Faculty Collaboration Database

Cardioprotective effects of nicorandil. J Cardiovasc Pharmacol 1992;20 Suppl 3:S22-8

Date

01/01/1992

Pubmed ID

1282172

DOI

10.1097/00005344-199206203-00006

Scopus ID

2-s2.0-0026641143 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

The effects of nicorandil, a nicotinamide nitrate with K(+)-channel-opening activity, was investigated in several models of ischemia-reperfusion injury in conscious and anesthetized dogs or isolated buffer-perfused rat hearts. In several models of reversible ischemic injury (stunned myocardium) in dogs, nicorandil resulted in an enhanced recovery of regional systolic shortening during reperfusion after a single episode of coronary artery occlusion (10-15 min). These beneficial actions of nicorandil were not shared by the nitrovasodilator sodium nitroprusside but were mimicked by the selective K(+)-channel opener EMD 52692. In a model of irreversible ischemia-reperfusion injury (i.e., 2 h of coronary occlusion followed by reperfusion) in anesthetized dogs, nicorandil produced a marked reduction of myocardial infarct size. An equihypotensive dose of the calcium antagonist nifedipine had no significant effect; however, EMD 52692 produced the same reduction in infarct size as had nicorandil. In isolated, perfused rat hearts subjected to 20 min of low-flow (1.0 ml/min) global ischemia followed by 30 min of reperfusion, nicorandil (7 microM) resulted in a significant improvement in the recovery of isovolumic left ventricular minute work during reperfusion compared with untreated hearts. Finally, the results of in vitro experiments indicated that nicorandil (10(-6) to 10(-3) M) produced a concentration-dependent inhibition of superoxide anion free radical production by human and canine neutrophils. The K(+)-channel opener EMD 52692 also inhibited superoxide production in canine neutrophils. These results indicate that nicorandil is a highly efficacious myocardial protective agent in several animal models of reversible or irreversible ischemia-reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Gross GJ, Auchampach JA, Maruyama M, Warltier DC, Pieper GM

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

Animals
Benzopyrans
Coronary Circulation
Dihydropyridines
Dogs
Female
Heart
In Vitro Techniques
Male
Myocardial Infarction
Myocardial Reperfusion Injury
Neutrophils
Niacinamide
Nicorandil
Nifedipine
Potassium Channels
Rats
Rats, Sprague-Dawley
Reperfusion
Superoxides