In Vitro Cardiac Repolarization Assays: Guinea Pig Papillary Muscles Vs. Canine Purkinje Fibers

Abstract

Delayed or accelerated cardiac repolarization is potentially proarrhythmic. In this study, we compared a guinea pig papillary muscle APD (GPPM-APD) assay to a canine Purkinje fiber APD (CPF-APD) assay in assessing drug effects on cardiac repolarization. Papillary muscles (right ventricle) and Purkinje fibers were stimulated at 0.5 Hz, action potentials were recorded using microelectrode techniques, repolarization assessed using APD30, 50, 90 values, and the calculated triangulation parameter, APD30-90. Eight compounds (6 positives, 2 negatives) were tested in both preparations. Percent changes in APD90 values obtained with the GPPM-APD assay were less than those obtained in the CPF-APD assay (table). Repolarization parameters in the GPPM-APD assay exhibited a rank sensitivity order of APD30 < APD50 ≈ APD90 < APD30-90 in detecting effects of the five hERG blockers on repolarization. APD90 was the most sensitive parameter in detecting effects of the hERG activator (A-935142.0). These results suggest the GPPM-APD assay and the CPF-APD assay are valuable in assessing drug effects on cardiac repolarization with comparable effects in both assays.View Large Image | View Hi-Res Image | Download PowerPoint Slide