EFFECTS OF HYPOXIA, NALOXONE AND GLUCOSE ON FETAL BREATHING MOVEMENTS, ELECTROCORTICAL ACTIVITY AND HEART RATE.
Hypoxia and hypoglycemia reduce the incidence of breathing movements in fetal sheep. This thesis investigates (1) whether other aspects of the fetal responses to these conditions are similar and, hence, whether they may act by a common mechanism, and (2) whether responses are affected by blockade of endogenous opiates. Experiments were performed on chronically catheterized fetal sheep between 119 and 141 days' gestation. Maternal hypoxia was induced for one hour using a low oxygen gas mixture (9% O(,2), 3% CO(,2), 88% N(,2)) during which time naloxone HCl (N = 10) or saline (N = 11) was continuously infused via the fetal jugular vein. Time spent breathing fell significantly during hypoxia, but fetal breath amplitude, breathing frequency during episodes of breathing, and heart rate were not significantly affected. Naloxone- and saline-infused fetuses did not differ significantly in time spent breathing, breath amplitude, breathing frequency or heart rate during hypoxia. Plasma cortisol levels in naloxone-infused fetuses during hypoxia, however, were significantly higher than controls which suggests the dosage of naloxone was sufficient to exert effects. This experiment provides no evidence that endogenous opiates are involved in the fetal breathing response to hypoxia. Following a 24 h maternal fast, time spent breathing by the fetus was significantly reduced. Breathing incidence was not returned towards normal levels by naloxone infusion (N = 6) which again suggests endogenous opiates are not involved. The effect of maternal glucose infusion on fasted human fetuses near term was studied using ultrasound (N = 6) and results were compared with glucose infusion experiments performed on fasted fetal sheep (N = 8). Raising plasma glucose levels in fetal sheep caused a significant increase in breath amplitude, heart rate and time spent breathing. Maternal glucose infusion to pregnant humans had similar effects on the fetus suggesting that glucose may have a similar mechanism of action in these two species. Dissimilarities in physiological responses to alternations in fetal glucose and oxygen levels suggest they are not mediated by a common mechanism. Furthermore, results provide no evidence that the reduction in time spent breathing by fetuses during hypoxia and fasting is mediated by endogenous opiates.