Comparative antifibrillatory effects of d- and dl-sotalol in normal and ischaemic ventricular muscle of the cat.
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.
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Y W
YW
Kwan
A M
AM
Solca
M
M
Gwilt
K A
KA
Kane
R M
RM
Wadsworth
D000319:Adrenergic beta-Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D007545:Isoproterenol