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Transcardiac extraction of circulating endothelin-1 across the failing heart

2000; Elsevier BV; Volume: 86; Issue: 5 Linguagem: Inglês

10.1016/s0002-9149(00)01006-7

1879-1913

Takayoshi Tsutamoto, Atsuyuki Wada, Keiko Maeda, Naoko Mabuchi, Masaru Hayashi, Takashi Tsutsui, Masato Ohnishi, Masahide Sawaki, Masanori Fujii, Takehiro Matsumoto, Hajime Horie, Yoshihisa Sugimoto, Masahiko Kinoshita,

Pulmonary Hypertension Research and Treatments

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.