Behavioural, electroencephalographic and histological study of the protective effect of etomidate against histotoxic dysoxia produced by cyanide.
The acute toxicity of cyanide is largely due to the inhibition of cytochrome oxidase, and the subsequent breakdown of cellular metabolism. Breakdown in cellular metabolism, leading to a disruption of cellular integrity lies at the heart of the permanent neurological damage resulting from ischemic/hypoxic brain insult. In 200 g male Wistar rats treated with 5 mg/kg KCN i.v. and ventilated until spontaneous breathing restarted, the cornea reflex, tail-pinch reaction and righting reflex disappeared for about 20 min. In curarized and artificially ventilated rats the EEG remained flat for a similar period before slowly returning. Saline treated animals which survive the KCN injection die significantly earlier than non-KCN treated animals when injected with 120 mg/kg metrazol s.c. one week later. Histological examination of KCN treated animals revealed swollen mitochondria at 20 min, and microvacuolization and ischemic cell changes at 1 week. In rats pretreated with etomidate 10 mg/kg s.c. 30 min before cyanide the cornea, tail-pinch and righting reflex were absent for the same time as in controls. The EEG was similar to that seen in saline/KCN animals, however, the time to EEG was similar to that seen in saline/KCN animals, however, the time to EEG silence was doubled. One week after the cyanide injection their reaction to the metrazol injection was similar to animals treated one week earlier with saline. Although there was evidence of swollen mitochondria 20 min after KCN, one week after KCN there was no evidence of ischemic hypoxic brain damage. These results demonstrate that under similar conditions of dysoxia, etomidate treated animals appear to be protected from the behavioural and histological sequelae of those conditions.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000648:ultrastructure; D003486:Cyanides / Q000037:antagonists & inhibitors*; D004569:Electroencephalography; D005045:Etomidate / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000648:ultrastructure; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008933:Mitochondrial Swelling; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects
D003486:Cyanides; D007093:Imidazoles; D005045:Etomidate