Cardioprotective effects of YM934, an ATP-sensitive potassium channel opener, on stunned myocardium in anesthetized dogs.
The effects of YM934 [2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl) pyridine N-oxide], an adenosine triphosphate (ATP)-sensitive potassium channel opener, on stunned myocardium were examined. Forty eight anesthetized dogs were subjected to 15 min of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. To elucidate the possible contribution of the cardioprotective property of YM934 to stunned myocardium, a nonhypotensive dose of YM934 was directly injected into the LAD coronary artery before the ischemic insults. Intracoronary artery infusion (i.c.) of YM934 (0.1 microg/kg/min) produced a marked improvement in post-ischemic regional contractile dysfunction. The effects were not associated with improvement of hemodynamics, including regional myocardial blood flow during ischemia, heart rate and mean arterial blood pressure. The anatomic areas at risk expressed as a percentage of the left ventricle and regional myocardial blood flow were not significantly different between groups. The cardioprotective effect of YM934 was completely blocked by pretreatment with an ATP-sensitive potassium channel blocker, glibenclamide (1.0 mg/kg i.v. bolus). These results suggest that YM934 exerts cardioprotective effect on stunned myocardium through opening myocardial ATP-sensitive potassium channels.
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Tsukuba, Ibaraki, Japan. taguchit@yamanouchi.co.jp
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Taguchi
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Uchida
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Takenaka
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Takeo
D000255:Adenosine Triphosphate / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D048588:Benzoxazines; D003326:Coronary Circulation / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D017682:Myocardial Stunning / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010078:Oxazines / Q000494:pharmacology*; D015221:Potassium Channels / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D048588:Benzoxazines; D003497:Cyclic N-Oxides; D006834:Hydrazines; D007004:Hypoglycemic Agents; D010078:Oxazines; D015221:Potassium Channels; D014665:Vasodilator Agents; C029424:hydrazine; D000255:Adenosine Triphosphate; D005905:Glyburide; C084963:2H-1,4-benzoxazine, 3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-pyridinyl)-, N-oxide