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Journal of Pharmacology and Experimental Therapeutics 1975-Jun

Influence of carbon monoxide, hypoxic hypoxia or potassium cyanide pretreatment on acute carbon monoxide and hypoxic hypoxia lethality.

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J M Winston
R J Roberts

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Pre-exposure of mice to 500 or 1000 ppm of carbon monoxide (CO) for 4 hours resulted in a significant decrease in lethality induced by exposure to 2500 ppm of CO 24 hours later. Pre-exposure to CO had no effect on lethality induced by hypoxic hypoxia (low inspired O2 tension) or potassium cyanide (KCN). Pre-exposure to 10% O2 for 4 hours significantly decreased lethality induced 24 hours later by CO or 7% O2 exposures lethality induced 24 hours later by CO or 7% O2 exposures but had no effect on KCN-induced lethality. Pretreatment with a nonlethal dose of KCN had no significant effect on lethality induced 24 hours later by exposure to CO (2500 ppm), 7% O2 or KCN. The alterations in CO lethality were not associated with alterations in carboxyhemoglobin levels. Studies of oxygen consumption and indicators of oxygen delivery to tissues (P50 and red blood cell 2,3-diphosphoglycerate) failed to provide any evidence of pretreatment alteration. Examination of blood lactate, pyruvate and lactate/pyruvate ratios in control and pre-exposed mice after a short exposure to 2500 ppm of CO showed significantly lower lactate and lactate/pyruvate ratios in the pre-exposed mice as compared to controls. These data suggest that animals pre-exposed to 1000 ppm of CO and 10% O2 are less hypoxic than non-pre-exposed animals even through their oxygen delivery system is unchanged.

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