Generation and regulation of breathing in utero: fetal CO2 response test

Breathing responses to increasing fetal arterial CO2 pressure (PaCO2) were measured in 15 mature fetal lambs in utero during hyperoxic CO2 rebreathing in the ewe. Fetal breathing was expressed as 1) respiratory drive (RD), i.e., the early slope of intratracheal pressure during inspiration, and 2) ventilation equivalent (VEq), i.e., the product of intratracheal pressure and frequency of breathing. RD and VEq increased linearly with increasing PaCO2. CO2 threshold beyond which apneic fetuses started breathing was higher than the extrapolated CO2 threshold in spontaneously breathing fetuses. Afferent sciatic nerve stimulation, which induced regular breathing in apneic fetuses, lowered their CO2 threshold but did not alter their sensitivity to CO2. Naloxone resulted in initiation of fetal breathing, decreased CO2 threshold, and increased sensitivity to CO2. These studies demonstrate that respiratory center responsivity can be quantified in the lamb fetus in utero, that nonspecific somatic stimulation lowers fetal breathing threshold to CO2, and that endogenous opioid peptides could participate in the physiological suppression of breathing in fetal life.