Skip Navigation LinksHome > August 1995 - Volume 26 - Issue 2 > Pharmacological Analysis in Rat of the Role of the ATP-Sensi...
Journal of Cardiovascular Pharmacology:
Article: PDF Only

Pharmacological Analysis in Rat of the Role of the ATP-Sensitive Potassium Channel as a Potential Target for Antifibrillatory Intervention in Acute Myocardial Ischaemia.

Rees, Sian A.; Curtis, Michael J.

Collapse Box

Abstract

Summary: We tested the hypothesis that blockade of the ATP-sensitive K+ channel (IK(ATP)) is an antiarrhythmic mechanism in acute myocardial ischaemia, using an opener of the channel (10[mu]M RP 49356, RP) and a blocker of the channel (10 [mu]M glibenclamide, GL) and a combination of the two drugs (GL + RP, 10 [mu]M each) in a randomised blinded study. Isolated rat hearts (n = 8 per group) were subjected to 30-min left regional ischaemia. GL and GL + RP widened QT interval after 10-min ischaemia (197 +/- 39 and 203 +/- 20 ms, respectively vs. 154 +/- 12 ms in controls), whereas RP significantly shortened QT interval (123 +/- 6 ms). GL and GL + RP decreased coronary flow (p < 0.05). RP caused slight increase in flow during ischaemia. These effects are all consistent with modulation of vascular and cardiac IK(ATP). RP alone had no effect on ischaemia-induced arrhythmias. Neither did GL have any effect on the incidence of ventricular fibrillation (VF: 88 vs. 100% in controls). However, GL reduced the incidence of sustained VF (VF lasting continuously for >2 min) to 14% vs. 88% in controls (p < 0.05). Therefore, GL had defibrillatory activity. Surprisingly, in view of these findings, the GL + RP combination significantly reduced the incidence of VF to 25% (from 100% in control hearts, p < 0.05) i.e., had an antifibrillatory effect. So, two agents that produce pharmacological effects attributable to block and opening of IK(ATP) when administered singly had no effects on the incidence of ischaemia-induced VF. The profound and unexpected antiarrhythmic effect observed with the combination of these drugs is best explained by an IK(ATP)-independent pharmacological action of GL, the identity of which remains uncertain. The data do not support the hypothesis that IK(ATP) blockade is a specific antifibrillatory mechanism in acute myocardial ischaemia, although IK(ATP) blockade may represent a defibrillatory mechanism.

(C) Lippincott-Raven Publishers.

Follow Us!

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.