Drug‐Induced Afterdepolarizations and Triggered Activity Occur in a Discrete Subpopulation of Ventricular Muscle Cells (M Cells) in the Canine Heart:

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Abstract
EADs and DADs in M Cells. Introduction: Oscillations of membrane potential that attend or follow the cardiac action potential and depend on preceding Tran membrane activity for their manifestation are known as aflerdepolarizations. Early aflerdepolarizations (EADs) interrupt or retard repolarization of the cardiac action potential, whereas delayed afterdepolarizations (DADs) arise after full repolarization. EADs and DADs can give rise to spontaneous action potentials or triggered activity believed to be responsible for a variety of cardiac arrhythmias. Recent studies from our laboratory have highlighted differences in the electrophysiology and pharmacology of three functionally distinct myocardial cell types found in the canine ventricle. Epicardial, M region, and endocardia tissues and cells show distinct, sometimes opposite, responses to a variety of drugs, including those capable of inducing EADs and DADs. Methods and Results: In the present study, we used standard microelectrode techniques to examine the pharmacologic response of these cellular subtypes to therapeutic levels of quinidine and toxic levels of digitalis. Quinidine readily produced prominent EADs and EAD induced triggered activity in tissue preparations from the M region (deep subepicardium), but not in those from epicardium. endocardium, or deep subendocardium of the canine ventricle. Acetylstrophanthidin produced prominent DADs in M cell preparations and subendocardiat Purkinje fibers but only minute DADs, if any, in epicardium, endocardium, or deep subendocardium. DAD‐induced triggered activity was observed to arise only in Purkinje and M cells and never in myocardial tissues from the epicardial, endocardial, or deep subendocardial regions of the ventricular wall. Conclusion: We conclude that EADs, DADs, and triggered activity caused by therapeutic levels of quinidine and toxic levels of digitalis are limited to or much more readily induced in a select population of cells in the deep subepicardial (M cell) region of the canine ventricle in addition to the Purkinje system of the heart.