Antiarrhythmic actions of tocainide in canine models of previous myocardial infarction.
The antiarrhythmic and antifibrillatory efficacies of the class IB antiarrhythmic agent tocainide were characterized in conscious dogs in the early subacute phase of anterior myocardial infarction (48 hours after infarction) and in anesthetized dogs with ventricular tachyarrhythmias that were inducible by programmed stimulation more chronically (10.8 +/- 1.0 days) after anterior myocardial infarction. The frequency of spontaneous premature ventricular complexes in the early subacute postinfarction phase was reduced significantly from 48.4% +/- 10.5% to 8.2% +/- 5.0% of total complexes (p less than 0.01) by the cumulative intravenous administration of 10 mg/kg tocainide. In the late postinfarction setting, the intravenous administration of tocainide (6 mg/kg intravenous loading dose + 100 micrograms/kg/min intravenous maintenance infusion) suppressed the initiation of ventricular tachyarrhythmias by programmed stimulation in 5 of 12 animals that were tested and slowed the rate of tachycardia in 3 additional animals. However, the incidence of ventricular fibrillation and of the total number of arrhythmia-related deaths that resulted from the occurrence of a secondary ischemic insult in the presence of previous infarction did not differ significantly between tocainide (75% [9 of 12] incidence of both ventricular fibrillation and of total number of arrhythmia-related deaths) and saline-vehicle control groups (80% [12 of 15] incidence of ventricular fibrillation; 93.3% [14 of 15] incidence of total number of arrhythmia-related deaths). These findings suggest that although class I agents such as tocainide may be efficacious in the suppression of spontaneous premature ventricular complexes and ventricular arrhythmias immediately after myocardial infarction, they may be of limited value in the prevention of malignant ischemic arrhythmias that occur later after myocardial infarction.
Wallace
A A
AA
Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, West Point, PA 19486.
Stupienski
R F
RF
Heaney
L A
LA
Gehret
J R
JR
Lynch
J J
JJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D005117:Cardiac Complexes, Premature / Q000209:etiology / Q000517:prevention & control*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D013610:Tachycardia / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016677:Tocainide
D000889:Anti-Arrhythmia Agents; D016677:Tocainide; D008012:Lidocaine