Class III antiarrhythmic action and inotropy: effects of almokalant in acute ischaemic heart failure in dogs.
We studied the haemodynamic and metabolic effects of the novel class III antiarrhythmic agent almokalant (H 234/09) in acute ischaemic heart failure at a dose prolonging ventricular repolarization. In pentobarbital anaesthetized dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular end-diastolic pressure (LVEDP) of 32 +/- 2 mmHg was achieved. Embolization depressed LV dP/dt(max), LV dP/dt(min), left ventricular systolic pressure (LVSP) and cardiac output. After intravenous infusion of almokalant (0.35 micrograms/kg) LV dP/dt(max) and LV dP/dt(min) were not significantly changed at paced cycle length of 300 msec., whereas LVSP and aortic pressure decreased both at spontaneous and paced cycle length of 300 msec. LVEDP remained unchanged. Heart rate decreased from 185 +/- 7 to 167 +/- 5 beats/min., and corrected QT-time (QTc) increased from 9.5 +/- 0.3 to 10.4 +/- 0.5 msec. Arterial concentration and net myocardial uptake of glucose, lactate and free fatty acids were not significantly influenced by almokalant. In conclusion, almokalant at a dose prolonging ventricular repolarization had no negative inotropic effect in acute ischaemic heart failure.
Mortensen
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E
Department of Medical Physiology, University of Tromsø, Norway.
Yang
T
T
Refsum
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H
D000208:Acute Disease; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D004621:Embolization, Therapeutic; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D011412:Propanolamines; C074334:almokalant