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From the Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Address correspondence and reprint requests to Dr. C. J. Zuurbier, Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Address e-mail to c.j.zuurbier{at}amc.uva.nl.
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 KATP-channels and 
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 KATP channel (5-hydroxydecanoate acid) or the 2-adrenergic receptor (yohimbine) did not prevent ISO-induced hyperglycemia. Only the nonspecific KATP channel inhibitor glibenclamide was able to prevent hyperglycemia by ISO. Cytoslic 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 KATP channel activation. The use of PENTO and SPM is not associated with hyperglycemia. SPM and KMA reduce the antiapoptotic association of HK with mitochondria.
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