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.

Summary

Background and objective: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo.

Methods: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1.

Results: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane.

Conclusions: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.