Pentoxifylline reduces lung allograft reperfusion injury

Abstract

Early graft dysfunction remains a significant problem in clinical lung transplantation. Pentoxifylline, a methylxanthine derivative, has been shown to have various beneficial effects on neutrophil-induced lung injury. We investigated effects of pentoxifylline on early posttrans-plantation 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 °C. In five experiments (group I), pentoxifylline was added to the flush and storage solutions (200 mg/L) at the time of harvest. The recipient animals received pentoxifylline (20 mg/kg intravenously) before reperfusion followed by pentoxifylline (0.1 mg · kg −1 · min −1 intravenously) during the 6-hour posttransplantation assessment period. In group II, donors and recipients received no pentoxifylline. To evaluate only allograft function, the right main pulmonary 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 difference in gas exchange between the groups, which persisted until the end of the study. By the end of the 6-hour assessment, the mean arterial 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 different between groups. Significant differences in wet-to-dry weight ratio (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 conclude that pentoxifylline improves early postoperative lung allograft function by attenuating neutrophil mediated ischemia-reperfusion injury.