Nakagawa Masahiro, Hori Shingo, Adachi Takeshi, Miyazaki Koji, Inoue Soushin, Suzuki Masaru, Mori Hidezo, Nakazawa Hiroe, Aikawa Naoki, Ogawa Satoshi
Department of Internal Medicine, Cardiopulmonary Division, Keio University School of Medicine, Research Park, Tokyo, Japan.
Shock. 2008 Aug;30(2):178-83. doi: 10.1097/shk.0b013e318160d990.
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.
失血性休克（HS）期间的心脏功能障碍与心肌缺血有关，在此期间三磷酸腺苷（ATP）敏感性钾（K(ATP)）通道可被激活。我们研究了K(ATP)通道在HS诱导的心肌缺血中的作用。使用主动脉储液器诱导犬失血性休克，将主动脉压力维持在恒定的40 mmHg。为了将心肌缺血可视化为烟酰胺腺嘌呤二核苷酸（NADH）荧光区域，在HS 10分钟后，使用采样装置对跳动的心脏进行快速横切（120毫秒）并冷冻钳夹（-190℃）。还对K(ATP)通道阻滞剂格列本脲（1 mg/kg，静脉注射）对心肌缺血的影响进行了量化。使用加载重元素的非放射性微球测量局部心肌血流量。单纯HS组的心内膜下出现心肌缺血，而格列本脲治疗组的心肌缺血扩展至所有心肌层。K(ATP)通道开放剂克罗卡林（50 μg/kg，静脉注射）与格列本脲联合使用可防止心肌缺血扩展至心外膜下。HS期间，格列本脲选择性降低心外膜下的心肌ATP浓度。HS使心肌血流量全层降低，给予格列本脲后，心外膜下血流量进一步选择性降低。这些结果表明，HS期间K(ATP)通道被激活，可实现心外膜下冠状动脉选择性扩张，并保护心肌免受心肌缺血向心外膜下扩展的影响。
