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

Journal of Cardiovascular Pharmacology
E VanoliP J Schwartz

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, and Ikr blocker, d,l-sotalol, its racemic compound which blocks Ikr, 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 ...Continue Reading

Citations

Sep 5, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Arun SridharCynthia A Carnes
Nov 26, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Tuomo NieminenRichard L Verrier
Sep 16, 1998·The American Journal of Cardiology·P T Sager
Sep 21, 2002·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Bente BrendorpLars Køber
Aug 18, 2009·American Journal of Physiology. Heart and Circulatory Physiology·George E Billman
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Joseph J LynchDavid A Claremon
Apr 30, 2003·Journal of Cardiovascular Pharmacology·Philip B AdamsonPeter J Schwartz

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