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)