Effects of pimobendan (UD-CG 115 BS), a new positive inotropic agent, on ventricular tachycardia and ischemic ventricular fibrillation in a conscious canine model of recent myocardial infarction.
Pimobendan (UD-CG 115 BS; 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl- 3(2H)- pyridazinone) is a newly developed, structurally novel compound with positive inotropic as well as coronary and peripheral vasodilator activities. In vitro, pimobendan has been reported to prolong the duration of the cardiac action potential of ventricular myocardial tissue, suggesting the potential for this agent to increase myocardial refractoriness and possibly exert antiarrhythmic activity in vivo. In the present study, the effects of pimobendan upon cardiac electrophysiologic parameters, the induction of ventricular tachycardia by programmed ventricular stimulation, and upon the development of ischemic ventricular fibrillation were assessed in 16 conscious dogs 3 to 5 days after experimental anterior myocardial infarction. The intravenous administration of 0.3 mg/kg pimobendan to postinfarction dogs significantly reduced the rate-corrected QTc and paced QT intervals, and reduced the relative and effective refractory periods in normal noninjured ventricular myocardium. Electrophysiologic parameters in infarcted ventricular myocardium were not altered by pimobendan. Ventricular tachycardia remained inducible early after anterior myocardial infarction in eight of eight pimobendan-treated postinfarction dogs tested. Six of the eight pimobendan-treated animals that had nonsustained tachyarrhythmias elicited as initial responses to baseline programmed stimulation testing had sustained tachycardias induced at postdrug testing, with a reduction in the number of programmed extrastimuli required to induce the postpimobendan tachyarrhythmias occurring in three animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Lynch
J J
JJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Kitzen
J M
JM
Hoff
P T
PT
Lucchesi
B R
BR
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003645:Death, Sudden; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D011724:Pyridazines / Q000494:pharmacology*; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology*
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan