Regional differences of superoxide dismutase activity enhance the superoxide–induced electrical heterogeneity in rabbit hearts

During myocardial ischemia and the subsequent reperfusion, free radicals are important intermediates of the cellular damage and rhythm disturbances. We examined the effects of superoxide radicals or hydrogen peroxide (H2O2) on the action potentials in isolated rabbit Purkinje fibers, atrial muscle and ventricular muscle. Reactive oxygen species (ROS) donors such as adriamycin, xanthine/xanthine oxidase and menadione induced prolongation of APD90 in Purkinje fibers. Menadione (30 µM), the most specific superoxide radical donor, prolonged the action potential duration at 90% repolarization (APD90) by 17% in Purkinje fibers, whereas it shortened the APD by 57% in ventricular muscle, and it did not affect the atrial APD. All these menadione–induced effects were completely blocked by 2,2,6,6–tetramethyl– 1–peperadinyloxy, a superoxide radical scavenger. Superoxide dismutase (SOD) activity was lowest in Purkinje fibers, it was moderate in atrial muscle and highest in ventricular muscle. H2O2 shortened the APDs of all three cardiac tissues in a concentration–dependent manner. These results suggest that the different electrical responses to O2●– in different cardiac regions may result from the regional differences in the SOD activity, thereby enhancing the regional electrical heterogeneity.