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 red uce anoxic damage in vitro. The current study examined the effect of low-do se lidocaine on infarct size in rats when administered before transient foc al cerebral ischemia. Methods: Male Wistar rats (weight, 280-340 g) were anesthetized with isoflu rane, intubated, and mechanically ventilated. After surgical preparation, a nimals were assigned to lidocaine 2-day (n = 10), vehicle 2-day (n = 12), l idocaine 7-day (n = 13), and vehicle 7-day (n = 14) groups. A 1.5-mg/kg bol us dose of lidocaine was injected intravenously 30 min before ischemia in t he 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 ischem ia. Rats were subjected to 90 min of focal cerebral ischemia using the intr aluminal suture method. Infarct size was determined by image analysis of 2, 3,5-triphenyltetrazolium chloride-stained sections at 48 h or hematoxylin a nd 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 lidocai ne 7-day group (130.4 +/- 62.9 mm(3)) was also significant compared with th e vehicle 7-day group (21.6.6 +/- 73.6 mm(3), P < 0.01). After 7 days of re perfusion, the rats in the lidocaine group demonstrated better neurologic o utcomes and less weight loss. Conclusions: The current study demonstrated that a clinical antiarrhythmic dose of lidocaine, when given before and during transient focal cerebral is chemia, significantly reduced infarct size, improved neurologic outcome, an d inhibited post-ischemic weight loss.