Transcardiac extraction of circulating endothelin-1 across the failing heart.
To determine the transcardiac gradient of plasma endothelin-1 (ET-1) in patients 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 significantly higher in the coronary sinus than in the aortic root; these findings were also shown in patients with mild CHF, suggesting that there was ET-1 spillover across the heart. In contrast, plasma ET-1 was significantly lower 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 was 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 multivariate analysis showed that the transcardiac gradient of plasma ET-1 was an independent and significant relation with the left ventricular end-diastolic volume index in patients with CHF (r = 0.665, p <0.0001). These findings 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 are upregulated in the failing ventricle and that the elevated circulating ET-1 might stimulate the process of left ventricular remodeling in patients with severe CHF.
Tsutamoto
T
T
First Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. tutamoto@belle.shiga-med.ac.jp
Wada
A
A
Maeda
K
K
Mabuchi
N
N
Hayashi
M
M
Tsutsui
T
T
Ohnishi
M
M
Sawaki
M
M
Fujii
M
M
Matsumoto
T
T
Horie
H
H
Sugimoto
Y
Y
Kinoshita
M
M
D000804:Angiotensin II / Q000097:blood; D001011:Aorta; D003331:Coronary Vessels; D019332:Endothelin-1 / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012016:Reference Values; D016277:Ventricular Function, Left
D019332:Endothelin-1; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D000804:Angiotensin II; D009638:Norepinephrine