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Protective effect of mitochondrial KATP activation in an isolated gracilis model of ischemia and reperfusion in dogs.

Abstract
Adenosine triphosphate-sensitive potassium channel (KATP) openers protect ischemic myocardium by direct protection of cardiac myocytes, which is thought to be a result of activation of mitochondrial KATP (mKATP). KATP is expressed in skeletal muscle, and the purpose of this study was to determine the effect of the mKATP opener BMS-191095 on infarct size in an isolated gracilis model of ischemia and reperfusion in dogs. The right and left gracilis muscles were isolated in anesthetized dogs except for the artery and vein supplying these muscles (pedicle). BMS-191095 (0.4 mg) or vehicle were infused directly into the artery supplying each gracilis muscle (each animal had one drug-treated and one vehicle-treated muscle). The pedicle was completely occluded for 5 hours followed by 48 hours of reperfusion, after which infarct size was determined. In the vehicle-treated gracilis muscles, significant necrosis was observed (82% +/- 3% of gracilis muscle). BMS-191095 significantly reduced the infarct size in the contralateral gracilis muscle (55% +/- 6%). Reflow into the gracilis muscle was significantly greater in BMS-191095-treated muscles. BMS-191095 appears to reduce damage in ischemic/reperfused skeletal muscle, suggesting that mKATP activation is an important protective mechanism in this tissue.
AuthorsGary J Grover, Dennis E Burkett, Charles S Parham, Robert J Scalese, Kenneth K Sadanaga
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 42 Issue 6 Pg. 790-2 (Dec 2003) ISSN: 0160-2446 [Print] United States
PMID14639102 (Publication Type: Journal Article)
Chemical References
  • BMS 191095
  • Benzopyrans
  • Cardiotonic Agents
  • Guanidines
  • Imidazoles
  • Membrane Proteins
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • BMS 180448
Topics
  • Animals
  • Benzopyrans (therapeutic use)
  • Cardiotonic Agents (therapeutic use)
  • Dogs
  • Female
  • Guanidines (therapeutic use)
  • Imidazoles (therapeutic use)
  • Male
  • Membrane Proteins (drug effects)
  • Myocardial Ischemia (prevention & control)
  • Potassium Channels
  • Reperfusion

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