Bunazosin induces use-dependent slowing of conduction in guinea-pig ventricular myocardium

The use-dependent effects of bunazosin on the maximal rate of rise (Vmax) of the action potential and conduction velocity were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential of the muscles. In the presence of 30 microM bunazosin, the time constants for the start of the use-dependent inhibition of Vmax during a 0.2, 1, 2 and 3 Hz stimulation were (means +/- S.E.M. in s) 30.9 +/- 8.0, 15.0 +/- 1.6, 7.4 +/- 0.9 and 3.9 +/- 0.7 (n = 4) and those for conduction velocity were 17.3 +/- 2.3, 17.3 +/- 5.2, 6.5 +/- 0.9 and 3.4 +/- 0.2, respectively. These results showed that in the cardiac ventricular muscle of the guinea-pigs, bunazosin produces use-dependent changes in conduction velocity with onset kinetics comparable to those measured simultaneously using Vmax. The characteristics of the use-dependent inhibition of conduction velocity induced by bunazosin are similar to those found with slow kinetic drugs such as disopyramide rather than with fast ones.