Systemic vascular effects during acute rejection of lung allografts

Circulating leukocytes activated during rejection of organ allografts could potentially have generalized effects on systemic blood vessels of the transplant recipient. Experiments were designed, therefore, to determine the function of the endothelium and smooth muscle of arteries from nontransplanted organs in dogs who received single lung transplants. Dogs underwent single lung allotransplantation and were immunosuppressed for 5 days. Immunosuppression was then withheld for 3 days, allowing rejection to occur. Dogs were studied at this time (rejecting) or following treatment for rejection for an additional 6-8 days (treated). Arteries from unoperated, untreated dogs also were studied to provide baseline responses of healthy tissue. Rings cut from left circumflex coronary, nonoperated native pulmonary, and renal arteries were suspended in organ chambers for measurement of isometric force. Endothelium-dependent relaxations to the calcium ionophore A23187 were not affected by rejection in any of the arteries. Contractions to angiotensin I were reduced significantly only in native pulmonary arteries. Contractions to KCl and endothelin-1 increased in renal arteries with endothelium during rejection. These contractions in renal arteries were reduced following treatment of rejection. None of the responses of the coronary arteries were affected significantly by rejection of the lung allograft. These results demonstrate that contractions of arteries in the transplant recipient's native organs are altered during rejection of lung allografts. The effects are organ specific, may include production of endothelium-derived contractile factors in renal arteries, and can be partially reversed by treatment of rejection.