Suppression of energy requirement by lidocaine in the ischemic mouse brain.

Abstract

Effects of lidocaine on parameters of membrane functional integrity were investigated in the mouse brain. Changes in the direct-current potential shift in the cerebral cortex provoked by decapitation ischemia were compared in animals given lidocaine (0.05, 0.25, or 1.0 micromol, intracerebroventricular) or saline 15 minutes before ischemia. The brain content of adenosine 5'-triphosphate (ATP) was measured in animals subjected to 0, 0.5, 1, and 2 minutes of decapitation ischemia, and the effect of preischemic administration of lidocaine (0.25 micromol, intracerebroventricular) was evaluated. Na+, K+-ATPase, and Ca2+-ATPase activity was evaluated in brains pretreated with lidocaine (0.25 micromol, intracerebroventricular) or saline 15 minutes before decapitation. Changes in the intracellular Ca concentration ([Ca2+]i) were evaluated in hippocampal slices and the effects of lidocaine (50, 100, or 400 microM) were assessed in the hippocampal CA1 field and dentate gyrus at pH 7.4 and pH 6.8 every 60s for a duration of 50 min. The preischemic administration of lidocaine (1.0 and 0.25 micromol) delayed the onset of anoxic depolarization to 49 seconds and 44 seconds, respectively, as compared with that in the saline group at 27 seconds. Lidocaine maintained ATP levels higher than those in corresponding saline groups, values being 165% after 1 minute of ischemia and 212% after 2 minutes, respectively. Lidocaine did not affect Na+, K+-ATPase, and Ca2+-ATPase activity. Lidocaine did not affect changes in the [Ca2+]i in either area at either pH. The findings may suggest that lidocaine maintains the energy level by delaying depolarization in neurons, which may contribute to removal of cytosolic Ca2+ in ischemic states.

• Authors: Frank-Joachim Seyfried, Naoto Adachi, Tatsuru Arai
• Journal: Journal of neurosurgical anesthesiology (J Neurosurg Anesthesiol) Vol. 17 Issue 2 Pg. 75-81 (Apr 2005) ISSN: 0898-4921 [Print] United States
• PMID: 15840992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Local
• Adenosine Diphosphate
• Adenosine Triphosphate
• Lidocaine
• Calcium-Transporting ATPases
• Sodium-Potassium-Exchanging ATPase
• Calcium

Topics

• Acidosis (metabolism)
• Acidosis, Lactic (metabolism)
• Adenosine Diphosphate (metabolism)
• Adenosine Triphosphate (metabolism)
• Anaerobiosis
• Anesthetics, Local (pharmacology)
• Animals
• Brain Ischemia (metabolism)
• Calcium (metabolism)
• Calcium-Transporting ATPases (metabolism)
• Energy Metabolism (drug effects)
• Lidocaine (pharmacology)
• Male
• Mice
• Sodium-Potassium-Exchanging ATPase (metabolism)