Local Cerebral Blood Flow during Lidocaine-induced Seizures in Rats

Abstract

Neurophysiologic and local cerebral metabolic mapping techniques indicate that seizures associated with lidocaine toxicity originate in subcortical brain structures. Normally local cerebral blood flow (1-CBF) is quantitatively coupled to local cerebral metabolic rate for glucose (1-CMRg). In the present study the response of 1-CBF to a lidocaine-induced preconvulsive state (localized seizure activity in the absence of a grand mal seizure) was evaluated in rats anesthetized with 60% nitrous oxide. Lidocaine administered as a bolus (20 mg/kg) followed by an infusion (4 mg/kg) over 5.5 min resulted in progressive alteration in the electroencephalogram (EEG). L-CBF was studied with the 14C-iodoantipyrine autographic method when the preconvulsive EEG pattern consisted of a repetitive spike and wave complex at a frequency of 14 .+-. 1 .cntdot. min-1 complexes, superimposed on practically isoelectric background activity. Under these conditions high doses of lidocaine significantly (P < 0.05) decreased (range -30% to -68%) 1-CBF in 71% of the 34 brain regions studied. The greatest exception to this trend for 1-CBF to decrease was observed in the limbic system wherein 1-CBF remained within control ranges in eight of the 11 structures evaluated. Qualitative comparison of lidocaine 1-CBF changes with 1-CMRg changes obtained under similar conditions indicated a general trend for local flow and metabolism to decrease in parallel. Exceptions to this were confined to certain limbic areas (amygdala and hippocampus) in which increases in 1-CMRg were more than 100% greater than slight (P > 0.05) increases in 1-CBF. This comparison demonstrates uncoupling of local brain metabolism from blood flow during lidocaine-induced subcortical epileptoid discharges (preconvulsive state) in areas recognized to be prone to irreversible damage when seizure activity is much prolonged beyond the duration of this study.