Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats.
OBJECTIVE
Sevoflurane and propofol reduce the extent of necrosis and improve neurological outcome in rodent models of cerebral ischaemia and reperfusion. However, the effects of these anaesthetics on programmed cell death (apoptosis) are unclear. The present study investigates whether sevoflurane and propofol affect the expression of apoptosis-regulating proteins after cerebral ischaemia in rats.


METHODS
Thirty-two fasted male Sprague-Dawley rats were tracheally intubated and the lungs were ventilated (isoflurane and N2O/O2 anaesthesia). After surgical preparation, the animals were randomly assigned to one of the following groups: control (n = 8): fentanyl intravenous (10 microg kg(-1) bolus and 25 microg kg(-1) h(-1) infusion) with N2O/O2; sevoflurane (n = 8): 2.0% sevoflurane (end-tidal concentration) and O2/air; propofol (n = 8): 0.8-1.0 mg kg(-1) min(-1) propofol intravenous and O2/air; sham-operated (n = 8): 25 microg kg(-1) h(-1) fentanyl intravenous and N2O/O2, no cerebral ischaemia. Ischaemia (30 min) was induced by unilateral common carotid artery occlusion plus haemorrhagic hypotension to a mean arterial pressure of 30-35 mmHg. Four hours after cerebral ischaemia the brains were removed and the expression of apoptosis-regulating proteins (Bax, Bcl-2, p53, Mdm-2) was determined using immunofluorescence and Western-blot analyses.


RESULTS
The expression of the pro-apoptotic protein Bax was greater in control animals than in sevoflurane or propofol anaesthetized rats and than in sham-operated animals. The concentrations of Bcl-2, p53 and Mdm-2 were not changed 4 h after cerebral ischaemia.


CONCLUSIONS
In addition to the anti-necrotic effects of sevoflurane and propofol, these anaesthetics also reduce the concentration of the apoptosis-inducing protein Bax as early as 4 h after ischaemia.
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany. k.engelhard@lrz.tum.de
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K
Engelhard
C
C
Werner
E
E
Eberspächer
M
M
Pape
M
M
Blobner
P
P
Hutzler
E
E
Kochs
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; C494828:Bax protein, rat; D008738:Methyl Ethers; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000077149:Sevoflurane; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2; D015742:Propofol