JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mertz, T. E.
Right arrow Articles by Kaplan, H. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mertz, T. E.
Right arrow Articles by Kaplan, H. R.

Pirmenol hydrochloride (CI-845) and reference antiarrhythmic agents: effects on early ventricular arrhythmias after acute coronary artery ligation in anesthetized rats

TE Mertz and HR Kaplan

The coronary artery-ligated rat was investigated as an experimental model for studying the effects of pirmenol hydrochloride and reference for studying the effects of pirmenol hydrochloride and reference agents on early ventricular arrhythmias. Coronary artery ligation caused 89% lethality (ventricular fibrillation) within 10 min in untreated control rats. Vagal stimulation applied during periods of high-rate ventricular tachycardia reduced sinus, atrioventricular nodal and ventricular ectopic beats, with no uncoupled ectopic beats seen during stimulation. Rats studied with composite epicardial electrodes showed continuous electrical activity throughout diastole. These factors indicate that a reentry mechanism is likely involved. Pretreatment with pirmenol afforded protection in a dose-related fashion. A dose of 1.25 mg/kg increased survival to 58%, and all rats dosed with 2.5 to 10 mg/kg survived. Suppression of ventricular fibrillation was dose related and was complete at 5 mg/kg. The pirmenol plasma levels of 1.2 +/- 0.1 microgram/ml seen after the 5 mg/kg dose are similar to plasma levels seen at clinically effective doses, as well as at doses effective in other experimental arrhythmias. The reference agent quinidine was also highly effective in this model, all rats pretreated with 5 mg/kg survived with reduced premature ventricular beats and without a single episode of ventricular fibrillation or death. Fibrillation and/or death were also reduced by the reference agents, bretylium, lidocaine, propranolol and verapamil. The high efficacy of pirmenol against early ventricular arrhythmias in this study further defines its spectrum of activity, and suggests that pirmenol may be effective in a clinical setting where a reentrant mechanism is operative.

Volume 223, Issue 2, pp. 580-586, 11/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
E.J.F. Danson, Y.H. Zhang, C.E. Sears, A.R. Edwards, B. Casadei, and D.J. Paterson
Disruption of inhibitory G-proteins mediates a reduction in atrial {beta}-adrenergic signaling by enhancing eNOS expression
Cardiovasc Res, September 1, 2005; 67(4): 613 - 623.
[Abstract] [Full Text] [PDF]

Home page
 ANGIOLOGYHome page
H. R. Kaplan
Bevantolol Hydrochloride Preclinical Pharmacologic Profile
Angiology, March 1, 1986; 37(3): 254 - 262.
[Abstract] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1982 by the American Society for Pharmacology and Experimental Therapeutics.