Document Detail

A K(ATP) channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias.
MedLine Citation:
PMID:  11348633     Owner:  NLM     Status:  MEDLINE    
Low concentrations of certain K(ATP) channel openers have been reported to exert a moderate inhibitory effect on arrhythmias during post-ischaemic early myocardial reperfusion, but the accompanying effects on the time course of changes in action potentials in intact hearts have not yet been studied. We report that in rat isolated hearts, reperfusion following 10 min of regional no-flow ischaemia was associated with both an acute, marked, but transient, shortening of ventricular repolarisation (by 63%) during reperfusion, and a high incidence (90%) of ventricular tachyarrhythmias. The K(ATP) channel opener Ro 31-6930 [2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide], delivered prior to ischaemia at a relatively low concentration (0.5 microM), significantly reduced the incidence and duration of reperfusion arrhythmias, and prevented the associated acute action potential shortening during reperfusion, each in a glibenclamide (1 microM)-sensitive manner (P<0.05, n=10-15 hearts). This was associated with a moderate and non-arrhythmogenic action potential shortening during ischaemia (a potentially "cardioprotective" effect). However, these data highlight the potential harm these drugs may cause, since a higher concentration of Ro 31-6930 caused marked shortening of action potentials and significant pro-arrhythmia during ischaemia.
A J Workman; I MacKenzie; B J Northover
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  419     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-11     Completed Date:  2001-08-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  73-83     Citation Subset:  IM    
Department of Pharmacology, School of Applied Sciences, De Montfort University, The Gateway, LE1 9BH, Leicester, UK.
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MeSH Terms
Action Potentials / drug effects
Adenosine Triphosphate / metabolism*
Antihypertensive Agents / pharmacology
Arrhythmias, Cardiac / drug therapy,  physiopathology
Benzopyrans / pharmacology*
Dose-Response Relationship, Drug
Glyburide / pharmacology
Heart / drug effects*,  physiopathology
Hypoglycemic Agents / pharmacology
Myocardial Ischemia / physiopathology
Myocardial Reperfusion
Myocardial Reperfusion Injury / drug therapy*,  physiopathology*
Potassium Channels / chemistry,  metabolism*
Pyridines / pharmacology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antihypertensive Agents; 0/Benzopyrans; 0/Hypoglycemic Agents; 0/Potassium Channels; 0/Pyridines; 10238-21-8/Glyburide; 120280-37-7/Ro 31-6930; 56-65-5/Adenosine Triphosphate

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