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 anaesthetized 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.