TRANSPLANTED RAT LUNGS BY NITROGLYCERIN BUT NOT HYDRALAZINE - REQUIREMENT FOR GRAFT VASCULAR HOMEOSTASIS BEYOND HARVEST VASODILATION

Nitric oxide (NO) produced within the lungs maintains pulmonary vascul ar homeostatic properties, modulating leukocyte traffic, platelet aggr egation, and vasomotor tone. Because reactive oxygen intermediates gen erated during reperfusion react rapidly with available NO, we hypothes ized that the NO donor nitroglycerin (NTG) would enhance lung preserva tion for transplantation by improving graft blood flow and reducing gr aft neutrophil and platelet sequestration. By use of an orthotopic rat left lung transplant model, with ligation of the native right pulmona ry artery to ensure that recipient survival and physiological measurem ents depend entirely on the transplanted lung, transplants were perfor med in 70 male Lewis rats after 6-hour 4 degrees C preservation in Eur o-Collins solution (EC) alone or EC with supplemental NTG. Compared wi th EC alone, supplemental NTG significantly increased pulmonary arteri al flow (2.2+/-1.4 to 21.4+/-2.9 mL/min, P<.01), decreased pulmonary v ascular resistance (7.4+/-2.0 to 1.4+/-0.1x10(3) Woods units, P<.05), improved arterial oxygenation (163+/-57 to 501+/-31 mm Hg, P<.01), and enhanced recipient survival (17% to 100%, P<.001). These beneficial e ffects of NTG were dose dependent over a range of 0.001 to 0.1 mg/mL. Although NTG caused significant pulmonary vasodilation during the harv est/flushing period, the direct-acting vasodilator hydralazine caused greater vasodilation than did NTG but was associated with poor graft f unction, elevated pulmonary vascular resistance, and poor recipient su rvival. To explore nonvasodilator protective mechanisms of NTG, graft neutrophil and platelet sequestration were studied; supplemental NTG s ignificantly reduced both neutrophil and platelet accumulation compare d with either hydralazine or EC alone. These findings suggest that vas odilation alone at the lime of harvest is insufficient to protect the lungs. NTG, which produces antineutrophil and antiplatelet effects as well as harvest vasodilation, appears to be a simple and effective add itive that will improve lung preservation for transplantation.