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

Emilio Vanoli, Stephen S. Hull, Philip B. Adamson, Robert D. Foreman, Peter J. Schwartz

Research output: Contribution to journalArticlepeer-review

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 Ikr blocker, d, l-sotalol, its racemic compound which blocks Ikr, and β-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 rf-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.

Original languageEnglish
Pages (from-to)847-854
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume26
Issue number6
Publication statusPublished - 1995

Keywords

  • Antiarrhythmic drugs
  • Sudden cardiac death
  • Ventricular repolarization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

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