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Do KATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart?

Workman, A.J., MacKenzie, I., and Northover, B.J. (2000) Do KATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart? Basic Research in Cardiology, 95 (3). pp. 250-260. ISSN 0300-8428 (doi:10.1007/s003950050188)

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Publisher's URL: http://dx.doi.org/10.1007/s003950050188

Abstract

The objective was to investigate whether myocardial adenosine triphosphate-sensitive K+ (KATP) channels open during the first 10 min of regional ischaemia in Langendorff-perfused rat hearts. Changes in monophasic action potentials and arrhythmias were studied during myocardial ischaemia in both the presence and absence of pharmacological KATP modulation. Ligation of the left main coronary artery for 10 min did not shorten the action potential duration (APD). The APD50 and APD80 (15.5 +/- 1.0 and 38.1 +/- 2.3 ms, respectively [mean +/- S.E., n = 15 hearts], immediately prior to ligation) increased transiently during the first 4 min of ligation (by 160 and 79% respectively, P < 0.05), before returning to pre-ligation values, but without a significant below-baseline-shortening. The cardiac electrogram showed no accompanying ventricular tachyarrhythmia (VT). These results raised the possibility that the myocardial KATP channels had not opened during the ligation. The KATP opener Ro 31-6930 (0.5 and 5 microM) shortened the APD50 and APD80 during coronary ligation, to significantly below both their control and pre-occlusion values (P < 0.05), and caused a concentration-dependent increase in both the incidence and duration of VT during the ligation. Ro 31-6930 at 5 microM also shortened APD50 and APD80 even before ligation (by 50 and 62% respectively, P < 0.05), and abolished the normal APD-lengthening seen during ischaemia. The KATP blocker glibenclamide (1 μM) abolished both the APD-shortening and pro-arrhythmic effects of the KATP opener, both before and during coronary ligation, yet when delivered on its own, at the same concentration which abolished the effects of KATP activation, it had no significant effect on the APD changes seen during the coronary ligation alone. These results suggest that, in Langendorff-perfused rat hearts in the absence of drugs, KATP channels do not open during early myocardial ischaemia.

Item Type:Article
Status:Published
Refereed:Yes
Glasgow Author(s):Workman, Dr Antony
Authors: Workman, A.J., MacKenzie, I., and Northover, B.J.
Subjects:R Medicine > RC Internal medicine
Q Science > QP Physiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:Basic Research in Cardiology
Publisher:Springer
ISSN:0300-8428
Copyright Holders:Copyright © 2000 Springer

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