Background: The authors' previous study demonstrated that a clinical antiarrhythmic dose of lidocaine, when given before ischemia, is neuroprotective in a rat model of transient focal cerebral ischemia. In this study, the authors investigated whether the administration of this dose of lidocaine, when delayed until 45 min after the onset of ischemia, also reduces ischemic brain injury.
Methods: Lidocaine was administered as an intravenous bolus (1.5 mg/kg) followed by an intravenous infusion (2 mg. kg(-1).h(-1)) for 165 min, beginning 45 min after the onset of a 90-min period of transient focal cerebral ischemia. Control animals were given the same volume of saline. Focal cerebral ischemia was induced by occluding the right middle cerebral artery using an intraluminal suture. Neurologic outcome and body weight loss were quantified 7 days later. The brain was fixed 7 days after ischemia and brain sections were stained with hematoxylin and eosin for assessment of infarct size and the number of intact neurons. In separate experiments, local cerebral blood flow and the electroencephalogram were measured during ischemia and 180 min into the reperfusion period. Infarct size was assessed after 24 h.
Results: Infarct size, at either 24 h or 7 days after ischemia, was not significantly reduced in the lidocaine group. However, the number of intact neurons was significantly increased in both the ischemic penumbra and core of the lidocaine group 7 days after ischemia, compared with the vehicle group. Rats treated with lidocaine demonstrated better neurologic outcome and less weight loss (P < 0.05). Lidocaine treatment had no significant influence on local cerebral blood flow and electroencephalogram during ischemia and reperfusion.
Conclusions: Administration of a clinical antiarrhythmic dose of lidocaine, beginning 45 min after the onset of ischemia, reduces ischemic brain injury after transient focal cerebral ischemia in the rat. This indicates that delayed administration of neuroprotective agents may reduce brain damage resulting from ischemia.