Alpha1‐Adrenergic Blockade and Sudden Cardiac Death

INTRODUCTION: The primary goal of the present study was to test whether selective pharmacologic blockade of alpha 1 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 1 receptors, and in particular the subtype alpha 1a, may be involved in the genesis of malignant arrhythmias during acute myocardial ischemia and reperfusion. Despite this evidence, questions have been raised about the actual antifibrillatory 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; 1 micrograms/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 1 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.