IMPAIRED ENDOTHELIUM-MEDIATED VASODILATATION IN THE PERIPHERAL VASCULATURE OF PATIENTS WITH ACUTE PULMONARY ALLOGRAFT-REJECTION

Background: Experimental studies have provided evidence that, during a cute pulmonary allograft rejection, endothelial dysfunction occurs not only in the transplanted lung but also in arteries of organs native t o the transplant recipient. We therefore tested the hypothesis that al lograft rejection leads to the release of factors into the circulation that could affect the endothelial function in lung transplant recipie nts. Methods: Acetylcholine (10, 30, and 60 mu g/min) and sodium nitro prusside (1, 3, and 6 mu g/min) were infused into the brachial artery in nine transplant recipients (five single lung, one double lung, thre e heart-lung) 2 to 37 weeks after transplantation, during both acute r ejection and rejection-free episodes. Changes in forearm blood flow we re assessed with venous occlusion plethysmography. Plasma levels of in terleukin-2, -6, and -8, endothelin-1, L-arginine, and asymmetric dime thylarginine were measured and correlated to rejection episodes. Resul ts: The vasodilatory response to acetylcholine was significantly reduc ed during acute rejection compared with rejection-free episodes (perce ntage increase from basal flow: 156% +/- 21%, 395% +/- 65%, and 585% /- 87% during rejection versus 272% +/- 75%, 633% +/- 113%, and 933% /- 158% during absence of rejection, p < 0.05). No statistically signi ficant difference was found between vasodilatory responses to nitropru sside during acute rejection and rejection-free episodes. Plasma level s of L-arginine, asymmetric dimethylarginine, interleukin-6, and endot helin-1 were not significantly altered during lung rejection. Conclusi ons: These data indicate that a reversible peripheral decrease in endo thelium-dependent vasodilatation occurs during acute rejection in lung transplant recipients. This result may be due to interactions among c irculating cytokines and leukocytes activated by the rejection process and the endothelium.