title: Cocaine suppression of triggered activity. A possible mechanism of antiarrhythmic action.
abstract: The cellular mechanisms of cocaine-induced arrhythmias are not clear. Production of early afterdepolarizations (EADs) in single myocytes have been proposed as a possible mechanism of cocaine arrhythmogenesis. The objective of this investigation was to determine whether cocaine exerts arrhythmogenic or antiarrhythmic actions related to the production or inhibition of afterdepolarizations in multicellular preparations. Rat and guinea pig papillary muscles superfused in vitro with Tyrode's solution at 37 degrees C were stimulated at 1 Hz. Standard intracellular microelectrodes were used to record membrane potentials. Cocaine administered at 2.9-58 microM never induced EADs; also, overdrive in the presence of cocaine never induced delayed afterdepolarizations (DADs). On the other hand, cocaine administered at 58 microM suppressed DADs and triggered activity induced by overdrive in the presence of ouabain octahydrate and isoproterenol. Thus, cocaine acting on multicellular ventricular preparations in vitro did not induce EADs or DADs. On the contrary, cocaine inhibited DADs and triggered activity induced by other drugs.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059.
authors.forename: R G
authors.initials: RG
authors.lastname: Carpentier
authors.forename: H T
authors.initials: HT
authors.lastname: Sherief
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D003042:Cocaine / Q000009:adverse effects / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003042:Cocaine