Non-additive positive inotropic effects of amrinone and ouabain on cat papillary muscles

Amrinone has been shown to produce haemodynamic benefits in digitalis-treated patients. Since amrinone is a positive inotropic agent on isolated heart muscle, these benefits may mean that amrinone increases the maximal ouabain-induced increase in force of contraction, without causing toxicity. We have therefore measured, in cat right ventricular papillary muscles, the inotropic effects of ouabain, amrinone alone and amrinone with a maximally effective, non-toxic ouabain concentration (2 X 10(-7) M). Ouabain is much more potent than amrinone (EC50-values: ouabain, 8 X 10(-8) M, amrinone, 1-2.8 X 10(-3) M). The highest amrinone concentration used (6 X 10(-3) M) produced a significantly lower increase in force of contraction than ouabain (2 X 10(-7) M) in the same muscles. After ouabain (2 X 10(-7) M) produced a stable effect, no further increase in force of contraction was observed with any amrinone concentration. Sustained arrhythmias were observed in five of six muscles at 3 X 10(-3) M amrinone with ouabain (2 X 10(-7) M), but in only one of these muscles with amrinone 3 X 10(-3) M alone. Since the positive inotropic effects of amrinone are not additive with those from a maximally effective ouabain concentration, the haemodynamic benefits seen in patients are probably due to non-cardiac effects of amrinone such as vasodilatation.