Anesthesia's effects on plasma glucose and insulin and cardiac hexokinase at similar hemodynamics and without major surgical stress in fed rats.
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 alpha2-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. 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 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.
Zuurbier
Coert J
CJ
Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. c.j.zuurbier@amc.uva.nl
Keijzers
Peter J M
PJ
Koeman
Anneke
A
Van Wezel
Harry B
HB
Hollmann
Markus W
MW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000777:Anesthetics / Q000009:adverse effects*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D003652:Decanoic Acids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism*; D006880:Hydroxy Acids / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology; D007328:Insulin / Q000097:blood*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D019518:Postprandial Period; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000777:Anesthetics; D001786:Blood Glucose; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018341:Receptors, Adrenergic, alpha-2; C117780:mitochondrial K(ATP) channel; D015016:Yohimbine; C052853:5-hydroxydecanoic acid; D006593:Hexokinase; D005905:Glyburide