Alpha1-Adrenergic Blockade and Sudden Cardiac Death

Alpha₁-Adrenergic Blockade and Sudden Cardiac Death. Introduction: The primary goal of the present study was to test whether selective pharmacologic blockade of alpha₁ receptors, and specifically of the subtype alpha_1a could prevent ventricular fibrillation (VF) during acute myocardial ischemia. Background: The development of new autonomic interventions is of clinical interest in view of the failure of traditional; antiarrhythmic drugs to prevent sudden death. Experimental evidence indicates that alpha, receptors, and in particular the subtype alpha_1a may he involved in the genesis of malignant arrhythmias during acute myocardial ischemia and reperfusion. Despite this evidence, questions have been raised about the actual antifibrillatorv efficacy of alpha-adrenergic blockade in the acutely ischemic myocardium. The effects of prazosin and of abanoquil (UK 52,046), a highly selective alpha_1a receptor blocker, were tested and compared with propranolol in a conscious animal preparation for sudden death. Methods and Results: Ten dogs with a 1-month-old anterior wall myocardial infarction were studied. These dogs had all developed, in control conditions, VF during a 2-minute occlusion of the circumflex coronary artery while exercising (n=9) or lying on the table (n=1). Afterwards, the dogs underwent additional tests with the following intravenously administered drugs: abanoquil (n=10; 1μg/kg. prazosin (n=9; 0.1 mg/kg), and propranolol (n=10; 1 mg/kg). Internal control analysis was used. All dogs tested had recurrence of VF with both alpha-adrenergic blockers. Propranolol significantly reduced heart rate during ischemia and prevented VF in 5 of 10 dogs tested (P < 0.05). When heart rate was kept constant by atrial pacing (n = 3), 2 of the 3 animals remained protected by propranolol. Just prior to onset of VF, heart rate was not significantly different in the control and in the abanoquil tests (237 ± 45 and 253 ± 34 beats/min, respectively), whereas it was higher (P < 0.05) with prazosin (288 ± 40 beats/min). Conclusions: Alpha, and alpha_1a receptor blockers do not prevent VF secondary to acute myocardial ischemia in the presence of elevated sympathetic activity and heart rate. In the same setting, beta-adrenergic blockade prevents the reflex heart rate increase due to ischemia and provides a significant protection.