EFFECTS OF COCAINE ON CARDIAC VAGAL TONE BEFORE AND DURING CORONARY-ARTERY OCCLUSION - COCAINE EXACERBATES THE AUTONOMIC RESPONSE TO MYOCARDIAL-ISCHEMIA

Cocaine is a potent sympathomimetic drug that can provoke lethal cardi ac events. Cocaine-induced alterations in autonomic balance, particula rly during myocardial ischemia, could contribute significantly to thes e adverse reactions. To test this hypothesis, we produced a 2-min left circumflex coronary artery (LCX) occlusion in unanesthetized mongrel dogs (n = 7) instrumented to measure left ventricular pressure (LVP), ventricular electrogram, and coronary blood flow (CBF) with and withou t various doses of cocaine (0.0, 0.5, 1, 2, and 4 mg/kg). At least 24 h elapsed between cocaine doses, which were given in random order. Tim e series analysis of heart rate (HR) variability was used as an index of cardiac vagal tone (0.24-1.04 Hz). Cocaine elicited dose-dependent increases in HR that were accompanied by corresponding decreases in ca rdiac vagal tone. The peak response was achieved approximately 1 min a fter cocaine was given and returned to precocaine values 15 (0.5 and 1 mg/kg), 30 (2 mg/kg), or 60 (4 mg/kg) min later. Myocardial ischemia elicited significant increases in HR and reductions in cardiac vagal t one that were accentuated by cocaine (1, 2, and 4 mg/kg); e.g., cocain e (2 mg/kg) elicited a greater HR (control 119.3 +/- 5.9, occlusion 14 9.7 +/- 9.6; cocaine 144 +/- 11.9, occlusion 178.3 +/- 10.4 beats/min) and vagal tone (control 5.6 +/- 0.7, occlusion 2.6 +/- 0.3; cocaine 5 .2 +/- 0.7, occlusion 1.3 +/- 0.5 In s2) response to 2-min coronary oc clusion. Beta-Adrenoceptor blockade (propranolol HCl 1 mg/kg) attenuat ed the HR response but elicited greater reduction (lower values were a chieved) in vagal tone during coronary artery occlusion. These data de monstrate that cocaine not only provokes an increase in adrenergic act ivity but also reduces cardiac vagal tone. In particular, cocaine exac erbates the autonomic response to myocardial ischemia. The resulting a utonomic imbalance could increase the propensity for malignant arrhyth mias.