Rapid infusions of bidisomide or disopyramide in conscious dogs: effect of myocardial infarction on acute tolerability.
The acute tolerability of rapid infusions of bidisomide or disopyramide was evaluated in normal conscious dogs and in conscious dogs 48 h after the creation of myocardial infarctions (MIs). Both drugs were given in total doses of 15 mg/kg (1.5 x the canine antiarrhythmic dose for each drug). Bidisomide was well tolerated at infusion rates of 3, 5, 11, and 15 mg/kg/min by normal dogs. Disopyramide was well tolerated, except for anticholinergic effects, by normal dogs given infusions at rates of 1.5 and 3 mg/kg/min. Disopyramide caused a ventricular arrhythmia at 4.5 mg/kg/min in one dog, however. Bidisomide (15 mg/kg/min) was well tolerated and antiarrhythmic in dogs with infarctions. Disopyramide (3 and 4.5 mg/kg/min) was lethal in dogs that had myocardial infarctions. A 1 mg/kg/min infusion rate of disopyramide was antiarrhythmic and well tolerated, except for anticholinergic effects, in the post-MI dogs. Both drugs prolonged the ECG lead II P duration, PR interval (bidisomide more so than disopyramide), and QRS duration. Both bidisomide and disopyramide shifted the mean electrical axis of the QRS complex from a right axis deviation to the normal range in dogs with infarctions. The data indicated that the desired cardiac electropharmacologic effects of bidisomide can be achieved in a 1 min infusion. Normal dogs, and especially dogs with infarctions, revealed the potential hazards of rapidly infusing disopyramide.
Schmidt
J J
JJ
Department of Cardiovascular Diseases Research, Searle Research and Development, Skokie, Illinois 60077.
Frederick
L G
LG
Garthwaite
S M
SM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004206:Disopyramide / Q000008:administration & dosage* / Q000009:adverse effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004562:Electrocardiography; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C061991:bidisomide; D004206:Disopyramide