Implications of hypoxic hypometabolism during mammalian ontogenesis

During hypoxia, many newborn mammals, including the human infant, decrease metabolic rate, therefore adopting a strategy common to many living creatures of all classes, but usually not adopted by adult humans and other large mammals. In acute hypoxic conditions, hypometabolism largely consists in actively dropping mechanisms of thermoregulation. One implication is a decrease in body temperature. This is a safety mechanism, which favours hypoxic survival. Indeed, artificial warming during hypoxia can be counterproductive. Because carbon dioxide is an important stimulus for pulmonary ventilation, the drop in its metabolic production may tilt the balance of ventilatory control in favor of respiratory inhibition. Some experimental data support this view. In conditions of sustained hypoxia, the newborn's hypometabolism also results from a depression of tissue growth and differentiation. Some organs are affected more than others. To what extent the blunted organ growth will be compatible with survival depends not only on the severity and duration of hypoxia, but also on the timing of its occurrence during development. Upon termination of hypoxia, the newborn's metabolic rate recovers and growth resumes at higher rate. Even if body weight may be completely regained, alterations in the respiratory mechanical properties and in aspects of ventilatory control can persist into adulthood, a phenomenon not seen when the hypoxia was experienced at later stages of development. Some of the long-term respiratory effects of neonatal hypoxia are reminiscent of those observed in adult animals and humans native and living in high altitude regions. (C) 2004 Elsevier B.V. All rights reserved.