Mechanisms regulating hypoxic respiratory depression during fetal and postnatal life.
Selected topics in the respiratory response to acute hypoxia in the fetus and newborn are reviewed. Peripheral chemoreceptors acting through ionotrophic glutamate receptors play an important role in affecting the initial augmentation phase. Whether fall off in peripheral chemoreceptor activity contributes 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 converged 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 mediated by catecholamines acting at alpha(2)-adrenergic receptors. Tonic activity in early 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 demonstrated in respiratory-related neurons both in vivo and in vitro. The role that this process might play in the depressive phase of the hypoxic ventilatory response has not been established. In vitro experiments with isolated brain stem-spinal cord preparations or transverse brain stem slices usually involve anoxia, whereas whole animal experiments use 8-15% O(2). Therefore, caution must be exercised in attempting to construct a unifying framework from these two approaches.
Bissonnette
J M
JM
Departments of Obstetrics and Gynecology and Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA. bissonne@ohsu.edu
D000818:Animals; D005311:Fetal Hypoxia / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007231:Infant, Newborn; D012131:Respiratory Insufficiency / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology*