Effects of bupivacaine on contraction and membrane potential in isolated canine papillary muscles.

The effects of bupivacaine on myocardial contraction and membrane potential were examined in isolated canine right ventricular papillary muscles. Bupivacaine (10(-6) to 10(-4) mol/l) produced a dose-dependent and reversible decrease in the electrically induced contractile response of canine right ventricular papillary muscles. The inhibitory effects of bupivacaine on contraction were more pronounced at high stimulation frequencies (2 and 3 Hz) than at low frequency (< 1 Hz). The resting membrane potential was not affected by bupivacaine. The maximal upstroke velocity of the action potential was reduced by 10(-6) mol/l bupivacaine (74 +/- 28% of control), and these effects were also dose dependent. At 10(-4) mol/l, bupivacaine blocked fast action potentials in normal Tyrode's solution. Furthermore, bupivacaine (10(-4) and 10(-3) mol/l) decreased both slow action potential duration and associated contractions in high-K+ (26 mmol/l) Tyrode's solution in the presence of isoproterenol. Our results suggest that low concentrations of bupivacaine depress contraction mainly due to an Na+ channel block, whereas at higher concentration, this local anesthetic may block Ca2+ channels.