BACKGROUND: The effects of various concentration (20, 50, 100? M) of mepivacaine were studied in isolated guinea pig and rat right ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiological parameters. METHODS: Isometric force of isolated guinea pig ventricular papillary muscle was studied in modified normal and 26 mM K+ Tyrode's solution. Rat papillary muscle was used to evaluate the effect on Ca2+ release from the sarcoplasmic reticulum (SR) at low stimulation rates. Normal and slow action potentials (APs) were evaluated by using conventional microelectrode technique. Rapid cooling contractures (RCCs), an index of SR Ca2+ content, which are known to be activated by Ca2+ released from the SR were performed. RESULTS: Mepivacaine caused dose-dependent depression of peak force from 0.5 to 3 Hz stimulation rates in guinea pig papillary muscles. Conduction block was frequently noted especially at higher stimulation rates (2 and 3 Hz) at all concentration ranges. In rat, ~20% depression of peak force was shown at rested state contraction. Shortening of AP duration and rate-dependent depression of dV/dt max could be observed at 100 M mepivacaine. In 26 mM K+ Tyrode's solution, 50 and 100 M mepivacaine caused dose-dependent depression of early and late force development. In slow APs, neither shortening of AP duration nor changes of dV/dtmax were not shown at 100 M mepivacaine. ~30% depression of RCC after 2 Hz stimulation rate was shown at 100 M mepivacaine. CONCLUSION: It may be concluded that the direct myocardial depressant effects of mepivacaine may partly be related to inhibition of Ca2+ release from the SR. Shortening of AP duration in normal APs seems to be partly related by blockade of TTX-sensitive ""window"" Na+ current.