The Positive Inotropic Effect of Felodipine in Isovolumically Beating Dog Heart

Abstract

Felodipine is a potent arteriolar vasodilator. Its possible myocardial effects were studied by placing dogs anaesthetized with chloralose on cardiopulmonary bypass. A balloon was then inserted into the left ventricular cavity with a vent alongside it. Isovolumic contractions (developed pressure or maximal rate of rise of pressure) were studied as the intraventricular balloon was inflated to various levels. Total coronary venous return was collected to measure coronary blood flow and felodipine concentrations. In seven vagotomized and beta-blocked preparations, a small positive inotropic effect was found [32 +/- 11 (SEM)%, p less than 0.05]; the maximum effect was reached at arterial plasma felodipine concentrations of between 7 and 20 nM and was accompanied by appreciable coronary vasodilatation. In five dogs, infusion of the solvent vehicle (5% polyethylene glycol) alone had no effect. In three more dogs, an infusion of nitroprusside caused coronary vasodilatation, but no positive inotropic effect. The results show that at low concentrations, felodipine has a positive inotropic effect in vivo. These findings suggest that the properties of myocardial calcium agonist and vascular smooth muscle antagonist properties may coexist in the same dihydropyridine molecule. The favorable effects of this drug in the treatment of heart failure can be explained not only by reduction of peripheral resistance, but also by a moderate positive inotropic effect.