Computerized evaluation of drug-induced changes in guinea-pig epicardial monophasic action potentials

The monophasic action potential (MAP) has been widely used for the study of drug effects on cardiac repolarization in vivo. There is, however, no study of drug-induced effects on MAP depolarization, i.e. effects on MAP Vmax and/or MAP rise-time. For this study, we developed a method in the anesthetized open chest guinea-pig. MAP signals were recorded and subjected to on-line computerized analysis, in which parameters describing both depolarization and repolarization were calculated. With the MAP electrode kept at the same epicardial position the MAP rise-time did not vary with time. If the influences of heart rate were eliminated, the intra- and interindividual variation in the MAP duration was very low. Sotalol significantly and dose-dependently prolonged MAP duration, but did not affect rise-time, whereas tocainide significantly and dose-dependently shortened MAP duration and increased rise-time. The effect of tocainide on rise-time is most likely secondary to a reduction in conduction velocity due to a decrease in Vmax in the single cell action potential. These results suggest that monophasic action potential recordings coupled with an on-line computerized analysis may be used for rapid and simple evaluation of drug effects, both on cardiac depolarization and repolarization.