Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.
J Cardiovasc Pharmacol. 2010 Apr;55(4):348-57. doi: 10.1097/FJC.0b013e3181d26583.
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 < 0.01). Hyperglycemia inhibited the cardioprotective effect of isoflurane: myocardial infarction size was 46% +/- 4% and CK-MB increased to 241% +/- 11% above baseline. Phosphorylated Akt and eNOS protein expression increased after isoflurane postconditioning compared with the I/R group. These effects were also inhibited by hyperglycemia. iNOS expression, however, did not change significantly within the various experimental groups. There were increased tissue levels of nitrite and nitrate (NO(x)) in the postconditioning group. This was also blocked by hyperglycemia. Our results suggest that hyperglycemia inhibits cardioprotection provided by isoflurane postconditioning. This effect seems to be mediated via modulation Akt and eNOS.
高血糖可抑制缺血和麻醉预处理。我们检测了高血糖是否抑制异氟醚麻醉后处理，以及这种效应是否通过磷脂酰肌醇-3-激酶/蛋白激酶 B（Akt）和一氧化氮信号传导介导。新西兰白兔接受 40 分钟心肌缺血，然后再灌注 3 小时，分为以下几组：缺血再灌注（I/R）、异氟醚（1 最小肺泡浓度）后处理和高血糖异氟醚后处理（水中输注 15%葡萄糖）。还包括高血糖+I/R 的对照组。肌酸激酶同工酶（CK-MB）的 MB 片段水平作为心肌损伤的指标进行评估，并评估梗死面积。通过免疫印迹法评估 Akt、诱导型一氧化氮合酶（iNOS）和内皮型一氧化氮合酶（eNOS）的表达。还测定了心肌中硝酸盐和亚硝酸盐的水平。与 I/R 组相比，异氟醚后处理降低了梗死面积：25% +/- 4%对 49% +/- 5%（P < 0.01）。后处理动物的 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%；P < 0.01）。高血糖抑制了异氟醚的心脏保护作用：心肌梗死面积为 46% +/- 4%，CK-MB 增加至比基线高 241% +/- 11%。与 I/R 组相比，异氟醚后处理后磷酸化 Akt 和 eNOS 蛋白表达增加。这些作用也被高血糖抑制。然而，iNOS 表达在各个实验组中没有显著变化。后处理组组织中硝酸盐和亚硝酸盐（NOx）水平升高。这也被高血糖阻断。我们的结果表明，高血糖抑制异氟醚麻醉后处理提供的心脏保护作用。这种作用似乎是通过调节 Akt 和 eNOS 来介导的。
