AMELIORATION OF REPERFUSION INJURY BY PENTOXIFYLLINE AFTER LUNG TRANSPLANTATION

Background: Pentoxifylline attenuates neutrophil-mediated lung injury in several models of acute lung inflammation. Methods: Because pulmona ry neutrophil sequestration is the main determinant of lung reperfusio n injury, we sought to determine whether pentoxifylline prevented repe rfusion injury in isolated perfused rat lung (4-hour cold ischemia, 1- hour reperfusion; pentoxifylline intravenously 40 mg) and in pigs afte r left lung allotransplantation (24-hour cold ischemia, 4-hour reperfu sion; pentoxifylline 1.5 mg/kg/hr intravenously), In the pigs, inflata ble cuffs placed around each pulmonary artery enabled us to evaluate e ach lung separately. Results: In rat lungs, the coefficient of lung pe rmeability increased by 75% +/- 10% in controls and by 3% +/- 2% (p < 0.01) in pentoxifylline-treated lungs. In the pigs, with blood flow to the transplanted lung alone and ventilation with an inspired oxygen f raction of 1, the arterial oxygen tension was greater in the pentoxify lline group than in the control group (423 +/- 49 versus 265 +/- 43 mm Hg,p < 0.05), whereas the total pulmonary vascular resistance was low er (15 +/- 1 versus 30 +/- 9 mm Hg/L/min, p < 0.02). After reperfusion , the decrease in circulating leukocyte count fell by 35% +/- 3% in th e control group and remained unchanged in the pentoxifylline group, an d the leukocytes count per microscopic field in the transplanted lung was lower in the pentoxifylline group than in the control group (15 +/ - 2 versus 140 +/- 50, p < 0.02). Conclusions: These data suggest that pentoxifylline prevented reperfusion injury by decreasing neutrophil lung sequestration.