Document Detail


Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts.
MedLine Citation:
PMID:  9687827     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The delayed outward rectifier K+ channel has a role in the increase in automaticity of myocytes under pathophysiological conditions. The purpose of the present study was to clarify the effect of blockade of outward rectifier K+ channels by a class III antiarrhythmic drug, E4031, on ischemia- and reperfusion-induced arrhythmias. Ion fluxes, energy metabolites and cardiac function were measured and the epicardial electrocardiograms of Langendorff-perfused rat hearts were recorded during initial perfusion, global or regional ischemia and reperfusion. 10(-7) M of E4031 administered during the initial perfusion did not prolong the QT interval, but slowed the heart rate (Control: 222, E4031: 183 bpm, p < 0.05), increased myocardial 45Ca2+ uptake (Control: 2.1, E4031: 2.9 mumol/g dwt, p < 0.05) and attenuated the loss of intracellular K+ during ischemia (Control: 238, E4031: 248 mumol/g dwt, p < 0.05). E4031 tended to reduce ischemia-induced ventricular tachyarrhythmias (Control: 60, E4031: 30%, n.s.), but reperfusion-induced ventricular tachyarrhythmias were sustained longer by the administration of E4031 (Control: 255, E4031: 623 sec, p < 0.05). Prior exposure to E4031 decreased the depletion of high energy phosphates during ischemia, but suppressed their recovery during reperfusion. These results suggest that the attenuated loss of K+ from the ischemic myocardium and the decrease in heart rate by E4031 contributed to the reduction of ischemia-induced arrhythmias. However, the increase in myocardial Ca2+ uptake and altered energy metabolism may be responsible for the increase in reperfusion-induced arrhythmias.
Authors:
K Shinmura; M Tani; H Hasegawa; Y Ebihara; Y Nakamura
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Japanese heart journal     Volume:  39     ISSN:  0021-4868     ISO Abbreviation:  Jpn Heart J     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-08-18     Completed Date:  1998-08-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0401175     Medline TA:  Jpn Heart J     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  183-97     Citation Subset:  IM    
Affiliation:
Department of Geriatric Medicine, Keio University School of Medicine, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / pharmacology,  therapeutic use*
Arrhythmias, Cardiac / drug therapy*,  physiopathology
Calcium / metabolism
Energy Metabolism / drug effects
Heart / drug effects*
Male
Myocardial Reperfusion Injury / drug therapy*,  physiopathology
Myocardium / metabolism
Piperidines / pharmacology,  therapeutic use*
Potassium Channels / drug effects
Pyridines / pharmacology,  therapeutic use*
Rats
Rats, Sprague-Dawley
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Piperidines; 0/Potassium Channels; 0/Pyridines; 113558-89-7/E 4031; 7440-70-2/Calcium

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


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