Mechanisms regulating hypoxic respiratory depression during fetal and postnatal life

Selected topics in the respiratory response to acute hypoxia in the fetus a nd newborn are reviewed. Peripheral chemoreceptors acting through ionotroph ic glutamate receptors play an important role in affecting the initial augm entation phase. Whether fall off in peripheral chemoreceptor activity contr ibutes to the secondary depressive phase remains controversial. A number of approaches including permanent electrolytic and reversible cooling lesions , Fos protein activation, and double-labeling immunohistochemistry has conv erged to show that an area in and around the locus ceruleus in the rostral pons affects the central depression. There is evidence that this is mediate d by catecholamines acting at a 2-adrenergic receptors. Tonic activity in e arly expiratory (postinspiratory) neurons may contribute to hypoxia-induced apneic episodes in the fetus and newborn. Desensitization of alpha-amino-3 -hydroxy-5-methylisoxazole-4-proprionic acid receptors has been demonstrate d in respiratory-related neurons both in vivo and in vitro. The role that t his process might play in the depressive phase of the hypoxic ventilatory r esponse has not been established. In vitro experiments with isolated brain stem-spinal cord preparations or transverse brain stem slices usually invol ve anoxia, whereas whole animal experiments use 8-15% O-2. Therefore, cauti on must be exercised in attempting to construct a unifying framework from t hese two approaches.