Toller W G, Gross E R, Kersten J R, Pagel P S, Gross G J, Warltier D C
Departments of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Anesthesiology. 2000 Jun;92(6):1731-9. doi: 10.1097/00000542-200006000-00033.
Volatile anesthetic-induced preconditioning is mediated by adenosine triphosphate-dependent potassium (KATP) channels; however, the subcellular location of these channels is unknown. The authors tested the hypothesis that desflurane reduces experimental myocardial infarct size by activation of specific sarcolemmal and mitochondrial KATP channels.
Barbiturate-anesthetized dogs (n = 88) were acutely instrumented for measurement of aortic and left ventricular pressures. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle (0.9% saline) or the nonselective KATP channel antagonist glyburide (0.1 mg/kg intravenously) in the presence or absence of 1 minimum alveolar concentration desflurane. In four additional groups, dogs received 45-min intracoronary infusions of the selective sarcolemmal (HMR 1098; 1 microg. kg-1. min-1) or mitochondrial (5-hydroxydecanoate [5-HD]; 150 microg. kg-1. min-1) KATP channel antagonists in the presence or absence of desflurane. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.
Desflurane significantly (P < 0.05) decreased infarct size to 10 +/- 2% (mean +/- SEM) of the area at risk as compared with control experiments (25 +/- 3% of area at risk). This beneficial effect of desflurane was abolished by glyburide (25 +/- 2% of area at risk). Glyburide (24 +/- 2%), HMR 1098 (21 +/- 4%), and 5-HD (24 +/- 2% of area at risk) alone had no effects on myocardial infarct size. HMR 1098 and 5-HD abolished the protective effects of desflurane (19 +/- 3% and 22 +/- 2% of area at risk, respectively).
Desflurane reduces myocardial infarct size in vivo, and the results further suggest that both sarcolemmal and mitochondrial KATP channels could be involved.
挥发性麻醉药诱导的预处理由三磷酸腺苷依赖性钾（KATP）通道介导；然而，这些通道的亚细胞定位尚不清楚。作者检验了以下假设：地氟醚通过激活特定的肌膜和线粒体KATP通道来减小实验性心肌梗死面积。
用巴比妥类药物麻醉的犬（n = 88）进行急性仪器植入，以测量主动脉和左心室压力。所有犬均接受60分钟的左前降支冠状动脉闭塞，随后进行3小时的再灌注。在四个独立的组中，犬在有或没有1个最低肺泡浓度地氟醚的情况下接受载体（0.9%生理盐水）或非选择性KATP通道拮抗剂格列本脲（0.1 mg/kg静脉注射）。在另外四个组中，犬在有或没有地氟醚的情况下接受45分钟的冠状动脉内输注选择性肌膜（HMR 1098；1微克·千克-1·分钟-1）或线粒体（5-羟基癸酸[5-HD]；150微克·千克-1·分钟-1）KATP通道拮抗剂。分别用放射性微球和三苯基四氮唑染色测量心肌灌注和梗死面积。
与对照实验（危险区域面积的25±3%）相比，地氟醚显著（P < 0.05）将梗死面积减小至危险区域面积的10±2%（平均值±标准误）。格列本脲消除了地氟醚的这种有益作用（危险区域面积的25±2%）。单独使用格列本脲（24±2%）、HMR 1098（21±4%）和5-HD（危险区域面积的24±2%）对心肌梗死面积无影响。HMR 1098和5-HD消除了地氟醚的保护作用（分别为危险区域面积的19±3%和22±2%）。
地氟醚可减小体内心肌梗死面积，结果进一步表明肌膜和线粒体KATP通道可能均参与其中。
