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We questioned whether the prevailing fetal PaO2 conditions the distribution and organization of states and responses in the fetus and newborn. To investigate this we mechanically ventilated the fetal lungs in chronically instrumented fetal sheep. Electrodes (for ECoG, ECG, EDG and EMG of diaphragm - DP, posterior neck and biceps brachii muscles), catheters (carotid artery, jugular vein, trachea and amniotic cavity), and the endotracheal tube and ventilator tubes were placed at 122-127 days GA. Experiments were begun 3 to 5 days later. Thus far 12 ventilation experiments have been carried out in 5 fetal sheep 3 to 13 days after operation. At the onset of mechanical ventilation both the FHR and fetal blood pressure (BP) decreased abruptly. Ventilatory arrhythmia appeared and its amplitude varied inversely with frequency. During ventilation with either O2 or N2 the proportion of high voltage (HV) ECoG increased. Fetal movements decreased during mild hypoxaemia, continuous tonic neck EMG was not observed. End-inspiratory bursts of DP EMG activity were observed more often during LV at normal and elevated PaO2's and did not beccne continuous in either state and it varied with PaCO2. Switching abruptly to N2 after up to 4 h of hyperoxia did not result in stimulation of phasic DP EMG. At end of experiments PaO2 and PaCO2 returned rapidly to normal fetal levels and normal fetal state-cycling was resumed. Occlusion of the umbilical cord with a constant flew of O2 through the tubes resulted in the initiation of sustained, continuous breathing in only one of 4 such trials. Conclusions: 1. Mechanical ventilation appears to increase HV state. 2. Elevation of PaO2 does not result in ‘arousal’, continuous breathing, or tonic activity in the antigravity muscles. 3. Fetal response to hypoxemia is not modified and 4. umbilical circulation remained open.

We used mechanical ventilation of the fetal lung in utero to alter fetal bleed gases and thus separate the influences of PO2 and PCO2 on the onset of extrauterine breathing. Acute experiments: 7 pregnant sheep were operated under spinal anesthesia at 140-145 days' GA. An endotracheal tube, connecting tubes to the ventilator and a carotid artery catheter were placed in the fetus under local anesthesia, and the uterus was closed. Mechanical ventilation was started using O2, N2 and CO2 to achieve the desired bleed gas pattern. After 2 h the uterus was reopened, the fetus delivered, the umbilical cord clamped and the fetus placed either in a 40°C saline bath or on a cold table. Mechanical ventilation was stopped 2 min after delivery and the time to onset of breathing was observed. Chronic: Fetal electrodes, vascular catheters, endotracheal and ventilator tubes and an inflatable occluder on the umbilical cord were placed in 2 pregnant sheep at 127 days' GA. The fetuses were ventilated in utero 5 or irore days later with O2 or N2 ± CO2. The ventilator was stopped, the cord occluded, and the time to onset of breathing (diaphragm EMG) recorded: Results are given in the table. Conclusions: 1. Cold and hypercapnia are important stimuli for the onset of neonatal respiration. 2. Hypoxia depresses breathing at this time. 3. Cord clamping without change in bleed gases does not result in breathing.