Nicorandil attenuates myocardial dysfunction associated with transient ischemia by opening ATP-dependent potassium channels

J Cardiovasc Pharmacol. 1992;20(5):765-71.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Blood Glucose / analysis
  • Blood Pressure / drug effects
  • Coronary Circulation / drug effects
  • Dogs
  • Female
  • Glyburide / pharmacology
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Rate / drug effects
  • Male
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Nicorandil
  • Potassium Channels / drug effects*
  • Ventricular Function, Left / drug effects

Substances

  • Blood Glucose
  • Potassium Channels
  • Niacinamide
  • Nicorandil
  • Adenosine Triphosphate
  • Glyburide