Cellular mechanism underlying the efficacy of the sotalol-quinidine combination.
The combination of quinidine and sotalol is very effective in prevention of recurrent sustained ventricular tachycardia (SVT). The cellular mechanisms underlying this efficacy were examined in guinea pig papillary muscle, using standard microelectrode techniques and stimulation frequencies of 1, 2, and 3 Hz. Action potential duration (APD) and effective refractory period (ERP) were measured under control conditions, after 30-min perfusion with quinidine (5 microM) or sotalol (6 microM), and after an additional 30 min of quinidine + sotalol (5 and 6 microM, respectively). Quinidine, sotalol, and quinidine + sotalol all prolonged APD at 90% repolarization (APD90) by 9 +/- 1, 13 +/- 1, and 15 +/- 2%, respectively (at 3 Hz; p = NS, comparison of the three drugs; p < 0.05 for each drug as compared with control). Quinidine + sotalol prolonged ERP (at 3 Hz) by 27 +/- 2% as compared with 11 +/- 2% after sotalol and 18 +/- 2% after quinidine alone (p < 0.05). As a result, the ERP/APD ratio was increased by the combination to 0.87 +/- 0.2 (p < 0.05) as compared with 0.78 +/- 0.2 for control 0.79 +/- 0.1 for sotalol, and 82 +/- 0.1 for quinidine (at 3 Hz). Although sotalol alone decreased the maximum rate of depolarization of phase 0 of the AP (Vmax) by only 3 +/- 2% (p = NS), sotalol attenuated Vmax decrease of quinidine (at 3 Hz) from 40 +/- 4 to 16 +/- 3% (p < 0.05). Effects at 1 and 2 Hz were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Berman
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ND
Division of Cardiology, University of Toronto, Ontario, Canada.
Dorian
P
P
D000200:Action Potentials; D000818:Animals; D004338:Drug Combinations; D004558:Electric Stimulation; D006168:Guinea Pigs; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology*; D013015:Sotalol / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000517:prevention & control
D004338:Drug Combinations; D013015:Sotalol; D011802:Quinidine