Hemodynamic effects of d-sotalol in acute ischemic heart failure in dogs.
This study was designed to determine the hemodynamic effects of the class III antiarrhythmic agent d-sotalol in acute ischemic heart failure at concentrations that prolong ventricular repolarization. In pentobarbital-anesthetized open-chest dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular (LV) end-diastolic pressure of 25 +/- 2 mm Hg was achieved. Embolization shortened the QT interval by 30 +/- 11 msec, while 1 and 2 mg/kg d-sotalol intravenously after embolization lengthened the QT interval by 23 +/- 7 and 39 +/- 7 msec, respectively (n = 7). Heart rate increased after embolization by 19 +/- 7 beats/min, while it decreased by 12 +/- 6 beats/min and by 21 +/- 5 beats/min after d-sotalol. The depressed LV function after embolization assessed by LV pressures, stroke volume, cardiac output, ultrasonometrically estimated LV volume, the pressure-volume relationship, and the time for isovolumic relaxation was not changed following infusion of 1 or 2 mg/kg d-sotalol. Plasma concentrations of d-sotalol were 1.55 +/- 0.33 and 2.58 +/- 0.50 micrograms/ml, respectively. In conclusion, d-sotalol at concentrations prolonging repolarization was devoid of cardiodepressive effects in acute ischemic heart failure in dogs.
Mortensen
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Department of Medical Physiology, University of Tromsø, Norway.
Tande
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PM
Kløw
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Refsum
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D000208:Acute Disease; D000818:Animals; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D008297:Male; D013015:Sotalol / Q000097:blood / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects / Q000502:physiology
D013015:Sotalol