title: Central stimulation of breathing movements in fetal lambs by prostaglandin synthetase inhibitors.
abstract: In unanaesthetized fetal lambs at 125-135 days gestation in utero central acidosis caused by perfusion of the cerebral ventricular system with a solution containing less than 1 mM-HCO3- (cerebrospinal fluid (c.s.f.) pH 6.98) or intravenous 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 acetylsalicylic 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 had been sectioned in the upper pons or the inferior colliculus, sodium meclofenamate induced prolonged deep breathing. Intravenous prostaglandin E2 abolished the continuous breathing induced by meclofenamate, but not breathing movements enhanced by hypercapnia or hypoxia. It is concluded that the central chemoreceptors respond to acidosis in near-term lamb fetuses qualitatively as in adult animals. Secondly, the results suggest that prostaglandin E2 and the inhibitors of prostaglandin synthesis also act centrally in the lower pons or medulla to modulate fetal breathing.
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D001933:Brain Stem / Q000502:physiology; D002245:Carbon Dioxide / Q000502:physiology; D002552:Cerebral Ventricles; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D008469:Meclofenamic Acid / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology; D011458:Prostaglandins E / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*; D012756:Sheep / Q000502:physiology*
chemical_list: D001639:Bicarbonates; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D000643:Ammonium Chloride; D002245:Carbon Dioxide; D008469:Meclofenamic Acid; D015232:Dinoprostone; D001241:Aspirin; D010100:Oxygen