Endothelin-1 may play an important role in the Fontan circulation

Objectives Our goal was to evaluate whether endothlin-1 (ET-1) plays an important role in the Fontan circulation. Methods Thirteen patients with single-ventricle physiology (Glenn circulation, n = 7; Fontan circulation, n = 6) were evaluated using lung histopathological and immunohistochemical studies and then compared with the normal autopsied controls without congenital heart disease (n = 13). We evaluated the medial thickness of the small pulmonary arteries. For 10 of these patients, quantitative real-time polymerase chain reaction analyses of ET-1, endothelin receptors Type A and Type B, endothelin-converting enzyme-1 and endothelial nitric oxide synthase were performed. Results The medial thickness of the small pulmonary arteries in patients with single-ventricle physiology was greater than that of those in the control group (P = 0.0341). Severe medial hypertrophy of the pulmonary arteries was observed in patients who had poor outcomes. Immunohistochemical studies revealed that the marked expression of ET-1 was observed in the endothelium and media of their pulmonary arteries. In these patients, the messenger RNA expression of ET-1 was also increased. Two patients showed high levels of expression of ETAR and ETBR, although these 2 cases maintain good Fontan circulation. Conclusions Medial hypertrophy and the overexpression of ET-1 in the pulmonary arteries were observed in some patients in whom the Fontan circulation failed. Our data suggest that ET-1 may play an important role in maintaining the Fontan circulation.