Adenosine triphosphate-sensitive potassium channels prevent extension of myocardial ischemia to subepicardium during hemorrhagic shock

Masahiro Nakagawa, Shingo Hori, Takeshi Adachi, Koji Miyazaki, Soushin Inoue, Masaru Suzuki, Hidezo Mori, Hiroe Nakazawa, Naoki Aikawa, Satoshi Ogawa

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Abstract

Cardiac dysfunction during hemorrhagic shock (HS) is associated with myocardial ischemia, during which adenosine triphosphate (ATP)-sensitive potassium (KATP) channels can be activated. We investigated the role of KATP channels in HS-induced myocardial ischemia. Canine HS was induced using an aortic reservoir to maintain the aortic pressure at a constant 40 mmHg. To visualize the myocardial ischemia as a nicotinamide adenine dinucleotide (NADH) - fluorescent area, the beating hearts were rapidly cross-sectioned (120 ms) and freeze-clamped (-190°C) using a sampling device after 10 min of HS. The effect of a KATP channel blocker, glibenclamide (1 mg/kg, i.v.), on myocardial ischemia was also quantified. Regional myocardial blood flow was measured using heavy element-loaded nonradioactive microspheres. Myocardial ischemia developed in the subendocardium in the HS alone group, whereas it extended through all the cardiac layers in the glibenclamide-treatment group. The coadministration of a KATP channel opener, cromakalim (50 μg/kg, i.v.), with glibenclamide prevented the extension of myocardial ischemia to the subepicardium. Glibenclamide decreased the myocardial ATP concentration selectively in the subepicardium during HS. The HS decreased myocardial blood flow transmurally, and following the administration of glibenclamide, further decreased the blood flow selectively in the subepicardium. These results suggest that KATP channels are activated during HS, enabling selective subepicardial coronary dilatation and protecting the myocardium from the extension of myocardial ischemia to the subepicardium.

Original languageEnglish
Pages (from-to)178-183
Number of pages6
JournalShock
Volume30
Issue number2
DOIs
Publication statusPublished - 2008 Aug

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Keywords

  • Coronary circulation
  • Cromakalim
  • Glibenclamide
  • Myocardial metabolism
  • NADH fluorescence
  • Subepicardial blood flow

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Nakagawa, M., Hori, S., Adachi, T., Miyazaki, K., Inoue, S., Suzuki, M., Mori, H., Nakazawa, H., Aikawa, N., & Ogawa, S. (2008). Adenosine triphosphate-sensitive potassium channels prevent extension of myocardial ischemia to subepicardium during hemorrhagic shock. Shock, 30(2), 178-183. https://doi.org/10.1097/SHK.0b013e318160d990