Thiopental attenuates hypoxic changes of electrophysiology, biochemistry, and morphology in rat hippocampal slice CA1 pyramidal cells.
OBJECTIVE
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 micromol/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.
Wang
T
T
Department of Anesthesiology, State University of New York Health Science Center, Brooklyn, NY 11203-2098, USA.
Raley-Susman
K M
KM
Wang
J
J
Chambers
G
G
Cottrell
J E
JE
Kass
I S
IS
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001669:Biochemical Phenomena; D001671:Biochemistry; D002545:Brain Ischemia / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013874:Thiopental / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D011506:Proteins; D000255:Adenosine Triphosphate; D012964:Sodium; D013874:Thiopental; D011188:Potassium; D002118:Calcium