Indecainide: effects on arrhythmias, electrophysiology, and cardiovascular dynamics.
The cardiovascular pharmacology of indecainide, a new class I antiarrhythmic agent, was studied in intact animals. Arrhythmias produced by ouabain were converted to sinus rhythm by indecainide (100 micrograms/kg/min, i.v.) at 0.7 +/- 0.1 mg/kg and a corresponding plasma concentration of 1.7 +/- 0.2 micrograms/ml at the time of conversion. Infusion at a slower rate (20 micrograms/kg/min) converted to sinus rhythm at 0.4 +/- 0.1 mg/kg and 0.4 +/- 0.2 micrograms/ml plasma. Arrhythmias produced by prior (24 h) coronary artery occlusion were converted to 50% sinus rhythm by indecainide (100 micrograms/kg/min, i.v.) at 1.3 mg/kg. In conscious dogs, 6 mg/kg indecainide p.o. prolonged the PR and QRS intervals by 31 +/- 5 and 13 +/- 3%, respectively, at a corresponding plasma concentration of 2.8 +/- 0.5 micrograms/ml. His bundle studies revealed that the PR interval prolongation was due to an increase in both A-H and H-V intervals. In anesthetized dogs, indecainide (1-5 mg/kg, i.v.) decreased cardiac contractility, however, this effect was comparable to or less than that produced by other class I agents and was likely due to the Na+-channel-blocking activity of the drug. The autonomic effects of indecainide were slight and no effects were produced on peripheral hemodynamics, the QTc interval, or the central nervous system. It was concluded that indecainide is a potent class I antiarrhythmic agent that would appear to have only minimal propensity for producing adverse side effects in humans.
Holland
D R
DR
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Lacefield
W B
WB
Gonzales
C R
CR
Johnston
S R
SR
Turk
J A
JA
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001073:Aprindine / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D002036:Bundle of His / Q000187:drug effects; D002415:Cats; D002698:Chloralose; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D005449:Fluorenes / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain
D000889:Anti-Arrhythmia Agents; D005449:Fluorenes; D002698:Chloralose; C042398:indecainide; D010042:Ouabain; D001073:Aprindine