ABSTRACT
BACKGROUND: The effects of various concentrations (10, 25 micrometer) of azumolene, an analogue of dantrolene, were studied in isolated guinea pig ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiologic parameters. METHODS: Isometric forces were studied in normal and 26 mM K Tyrode's solution. Rapid cooling contracture, an index of SR Ca2 content, was performed. Normal and slow action potentials (APs) were evaluated by using conventional microelectrode technique. RESULTS: Ten and 25 micrometer azumolene depressed peak force and maximum rate of force development ( 30 40%). Dose-dependent depression was shown at 2 and 3 Hz stimulation rate. Rapid cooling contractures following 10 and 25 micrometer azumolene was not altered compared to control while peak force at 2 Hz stimulation rate just prior to cooling was depressed similarly to normal Tyrode's solution. In 26 mM K Tyrode's solution, 10 and 25 micrometer azumolene caused depression of early (10 micrometer: 20%) and late (10 micrometer: 50%) force development. In slow APs, shortening of AP duration at 20, 50, and 90% of the repolarization phase, as well as a small but significant reduction of dV/dt-max ( 20%) were shown at 0.25 Hz stimulation rate. There was no alteration in AP parameters in normal APs. CONCLUSIONS: The direct myocardial depressant action of azumolene seems to be at least in part caused by inhibition of Ca2 influx via the Ca2 channel in sarcolemma. It seems likely that azumolene does not alter the sarcoplasmic reticulum function such as Ca2 uptake and release in cardiac muscle.
