Endothelium-dependent microvascular vasomotion and its correlation with vasoactive mediators early after cardiac transplantation in humans

<E6>Abstract</E6> Endothelial dysfunction precedes and predicts transplant vasculopathy. We investigated the relationship between endothelial dysfunction and the vasoactive mediators nitric oxide and endothelin, 33.7 ± 2.0 days after heart transplantation. Coronary flow was measured in 18 patients to determine the endothelial microvascular vasomotor response to acetylcholine. Endomyocardial biopsies were taken to determine the levels of gene expression of isozymes of endothelin and nitric oxide synthases (NOS). Blood samples from the coronary sinus and aorta were withdrawn for measurement of endothelin, nitrite and cytokines. Five patients (30 %) showed an impaired coronary flow reserve response to acetylcholine, significantly higher inducible NOS gene expression and significant transcardiac nitrite production. Plasma nitrite correlated with tumour necrosis factor-alpha levels in coronary sinus and a transcardiac net extraction of endothelin was noted in all patients. In conclusion, 30 % of patients develop endothelial dysfunction early after heart transplantation; this correlates with the expression and activation of vasoactive and immunomodulatory mediators, which may predict the development of transplant vasculopathy.