A placental extract inhibits breathing induced by umbilical cord occlusion in fetal sheep.

Umbilical cord occlusion in the presence of adequate oxygenation induces continuous breathing and arousal in the chronic unanesthetized fetal sheep preparation. The mechanism responsible for this is unknown. We hypothesized that if a placental factor is responsible for the inhibition of breathing in the fetus, the administration of a placental extract while the fetus is breathing continuously after cord occlusion should reverse these changes. Thus, at about 10 min after the induction of continuous breathing by cord occlusion, we administered a placental extract and three subfractions separated by ultrafiltration to 14 chronically instrumented fetal sheep at 133 +/- 1 day gestation. The Krebs solution in which the placental extract was prepared was used as control. Within two minutes of the infusion of the whole placental extract in the carotid artery of the fetus, breathing output (integral of EMGdi x f) diminished in all experiments and was completely abolished in 15/17 (88%). Krebs solution had no effect on breathing. The infusion of subfractions of different molecular weight showed that the inhibition was primarily related to the subfraction between 3.5 and 10 kD. There were no significant changes in blood gas tensions, pH, blood pressure, and heart rate associated with the infusions of the extracts. The ECoG switched from low to high voltage in the majority of the experiments using whole extract and the subfraction 3.5 to 10 kD. These findings suggest that a placental factor, probably a peptide with a molecular weight between 3.5 and 10 kD, inhibits breathing in fetal life.