Read/Search this Article
We tested whether acute pressure overloading of the left ventricle (LV) had spatially different effects on repolarization, thereby causing arrhythmias. The effects of gadolinium (Gd^<3+>, a nonspecific blocker of stretch-activated channels were also examined. In anesthetized dogs, 5s clamping of the ascending aorta (AC), separated by 5-min intervals, was repeated while monophasic action potentials (MAPs) were recorded from the LV endocardium and epicardium. Gd^<3+> was injected into the left atrium before the second (500 μmol) and third AC (2500 μmol)(n=10). In a separate group (n=7), the effects of Gd^<3+> in the presence of verapamil were examined. Epicardial MAP durations at 50% and 90% repolarization (APD_<50>;APD_<90> shortened in response to LV pressure rise and elongation of the segment length induced by the first AC, whereas endocardial MAP durations remained unchanged. Thus, the difference in APD_<50> and APD_<90> increased. Consistent with these changes, premature ventricular contractions (PVCs) developed. Gd^<3+> had no effect on baseline MAP durations, however it prevented an AC-induced increase in the difference by suppressing epicardial MAP shortening. Gd^<3+> also reduced PVCs in a dose-dependent manner at plasma concentrations of 1-4 μmol/L. The effects were also evident after administration of verapamil. Thus, gadolinium suppressed an increase in the spatial dispersion of repolarization and arrhythmias via a mechanism of action different from that of verapamil.