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The new K+ channel opener Aprikalim (RP 52891) reduces experimental infarct size in dogs in the absence of hemodynamic changes. J Pharmacol Exp Ther 1991 Dec;259(3):961-7

Date

12/01/1991

Pubmed ID

1762089

Scopus ID

2-s2.0-0026346285   119 Citations

Abstract

The objective of the present study was to determine the effect of a novel K+ channel opener, Aprikalim (RP 52891; [trans-(-)-N-methyl-2-(3-pyridyl)-2-tetrahydrothio-pyran carbothiamide-1-oxide]), on myocardial infarct size in barbital-anesthetized dogs subjected to 90 min of left circumflex coronary artery occlusion followed by 5 hr of reperfusion. To determine if RP 52891 is mediating its effects by opening adenosine triphosphate regulated potassium channels (KATP), glibenclamide, a KATP channel antagonist was used. Dogs were pretreated with vehicle, a nonhypotensive dose of RP 52891 (10 micrograms/kg + 0.1 microgram/kg/min i.v.), glibenclamide (1 mg/kg; i.v. bolus) or RP 52891 (10 micrograms/kg and 0.1 microgram/kg/min i.v.) after pretreatment with glibenclamide (1 mg/kg i.v. bolus). At the end of reperfusion, myocardial infarct size was determined by triphenyltetrazolium staining. There were no significant differences in systemic hemodynamics, myocardial oxygen demand, collateral blood flow or ischemic bed size among groups with the exception of an increase in coronary blood flow to the ischemic area at 3 and 5 hr of reperfusion in both RP-treated groups. However, myocardial infarct size, expressed as a percentage of the area at risk, was significantly (P less than .05) reduced (38%) by RP 52891 and significantly increased (38%) by glibenclamide (vehicle, 39 +/- 4%; RP 52891, 24 +/- 2%; and glibenclamide, 54 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

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

Animals
Blood Glucose
Coronary Circulation
Coronary Vessels
Dogs
Female
Glyburide
Hemodynamics
Male
Myocardial Infarction
Myocardial Reperfusion Injury
Picolines
Potassium Channels
Pyrans
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0