The new K+ channel opener Aprikalim (RP 52891) reduces experimental infarct size in dogs in the absence of hemodynamic changes.
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)
Auchampach
J A
JA
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Maruyama
M
M
Cavero
I
I
Gross
G J
GJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010847:Picolines / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; D005905:Glyburide