Alinidine reduces the incidence of ischemic ventricular fibrillation in a conscious canine model, a protective effect antagonized by overdrive atrial pacing.
The antiarrhythmic and antifibrillatory effects of the specific bradycardic agent alinidine were evaluated in a conscious canine model of myocardial infarction and sudden death, and by determination of ventricular fibrillation thresholds (VFT) in anesthetized dogs. Programmed electrical stimulation (PES) was performed in conscious animals, 3-5 days after a 2-h occlusion/reperfusion of the left anterior descending coronary artery (LAD). Dogs in which PES resulted in a reproducible nonsustained or sustained ventricular tachycardia (VT) were randomized to receive either intravenous alinidine (1 mg/kg, n = 11) or intravenous vehicle (n = 10). Programmed electrical stimulation and measurement of electrophysiologic parameters were repeated after 30 min, and the animals were entered into the sudden death protocol by introducing a 150 microA anodal current to the lumen of the left circumflex coronary artery (LCX) via a surgically implanted silver wire electrode. A second alinidine-treated group (n = 3) had heart rates controlled by atrial pacing during this period. Alinidine failed to prevent the programmed electrical induction of VT in 10 of 11 animals, but significantly reduced both sudden (less than 1 h ischemia) and 24-h mortality as compared to the ventricle group. Infarct sizes were similar in the two groups, but the ischemia-related increase in heart rate was attenuated (p less than 0.05) by alinidine and the onset of ischemia tended to be delayed. All of the atrial-paced animals died acutely. Heart rate decreased after alinidine (p less than 0.01), but apart from a single index of refractoriness, the drug was without electrocardiographic or electrophysiologic effects. Neither alinidine nor vehicle demonstrated any effect upon VFT in two groups of five animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Uprichard
A C
AC
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Chi
L G
LG
Lynch
J J
JJ
Driscoll
E M
EM
Frye
J W
JW
Lucchesi
B R
BR
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents; D002304:Cardiac Pacing, Artificial; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003645:Death, Sudden; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; C022192:alinidine; D003000:Clonidine