INTRACELLULAR CALCIUM CHELATOR, BAPTA-AM, PREVENTS COCAINE-INDUCED VENTRICULAR-FIBRILLATION

Cocaine is a potent cardiac stimulant that can provoke lethal cardiac events, including ventricular fibrillation (VF). The cocaine-induced a ccumulation 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 witho ut cocaine failed to induce arrhythmias. Pretreatment with the intrace llular calcium-specific chelator ,2-bis(2-aminophenoxy)ethane-N,N,N',N '-tetraacetic acid-acetoxymethyl ester (BAPTA-AM; 1.0 mg/kg iv) preven ted 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 d evelopment (dP/dt(max); control 5,251 +/- 317.6, cocaine 6,016 +/- 435 .1 mmHg/s). BAPTA-AM attenuated the increase in LV dP/dt(max) (BAPTA-A M 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 rep eated after nitroprusside. The nitroprusside prevented cocaine-induced increases in LV systolic pressure but failed to prevent VF. These dat a suggest that BAPTA-AM may prevent cocaine-induced VF independently o f its vascular actions.