Central stimulation of breathing movements in fetal lambs by prostaglandin synthetase inhibitors.

Abstract

In unanesthetized fetal lambs at 125-135 days gestation in utero central acidosis caused by perfusion of the cerebral ventricular system with a solution containing < 1 mM-HCO3- (C.S.F.) pH 6.98) or i.v. infusion of ammonium chloride (C.S.F. pH 7.1) produced an increase in the depth and frequency of episodic breathing but no change in electrocortical activity, heart rate or arterial pressure. Administration of prostaglandin synthetase inhibitors, sodium meclofenamate (0.8-10 mg/kg i.v. or 0.6-2.6 mg/kg intracerebrally) or acetylsalicyclic acid (6.7 mg/kg i.v.) caused prolonged episodes of fetal breathing during low and high voltage electrocortical activity, with a large increase in breath amplitude. Blood gas values, heart rate, blood pressure, electrocortical activity and eye movements were not altered. In fetuses whose brain stems were sectioned in the upper pons or the inferior colliculus, sodium meclofenamate induced prolonged deep breathing. I.v. prostaglandin E2 abolished the continuous breathing induced by meclofenamate, but not breathing movements enhanced by hypercapnia or hypoxia. Apparently, the central chemoreceptors respond to acidosis in near-term lamb fetuses qualitatively as in adult animals. Prostaglandin E2 and the inhibitors of prostaglandin synthesis also evidently act centrally in the lower pons or medulla to modulate fetal breathing.