Survival under hypoxia. Age dependence and effect of cholinergic drugs

Survival under hypoxia (5% O2; 95% N2) was tested in mice 1 day to 50-weeks-old. Survival Rate (ratio of number of animals that survived 30 min under 5% O2 to total number of animals exposed) and the time from onset of exposure until the last gasp (Survival Time) were maximum in newborn animals and decreased as a function of age. Survival Rate and Survival Time were strongly influenced by drugs affecting cholinergic transmission. Atropine decreased the high survival under hypoxia of 1-week-old mice in a dose-related manner. Physostigmine increased survival under hypoxia in mice 3 to 50-weeks-old. This effect was not related to a peripheral action of the drug since it was not mimicked by neostigmine, a cholinesterase inhibitor without central actions. Moreover, peripheral cholinergic blockade with glycopyrrolate, a quaternary cholinergic blocker, did not prevent the protective effect of physostigmine. Since atropine impairs the ability of very young mice to survive hypoxia and physostigmine improves survival at later ages, it is concluded that a central cholinergic mechanism, possibly related to blood flow regulation, plays a significant role in the acute adaptation to hypoxia.