Beneficial effects of supplemental nitric oxide donor given during reperfusion period in reperfusion-induced lung injury

Background: Reperfusion injury is a perplexing cause of early graft failure after lung transplantation and today we know that reperfusion may be more harmful to tissues than the preceding ischemia. We hypothesized that administration of the nitric oxide donor nitroglycerin (NTG) during flush perfusion and reperfusion periods would ameliorate reperfusion-induced lung injury. Methods: Using an in situ normothermic ischemic lung rabbit model, three groups were studied (n = 7/group): (1) NTG given during flush perfusion (ischemia group); (2) NTG given in the flush perfusion and the reperfusion period (reperfusion group); and (3) no NTG (control group). All groups were flushed with low potassium dextran glucose solution. Blood gas analysis, tissue nitrite (nitric oxide metabolite) level analysis, bronchoalveolar lavage (BAL) fluid examination and morphological examinations were performed. Results: Compared with the ischemia group, the reperfusion group had significantly improved arterial oxygenation (318 +/- 31.4 mmHg vs. 180 +/- 14.7 mmHg, p < 0.05), decreased BAL fluid neutrophil percentage (21 +/- 1.9% vs. 30 +/- 5.6%, p < 0.05), increased tissue nitrite level (32.55 < 4.12 nmol/g vs. 27.81 +/- 1.05 nmol/g, p < 0.05), and decreased tissue histopathological lesion scores (0.42 +/- 0.53 vs. 1.14 +/- 0.37, p < 0.05). Conclusions: This study suggests that nitric oxide donors supplemented during flush perfusion and reperfusion have more beneficial effects on lung functions against reperfusion injury than any other treatment modalities during in situ normothermic ischemic lung model.