| Mechanism of antifibrillatory action of Org 7797 in regionally ischemic pig heart. | |
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MedLine Citation:
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PMID: 1691395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M J Janse; F Wilms-Schopman; T Opthof |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 15 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1990 Apr |
Date Detail:
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Created Date: 1990-05-24 Completed Date: 1990-05-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 633-43 Citation Subset: IM |
Affiliation:
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Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Arrhythmia Agents / therapeutic use* Coronary Disease / complications Electric Stimulation Electrocardiography Estrenes / therapeutic use* Female Heart Conduction System / drug effects* Male Swine Ventricular Fibrillation / etiology, prevention & control* |
| Chemical | |
Reg. No./Substance:
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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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