Department of Anesthesia, McGill University, Montreal, Canada H3A 1A1.
J Clin Endocrinol Metab. 2011 May;96(5):1469-77. doi: 10.1210/jc.2010-1934. Epub 2011 Feb 23.
Coronary artery bypass grafting (CABG) is complicated by ischemia-reperfusion injury jeopardizing myocyte survival.
The aim of the study was to investigate whether glucose and insulin administration, while maintaining normoglycemia (GIN therapy) using a hyperinsulinemic-normoglycemic clamp technique, is cardioprotective in patients undergoing CABG.
We conducted a randomized controlled trial at a tertiary care university teaching hospital.
We studied 99 patients undergoing elective CABG.
Patients were randomly assigned to receive either GIN from the beginning of surgery until 24 h after CABG (GIN, n = 49) or standard metabolic care (control, n = 50).
We measured plasma concentrations of cardiac troponin I and free fatty acids, cardiac function as assessed by transesophageal echocardiography, glycogen content, glycogen synthase activity, and the expression of AMP-activated protein kinase (AMPK) and protein kinase B (AKT) in cardiomyocytes.
Patients receiving GIN therapy showed an attenuated release of cardiac troponin I (P < 0.05) and improved myocardial function (P < 0.05). Systemic free fatty acid concentrations were suppressed (P < 0.05), whereas intracellular glycogen content and glycogen synthase activity were not altered. The AMPK activity remained unchanged during ischemia in the GIN group, whereas it increased in the control group (P < 0.05). Enhanced AKT phosphorylation before ischemia was observed (P < 0.05) in the presence of GIN. However, there was no evidence for AKT-dependent AMPK inhibition.
GIN therapy protects the myocardium and inhibits ischemia-induced AMPK activation.
冠状动脉旁路移植术（CABG）会发生缺血再灌注损伤，危及心肌细胞存活。
本研究旨在探讨在 CABG 患者中，使用高胰岛素-正常血糖钳夹技术维持正常血糖时给予葡萄糖和胰岛素（GIN 治疗）是否具有心脏保护作用。
我们在一家三级保健大学教学医院进行了一项随机对照试验。
我们研究了 99 例行择期 CABG 的患者。
患者被随机分配接受从手术开始到 CABG 后 24 小时接受 GIN（GIN，n=49）或标准代谢护理（对照组，n=50）。
我们测量了血浆心肌肌钙蛋白 I 和游离脂肪酸浓度、经食管超声心动图评估的心脏功能、心肌细胞中的糖原含量、糖原合酶活性以及 AMP 激活的蛋白激酶（AMPK）和蛋白激酶 B（AKT）的表达。
接受 GIN 治疗的患者心肌肌钙蛋白 I 释放减少（P<0.05），心肌功能改善（P<0.05）。全身游离脂肪酸浓度降低（P<0.05），而细胞内糖原含量和糖原合酶活性没有改变。在 GIN 组中，缺血期间 AMPK 活性保持不变，而在对照组中则增加（P<0.05）。在 GIN 存在的情况下，观察到缺血前 AKT 磷酸化增强（P<0.05）。然而，没有证据表明 AKT 依赖的 AMPK 抑制。
GIN 治疗可保护心肌并抑制缺血引起的 AMPK 激活。
