Contrasting inotropic effects of endogenous endothelin in the normal and failing human heart - Studies with an intracoronary ETA receptor antagonist

Article

关键词: LEFT-VENTRICULAR RELAXATION;    NITRIC-OXIDE;    ET(A) RECEPTOR;    CONSCIOUS DOG;    FAILURE;    BLOCKADE;    CONTRACTILITY;    INHIBITION;    MODULATION;    PRESSURE;   

DOI  :  10.1161/01.CIR.101.2.142

来源: SCIE

【 摘 要 】

Background-Endothelin-1 (ET-1) is a potent positive inotrope in vitro, but its physiological effects on intrinsic myocardial contractile function in humans in vivo are unknown. Plasma ET-1 levels are elevated in heart failure, and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the failing human heart are also unknown. Methods and Results-A specific ETA receptor antagonist, BQ123, was infused (40 nmol/min, 16 minutes) into the left coronary artery in 8 patients with atypical chest pain (normal left ventricular [LV] function and coronary arteries) and 8 patients with nonischemic dilated cardiomyopathy (DCM) who were undergoing diagnostic catheterization. In normal subjects, BQ123 rapidly induced a significant reduction in LV dP/dt(max) (-270+/-71 mm Hg/s after 16 minutes; P<0.05) and in LV dP/dt at a developed pressure of 40 mm Hg (LV dP/dt(40)) (-179+/-54 mm Hg/s; P<0.05). In DCM patients, however, BQ123 caused no reductions in LV dP/dt(max) (62+/-49 mm Hg/s after 16 minutes) or LV dP/dt(40) (83+/-51 mm Hg/s; P<0.05 compared with normal subjects). BQ123 had no effect on heart rate, LV relaxation, LV end-diastolic pressure, right atrial pressure, or pulmonary pressure in either patient group. Conclusions-Endogenous ET-1 has a tonic positive inotropic effect in normal subjects, independent of effects on the peripheral vasculature and unmasked by inhibition of ETA receptors. However, the effect of short-term ETA blockade in DCM patients was opposite to that in normal subjects, which suggests that ET-1 may cause negative inotropic effects in the failing heart.

【 授权许可】

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