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Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats

Published online by Cambridge University Press:  23 December 2004

K. Engelhard ,
C. Werner ,
E. Eberspächer ,
M. Pape ,
M. Blobner ,
P. Hutzler  and
E. Kochs
K. Engelhard
Affiliation:
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany
C. Werner
Affiliation:
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany
E. Eberspächer
Affiliation:
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany
M. Pape
Affiliation:
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany
M. Blobner
Affiliation:
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany
P. Hutzler
Affiliation:
Institut für Pathologie, GSF-Forschungszentrum, Neuherberg, Germany
E. Kochs
Affiliation:
Technische Universität München, Klinik für Anaesthesiologie, Munich, Germany
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Extract

Summary

Background and 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 μg kg−1 bolus and 25 μg 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 μg 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.

Keywords

ANAESTHETICS, INHALATION, sevofluraneANAESTHETICS, INTRAVENOUS, propofolCELL DEATH, apoptosisCEREBROVASCULAR DISORDERS, brain ischaemia
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 21 , Issue 7 , July 2004 , pp. 530 - 537
Copyright
2004 European Society of Anaesthesiology

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