The hypoxic mouse model for screening cerebral protective agents: a re-examination.
The hypoxic mouse model, in which mice are subjected to an atmosphere of 5% O2 in nitrogen, has been used to screen anesthetics for possible cerebral protection by measuring their ability to prolong survival in mice exposed to hypoxia. Although prolonged survival time in this model is primarily due to a decreased cerebral metabolic rate produced by a specific anesthetic, results can also be influenced by body temperature, dose of anesthetic, and ventilatory or circulatory depression produced by the anesthetic. Using the hypoxic mouse model, the effects of thiopental in conjunction with changes in ambient temperature, changes in thiopental dose, and the presence or absence of nitrous oxide (N2O) were examined. Survival times were measured in eight groups of animals, either untreated animals or animals pretreated with 100 mg/kg thiopental intraperitoneally; exposed to hypoxia in the presence or absence of N2O; at ambient temperatures of either 25 degrees C or 35.5 degrees C. Survival times of seven additional groups of mice, either untreated or treated with doses of 50, 60, 70, 80, 90 or 120 mg/kg thiopental intraperitoneally, exposed to hypoxia in an ambient temperature of 35.5 degrees C were measured to determine a dose-response curve. At an ambient temperature of 35.5 degrees C in which the rectal temperature of both untreated and thiopental-treated animals was maintained near 36 degrees C, thiopental-treated animals did not survive any longer than the untreated animals. Exposure to N2O shortened survival times of both groups by approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905.
D000777:Anesthetics; D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000187:drug effects*; D004341:Drug Evaluation; D000860:Hypoxia / Q000378:metabolism / Q000401:mortality*; D051379:Mice; D008954:Models, Biological; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010101:Oxygen Consumption; D013874:Thiopental / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D014692:Ventilation-Perfusion Ratio
D000777:Anesthetics; D013874:Thiopental; D009609:Nitrous Oxide