Neuroprotective effect of low-dose lidocaine in a rat model of transient focal cerebral ischemia

Background: A low concentration of lidocaine (10 muM) has been shown to reduce anoxic damage in vitro. The current study examined the effect of low-dose lidocaine on infarct size in rats when administered before transient focal cerebral ischemia. Methods: Male Wistar rats (weight, 280-340 g) were anesthetized with isoflurane, intubated, and mechanically ventilated. After surgical preparation, animals were assigned to lidocaine 2-day (n = 10), vehicle 2-day (n = 12), lidocaine 7-day (n = 13), and vehicle 7-day (n = 14) groups. A 1.5-mg/kg bolus dose of lidocaine was injected intravenously 30 min before ischemia in the lidocaine 2-day and 7-day groups. Thereafter, an infusion was initiated at a rate of 2 mg . kg(-1) . h(-1) until 60 min of reperfusion after ischemia. Rats were subjected to 90 min of focal cerebral ischemia using the intraluminal suture method. Infarct size was determined by image analysis of 2,3,5-triphenyltetrazolium chloride-stained sections at 48 h or hematoxylin and eosin-stained sections 7 days after reperfusion. Neurologic outcome and body weight loss were also evaluated. Results: The infarct size was significantly smaller in the lidocaine 2-day group (185.0 +/- 43.7 mm(3)) than in the vehicle 2-day group (261.3 +/- 45.8 mm(3), P < 0.01). The reduction in the size of the infarct in the lidocaine 7-day group (130.4 +/- 62.9 mm(3)) was also significant compared with the vehicle 7-day group (21.6.6 +/- 73.6 mm(3), P < 0.01). After 7 days of reperfusion, the rats in the lidocaine group demonstrated better neurologic outcomes and less weight loss. Conclusions: The current study demonstrated that a clinical antiarrhythmic dose of lidocaine, when given before and during transient focal cerebral ischemia, significantly reduced infarct size, improved neurologic outcome, and inhibited post-ischemic weight loss.