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Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning. Circulation 1992 Jul;86(1):311-9

Date

07/01/1992

Pubmed ID

1301066

DOI

10.1161/01.cir.86.1.311

Scopus ID

2-s2.0-0026748339   169 Citations

Abstract

BACKGROUND: Several recent studies suggest that activation of ATP-dependent potassium (K(ATP)) channels in the myocardium plays an important cardioprotective role during ischemia. The present study was undertaken to examine further the role of this ion channel in vivo in a model of "stunned" myocardium.

METHODS AND RESULTS: Barbital-anesthetized dogs were subjected to 15 minutes of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. Regional myocardial blood flow was measured by radioactive microspheres and segment function by sonomicrometry. Intravenous administration of the potassium channel opener aprikalim (RP 52891) at a dose that produced no significant systemic hemodynamic effects (10 micrograms/kg plus 0.1 microgram/kg/min) resulted in a marked improvement in segment shortening in the ischemic/reperfused myocardium compared with control animals (p less than 0.05) when given before the ischemic insult. However, administration of aprikalim immediately before reperfusion had no beneficial effect. Furthermore, pretreatment with the K(ATP) channel antagonist glibenclamide antagonized the recovery of contractile function afforded by aprikalim when administered at a low dose (0.3 mg/kg) that alone had no effect on postischemic recovery. In contrast, pretreatment with either a higher dose of glibenclamide (1.0 mg/kg) or the related sulfonylurea K(ATP) channel antagonist tolbutamide (100 mg/kg) resulted in a worsening of segment function after reperfusion. The ability of aprikalim and the K(ATP) channel antagonists to alter postischemic wall function occurred independently of differences in systemic hemodynamics, area at risk, and collateral blood flow during occlusion, the major determinants of the extent of myocardial stunning.

CONCLUSIONS: These results suggest that opening myocardial K(ATP) channels in the ischemic heart results in a marked cardioprotective effect in stunned myocardium and that these channels may serve an endogenous function, which is to provide protection from ischemic insults.

Author List

Auchampach JA, Maruyama M, Cavero I, Gross GJ

Author

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Blood Glucose
Dogs
Female
Glyburide
Hemodynamics
Male
Myocardial Contraction
Myocardial Reperfusion Injury
Myocardium
Picolines
Potassium Channels
Pyrans
Risk Factors
Tolbutamide
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0