title: Adenosine triphosphate-sensitive potassium channels prevent extension of myocardial ischemia to subepicardium during hemorrhagic shock.
abstract: Cardiac dysfunction during hemorrhagic shock (HS) is associated with myocardial ischemia, during which adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels can be activated. We investigated the role of K(ATP) 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 degrees C) using a sampling device after 10 min of HS. The effect of a K(ATP) 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 K(ATP) channel opener, cromakalim (50 microg/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 K(ATP) channels are activated during HS, enabling selective subepicardial coronary dilatation and protecting the myocardium from the extension of myocardial ischemia to the subepicardium.
authors: Department of Internal Medicine, Cardiopulmonary Division, Keio University School of Medicine, Research Park, Tokyo, Japan.
authors: Masahiro
authors: M
authors: Nakagawa
authors: Shingo
authors: S
authors: Hori
authors: Takeshi
authors: T
authors: Adachi
authors: Koji
authors: K
authors: Miyazaki
authors: Soushin
authors: S
authors: Inoue
authors: Masaru
authors: M
authors: Suzuki
authors: Hidezo
authors: H
authors: Mori
authors: Hiroe
authors: H
authors: Nakazawa
authors: Naoki
authors: N
authors: Aikawa
authors: Satoshi
authors: S
authors: Ogawa
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010496:Pericardium / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D054086:KATP Channels; D026902:Potassium Channel Blockers; D005905:Glyburide