Faculty Collaboration Database

Nicorandil attenuates myocardial dysfunction associated with transient ischemia by opening ATP-dependent potassium channels. J Cardiovasc Pharmacol 1992;20(5):765-71

Date

01/01/1992

Pubmed ID

1280739

DOI

10.1097/00005344-199220050-00012

Scopus ID

2-s2.0-0026648690 (requires institutional sign-in at Scopus site)   101 Citations

Abstract

The objective of this study was to determine whether ATP-dependent potassium channel activation is involved in the mechanism by which nicorandil reduces postischemic contractile dysfunction produced by a brief period of ischemia (myocardial stunning). Barbital-anesthetized dogs were subjected to 15-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. Saline or nicorandil (100 micrograms/kg + 25 micrograms/kg/min) were infused 15 min before and throughout occlusion with or without addition of the KATP channel antagonist, glibenclamide 0.3 mg/kg as an intravenous (i.v.) bolus. Regional myocardial blood flow was measured by radioactive microspheres, and left ventricular (LV) segment function was measured by sonomicrometry. There were no significant differences between the groups in area-at-risk size or collateral blood flow. In contrast, nicorandil significantly reduced mean aortic blood pressure (BP) and the rate-pressure product (RPP) which persisted throughout the occlusion period. In addition, nicorandil markedly accelerated recovery of segment shortening in the ischemic/reperfused region as compared with control dogs. Pretreatment of dogs with glibenclamide blocked none of the hemodynamic effects of nicorandil, but it did prevent improvement in reperfusion segment function. The small dose of glibenclamide used had no effect on hemodynamics or the degree of stunning. Thus, these results suggest that nicorandil attenuates stunning in anesthetized dogs by a direct cardioprotective effect as a result of KATP channel activation in ischemic myocardium.

Author List

Auchampach JA, 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
Blood Pressure
Coronary Circulation
Dogs
Female
Glyburide
Heart
Heart Rate
Male
Myocardial Ischemia
Myocardial Reperfusion Injury
Niacinamide
Nicorandil
Potassium Channels
Ventricular Function, Left