INHALED NITRIC-OXIDE AND PENTOXIFYLLINE IN RAT LUNG TRANSPLANTATION FROM NON-HEART-BEATING DONORS

Background: In non-heart-beating donor lung transplantation, postmorte m warm ischemia poses a special challenge, Inhaled nitric oxide and pe ntoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administr ation of inhaled nitric oxide and pentoxifylline would result in a syn ergistic effect on ischemia-reperfusion lung injury, Methods: Lungs we re harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4 degrees C before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was a dded during cadaver ventilation and reperfusion; pentoxifylline was gi ven intravenously throughout reperfrsion, The following groups were st udied (n = 8 each): control, pentoxifylline, nitric oxide, and nitric oxide + pentoxifylline, Hemodynamic indices and arterial blood gases w ere obtained after ligation of the right pulmonary artery. Lung myelop eroxidase and wet/dry ratio were measured after death, Results: All ra ts that did not receive nitric oxide died within 10 minutes after liga tion, Inhaled nitric oxide significantly decreased pulmonary vascular resistance and improved recipient survival, Nitric oxide + pentoxifyll ine improved pulmonary vascular resistance, arterial oxygen tension, a nd survival even further and reduced lung myeloperoxidase as compared with the group that received nitric oxide only. Preservation solution flush time was significantly decreased in both groups receiving nitric oxide, suggesting that inhaled nitric oxide used during cadaver venti lation allows for a more even distribution of the preservation solutio n. Conclusion: We conclude that treatment with inhaled nitric oxide pentoxifylline results in a synergistic protection from ischemia-reper fusion injury after non-heart-beating donor lung transplantation. This is likely the result of a dual action on the graft vasculature and ne utrophil sequestration.