Butanediol induced ketosis increases tolerance to hypoxia in the mouse

In previous studies from our laboratory a positive correlation between elevated blood ketone levels and the survival time (ST) during hypoxia (4-5% oxygen) was observed in fasted and alloxan diabetic mice. To test the hypothesis that ketosis was somehow increasing the tolerance of mice to hypoxia, we induced ketosis by either oral (PO), intraperitoneal (IP), or intravenous (IV) 1,3-butanediol (BD). Blood betahydroxybutyrate increased from 033 ± 0.06 mM to 3.32 ± 0.08 mM for PO, 1.2 ± 0.2 mM for IV and 0.83 ± 0.15 mM for IP. BD was associated with an increase in ST to 458% (n = 19) when given PO, 217% (n = 12) by IP route, and 560% (n = 13) by the IV route. The effect of ambient temperature (T_a) on this phenomenon was evaluated at 12, 22, 32, and 34° C. At each T_aIV BD at 1.4 mmole/mouse was associated with an increase in ST to 525,559,151, and 145% of control, respectively. The absolute ST of both control and treated mice was greater at Ta of 12 and 22°C than at 32 and 34°C. Rectal temperature was continuously recorded and no differences were detected between control and treated groups just prior to hypoxia except for the group treated at T_a of 12°C. Hypoxia, however, was associated with a decrease in body temperature in each group. It is concluded that the artificial induction of ketosis by BD is associated with an increase in ST of mice exposed to hypoxia.