Abstract

The effects of cibenzoline on transmembrane action potentials were examined in guinea pig papillary muscle. Cibenzoline (1-128 microM) did not alter the action potential durations at 50 and 90% of repolarization, the effective refractory period or the ratio of effective refractory period to action potential duration at 90% of repolarization. Likewise, the maximum diastolic potential was virtually unaffected. Cibenzoline depressed the maximum rate of rise of phase 0 (dV/dtmax). This effect was dependent on the rate of stimulation and occurred at a relatively low concentration (2 microM). The onset of use-dependent depression was monoexponential and dependent on the drug concentration, as well as the rate of stimulation. The rate of recovery from use-dependent depression also followed a single exponential time course but was independent of drug concentration and stimulation rate. When cibenzoline and lidocaine were combined in the tissue bath, dV/dtmax recovered with a double exponential time course. The first and second components of this recovery corresponded to the time course observed with lidocaine (first) and cibenzoline (second) alone. Also, the magnitude of the second component was less with the combination than with cibenzoline alone, indicating an interaction between the two drugs. In addition, cibenzoline shifted the curve relating normalized dV/dtmax to membrane potential in the hyperpolarizing direction. Finally, cibenzoline did not alter slow-response action potentials induced by elevated [K]o and isoproterenol. The authors conclude that cibenzoline acts as a class la antiarrhythmic agent in guinea pig papillary muscle.