Effects of myocardial α1-adrenergic receptor stimulation and blockade on contractility in humans

Abstract

Background. Although α-adrenergic receptors are present in both normal and failing human left ventricular myocardium and mediate a positive inotropic effect in several other species, it is not known whether stimulation of myocardial α-adrenergic receptors exerts a positive inotropic effect or contributes to basal contractile state in vivo in humans. Methods and Results. We studied 15 patients with angiographically normal coronary arteries (seven with normal left ventricular function and eight with left ventricular failure). To avoid the confounding effects of changes in ventricular loading conditions and systemic reflex mechanisms, the α-adrenergic receptor-selective antagonist phentolamine and agonist phenylephrine were infused directly into the left main coronary artery, and the change in contractile state was assessed by measuring left ventricular peak (+)dP/dt. Phentolamine alone had no effect on left ventricular contractility. Phenylephrine exerted a concentration-related positive inotropic effect in patients with normal as well as those with failing ventricles. The α-adrenergic effect of phenylephrine, defined as the component blocked by phentolamine, was significantly less in patients with ventricular failure (108±28 mm Hg/sec) than in normal subjects (248±54 mm Hg/sec; p<0.03). Conclusions. Myocardial α-adrenergic receptors do not contribute to the maintenance of basal left' ventricular contractile state in humans. However, stimulation of myocardial α-adrenergic receptors exerts a positive inotropic effect, the magnitude of which may be attenuated in patients with heart failure.