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Comparative antifibrillatory effects of d- and dl-sotalol in normal and ischaemic ventricular muscle of the cat.

Abstract
The aim of this study was to compare the effects of d- and dl-sotalol on the ventricular fibrillation threshold (VFT) and the effective refractory period (VERP) in anaesthetized cats subjected to coronary artery occlusion. Occlusion of the left anterior descending coronary artery caused a decrease in VFT (measured in mA) (1.40 +/- 0.1 to 0.6 +/- 0.1). dl-Sotalol (1 and 5 mg kg-1) increased VFT before the induction of ischaemia (1.7 +/- 0.1 to 33.8 +/- 1.0 and 38, respectively), and the higher dose prevented the ischaemia-induced fall in VFT. d-Sotalol (1 and 5 mg kg-1) caused only small increases in VFT in normal (1.9 +/- 0.3 to 2.3 +/- 0.3 and 2.6 +/- 0.3) and ischaemic (0.8 +/- 0.1 to 1.2 +/- 0.2 and 1.3 +/- 0.2) myocardium. Both d- and dl-sotalol increased VERP measured in normal myocardium. The % changes observed with 1 and 5 mg kg-1 of the racemate (17 +/- 1 and 57 +/- 4) were significantly greater than those with the d-isomer (8 +/- 3 and 16 +/- 2). dl-Sotalol, but not d-sotalol, prevented the haemodynamic responses to 50 ng kg-1 isoprenaline. These results suggest that VFT in anaesthetized cats is markedly increased by beta-adrenoceptor blockade and only marginally increased by the direct class III antiarrhythmic action of d-sotalol.
AuthorsY W Kwan, A M Solca, M Gwilt, K A Kane, R M Wadsworth
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 15 Issue 2 Pg. 233-8 (Feb 1990) ISSN: 0160-2446 [Print] United States
PMID1689418 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Sotalol
  • Isoproterenol
Topics
  • Adrenergic beta-Antagonists
  • Animals
  • Anti-Arrhythmia Agents
  • Cats
  • Coronary Disease (physiopathology)
  • Female
  • Heart (drug effects)
  • Heart Rate (drug effects)
  • Heart Ventricles (drug effects)
  • In Vitro Techniques
  • Isoproterenol (pharmacology)
  • Male
  • Papillary Muscles (drug effects)
  • Sotalol (pharmacology)
  • Stereoisomerism
  • Ventricular Fibrillation (physiopathology)

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