Raphael Jacob, Gozal Yaacov, Navot Nachum, Zuo Zhiyi
From the Department of Anesthesiology, University of Virginia, Health Sciences Center, Charlottesville, Virginia (J.R., Z.Z.); and Laboratory for Experimental Surgery (N.N.) and the Department of Anesthesiology and Critical Care Medicine, Shaarey Zedeq Medical Center (Y.G.), Hebrew University School of Medicine, Jerusalem, Israel.
Anesthesiology. 2015 Jun;122(6):1299-311. doi: 10.1097/ALN.0000000000000648.
Hyperglycemia is known to inhibit myocardial anesthetic postconditioning. The authors tested whether activation of adenosine triphosphate-regulated potassium (KATP) channels would restore anesthetic postconditioning during acute hyperglycemia.
Rabbits subjected to 40-min myocardial ischemia and 3-h reperfusion (ischemia-reperfusion [I/R]) were assigned to groups (n = 10 in each group) with or without isoflurane postconditioning (2.1% for 5 min) in the presence or absence of hyperglycemia and/or the KATP channel agonist diazoxide. Creatine kinase MB fraction and infarct size were measured. Phosphorylated protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were assessed. Oxidative stress was evaluated by measuring malondialdehyde, and apoptosis was assessed by dUTP nick-end labeling and activated caspase-3.
Postconditioning significantly reduced myocardial infarct size (26 ± 4% in the isoflurane [ISO] group vs. 53 ± 2% in the I/R group; P = 0.007); whereas, hyperglycemia inhibited this effect (infarct size: 47 ± 2%, P = 0.02 vs. the ISO group). Phosphorylated and eNOS levels increased, whereas malondialdehyde and myocardial apoptosis were significantly lower after isoflurane postconditioning compared with I/R. These effects were inhibited by acute hyperglycemia. Diazoxide restored the protective effect of isoflurane in the hyperglycemic animals (infarct size: 29 ± 2%; P = 0.01 vs. the I/R group), reduced malondialdehyde levels and myocardial apoptosis, but did not affect the expression of phosphorylated Akt or eNOS.
KATP channel activation restored anesthetic postconditioning-induced myocardial protection under acute hyperglycemia. This effect occurred without increasing Akt or eNOS phosphorylation, suggesting that KATP channels are located downstream to Akt and eNOS in the pathway of isoflurane-induced myocardial postconditioning.
已知高血糖会抑制心肌麻醉后适应。作者测试了在急性高血糖期间，三磷酸腺苷调节钾（KATP）通道的激活是否能恢复麻醉后适应。
将经历40分钟心肌缺血和3小时再灌注（缺血-再灌注[I/R]）的兔子分为几组（每组n = 10），在有或无高血糖和/或KATP通道激动剂二氮嗪的情况下，给予或不给予异氟烷后适应（2.1%，持续5分钟）。测量肌酸激酶同工酶MB分数和梗死面积。评估磷酸化蛋白激酶B（Akt）和内皮型一氧化氮合酶（eNOS）。通过测量丙二醛评估氧化应激，通过脱氧尿苷三磷酸缺口末端标记和活化的半胱天冬酶-3评估细胞凋亡。
后适应显著减小了心肌梗死面积（异氟烷[ISO]组为26±4%，而I/R组为53±2%；P = 0.007）；然而，高血糖抑制了这种作用（梗死面积：47±2%，与ISO组相比，P = 0.02）。与I/R相比，异氟烷后适应后磷酸化和eNOS水平升高，而丙二醛和心肌细胞凋亡显著降低。这些作用被急性高血糖抑制。二氮嗪恢复了异氟烷在高血糖动物中的保护作用（梗死面积：29±2%；与I/R组相比，P = 0.01），降低了丙二醛水平和心肌细胞凋亡，但不影响磷酸化Akt或eNOS的表达。
KATP通道激活在急性高血糖情况下恢复了麻醉后适应诱导的心肌保护作用。这种作用在不增加Akt或eNOS磷酸化的情况下发生，表明KATP通道在异氟烷诱导的心肌后适应途径中位于Akt和eNOS的下游。
