Anesthesia's effects on plasma glucose and insulin and cardiac hexokinase at similar hemodynamics and without major surgical stress in fed rats
Anesthesia's effects on plasma glucose and insulin and cardiac hexokinase at similar hemodynamics and without major surgical stress in fed rats
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DOI：
10.1213/01.ane.0000297299.91527.74
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发表时间：
2008-01-01
影响因子：
5.7
通讯作者：
Hollmann, Markus W.
中科院分区：
文献类型：
--
作者：
Zuurbier, Coert J.;Keijzers, Peter J. M.;Hollmann, Markus W.
背景技术背景：最近的证据表明，己糖激酶线粒体协会减弱细胞死亡，血糖和胰岛素浓度可以影响临床结果。在本研究中，我们研究了不同的麻醉剂本身如何影响葡萄糖代谢的这些变量，即，在相似的血流动力学条件下，在没有重大手术应激的情况下。在进食大鼠中，测定了戊巴比妥（PENTO）、异氟烷（ISO）、七氟烷（SEVO）、氯胺酮-美托咪定-阿托品（KMA）和舒芬太尼-丙泊酚-吗啡（SPM）对己糖激酶（HK）心脏细胞定位以及血浆葡萄糖和胰岛素水平的影响，并与非麻醉动物（对照）中获得的值进行了比较。线粒体和肌膜K-ATP通道和α 2肾上腺素能受体在ISO诱导的高血糖中的作用也进行了评估。与对照组（5.6 +/- 0.1 mM）相比，PENTO（5.3 +/-0.2 mM）和SPM（5.1 +/-0.2 mM）对血糖无显著影响。所有其他麻醉剂均诱导高血糖症：7.4 +/- 0.2 mM（SEVO）、9.9 +/- 0.3 mM（ISO）和14.8 +/- 1.0 mM（KMA）。与对照组（0.59 +/- 0.22 ng/mL）相比，PENTO组（2.13 +/- 0.13 ng/mL）的胰岛素浓度增加，但不受其他麻醉剂的影响。抑制线粒体K-ATP通道（5-羟基癸酸）或α（2）-肾上腺素能受体（育亨宾）不能预防ISO诱导的高血糖症。只有非特异性K-ATP通道抑制剂格列本脲能够通过ISO预防高血糖。Cytoshc HK相对于总HK按以下顺序增加：对照（35.5% +/- 2.1%），SEVO（35.5% +/- 2.7%），ISO（36.6% +/- 1.7%），PENTO（41.2% +/- 2.0%;与对照组相比P = 0.082），SPM（43.0% +/- 1.8%;与对照组相比P = 0.039）和KMA结论：挥发性麻醉剂和KMA诱导高血糖症，这至少可以部分地通过受损的葡萄糖诱导的胰岛素释放来解释。这些数据表明ISO对胰岛素释放的抑制是由肌膜K-ATP通道激活介导的。PENTO和SPM的使用与高血糖症无关。SPM和KMA减少HK与线粒体的抗凋亡关联。
BACKGROUND: Recent evidence suggests that hexokinase mitochondria association attenuates cell death, and that plasma glucose and insulin concentrations can influence clinical outcome. In the present study, we examined how different anesthetics per se affect these variables of glucose metabolism, i.e., under similar hemodynamic conditions and in the absence of major surgical stress.METHODS: In fed rats, the effects of pentobarbital (PENTO), isoflurane (ISO), sevoflurane (SEVO), ketamine-medetomidine-atropine (KMA), and sufentanil-propofol-morphine (SPM) on the cardiac cellular localization of hexokinase (HK) and levels of plasma glucose and insulin were determined and compared with values obtained in nonanesthetized animals (control). The role of mitochondrial and sarcolemmal K-ATP-channels and alpha(2)-adrenergic receptor in ISO-induced hyperglycemia was also evaluated.RESULTS: Mean arterial blood pressure was similar among the different anesthetic strategies. PENTO (5.3 +/- 0.2 mM) and SPM (5.1 +/- 0.2 mM) had no significant effect on plasma glucose when compared with control (5.6 +/- 0.1 mM). All other anesthetics induced hyperglycemia: 7.4 +/- 0.2 mM (SEVO), 9.9 +/- 0.3 mM (ISO), and 14.8 +/- 1.0 mM (KMA). Insulin concentrations were increased with PENTO (2.13 +/- 0.13 ng/mL) when compared with control (0.59 +/- 0.22 ng/mL), but were unaffected by the other anesthetics. Inhibition of the mitochondrial K-ATP channel (5-hydroxydecanoate acid) or the alpha(2)-adrenergic receptor (yohimbine) did not prevent ISO-induced hyperglycemia. Only the nonspecific K-ATP channel inhibitor glibenclamide was able to prevent hyperglycemia by ISO. Cytoshc HK relative to total HK increased in the following sequence: control (35.5% +/- 2.1%), SEVO (35.5% +/- 2.7%), ISO (36.6% +/- 1.7%), PENTO (41.2% +/- 2.0%; P = 0.082 versus control), SPM (43.0% +/- 1.8%; P = 0.039 versus control), and KMA (46.6 +/- 2.3%; P = 0.002 versus control).CONCLUSIONS: Volatile anesthetics and KMA induce hyperglycemia, which can be explained, at least partly, by impaired glucose-induced insulin release. The data indicate that the inhibition of insulin release by ISO is mediated by sarcolemmal K-ATP channel activation. The use of PENTO and SPM is not associated with hyperglycemia. SPM and KMA reduce the antiapoptotic association of HK with mitochondria.