PENTOXIFYLLINE REDUCES LUNG ALLOGRAFT REPERFUSION INJURY

Early graft dysfunction remains a significant problem in clinical lung transplantation, pentoxifylline, a methylxanthine derivative, has bee n shown to have various beneficial effects on neutrophil-induced lung injury. We investigated effects of pentoxifylline on early posttranspl antation lung function in a canine allograft model. Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution (50 mL/kg) and stored in an inflated state for 18 hours at 1 degrees C. In five experiments (group I), pentoxifylline was added to the flush and storage solutions (200 mg/L) at the time o f harvest. The recipient animals received pentoxifylline (20 mg/kg int ravenously) before reperfusion followed by pentoxifylline (0.1 mg . kg (-1) . min(-1) intravenously) during the 6-hour posttransplantation as sessment period. In group II, donors and recipients received no pentox ifylline. To evaluate only allograft function, the right main pulmonar y artery and bronchus were ligated immediately after implantation. For 6 hours thereafter hemodynamics and gas exchange were assessed at 15- minute intervals while the animal was ventilated at an inspired oxygen fraction of 1.0. After 1 hour of assessment there was a significant d ifference in gas exchange between the groups, which persisted until th e end of the study. By the end of the 6-hour assessment, the mean arte rial oxygen tension was 236.7 mm Hg for group I versus 101.1 mm Hg for group II (p < 0.01), and the alveolar-arterial oxygen difference was 443.1 mm Hg versus 562.2 mm Hg (p < 0.015). Hemodynamics were not diff erent between groups. Significant differences in wet-to-dry weight rat io (group I versus group II, 7.0 +/- 0.2 versus 8.3 +/- 0.4; p < 0.05) and myeloperoxidase activity assay (group I versus group II, 0.145 +/ - 0.012 versus 0.201 +/- 0.016 U/mg; p < 0.05) were observed. We concl ude that pentoxifylline improves early postoperative lung allograft fu nction by attenuating neutrophil mediated ischemia-reperfusion injury.