CO2 and naloxone modify sleep/wake state and activate breathing in the acute fetal lamb preparation

We studied locally anesthetized lamb fetuses (140-144 days' gestation) in utero on the day of surgical preparation (the acute preparation) to correlate sleep/wake (S/W) states with fetal breathing movements (FBM) activated by CO2 with and without endorphin displacement by naloxone. We placed electrodes for definition of S/W states, a carotid arterial catheter for injections and measurements of pressure, pHa, PaCO2 and PaO2, and intratracheal and intraesophageal catheters for measurement of FBM and esophageal motility. We recorded the onset, pattern and cessation of breathing and estimated fetal respiratory responsivity to CO2 rebreathing by the ewe using our fetal CO2 test (Moss, I.R. and Scarpelli , E.M., 1979, J. Appl. Physiol. 47: 527-531). Activation of breathing by CO2 either accompanied or followed wakefulness (W). FBM and W were sustained throughout CO2 stimulation. Cessation of breathing after the CO2 test was temporally associated with the resumption of sleep. When the test was started in active sleep (AS) and W, breathing threshold to CO2 was lower than when it was started in quiet sleep (QS). Naloxone treatment (1) resulted in activation of FBM in association with W, (2) lowered CO2 threshold as compared to that of CO2 tests entered in QS without naloxone, and (3) caused greater FBM responses to CO2 than without naloxone. These results extend previous reports from our laboratory in that they demonstrate the importance of W to normal respiratory responsivity to CO2 in the acute fetal preparation and the possible role of endorphins in respiratory control.