Amrinone activates K+-depolarized atrial and ventricular myocardium of guinea pigs

Amrinone is a new synthetic drug that increases contractile strength of mammalian heart muscle; however, its mechanism of positive inotropic action has not been determined. We now report that amrinone (0.053-5.3 mM) consistently restores typical slow response electromechanical activity fo K+-depolarized atrial and ventricular myocardial preparations from guniea pigs. This action was blocked in both tissues by D-600 (1 microM), but it was not significantly inhibited by either tetrodotoxin (23.5 microM), d,l-propranolol (1 microM), or phentolamine (10 microM). Cimetidine (3 microM) or metiamide (10 microM) slightly inhibited amrinone's effect only in the ventricle, whereas pyrilamine (10 microM) slightly inhibited amrinone's response only in the atrium. These data indicate that amrinone's positive inotropic action may involve augmented Ca++ influx via the slow inward Ca++ current, and that although this action is independent of adrenoceptor mechanisms, it seems to include a small histaminergic component.