Anesthetic actions of thiopental remain largely unaffected during cholinergic overstimulation in cultured cortical networks.
In case of military or terrorist use of organophosphorus (OP) compounds victims are likely to suffer from not only intoxication but physical trauma as well. Appropriate emergency care may therefore include general anesthesia to allow life-saving surgical intervention. Since there is evidence that drug potency and efficacy of several anesthetics are attenuated by high concentrations of acetylcholine in the CNS, this study was designed to evaluate the anesthetic actions of thiopental during cholinergic overstimulation. Making use of organotypic slice cultures derived from the mouse neocortex, drug effects were assessed by extracellular voltage recordings of network activity at basal cholinergic tone and during simulated cholinergic crisis (high cholinergic tone). The latter was achieved by inhibition of acetylcholinesterases via soman and an ambient acetylcholine concentration of 10μM. The induction of cholinergic crisis in vitro increased the network activity of cortical neurons significantly. Surprisingly, differences in network activity between basal and high cholinergic tone became less pronounced with rising concentrations of thiopental and drug potency and efficacy were almost equivalent. These results clearly distinguish thiopental from previously tested general anesthetics and make it a promising candidate for in vivo studies to identify suitable anesthetics for victims of OP intoxication.
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany; Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany. Electronic address: isabel.weimer@uni-tuebingen.de.
Isabel
I
Weimer
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Franz
F
Worek
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Thomas
T
Seeger
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Horst
H
Thiermann
Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany.
Christian
C
Grasshoff
Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany; Werner-Reichardt-Centre for Integrative Neuroscience, Eberhard-Karls-University, 72076 Tuebingen, Germany.
Bernd
B
Antkowiak
Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany.
Monika
M
Balk
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D012999:Soman / Q000633:toxicity*; D013874:Thiopental / Q000494:pharmacology*; D013997:Time Factors; D046509:Tissue Culture Techniques
D018686:Anesthetics, Intravenous; D002800:Cholinesterase Inhibitors; D012999:Soman; D013874:Thiopental; D000109:Acetylcholine
Acetylcholine; Anesthesia; Cortex; Organophosphorus compounds; Thiopental