Effects of Cocaine on Cardiac Vagal Tone Before and During Coronary Artery Occlusion: Cocaine Exacerbates the Autonomic Response to Myocardial Ischemia

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Cocaine is a potent sympathomimetic drug that can provoke lethal cardiac events. Cocaine-induced alterations in autonomic balance, particularly during myocardial ischemia, could contribute significantly to these 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 without 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. Time series analysis of heart rate (HR) variability was used as an index of cardiac vagal tone (0.24-1.04 Hz). Cocaine elicited dosedependent increases in HR that were accompanied by corresponding decreases in cardiac vagal tone. The peak response was achieved ˜1 min after 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 tone that were accentuated by cocaine (1,2, and 4 mg/kg); e.g., cocaine (2 mg/kg) elicited a greater HR (control 119.3 ± 5.9, occlusion 149.7 ± 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 occlusion. β-Adrenoceptor blockade (propranolol HCl 1 mg/kg) attenuated the HR response but elicited greater reduction (lower values were achieved) in vagal tone during coronary artery occlusion. These data demonstrate that cocaine not only provokes an increase in adrenergic activity but also reduces cardiac vagal tone. In particular, cocaine exacerbates the autonomic response to myocardial ischemia. The resulting autonomic imbalance could increase the propensity for malignant arrhythmias

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