A K_ATP channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias

Workman, A.J. , MacKenzie, I. and Northover, B.J. (2001) A K_ATP channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias. European Journal of Pharmacology, 419(1), pp. 73-83. (doi: 10.1016/S0014-2999(01)00972-4)

Abstract

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 μM), significantly reduced the incidence and duration of reperfusion arrhythmias, and prevented the associated acute action potential shortening during reperfusion, each in a glibenclamide (1 μM)-sensitive manner (P<0.05, <i>n</i>=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.

• Item Type: Articles
• Keywords: K+ channel, ATP-sensitive; Reperfusion; Heart, Isolated; Action potential; Ventricular arrhythmia
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Workman, Dr Antony
• Authors: Workman, A.J., MacKenzie, I., and Northover, B.J.
• Subjects: R Medicine > RC Internal medicine
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: European Journal of Pharmacology
• Publisher: Elsevier
• ISSN: 0014-2999
• Copyright Holders: Copyright © 2001 Elsevier
• First Published: First published in European Journal of Pharmacology 419(1):73-83
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.