The inhibitory actions of amiodarone on rested-state contraction in isolated guinea-pig ventricular muscle

1. To assess the mechanism(s) of the negative inotropic effects of amiodarone (AM), an effective anti-arrhythmic agent, the effects of AM on rested-state contraction (RSC) were studied in isolated ventricular papillary muscle from control (untreated) and AM-pretreated guinea-pigs. 2. The RSC was induced by stimulation, following a 30 sec- or 10 min-rest period. 3. The drug's effects were evaluated on an initial response (Ti) and steady-state response (Tss) of the RSC at the end of 1 min-stimulus train at 3.3 Hz. 4. In normal physiological solution, the magnitude of Ti was 2.1 times that of Tss in papillary muscles from untreated animals, but, 1.3 times, in AM-pretreated ones. 5. The effects of superfused AM (4.4 x 10(-5)M) were also evaluated in both muscle types. 6. The drug markedly decreased Ti and Tss in both control and AM-pretreated specimens. 7. However, the depression by superfused AM of RSC in control specimens was more likely to be marked than in AM-pretreated ones. 8. Further, verapamil and caffeine, which affect SR function, also depressed the RSC. 9. These results suggest that the negative inotropic actions of AM, at least in part, reflect a decrease in Ca2+ via Ca2+ channels and an impairment of Ca2(+)-sequestrating system.