Electrical and mechanical effects of amrinone on isolated guinea pig ventricular muscle

The electromechanical effects of amrinone on isolated guinea pig papillary muscle were studied at various driving frequencies and under the influence of several antagonists and a low calcium medium. Amrinone (3 X 10(-5)-2 X 10(-3)M) caused a positive inotropic effect on preparations driven at 1.0 Hz in a concentration-dependent manner. When the preparations were driven at a frequency lower than 0.5 Hz, the positive inotropic effect of the drug was markedly attenuated. Amrinone caused a significant prolongation in action potential duration at an early repolarization phase--but not at a late repolarization phase--without affecting any other parameters of action potential. These effects of amrinone were not blocked by a beta-adrenoceptor antagonist or tetrodotoxin, but were inhibited by treatment with verapamil (5 X 10(-6)M) or a low calcium medium (0.1 or 0.3 mM). In papillary muscles depolarized by 30 mM [K+]o, amrinone enhanced the slow action potentials. In voltage clamp experiments using a single sucrose-gap method, amrinone (6 X 10(-4)M) caused a marked increase in the peak amplitude of the slow inward current, while it did not affect the net outward current. The results suggest that the slow calcium inward current may play a predominant role in the positive inotropic effect of amrinone.