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

Summary

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 (2×10⁻⁷ M). Ouabain is much more potent than amrinone (EC₅₀-values: ouabain, 8×10⁻⁸ M, amrinone, 1–2.8×10⁻³ M). The highest amrinone concentration used (6×10⁻³ M) produced a significantly lower increase in force of contraction than ouabain (2×10⁻⁷ M) in the same muscles. After ouabain (2×10⁻⁷ 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 3×10⁻³ M amrinone with ouabain (2×10⁻⁷ M), but in only one of these muscles with amrinone 3×10⁻³ 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.