title: Intracellular calcium chelator, BAPTA-AM, prevents cocaine-induced ventricular fibrillation.
abstract: Cocaine is a potent cardiac stimulant that can provoke lethal cardiac events, including ventricular fibrillation (VF). The cocaine-induced accumulation of intracellular calcium could contribute significantly to the development of these lethal arrhythmias. To test this hypothesis, VF was induced in 12 mongrel dogs by the combination of cocaine (1.0 mg/kg) and a 2-min coronary occlusion during exercise. This test without cocaine failed to induce arrhythmias. Pretreatment with the intracellular calcium-specific chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM; 1.0 mg/kg iv) prevented VF in 8 of 12 animals (P < 0.001) and delayed the onset of lethal arrhythmias in 3 of the remaining animals. Cocaine induced significant increases in left ventricular (LV) systolic pressure (control 154.7 +/- 8.7, cocaine 167.4 +/- 8.4 mmHg), heart rate (control 195.9 +/- 6.1, cocaine 222.3 +/- 10.6 beats/min), and LV maximum rate of pressure development (dP/dtmax; control 5,251 +/- 317.6, cocaine 6,016 +/- 435.1 mmHg/s). BAPTA-AM attenuated the increase in LV dP/dtmax (BAPTA-AM 4,591 +/- 479.3 mmHg/s) and LV systolic pressure (BAPTA-AM 154.5 +/- 6.8 mmHg). Because vascular muscle relaxation could contribute to the cardioprotection, the cocaine and exercise plus ischemia test was repeated after nitroprusside. The nitroprusside prevented cocaine-induced increases in LV systolic pressure but failed to prevent VF. These data suggest that BAPTA-AM may prevent cocaine-induced VF independently of its vascular actions.
authors.affiliation: Department of Physiology, Ohio State University, Columbus 43210.
authors.forename: G E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D003042:Cocaine / Q000633:toxicity*; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology; D005082:Physical Exertion; D012433:Ryanodine / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D012433:Ryanodine; D004533:Egtazic Acid; D003042:Cocaine