Document Detail

Mechanism of antifibrillatory action of Org 7797 in regionally ischemic pig heart.
MedLine Citation:
PMID:  1691395     Owner:  NLM     Status:  MEDLINE    
Org 7797 is effective against ventricular fibrillation (VF) induced during ischemia. In Langendorff-perfused pig hearts, application of three premature stimuli to nonischemic myocardium between 3 and 5 min after coronary occlusion always resulted in VF in the absence of drug. In no instance when Org 7797 was present (2-10 microM) could VF be induced, although sustained and nonsustained ventricular tachycardias (VTs) could still be initiated in about two thirds of treated hearts. We determined the effects of Org 7797 on wavelength in normal and ischemic myocardium during regular driving at a cycle length of 350 ms. Wavelength, the algebraic product of conduction velocity and refractory period, is considered a useful parameter in assessing efficacy of antiarrhythmic agents in preventing reentrant arrhythmias. Conduction velocity was obtained by analyzing the spread of activation under 121 unipolar electrodes (1 mm apart) placed around a central stimulus electrode. Refractory periods were determined with premature test stimuli at an intensity of twice diastolic threshold. Both in normal and ischemic myocardium Org 7797 (5-10 microM) produced a marked shortening of wavelength. This should predispose to reentry. However, Org 7797 prolonged the refractory period at the fastest possible driving rate from 154 to 247 ms and attenuated (5 microM) or prevented (10 microM) shortening of the refractory period during application of subsequent premature stimuli. The antifibrillatory effect of the drug may be explained by prolongation of wavelength at very short cycles.
M J Janse; F Wilms-Schopman; T Opthof
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  15     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1990 Apr 
Date Detail:
Created Date:  1990-05-24     Completed Date:  1990-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  633-43     Citation Subset:  IM    
Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
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MeSH Terms
Anti-Arrhythmia Agents / therapeutic use*
Coronary Disease / complications
Electric Stimulation
Estrenes / therapeutic use*
Heart Conduction System / drug effects*
Ventricular Fibrillation / etiology,  prevention & control*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Estrenes; 80177-51-1/Org 7797

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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