Central effects of an alpha 2-adrenergic antagonist on fetal lambs: a possible mechanism for hypoxic apnea

In 12 chronically-prepared fetal lambs at 128-135 days gestation, a specific alpha 2-antagonist, L-657,743 (Merck) was infused into a lateral cerebral ventricle for periods of up to 24 h. Control infusions of artificial CSF had no effect. L-657,743 at a dose rate sufficient to block the actions of injected clonidine did not affect breathing incidence or episode duration, electrocortical activity, heart rate, arterial pressure or blood gases during normoxic conditions. However, 5 out of 6 preparations receiving L-657,743 while hypoxic continued to breathe during hypoxia instead of becoming apneic as normal. The central effects of alpha 2-adrenergic blockade appear to be specific to hypoxia. It is concluded that fetal hypoxic apnea may be mediated by inhibitory alpha 2-adrenergic receptors which can be blocked by the antagonist L-657,743.