Hypothermia as a mechanism for drug-induced resistance to hypoxia.

A linear regression line relating the logarithm of survival time in a standard hypoxia survival test (4.6% oxygen) with hypothermia was obtained upon cooling mice by exposure to either a graded hypoxia or a cold environment. When S/BT values (log minutes survival versus body temperature) of drug-treated animals were compared with this regression line, values for many drugs lay on the line, indicating that their effects upon hypoxic survival were no greater than those expected from the concomitant hypothermia. Among the drugs whose anti-hypoxia effects were explained by their production of hypothermia were adenosine, diazepam, diphenylhydantoin, pentobarbital and physostigmine. The anti-hypoxia activity of each drug had been reported previously by other investigators and ascribed to numerous mechanisms. The present observations relating hypothermia with increased survival in hypoxia provide a rationale for the protective effect of the above drugs in animals suddenly exposed to lethal hypoxia.