TREATMENT WITH AN ANTIOXIDANT INHIBITS VASCULAR CHANGES CAUSED BY CIRCULATING LYMPHOCYTES DURING ACUTE LUNG REJECTION IN DOGS

Background. Experiments were designed to evaluate the effect of treatm ent with sin inhibitor of lipid peroxidation, H 290/51, on the interac tion of lymphocytes and pulmonary arteries during acute lung rejection , It was hypothesized that inhibition of lipid peroxidation would redu ce contractions of the pulmonary arteries to autogenous rejection-acti vated lymphocytes. Methods, Single-lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression f or 8 days postoperatively; in group 2, immunosuppression was discontin ued on postoperative day 5, so that rejection occurred on postoperativ e day 8; in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 was given orally for 3 d ays, The pulmonary arteries were removed, cut into rings, sind suspend ed in organ chambers for measurement of isometric force. Results. Macr ophage-depleted mononuclear cells (MNCs; lymphocytes) isolated from bl ood caused cell number-dependent contractions in rings of the pulmonar y arteries from all dogs, In the rejecting dogs treated with H 290/51 (group 3), contractions to MNCs were significantly greater in rin(gs w ithout endothelium compared to rings with endothelium, Contractions to MNCs with or without endothelium were reduced by adding deteroxamine to the medium but not by adding superoxide dismutase and catalase. Con clusions. The results of this study show that treatment with a lipid p eroxidation inhibitor, H 290/51, does not prevent acute rejection of t ransplanted lungs, The treatment with the peroxidation inhibitor modif ies contractions of the pulmonary arteries in response to rejection-ac tivated lymphocytes, indicating that reactive oxidative metabolites ma y be involved in the vasoactive response resulting from this interacti on.