LASTING BENEFICIAL EFFECT OF SHORT-TERM INHALED NITRIC-OXIDE ON GRAFTFUNCTION AFTER LUNG TRANSPLANTATION

The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide, Because nitric oxide h as been shown to selectively dilate the pulmonary vasculature, abrogat e neutrophil adherence, and restore endothelial dysfunction, we hypoth esized that inhaled nitric oxide given for 4 hours during initial repe rfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange da ta, lung neutrophil sequestration, and pulmonary artery endothelial dy sfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assi gned to nitric oxide and control groups, Harvested lungs were preserve d in normal saline solution for 24 hours at 4 degrees C, During transp lantation, inflatable cuffs were placed around each pulmonary artery t o allow separate evaluation of each lung by occluding flow, Compared w ith the transplanted lungs in the control group, transplanted lungs in pigs treated with inhaled nitric oxide significantly improved gas exc hange, pulmonary vascular resistance, shunt fraction, and oxygen deliv ery at 4 and 24 hours after reperfusion, Neutrophil sequestration, as measured by the neutrophil-specific enzyme myeloperoxidase and the alv eolar leukocyte count per light microscopic field, was significantly l ower at 24 hours after reperfusion in the transplanted lungs of the ni tric oxide group, The nitric oxide-treated native right lungs exhibite d significantly reduced increase in neutrophil accumulation compared w ith that in control native right lungs, After 24 hours of reperfusion, endothelium-dependent relaxation to acetylcholine was similarly and s everely altered in both groups, We conclude that short-term inhaled ni tric oxide given during the first 4 hours of reperfusion after lung tr ansplantation significantly attenuates reperfusion injury, improving g raft function as long as 24 hours after operation, This effect is prob ably mediated by a decrease in neutrophil sequestration, A protective effect on the contralateral lung was also observed, Inhaled nitric oxi de may be a suitable agent when an acute reperfusion phenomenon is ant icipated.