LOW-DOSE NITRIC-OXIDE INHALATION DURING INITIAL REPERFUSION ENHANCES RAT LUNG GRAFT FUNCTION

Background. In ischemia-reperfusion injury, the production of nitric o xide by dysfunctional endothelium falls rapidly within minutes of the onset of reperfusion. Replenishment during this critical early period using inhaled nitric oxide may benefit lung grafts through modulation of vascular tone, endothelial permeability, neutrophil and platelet fu nction, and availability of reactive oxygen species. Methods. Rat lung grafts were flushed with 60 mL/kg cold University of Wisconsin soluti on and were reperfused either immediately (group I, n = 5) or after 24 -hour 4 degrees C storage (groups II and III, n = 5 each), for 60 minu tes in an ex vivo model incorporating a support animal. Graft ventilat ion was with room air. In group III, 20 parts per million inhaled nitr ic oxide was added during the initial 10 minutes of reperfusion, where as in groups I and II, equivalent flows of nitrogen were added to stan dardize oxygen concentration. Results. Compared with group I, graft fu nction in group II was poor, with reductions in oxygenation and blood now and elevations of mean pulmonary artery pressure, peak airway pres sure, and wet to dry weight ratio. In contrast, during nitric oxide in halation in group III, graft function improved to control levels. This improvement was subsequently sustained throughout the reperfusion per iod. Conclusions. Low-dose inhaled nitric oxide administration in the early phase of reperfusion of stored lung grafts can yield sustained i mprovement in function. There may be a role for inhaled nitric oxide i n the prevention of reperfusion injury in transplanted lungs.