Failure of pre-ischemic lidocaine administration to ameliorate global ischemic brain damage in the rat.
The cerebral protective effects of lidocaine were evaluated using a rat model of severe (near-complete) global ischemia produced by 10 min of bilateral carotid artery occlusion combined with systemic hypotension (MAP 45-55 mmHg). Prior to the induction of ischemia, 16 rats were given incremental doses of lidocaine intravenously until EEG slowing with sharp wave activity became evident. An equal number of rats (controls) received saline prior to the ischemic insult. Normoxia, normocapnia, and normothermia were maintained at all times. Following ischemia, the animals were allowed to recover. At 1.5 h post-ischemia, eight rats from each treatment group were reanesthetized, and regional brain water content was assessed gravimetrically. Brain specific gravity was significantly reduced from normal values in both treatment groups, and was unaltered by pre-ischemic lidocaine administration. Seven days post-ischemia, the remaining animals were reanesthetized; the brains were formalin fixed and processed for identification of irreversibly injured neurons in the hippocampus, neocortex, and caudate nucleus. Saline-treated rats displayed 75 +/- 4% (mean +/- SD) dead cells in the hippocampus (CA1); lidocaine-treated rats had similar injury (78 +/- 7%). In the neocortex and caudate nucleus, injury was graded as moderate, and no difference in severity could be distinguished between the treatment groups. The authors conclude that pre-ischemic treatment with maximal sub-epileptogenic doses of lidocaine had no effect on either early post-ischemic cerebral edema or delayed neuronal necrosis in this rat model of near-complete global ischemia.
Warner
D S
DS
Department of Anesthesiology, University of Iowa Hospitals and Clinics, Iowa City 52242.
Godersky
J C
JC
Smith
M L
ML
D000818:Animals; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000517:prevention & control; D002545:Brain Ischemia / Q000517:prevention & control*; D008012:Lidocaine / Q000627:therapeutic use*; D008297:Male; D009336:Necrosis; D011292:Premedication; D051381:Rats
D008012:Lidocaine