Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Pharmacology DOI: 10.1159/000334274 Time Course of Acute Neuroprotective Effects of Lidocaine Evaluated by Brain Impedanciometry in the Global Ischemia Model R. Wix-Ramos A. Eblen-Zajjur Laboratorio de Neurofisiología, Departamento de Ciencias Fisiológicas, Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela significantly higher than those of rats infused with Ringer’s solution (U = 100; p = 0.000089). The decay rates were –4.97 8 1.36% min –1 (fast phase) and –1.04 8 0.3% min –1 (slow phase) with  = 672.5 s (+211.9%; p = 0.000000). These results suggest that lidocaine significantly reduced cerebral imped- ance, hence exerting a strong early anti-edema effect prob- ably by blocking voltage-activated sodium channels. Copyright © 2011 S. Karger AG, Basel Introduction Lidocaine, a well-known drug used as a local anes- thetic [1], heart antiarrhythmic [2] and antiepileptic drug [3], produces a presynaptic block by reducing Na + inflow to the cell and K + outflow by means of the blockade of Na/K channels [4–6]. Experimental data suggest that lidocaine has a poten- tial benefit in cerebral ischemia, i.e. therapeutic doses used for heart arrhythmias decrease neuronal death [7, 8] and enhance neuronal functional restoration in experi- mental models of cerebral ischemia [9, 10]. The cytopro- tective effects of lidocaine probably depend on the affect- ed brain area [11], the duration of ischemia [12] or the moment and mode of lidocaine administration [13]. Key Words Brain edema  Ischemia  Neuroprotection  Lidocaine  Impedanciometry  Sodium channel Abstract Voltage-activated sodium channels play a primary role dur- ing ischemic brain edema and thus are a pharmacological target for therapy. Lidocaine, a sodium channel blocker, was tested in male Sprague-Dawley rats anesthetized with thio- barbital (60 mg kg –1 i.p.) and perfused i.v. with Ringer’s solu- tion (n = 9) or lidocaine (0.75 mg kg –1 , n = 9, or 1.5 mg kg –1 , n = 6). Two tungsten microelectrodes were implanted in the cerebral cortex to register changes in tissue impedance in response to the voltage fall of a square wave electric pulse (100 A, 10 ms), before and after infusion of lidocaine or Ringer’s solution and during global cerebral ischemia due to a respiratory arrest induced by D-tubocurarine. Lidocaine in- fusion under normoxic conditions did not change voltage values (Mann-Whitney U = 51; p 1 0.05). In animals infused with Ringer’s solution, the voltage fall induced by global ce- rebral ischemia was fast for 8 min at –8.0 8 2.3% min –1 followed by a slow decay at –0.96 8 0.17% min –1 . The time constant of voltage decay ( ) was 215.6 s (F = 547.4; p = 0.00000). Voltage values of lidocaine-infused animals were Received: August 18, 2011 Accepted after revision: October 3, 2011 Published online: $$$ A. Eblen-Zajjur Laboratorio de Neurofisiología, Departamento de Ciencias Fisiológicas Facultad de Ciencias de la Salud, Universidad de Carabobo, PO Box 3798 El Trigal, Valencia $$$ (Venezuela) Tel. +58 $$$ , E-Mail aeblen  @  uc.edu.ve © 2011 S. Karger AG, Basel 0031–7012/11/0000–0000$38.00/0 Accessible online at: www.karger.com/pha PHA334274.indd 1 PHA334274.indd 1 08.11.2011 16:03:08 08.11.2011 16:03:08