K+ channel blockade in the prevention of ventricular fibrillation in dogs with acute ischemia and enhanced sympathetic activity

Author(s): Hull, S. S., Adamson, P. B., Foreman, R. D., Schwartz, P. J.

Journal/Book: J Cardiovasc Pharmacol. 1995; 26: 227 East Washington Sq, Philadelphia, PA 19106. Raven Press. 847-854.

Abstract: The value of K+ channel blockade in preventing lethal arrhythmias, and specifically those triggered by acute myocardial ischemia and sympathetic hyperactivity, remains unproven. To address this issue, we tested the antifibrillatory effect of d-sotalol, an I-kr blocker, d,l-sotalol, its racemic compound which blocks I-kr, and beta-adrenoreceptors, and propranolol. Ten dogs with a healed anterior myocardial infarction (MI) had ventricular fibrillation (VF) during a 2-min occlusion of the circumflex coronary artery performed toward the end of a submaximal exercise stress test. In successive trials in the same animals, d-sotalol (three injections of 8 mg/kg, one every 12 h), d,l-sotalol (8 mg/kg), and propranolol (1 mg/kg) were tested. All three interventions significantly reduced heart rate (HR) response to exercise, but only d,l-sotalol and propranolol also blunted the reflex HR increase during acute myocardial ischemia. With d-sotalol, HR at 30 s of coronary occlusion was similar (253 +/- 28 beats/min) to that observed in the control tests (259 +/- 35 beats/min). d-Sotalol prevented recurrence of VF in only 1 of 10 dogs tested. One dog was lost to the continuation of the study after occurrence of VF with d-sotalol. Six of 9 dogs (67%) tested with d,l-sotalol and 5 (56%) of the same 9 dogs tested with propranolol were protected from VF. d-Sotalol does not reduce risk of VF during acute myocardial ischemia associated with sympathetic hyperactivity, and lethal events can be prevented by antiadrenergic interventions.

Note: Article PJ Schwartz, Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Biomed Sci Bldg, Room 653, POB 26901, Oklahoma City, OK 73190 USA

Keyword(s): antiarrhythmic drugs; sudden cardiac death; ventricular repolarization; HEART-RATE-VARIABILITY; ACUTE MYOCARDIAL-INFARCTION; CONSCIOUS DOGS; SUDDEN-DEATH; ANTIFIBRILLATORY ACTIONS; BAROREFLEX SENSITIVITY; SOTALOL; MORTALITY; AMIODARONE; ARRHYTHMIAS

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