Reduction by ATP-sensitive potassium channel opener, YM934, of experimental myocardial infarct size in anesthetized dogs.
The present study was undertaken to examine whether the ATP-sensitive potassium channel opener, YM934, would be effective in reducing infarct size in a model of myocardial infarction in anesthetized dogs. For this purpose the effects of nifedipine, a calcium channel blocker, and hydralazine, a vasodilator with unknown mechanisms, were also investigated for comparison. Severe, irreversible myocardial injury was produced by a 90-min occlusion of the proximal left anterior descending coronary artery followed by 5 h of reperfusion. Infusion of YM934 (0.1 microg/kg/min i.c.) during the last 15 min of pre-ischemia reduced the myocardial infarct size and attenuated the release of creatine kinase MB eluted from the hearts without alteration in hemodynamic parameters including regional myocardial blood flow. In contrast, the other vasodilators, hydralazine and nifedipine, did not reduce myocardial infarct size under the same coronary vasodilatory conditions. These observations indicate that intracoronary YM934 is cardioprotective and that this effect is independent of alterations in regional myocardial blood flow.
Taguchi
T
T
Cardiovascular Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan. taguchit@yamanouchi.co.jp
Uchida
W
W
Takenaka
T
T
Takeo
S
S
D000818:Animals; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003331:Coronary Vessels / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009543:Nifedipine / Q000627:therapeutic use; D010078:Oxazines / Q000627:therapeutic use*; D015221:Potassium Channels / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D003497:Cyclic N-Oxides; D010078:Oxazines; D015221:Potassium Channels; D014665:Vasodilator Agents; D006830:Hydralazine; D009543:Nifedipine; C084963:2H-1,4-benzoxazine, 3,4-dihydro-2,2-dimethyl-6-nitro-4-(2-pyridinyl)-, N-oxide