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Abstract

Positron emission tomography studies on volunteers showed that, at concentrations inducing the loss of consciousness, propofol, halothane and
isoflurane reduce glucose metabolism of neocortical neurones by 20-50. To find out whether these effects are caused by direct anaesthetic actions on
cortical structures, experiments were carried out on isolated neocortical brain slices. In these investigations an excellent correlation was observed between
anaesthetic concentrations causing a half-maximal depression of action potential firing in neocortical brain slices and anaesthetic blood concentrations
monitored during awaking from anaesthesia in humans. Furthermore, it could be shown that, at concentrations approximately one half the MAC-value,
isoflurance decreases the frequency of auditory evoked 30-40 Hz oscillations in the neocortex by 50. Similar quantitative effects were observed on
spontaneously occurring high frequency rhythms in neocortical brain slices. However, not all aspects of cerebral anaesthetic actions can be explained by
direct effects on cortical neurones. The EEG synchronisation and the amplitude reduction of mid latency auditory evoked potentials are probably related to
the inhibition of thalamic neurones. Halothane, isoflurance, enflurance and propofol reduced action potential firing of cortical neurones by enhancing GABAA
receptor-mediated synaptic inhibition. This molecular mechanism seems also to be involved in depressing painful stimuli-induced motor responses.
Nevertheless, there must be a difference between relevant anaesthetic mechanisms on the cerebral and spinal level. This follows from the observation that the
relation between the concentration causing the loss of consciousness and the concentration that depresses movements considerably varies among different
anaesthetic agents.