Gadolinium suppresses stretch-induced increases in the differences in epicardial and endocardial monophasic action potential durations and ventricular arrhythmias in dogs.
We tested whether acute pressure overloading of the left ventricle (LV) had spatially different effects on repolarization, thereby causing arrhythmias. The effects of gadolinium (Gd3+), a nonspecific blocker of stretch-activated channels were also examined. In anesthetized dogs, 5 s 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. Gd3+ was injected into the left atrium before the second (500 micromol) and third AC (2500 micromol) (n=10). In a separate group (n=7), the effects of Gd3+ in the presence of verapamil were examined. Epicardial MAP durations at 50% and 90% repolarization (APD50; APD90) 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 APD50 and APD90 increased. Consistent with these changes, premature ventricular contractions (PVCs) developed. Gd3+ had no effect on baseline MAP durations, however it prevented an AC-induced increase in the difference by suppressing epicardial MAP shortening. Gd3+ also reduced PVCs in a dose-dependent manner at plasma concentrations of 1-4 micromol/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.
Takagi
S
S
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. stms1129@mba.sphere.ne.jp
Miyazaki
T
T
Moritani
K
K
Miyoshi
S
S
Furukawa
Y
Y
Ito
S
S
Ogawa
S
S
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004285:Dogs; D004699:Endocardium / Q000187:drug effects / Q000503:physiopathology; D005682:Gadolinium / Q000494:pharmacology* / Q000627:therapeutic use; D007473:Ion Channels / Q000037:antagonists & inhibitors; D010496:Pericardium / Q000187:drug effects / Q000503:physiopathology; D013314:Stress, Mechanical; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
D007473:Ion Channels; D005682:Gadolinium