Neuronale Mechanismen der Narkose

Zusammenfassung.

Positronenemissionstomographische Studien an Probanden zur Wirkung von Propofol, Halothan und Isofluran haben gezeigt, dass bei Eintritt der Bewusstlosigkeit der Glukosemetabolismus in der Großhirnrinde um ca. 20 - 50 % reduziert ist. Um die Frage zu klären, ob dieser Befund auf eine unmittelbare Hemmung neokortikaler Netzwerke zurückgeführt werden kann, wurden Untersuchungen an isolierten Gehirnschnitten durchgeführt, in denen Nervenzellen der Großhirnrinde, nicht aber subkortikale Strukturen enthalten waren. Es ergab sich eine ausgezeichnete Korrelation zwischen den Konzentrationen, die die Feuerraten von Nervenzellen in Gehirnschnitten auf die Hälfte reduzierten und den Konzentrationen, die von verschiedenen Autoren im Blut von Patienten beim Aufwachen aus der Narkose gemessen wurden. Aus bereits veröffentlichten Untersuchungen an Probanden war des weiteren bekannt, dass Isofluran die Frequenz auditorisch evozierter hochfrequenter neuronaler Oszillationen in der Großhirnrinde halbiert, wenn eine Konzentration verabreicht wird, die etwa 50 % des MAK-Wertes beträgt. Vergleichbare quantitative Wirkungen wurden in Gehirnschnitt-Präparaten beobachtet, in denen hochfrequente Oszillationen neuronaler Aktivität spontan auftraten. Nicht alle Aspekte der zerebralen Wirkung von Allgemeinanästhetika lassen sich jedoch durch eine direkte Hemmung kortikaler Nervenzellen erklären. Die fortschreitende Synchronisation kortikaler Aktivität, die mit zunehmender Narkosetiefe im EEG sichtbar wird, sowie die Unterdrückung der Amplitude auditorisch evozierter Potentiale mittlerer Latenz ist wahrscheinlich auf die Hemmung thalamischer Neurone zurückzuführen. Halothan, Isofluran, Enfluran und Propofol reduzierten die Aktivität kortikaler Neurone in Gehirnschnitten, indem sie die GABA_A-Rezeptor-vermittelte synaptische Inhibition verstärkten. Ein ähnlicher molekularer Wirkmechanismus trägt wahrscheinlich auch zur Unterdrückung spinaler Schmerzreflexe bei. Allerdings müssen sich die zerebralen und spinalen Wirkmechanismen von Allgemeinanästhetika unterscheiden. Bildet man das Verhältnis zwischen den Konzentrationen die Bewusstlosigkeit induzieren und jenen die Schmerzreflexe unterdrücken, so erhält man für verschiedene Wirkstoffe deutlich voneinander abweichende Werte.

Neural Mechanisms of Anaesthesia.

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, isoflurane 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, isoflurane, enflurane and propofol reduced action potential firing of cortical neurones by enhancing GABA_A 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.

GABA_A-Rezeptor - Neokortex - Rückenmark - Allgemeinanästhetika - EEG - Schmerz - Bewusstsein

GABA_A-receptor - Neocortex - Spinal cord - General anaesthetics - EEG - Pain - Consciousness

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