BACKGROUND: Experimental studies have provided evidence that, during acute pulmonary allograft rejection, endothelial dysfunction occurs not only in the transplanted lung but also in arteries of organs native to the transplant recipient. We therefore tested the hypothesis that allograft rejection leads to the release of factors into the circulation that could affect the endothelial function in lung transplant recipients. METHODS: Acetylcholine (10, 30, and 60 micrograms/min) and sodium nitroprusside (1, 3, and 6 micrograms/min) were infused into the brachial artery in nine transplant recipients (five single lung, one double lung, three heart-lung) 2 to 37 weeks after transplantation, during both acute rejection and rejection-free episodes. Changes in forearm blood flow were assessed with venous occlusion plethysmography. Plasma levels of interleukin-2, -6, and -8, endothelin-1, L-arginine, and asymmetric dimethylarginine were measured and correlated to rejection episodes. RESULTS: The vasodilatory response to acetylcholine was significantly reduced during acute rejection compared with rejection-free episodes (percentage 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 significant difference was found between vasodilatory responses to nitroprusside during acute rejection and rejection-free episodes. Plasma levels of L-arginine, asymmetric dimethylarginine, interleukin-6, and endothelin-1 were not significantly altered during lung rejection. CONCLUSIONS: These data indicate that a reversible peripheral decrease in endothelium-dependent vasodilatation occurs during acute rejection in lung transplant recipients. This result may be due to interactions among circulating cytokines and leukocytes activated by the rejection process and the endothelium.
BACKGROUND: Experimental studies have provided evidence that, during acute pulmonary allograft rejection, endothelial dysfunction occurs not only in the transplanted lung but also in arteries of organs native to the transplant recipient. We therefore tested the hypothesis that allograft rejection leads to the release of factors into the circulation that could affect the endothelial function in lung transplant recipients. METHODS:Acetylcholine (10, 30, and 60 micrograms/min) and sodium nitroprusside (1, 3, and 6 micrograms/min) were infused into the brachial artery in nine transplant recipients (five single lung, one double lung, three heart-lung) 2 to 37 weeks after transplantation, during both acute rejection and rejection-free episodes. Changes in forearm blood flow were assessed with venous occlusion plethysmography. Plasma levels of interleukin-2, -6, and -8, endothelin-1, L-arginine, and asymmetric dimethylarginine were measured and correlated to rejection episodes. RESULTS: The vasodilatory response to acetylcholine was significantly reduced during acute rejection compared with rejection-free episodes (percentage 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 significant difference was found between vasodilatory responses to nitroprusside during acute rejection and rejection-free episodes. Plasma levels of L-arginine, asymmetric dimethylarginine, interleukin-6, and endothelin-1 were not significantly altered during lung rejection. CONCLUSIONS: These data indicate that a reversible peripheral decrease in endothelium-dependent vasodilatation occurs during acute rejection in lung transplant recipients. This result may be due to interactions among circulating cytokines and leukocytes activated by the rejection process and the endothelium.