Positive Inotropic Action of Amrinone

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Abstract
To investigate the positive inotropic effect of amrinone under conditions of maximal contractile stimulation, cumulative amrinone one-half log dose-response curves (dose range, 3.1 .times. 10-5-3.1 .times. 10-3 M amrinone) of isolated cat right ventricular papillary muscle in normal (2.5 mM) and high (7.5 mM) Ca Krebs solution. In 2.5 mM Ca, amrinone induced significant (P < 0.01) dose-dependent increases in peak developed tension (T), maximum dT/dt, which were accompanied by small but significant decreases in time-to-peak tension (TTP). At 10-3 M, changes in T, dT/dt and TTP were 61.9 (2.7 g/mm2); 98.1 (33.2 g/s per mm2), and -13.1% (-26 ms), respectively. In 7.5 mM Ca, the increases in T, dT/dt and -dT/dt, and the reduction of TTP, were markedly less at each concentration. At 10-3 M amrinone, T and dT/dt increased significantly by 16.7 (1.3 g/mm2) and 23.5% (17.4 g/s per mm2), respectively, with no change in TTP. The amrinone-induced reductions in one-half relaxation time and twitch duration persisted in high Ca and were similar in magnitude to those in 2.5 mM Ca. The substantial reduction of amrinone''s positive inotropic effect in high Ca2+ suggests that a major part of the drug''s action involves an augmentation of contractile Ca2+. An amrinone-induced effect on rate of Ca2+ delivery to the contractile apparatus or on myofilament Ca2+ sensitivity would be consistent with a persistent inotropic action in high Ca2+. Contractile changes induced by amrinone are discussed in relation to a possible effect on intracellualr cAMP levels.