Comparative hemodynamic effects of Org 7797, flecainide, and propafenone in anesthetized pigs with developing myocardial infarcts.
The hemodynamic effects of a new Ic antiarrhythmic agent (Org 7797) were compared with those of flecainide and propafenone in anesthetized pigs with developing myocardial infarcts. One hour after acute coronary artery occlusion, the only significant hemodynamic effect of an intravenous (i.v.) dose of Org 7797 (0.5 mg/kg) known to prevent ischemia-induced ventricular fibrillation (VF) in dogs was a decrease in heart rate (HR) (of 3%) while cardiac output (CO), stroke volume (SV), and left ventricular (LV) dP/dtP-1 were unchanged. At four times this dose, the only sustained and significant responses to Org 7797 were decreased CO and bradycardia, whereas decreases in arterial and LV pressures (BP and LVP) and LVdP/dtP-1 were transient. In contrast, a therapeutic dose of flecainide (2 mg/kg) induced sustained reductions in CO, SV, LVdP/dtP-1, and LVP whereas a similar (therapeutic) dose of propafenone decreased LVP, reduced CO partly as a result of bradycardia and decreased LVdP/dtP-1 but not sufficiently to decrease SV. Two electrical deaths occurred in each of the propafenone (n = 6) and flecainide (n = 7) groups, but arrhythmic deaths did not occur in Org 7797- or saline-treated animals. We conclude that Org 7797 in therapeutic doses, unlike propafenone and especially flecainide, is not cardiodepressant in animals whose cardiac function is already compromised. In addition, there was no evidence of proarrhythmogenicity at the doses of Org 7797 used.
Winslow
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E
Department of Pharmacology, Organon Laboratories Ltd., Newhouse, Lanarkshire, Scotland.
Mason
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R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D011405:Propafenone / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D004963:Estrenes; D011405:Propafenone; C061028:Org 7797; D005424:Flecainide