Transcardiac extraction of circulating endothelin-1 across the failing heart

To determine the transcardiac gradient of plasma endothelin-1 (ET-1] in pat ients with congestive heart failure (CHF), we measured plasma levels of ET- 1 in both the aortic root and the coronary sinus in 14 normal subjects and 79 consecutive patients with CHF. In normal subjects, plasma ET-1 was signi ficantly higher in the coronary sinus than in the aortic root; these findin gs were also shown in patients with mild CHF, suggesting that there was ET- 1 spillover across the heart. On contrast, plasma ET-1 wets significantly l ower in the coronary sinus than in the aortic root in patients with severe CHF, suggesting there was ET-1 extraction across the heart in patients with severe CHF. The transcardiac gradient of plasma ET-1 wets correlated with the left ventricular end-diastolic volume index (r = 0.501, p <0.0001) and plasma level of procollagen type III amino terminal peptide in the coronary sinus (r = 0.54, p = 0.0008), a marker of myocardial fibrosis, Stepwise mu ltivariate analysis showed that the transcardiac gradient of plasma ET-1 wa s an independent and significant relation with the left ventricular end-dia stolic volume index in patients with CHF (r = 0.665, p <0.0001). These find ings suggest that elevated circulating ET-1 is extracted across the failing heart with a significant correlation between the transcardiac gradient of plasma ET-1 and the left ventricular end-diastolic volume index, suggesting that ET receptors ore upregulated in the failing ventricle and that the el evated circulating ET-1 might stimulate the process of left ventricular rem odeling in patients with severe CHF, (C) 2000 by Excerpta Medica, Inc.