PENTOXIFYLLINE AND LUNG ISCHEMIA-REPERFUSION INJURY - APPLICATION TO LUNG TRANSPLANTATION

Pentoxifylline (PTX) attenuates neutrophil-mediated lung injury in sev eral models of acute lung inflammation. Because pulmonary neutrophil s equestration is the main determinant of ischemia-reperfusion (IR) inju ry in lung transplantation, we sought to determine whether or not PTX prevented IR injury in isolated perfused rat and rabbit lungs submitte d to IR, and in pigs after left lung allotransplantation. In rat lungs after IR, the coefficient of lung endothelial permeability (K-fc) inc reased by 112 +/- 12% in controls and by 27 +/- 8% (p < 0.001) in PTX- treated lungs. After IR, lung myeloperoxidase and blood neutrophil cou nt decrease were lower with PTX than in controls, and the changes in K -fc were correlated with the percentage decrease in blood neutrophils during reperfusion. In rabbit lungs, endothelium-dependent relaxation in isolated pulmonary arterial rings was decreased in the control grou p and normal in the PTX group. In pigs ventilated with pure oxygen, th e PaO2 was greater in the PTX group than in the control group (423 +/- 49 vs. 265 +/- 43 mm Hg; p < 0.05), whereas the total pulmonary vascu lar resistance was lower(15 +/- 1 vs. 30 +/- 9 mm Hg/L/min; p < 0.02). After reperfusion, the decrease in circulating leukocyte count fell b y 35 +/- 3% in the control group and remained unchanged in the PTX gro up, and the leukocyte count per microscopic field in the transplanted lung was lower in the PTX group than in the control group (p < 0.02). In conclusion, PTX prevented IR lung endothelium injury and improved p ost-IR lung function by decreasing neutrophil lung sequestration, and this agent might be useful in clinical lung transplantation.