The Effects of Forebrain Ischemia on Lidocaine-Induced Seizure Threshold in the Rat

Kim, Dong Chan; Song, He Sun

Abstract

BACKGROUND: Seizures are common following many cerebral insults, include global and focal ischemia. However, while the mechanism must relate to some change in the relative activities of excitatory and inhibitory pathway, the specific alterations in neurotransmitter concentrations and/or receptor sensitivities which underlie these events, remain unknown. The principal aim of this study was therefore to evaluate the effects of moderately severe forebrain ischemia on lidocaine-induced seizure thresholds, in hopes of gaining some insights into these processes.
METHODS
Halothane-anesthetized, normothermic Sprague-Dawley rats were chronically instrumented with screw electrodes and vascular catheters, and were then subjected to 10 min of forebrain ischemia, produced by bilateral carotid occlusion combined with hypotension (MAP = 30 mmHg). After reperfusion, animals were awakened. 6, 24 and 46 hours later, separate groups of awake animals were subjected to intravenous infusion of lidocaine at the rate of 2.6 mg/kg/min. The total dose of lidocaine infused prior to generalized tonic-clonic seizures were noted. Another group of Sham animals (no ischemia) served as control.
RESULTS
The lidocaine-induced seizure threshold was significantly increased at 24 h after forebrain ischemia (65.39 12.9 mg/kg vs 36.47 4.24 mg/kg, P < 0.05). Interestingly, at 6 h post-ischemia, rats treated with lidocaine consistently died before seizures. There were no significant differences in seizure threshold between the control and 48 h post-ischemia groups.
CONCLUSIONS
Ten minutes of forebrain ischemia is followed by a transient increase in the seizure threshold to infused lidocaine. By 48 h following reperfusion, lidocaine induced seizure threshold had returned to normal.