The electrocortical effects of enflurane: experiment and theory.
BACKGROUND
High concentrations of enflurane will induce a characteristic electroencephalogram pattern consisting of periods of suppression alternating with large short paroxysmal epileptiform discharges (PEDs). In this study, we compared a theoretical computer model of this activity with real local field potential (LFP) data obtained from anesthetized rats.


METHODS
After implantation of a high-density 8 x 8 electrode array in the visual cortex, the patterns of LFP and multiunit spike activity were recorded in rats during 0.5, 1.0, 1.5, and 2.0 minimum alveolar anesthetic concentration (MAC) enflurane anesthesia. These recordings were compared with computer simulations from a mean field model of neocortical dynamics. The neuronal effect of increasing enflurane concentration was simulated by prolonging the decay time constant of the inhibitory postsynaptic potential (IPSP). The amplitude of the excitatory postsynaptic potential (EPSP) was modulated, inverse to the neocortical firing rate.


RESULTS
In the anesthetized rats, increasing enflurane concentrations consistently caused the appearance of suppression pattern (>1.5 MAC) in the LFP recordings. The mean rate of multiunit spike activity decreased from 2.54/s (0.5 MAC) to 0.19/s (2.0 MAC). At high MAC, the majority of the multiunit action potential events became synchronous with the PED. In the theoretical model, prolongation of the IPSP decay time and activity-dependent EPSP modulation resulted in output that was similar in morphology to that obtained from the experimental data. The propensity for rhythmic seizure-like activity in the model could be determined by analysis of the eigenvalues of the equations.


CONCLUSIONS
It is possible to use a mean field theory of neocortical dynamics to replicate the PED pattern observed in LFPs in rats under enflurane anesthesia. This pattern requires a combination of a moderately increased total area under the IPSP, prolonged IPSP decay time, and also activity-dependent modulation of EPSP amplitude.
Sleigh
James W
JW
Department of Anaesthesiology, Waikato Clinical School, University of Auckland, Auckland, New Zealand. sleighj@waikatodhb.govt.nz
Vizuete
Jeannette A
JA
Voss
Logan
L
Steyn-Ross
Alistair
A
Steyn-Ross
Moira
M
Marcuccilli
Charles J
CJ
Hudetz
Anthony G
AG
D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004737:Enflurane / Q000633:toxicity*; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D008959:Models, Neurological; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013997:Time Factors; D014793:Visual Cortex / Q000187:drug effects* / Q000503:physiopathology
D018685:Anesthetics, Inhalation; D004737:Enflurane