We compared the efficacy of four different classes of
anesthetics to arrest the progression of brain damage after chemoconvulsant-induced
seizures in rats. In two series of experiments, ventilated, paralyzed Long-Evans rats were subjected to 30 or 45 min of continuous
seizures induced by intravenous (IV) mercaptopropionic
acid (MPA) or inhaled
flurothyl, respectively. In the first series,
seizures produced with MPA were treated with: 1)
thiopental, 15 mg/kg IV bolus (controls); 2)
thiopental, 27 mg/kg IV followed by 20.9 mg.kg-1.h-1 for 2 h; 3)
isoflurane 4% inhaled concentration for 1 min followed by 1%-2% for 2 h; 4)
ketamine 30 mg/kg IV followed by 9.12 mg.kg-1.h-1 for 2 h; 5)
midazolam 25 mg/kg IV followed by 9.7 mg.kg-1.h-1 for 2 h. In a second series,
seizures were produced by
flurothyl and, based on suggestive results in the MPA series, control rats were compared with rats receiving
midazolam 25 mg/kg IV followed by 9.7 mg.kg-1.h-1. In all instances, seizure activity, recorded by electroencephalograph, stopped with
anesthetic treatment. In MPA-treated rats extranigral damage was mild, with no differences apparent between
anesthetics. Control animals sustained severe lesions in the substantia nigra pars reticulata (SNPR). No statistically significant differences between
anesthetic groups were present, although an effect was suggested for
midazolam to decrease SNPR lesional area (P = 0.06). In
flurothyl-treated rats, there were significant reductions in SNPR neuropathologic grade (P = 0.025) and lesional area (P = 0.025) with
midazolam. We conclude that
midazolam attenuates postseizure SNPR damage in rats.