Inotropic mechanisms of amrinone in papillary muscles from guinea‐pig hearts

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Abstract
Isometric force and action potentials were recorded in papillary muscles from guinea‐pigs (temperature 33 d̀C, stimulation frequency 0.5 Hz). Amrinone (1 mM) increased peak twitch force (to 220% of control,n= 12) and rate of rise of force (to 221% of control,n= 12), while time from peak to half‐relaxation was markedly reduced (to 70% of control). The time to peak force was not significantly changed. Action potential at 50% repolarization was shortened (93.3% of control,n= 8), whereas plateau voltage became more positive. Peak twitch force in response to a test stimulus after a varied interval, i.e. mechanical restitution, was increased at all intervals by the drug. However, the time to full mechanical restitution (1.5 s) was not affected. Forces in response to the test interval preceding the previous contraction (post‐extrasystolic potentiation) were analysed. Maximum potentiation was 16.0 mN mm‐2(2.7 ± 0.4%) before and 22.6 mN mm‐2(1.7 ± 0.1%) after addition of the drug, i.e., the relative potentiation was diminished in the presence of the drug. The test interval for optimum potentiation was shortened from 370 to 320 ms (P < 0.05,n= 12) in 1 mM amrinone. During decay of post‐extrasystolic potentiation peak force of the post‐potentiated contraction was linearly related to force of the potentiated contraction. The slope of this line (which is believed to monitor recirculation of activator calcium) was increased by amrinone from 0.37 to 0.50 (P < 0.01,n= 12). The results support the view that the positive inotropic action of amrinone is due to (1) an enhanced calcium inflow during excitation and (2) a more rapid and (3) a more effective calcium uptake by the sarcoplasmic reticulum.