ATTENUATION OF LUNG GRAFT REPERFUSION INJURY BY A NITRIC-OXIDE DONOR

Objective: One of the primary features of ischemia-reperfusion injury is reduced production of protective autocoids, such as nitric oxide, b y dysfunctional endothelium, Administration of a nitric oxide donor du ring reperfusion of lung grafts may therefore be beneficial through mo dulation of vascular tone and leukocyte and platelet function, Methods : Rat lung grafts were flushed with University of Wisconsin solution a nd reperfused for 1 hour in an ex vivo model incorporating a support a nimal, Group I grafts (n = 6) were reperfused immediately after explan tation, group II (n = 6) and III (n = 5) grafts after 24 hours of stor age at 4 degrees C. In group III, glyceryl trinitrate, a nitric oxide donor, was administered during the first 10 minutes of reperfusion at a rate of 200 mu g/min. In an additional group (n = 5), 200 mu g/min h ydralazine was administered instead, to assess the effect of vasodilat ion alone, Results: Graft function in group II deteriorated compared w ith that in group I, with significant reduction of graft effluent oxyg en tension and blood flow and elevation of pulmonary artery pressure, peak airway pressure, and wet/dry weight ratio, In contrast, in group III, glyceryl trinitrate treatment improved graft function to baseline levels in all these parameters, Administration of hydralazine, meanwh ile, produced mixed results with only two out of five grafts functioni ng at control levels, Conclusions: In this model, administration of gl yceryl trinitrate to supplement the nitric oxide pathway in the early phase of reperfusion has a sustained beneficial effect on lung graft f unction after 24-hour hypothermic storage, probably through mechanisms beyond vasodilation alone.