Regular fetal breathing induced by pilocarpine infusion in the near-term fetal lamb

We report that pilocarpine, a cholinergic drug, stimulated regular sustained breathing movements in 10 near-term fetal lambs with chronically implanted catheters in the carotid artery, jugular vein, and trachea. With increasing doses of pilocarpine (0.1-5.0 mg), there was an enhanced respiratory response as measured by the duration of continuous breathing movements (14 ± 12 min, increasing to 82 ± 50 min; mean ± SD), and the mean tracheal pressure per breath at end inspiration during the first 2 min after drug infusion (18 ± 5, increasing to 38 ± 12 mmHg). The mean pressure per breath during the control periods was 8 ± 3 mmHg. There was no significant change in the breath frequency with increasing drug dose. A similar breathing response was not seen with epinephrine, suggesting that pilocarpine does not act by stimulating release of endogenous catecholamines. There was no fetal breathing response to pilocarpine infusion in atropine-pretreated fetal lambs, suggesting that pilocarpine acts through a muscarinic mechanism. In eight acute experiments on exteriorized fetal lambs, we measured responses to pilocarpine before and after carotid sinus nerve ligation. The response to pilocarpine was abolished by sinus nerve section, suggesting possible mechanisms whereby pilocarpine may stimulate fetal breathing: the drug may increase peripheral chemoreceptor output, may sensitize the central respiratory centers to peripheral chemoreceptor input, or both.