Hyperglycemia Inhibits Anesthetic-induced Postconditioning in the Rabbit Heart via Modulation of Phosphatidylinositol-3-kinase/Akt and Endothelial Nitric Oxide Synthase Signaling

Hyperglycemia Inhibits Anesthetic-induced Postconditioning in the Rabbit Heart via Modulation of Phosphatidylinositol-3-kinase/Akt and Endothelial Nitric Oxide Synthase Signaling
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DOI:
10.1097/fjc.0b013e3181d26583
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发表时间:
2010-04-01
影响因子:
3
通讯作者:
Zuo, Zhiyi
Zuo, Zhiyi
中科院分区:
医学4区
文献类型:
--
作者:
Raphael, Jacob;Gozal, Yaacov;Zuo, Zhiyi

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高血糖症可抑制缺血预处理和麻醉预处理。我们测试了高血糖是否会抑制异氟醚麻醉后适应,以及这种作用是否通过磷脂酰肌醇-3-激酶/Akt和一氧化氮信号介导。将心肌缺血40 min后再灌注3 h的新西兰大白兔分为缺血再灌注(I/R)组、异氟醚(1最小肺泡浓度)后处理组和异氟醚后处理伴高血糖(15%葡萄糖输注)组。另设高血糖+ I/R对照组。评估肌酸激酶MB分数(CK-MB)水平作为心肌损伤的指标,并评估梗死面积。免疫印迹法检测Akt、iNOS和内皮型一氧化氮合酶(eNOS)的表达。同时测定心肌亚硝酸盐和硝酸盐水平。与I/R组相比,异氟醚后处理减少梗死面积:25% +/- 4% vs 49% +/- 5% (P < 0.01)。后条件组CK-MB浓度(比基线水平高124% +/- 14%)低于I/R组(比基线水平高236% +/- 9%)
Hyperglycemia is known to inhibit ischemic and anesthetic preconditioning. We tested whether hyperglycemia inhibits anesthetic postconditioning with isoflurane and whether this effect is mediated via phosphatidylinositol-3-kinase/Akt and nitric oxide signaling. New Zealand white rabbits subjected to 40 minutes of myocardial ischemia, followed by 3 hours of reperfusion were assigned to the following groups: ischemia and reperfusion (I/R), isoflurane (1 minimal alveolar concentration) postconditioning, and isoflurane postconditioning with hyperglycemia (15% dextrose in water infusion). A control group of hyperglycemia + I/R was also included. Levels of MB fraction of creatine kinase (CK-MB) were assessed as an indicator of myocardial damage, and infarct size was evaluated. Akt, iNOS, and endothelial nitric oxide synthase (eNOS) expression was assessed by immunoblotting. Determination of nitrite and nitrate levels in the myocardium was also performed. Isoflurane postconditioning reduced infarct size compared with the I/R group: 25% +/- 4% versus 49% +/- 5% (P < 0.01). CK-MB concentrations in the postconditioned animals (124% +/- 14% above baseline levels) were lower than those in the I/R group (236% +/- 9% above baseline levels; P