Treatment with an antioxidant inhibits vascular changes caused by circulating lymphocytes during acute lung rejection in dogs

Lars Wiklund, Folke Nilsson, Henrik Scherstén, Per Ove Sjöquist, Henry Tazelaar, Virginia M. Miller, Christopher G.A. McGregor

Research output: Contribution to journalArticle

Abstract

Background. Experiments were designed to evaluate the effect of treatment with an inhibitor of lipid peroxidation, H 290/51, on the interaction of lymphocytes and pulmonary arteries during acute lung rejection. It was hypothesized that inhibition of lipid peroxi-dation would reduce contractions of the pulmonary arteries to autogenous rejection- activated lymphocytes. Methods. Single-lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days postoperatively; in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8; in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 was given orally for 3 days. The pulmonary arteries were removed, cut into rings, and suspended in organ chambers for measurement of isometric force. Results. Macrophage-depleted mononuclear cells (MNCs; lymphocytes) isolated from blood caused cell number-dependent contractions in rings of the pulmonary arteries from all dogs. In the rejecting dogs treated with H 290/51 (group 3), contractions to MNCs were significantly greater in rings without 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. Conclusions. The results of this study show that treatment with a lipid peroxidation inhibitor, H 290/51, does not prevent acute rejection of transplanted lungs. The treatment with the peroxidation inhibitor modifies contractions of the pulmonary arteries in response to rejection-activated lymphocytes, indicating that reactive oxidative metabolites may be involved in the vasoactive response resulting from this interaction.

Original languageEnglish (US)
Pages (from-to)807-811
Number of pages5
JournalTransplantation
Volume64
Issue number6
DOIs
StatePublished - Sep 27 1997

ASJC Scopus subject areas

  • Transplantation

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