PREVENTION OF REPERFUSION INJURY BY INHALED NITRIC-OXIDE IN LUNGS HARVESTED FROM NON-HEART-BEATING DONORS

Background. In lung transplantation using non-heart-beating donors (NH BD), the postmortem period of warm ischemia exacerbates lung ischemia- reperfusion injury. We hypothesized that inhaled nitric oxide (NO) wou ld reduce ischemia-reperfusion injury, and thus ameliorate the viabili ty of the lung graft. Methods. A blood-perfused, isolated rat lung mod el was used. Lungs were flushed and harvested from non-heart-beating d onors after 30 minutes of in situ warm ischemia. The lung was then sto red for 2 hours at 4 degrees C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after I hour o f reperfusion by measuring pulmonary vascular resistance, coefficient of filtration wet-to-dry lung weight ratio, and myeloperoxidase activi ty. Results. A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary va scular resistance (6.83 +/- 0.36 mm Hg . mL(-1). min(-1)), coefficient of filtration (3.02 +/- 0.35 mL . min(-1). cm H2O-1. 100 g(-1)), and wet-to-dry lung weight ratio (8.07 +/- 0.45). Lower values (respective ly, 3.31 +/- 0.44 mm Hg . mL(-1). min(-1), 1.49 +/- 0.34 mL . min(-1). cm H2O-1. 100 g(-1), and 7.44 +/- 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improve d when NO was given during reperfusion only All measured variables, in cluding myeloperoxidase activity were significantly improved when NO w as given during both ischemia and reperfusion. Myeloperoxidase activit y was significantly correlated with coefficient of filtration (r = 0.4 65; p < 0.05). Conclusions. These data suggest that inhaled NO signifi cantly reduces ischemia-reperfusion injury in lungs harvested from non -heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.