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Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
Abstract
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°C or 35.5°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°C were measured to determine a dose-response curve. At an ambient temperature of 35.5°C in which the rectal temperature of both untreated and thiopental-treated animals was maintained near 36°C, thiopental-treated animals did not survive any longer than the untreated animals. Mean survival time was 4.32 ± 0.44 minutes in the thiopental-treated animals and 5.04 ± 0.28 (± SE) in the untreated animals. Exposure to N2O shortened survival times of both groups by approximately 20%. Varying the dose of thiopental had no effect on survival times. However, when similar groups were studied in an ambient temperature of 25°C, survival time in thiopental-treated animals (11.84 ± 2.21 minutes) zoas significantly longer than in untreated animals (4.82 ± 0.37 minutes) studied simultaneously. At 25°C, exposure to N2O before and during hypoxia did not alter the survival times; i.e., thiopental-treated animals survived significantly longer (11.59 ± 1.52 minutes) than untreated animals (6.14 ±1.10 minutes) in 50% N2O, 5% O2. At an ambient temperature of 25°C untreated mice maintained rectal temperatures at 36.5°C, whereas those given thiopental had a significant decrease in body temperature to 30.4°C during the study period. In conclusion, the interference with thermoregulation produced by thiopental results in hypothermia if measures are not taken to maintain body temperature, and this hypothermia accounts for the prolonged survival observed with thiopental. Furthermore, N2O has little effect on survival in the hypoxic mouse model.
Key Words: ANESTHETICS, GASES—nitrous oxide. • ANESTHETICS, INTRAVENOUS—thiopental, pentobarbital. • BRAIN—hypoxia, protection. • HYPOTHERMIA. HYPOXIA—cerebral.
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  E. F. Cregan, J. Peeling, D. Corbett, A. M. Buchan, J. Saunders, R. N. Auer, M. Gao, D. J. Mccarthy, M. S. Eisman, T. M. Campbell, et al. [(S)-Alpha-Phenyl-2-Pyridine-Ethanamine Dihydrochloride], A Low Affinity Uncompetitive N-Methyl-D-Aspartic Acid Antagonist, Is Effective in Rodent Models of Global and Focal Ischemia J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1412 - 1424. [Abstract] [Full Text]
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