Effects of pilocarpine on breathing movements in normal, chemodenervated and brain stem-transected fetal sheep.

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Abstract
We examined the effects on fetal breathing movements (FBM) and electrocortical activity (ECoG) of the administration of pilocarpine to three groups of fetal sheep in utero: one group had peripheral chemodenervation: one group had peripheral chemodenervation and transection of the brain stem at the level of the colliculi; a third group of sham-operated animals acted as a control. Pilocarpine induced a period of FBM characterized by their high amplitude (ca. 24 mmHg) and low frequency (ca. 0.65 Hz). It also produced low-voltage ECoG. These effects were seen both in normoxia and in hypoxia. They were independent of the ECoG state in which the drug was given. In normoxia, pilocarpine-induced FBM were blocked by cholinergic antagonists which enter the central nervous system, atropine sulphate and scopolamine hydrobromide, but were either unaffected or were reduced in amplitude by antagonists with restricted access to the central nervous system, atropine methylnitrate and scopolamine methylbromide. In hypoxia, atropine sulphate and scopolamine hydrobromide again blocked FBM but now scopolamine methylbromide and atropine methylnitrate blocked the FBM in 42% of trials. In the remaining trials FBM remained virtually unchanged. No differences were observed in the effects of pilocarpine on FBM or ECoG between chemodenervated fetuses and those which had been sham-operated. In fetuses with transection of the brain stem, breathing was continuous irrespective of the ECoG. Pilocarpine increased the amplitude of FBM but did not alter the frequency of these FBM. These effects occurred both in normoxia and in hypoxia. We conclude that pilocarpine produces effects on fetal behaviour via at least two sites in the central nervous system. One site lies in the pons or medulla and is two sites in the central nervous system. One site lies in the pons or medulla and is responsible for the stimulation of FBM. The other site is above the level of the colliculi and is responsible for producing sustained low-voltage ECoG. These effects do not require the integrity of the peripheral chemoreceptors and we find no evidence to support the previous suggestion that the action of pilocarpine is via stimulation of these receptors.