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(Stroke. 1999;30:2400-2407.)
© 1999 American Heart Association, Inc.

Original Contributions

Thiopental Attenuates Hypoxic Changes of Electrophysiology, Biochemistry, and Morphology in Rat Hippocampal Slice CA1 Pyramidal Cells

Ting Wang, MD; Kathleen M. Raley-Susman, PhD; Jun Wang, MD; Geoffrey Chambers, MS; James E. Cottrell, MD Ira S. Kass, PhD

From the Department of Anesthesiology (T.W., J.W., G.C., J.E.C., I.S.K.) and the Department of Physiology and Pharmacology (I.S.K.), State University of New York Health Science Center, Brooklyn, NY, and the Department of Biology (K.M.R.-S.), Vassar College, Poughkeepsie, NY.

Correspondence to Ira S. Kass, PhD, Anesthesiology Department, SUNY Health Science Center, 450 Clarkson Ave, Brooklyn, NY 11203-2098. E-mail ikass{at}netmail.hscbklyn.edu

Background and Purpose—Thiopental has been shown to protect against cerebral ischemic damage; however, it has undesirable side effects. We have examined how thiopental alters histological, physiological, and biochemical changes during and after hypoxia. These experiments should enable the discovery of agents that share some of the beneficial effects of thiopental.

Methods—We made intracellular recordings and measured ATP, sodium, potassium, and calcium concentrations from CA1 pyramidal cells in rat hippocampal slices subjected to 10 minutes of hypoxia with and without 600 µmol/L thiopental.

Results—Thiopental delayed the time until complete depolarization (21±3 versus 11±2 minutes for treated versus untreated slices, respectively) and attenuated the level of depolarization at 10 minutes of hypoxia (-33±6 versus -12±5 mV). There was improved recovery of the resting potential after 10 minutes of hypoxia in slices treated with thiopental (89% versus 31% recovery). Thiopental attenuated the changes in sodium (140% versus 193% of prehypoxic concentration), potassium (62% versus 46%), and calcium (111% versus 197%) during 10 minutes of hypoxia. There was only a small effect on ATP (18% versus 8%). The percentage of cells showing clear histological damage was decreased by thiopental (45% versus 71%), and thiopental improved protein synthesis after hypoxia (75% versus 20%).

Conclusions—Thiopental attenuates neuronal depolarization, an increase in cellular sodium and calcium concentrations, and a decrease in cellular potassium and ATP concentrations during hypoxia. These effects may explain the reduced histological, protein synthetic, and electrophysiological damage to CA1 pyramidal cells after hypoxia with thiopental.

Editorial Comment

Daniel J. Cole, MD, Guest Editor

Department of Anesthesiology, Loma Linda University, Loma Linda, California

Piyush M. Patel, MD, Guest Editor John C. Drummond, MD, Guest Editor

Department of Anesthesiology, University of California, San Diego, La Jolla, California

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