Document Detail


Effects of pinacidil on electrophysiological properties of epicardial border zone of healing canine infarcts: possible effects of K(ATP) channel activation.
MedLine Citation:
PMID:  12010915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: K(ATP) channels, activated by ischemia, participate in the arrhythmogenic response to acute coronary occlusion. The function of these channels in border zones of healing infarcts, where arrhythmias also arise, has not been investigated. Do these channels remain maximally activated during infarct healing, or do they downregulate after a period of time? Both might preclude further activation. METHODS AND RESULTS: Myocardial infarction was produced in dogs by ligation of the left anterior descending coronary artery. Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing infarcts was mapped during administration of pinacidil, a K(ATP) channel activator, directly into the EBZ coronary blood supply. Pinacidil restored conduction and excitability when the EBZ was initially inexcitable and had large regions of block (6 of 8 experiments). This allowed reentrant circuits to form in the EBZ, causing tachycardia (4 of 8 experiments). In hearts with an initially excitable EBZ, pinacidil shortened the effective refractory period and abolished conduction block at short cycle lengths (7 experiments). This effect prevented initiation of reentry (1 of 2 experiments). CONCLUSIONS: The response to pinacidil indicates that K(ATP) channels in the EBZ remain functional and can be activated to influence electrophysiological properties and arrhythmogenesis.
Authors:
James Coromilas; Constantinos Costeas; Bernard Deruyter; Stephen M Dillon; Nicholas S Peters; Andrew L Wit
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-15     Completed Date:  2002-05-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2309-17     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology and the Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. jc47@columbia.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Disease Models, Animal
Dogs
Dose-Response Relationship, Drug
Electric Stimulation
Electrocardiography / methods
Electrodes
Electrophysiologic Techniques, Cardiac
Fluorescent Dyes / administration & dosage
Heart / drug effects*,  physiopathology*
Heart Conduction System / drug effects,  physiopathology
Injections, Intra-Arterial
Myocardial Infarction / physiopathology*
Pinacidil / administration & dosage,  pharmacology*
Potassium Channels / drug effects*,  metabolism
Tachycardia, Ventricular / physiopathology
Vasodilator Agents / pharmacology*
Grant Support
ID/Acronym/Agency:
HL-30557/HL/NHLBI NIH HHS; R37-HL-31393/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fluorescent Dyes; 0/Potassium Channels; 0/Vasodilator Agents; 85371-64-8/Pinacidil

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


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