Recording of monophasic action potentials in the horizontally perfused guinea pig heart: An in vitro method to study drug-induced changes in cardiac electrophysiology

Abstract

An in vitro technique has been developed for the recording of monophasic action potentials to enable the measurement of changes in the duration of repolarization and in rise time produced by known concentrations of drugs and ions. Guinea pig hearts were perfused horizontally at constant pressure (60 cm H 2O) and temperature (37°C) with Krebs-Henseleit buffer. Epicardial monophasic action potentials were recorded from the right ventricular base using a bipolar Ag AgCI electrode to which a suction pressure of 400 mm Hg was applied. The monophasic action potential signals had smooth depolarization and repolarization phases with amplitudes of 25–65 mV; repeated measurements of monophasic action potential duration at the 50, 75, and 90% repolarization levels (MAPD 50, 75, and 90) and rise time, determined by computer analysis, were reproducible for at least 150 min of perfusion. There was an excellent linear correlation between heart rate and monophasic action potential duration. The ability of the method to detect drug-induced changes was confirmed using clofilium (10 −9 to 10 −5 M), which significantly prolonged monophasic action potential duration 50, 75, and 90 in a concentration-dependent manner, and tocainide (3 × 10 −4 M), which significantly decreased monophasic action potential duration 50, 75, and 90 and increased rise time.