Sotalol facilitates spontaneous ventricular defibrillation by enhancing intercellular coupling. An entirely new mechanism for its antiarrhythmic action.
We have previously shown that sotalol, a class III antiarrhythmic agent, helps spontaneous ventricular defibrillation in various mammalian species. Since we hypothesized that self ventricular defibrillation depends on a high degree of intercellular synchronization, and since the major electrophysiological action of sotalol causing prolongation of action potential duration (APD), cannot fully explain its defibrillating property, we carried out a series of studies to examine the effect of sotalol on intercellular myocardial coupling. Guinea pig right ventricular muscle preparations were superfused in a tissue bath and the spread of intracellularly injected fluorescent dye (Lucifer yellow CH) to the neighboring cells was studied under various conditions. When either the Ca2+ concentration of Tyrode's solution was elevated to 6 mM or the solution was made hypoxic by not bubbling O2 (n = 3 each), no spread of the injected dye was observed. The addition of 1 microM sotalol to the high Ca2+ solution or 0.5 microM to the hypoxic superfusate (n = 3 each) caused a wide spreading of the dye, thus strongly suggesting a marked improvement in the intercellular coupling. These results show an entirely new property of sotalol, i.e., enhancement of cellular synchronization, which may better explain its ability to cause spontaneous ventricular defibrillation than its class III action. Our previous demonstration of successful spontaneous ventricular defibrillation by several other agents that are known to enhance intercellular coupling but have contrasting actions on APD further substantiates our hypothesis.
Cardiovascular Institute, Fujita Health University, Aichi, Japan.
H
H
Uchiyama
M
M
Manoach
E
E
Miyachi
Y
Y
Watanabe
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects; D046508:Culture Techniques; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D013015:Sotalol / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D002118:Calcium