Modulation of reperfusion injury after single lung transplantation by pentoxifylline, inositol polyanions, and SIN-1

Objective: Previous studies have suggested reductions in lung reperfusion i njury with pentoxifylline, inositol polyanions, and the nitric oxide donor, SIN-1, but these agents have never been directly compared to ascertain whi ch is superior. We investigated these agents in a porcine model of left sin gle lung transplantation. Methods: Donor lungs were preserved with modified Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil t rapping in the graft, pulmonary vascular resistance, free radical release ( measured by malonaldehyde levels) and gas exchange were assessed over a 12- hour period. All groups were reperfused at an initial pulmonary artery pres sure of 20 mm Hg, Group A (n = 5) was a control group with no interventions added; group B was reperfused with the addition of intravenous inositol po lyanions (0.02 mg/kg/h), and group C was reperfused with intravenous SIN-1 (0.02 mg/kg/h), Group D was reperfused with the addition of intravenous pen toxifylline (2 mg/kg/h), Results: Neutrophil sequestration was observed wit hin 10 minutes of reperfusion in group A. This was attenuated significantly by interventions in groups B, C, and D, In group D, malonaldehyde levels w ere significantly lower than in other groups and was associated with superi or oxygenation. Pulmonary vascular resistance was reduced in groups B, C, a nd D compared with group A. Conclusions: Pentoxifylline, when administered only to recipient animals was superior to the other interventions studied. Inositol polyanions are promising as a possible therapeutic intervention bu t were not as effective as the other agents studied.