Physiological and genomic consequences of intermittent hypoxia - Invited review: Respiratory plasticity following intermittent hypoxia: developmentalinteractions

Intermittent hypoxia (IH) is the most frequent form of hypoxia occurring in the developing mammal. On one hand, the maturational process of neural, me chanical, pulmonary, and sleep state-dependent factors will favor the occur rence of IH during early postnatal life. On the other hand, it has also bec ome clear that hypoxia, even when short lasting, can modify subsequent resp iratory responses to hypoxia and induce a variety of genes whose consequenc es will persist for much longer periods than the duration of the hypoxic st imulus itself, i.e., functional and adaptive plasticities. The dynamic inte ractions between the overall duration and recurring frequency of IH, the se verity of IH, and the level of neural maturity at the time of IH will modif y the ventilatory, metabolic, and cardiovascular responses to hypoxia. We p ropose that the earlier IH will occur in the developmental course the more likely that the physiological responses to an ulterior hypoxic challenge wi ll be altered even into adulthood. At this point in time, a critical examin ation of the field would suggest that the shortterm alterations of the hypo xic ventilatory response (HVR) of the developing mammal to IH are qualitati vely similar to those of the adult and display a biphasic pattern, namely, initial enhancement of the HVR followed by a reduction in HVR. However, the short- and long-term effects of IH on the modulation of neurotransmitter r elease, receptor binding and expression, intracellular signaling cascades, transcriptional regulation, and gene expression as a function of animal mat urity are almost completely unknown. Further delineation of such complex re sponses to IH may permit the formulation of interventional strategies aimin g at reducing the overall vulnerability of the young infant and child to ap nea and sudden death.