Summary

Background and objective: Neurological dysfunction is a common problem after cardiac surgery with cardiopulmonary bypass (CPB). Cerebral ischaemia associated with the use of CPB may result in a release of neuronal–ischaemic markers and a subsequent cerebral inflammatory response which may additionally release inflammatory cytokines. In order to locate the origin and to quantify the release of neuronal–ischaemic markers and cytokines we investigated arterial–cerebral venous concentration gradients during and after CPB in a clinical setting.

Methods: In twenty-five patients scheduled for coronary artery bypass grafting surgery we measured the plasma concentration of neuron-specific enolase, S-100β protein as well as interleukins (IL) IL-6, IL-8 and IL-10 from arterial and cerebral venous blood samples prior to surgery (baseline), during hypothermic CPB at 32°C, after termination of bypass, as well as 2, 4 and 6 h after admission to the intensive care unit.

Results: Arterial–cerebral venous concentration gradients of neuron-specific enolase, S-100β, IL-6, IL-8 and IL-10 were neither detectable during nor after CPB. Compared to the baseline period, S-100β and neuron-specific enolase significantly increased during hypothermic CPB. After termination of CPB, neuronal–ischaemic markers as well as cytokines were increased and remained elevated during the investigated time course without reaching baseline values.

Conclusions: Although we found an overall increase in plasma concentrations of neuronal–ischaemic markers, IL-6, IL-8 and IL-10 during and after CPB, arterial–cerebral venous gradients were not detectable for any of these parameters. Our results suggest that the increase of investigated parameters associated with the use of CPB are not primarily caused by a cerebral inflammatory response but rather reflect a release from other sources in the systemic circulation.

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.