Time domains of the hypoxic ventilatory response in ectothermic vertebrates.

Over a decade has passed since Powell et al. (Respir Physiol 112:123-134, 1998) described and defined the time domains of the hypoxic ventilatory response (HVR) in adult mammals. These time domains, however, have yet to receive much attention in other vertebrate groups. The initial, acute HVR of fish, amphibians and reptiles serves to minimize the imbalance between oxygen supply and demand. If the hypoxia is sustained, a suite of secondary adjustments occur giving rise to a more long-term balance (acclimatization) that allows the behaviors of normal life. These secondary responses can change over time as a function of the nature of the stimulus (the pattern and intensity of the hypoxic exposure). To add to the complexity of this process, hypoxia can also lead to metabolic suppression (the hypoxic metabolic response) and the magnitude of this is also time dependent. Unlike the original review of Powell et al. (Respir Physiol 112:123-134, 1998) that only considered the HVR in adult animals, we also consider relevant developmental time points where information is available. Finally, in amphibians and reptiles with incompletely divided hearts the magnitude of the ventilatory response will be modulated by hypoxia-induced changes in intra-cardiac shunting that also improve the match between O(2) supply and demand, and these too change in a time-dependent fashion. While the current literature on this topic is reviewed here, it is noted that this area has received little attention. We attempt to redefine time domains in a more 'holistic' fashion that better accommodates research on ectotherms. If we are to distinguish between the genetic, developmental and environmental influences underlying the various ventilatory responses to hypoxia, however, we must design future experiments with time domains in mind.

Hypoxia reduces the hypothalamic thermogenic threshold and thermosensitivity.

Hypoxia is well known to reduce the body temperature (T(b)) of mammals, although the neural origins of this response remain uncertain. Short-term hypoxic exposure causes a reduction in the lower critical temperature of the thermal neutral zone and a reduction in whole body thermal conductance of rodents, providing indirect support that hypoxia lowers T(b) in a regulated manner. In this study, we examined directly the potential for changes in central thermosensitivity to evoke the hypoxic metabolic response by heating and cooling the preoptic area of the hypothalamus (the area which integrates thermoreceptor input and regulates thermoeffector outputs) using chronic, indwelling thermodes in ground squirrels during normoxia and hypoxia (7, 10 and 12% O(2)). We found that the threshold hypothalamic temperature for the metabolic response to cooling (T(th)) of approximately 38 degrees C in normoxia was proportionately reduced in hypoxia (down to 28-31 degrees C at 7% O(2)) and that the metabolic thermosensitivity (alpha; the change in metabolic rate for any given change in hypothalamic temperature below the lower critical temperature) was comparatively reduced by 5 to 9 times. This provides strong support for the hypothesis that the fall in temperature that occurs during hypoxia is the result of a reduction in the activation of thermogenic mechanisms. The decrease in the central thermosensitivity in hypoxia, however, appears to be a critical factor in the alteration of mammalian T(b). We suggest, therefore, that an altered central thermosensitivity may provide a proximate explanation of how low oxygen and similar stressors reduce normal fluctuations in T(b) (i.e. circadian), in addition to the depression in regulated T(b).

Respiratory rhythm of brainstem-spinal cord preparations: Effects of maturation, age, mass and oxygenation.

We examined the effect of age, mass and the presence of the pons on the longevity (length of time spontaneous respiratory-related activity is produced) of brainstem-spinal cord preparations of neonatal rodents (rats and hamsters) and the level of oxygenation in the medulla respiratory network in these preparations. We found the longevity of the preparations from both species decreased with increasing postnatal age. Physical removal of the pons increased respiratory frequency and the longevity of the preparation. However, tissue oxygenation at the level of the medullary respiratory network was not affected by removal of the pons or increasing postnatal age (up to postnatal day 4). Taken together, these data suggest that the effect of removing the pons on respiratory frequency and the longevity of brainstem-spinal cord preparations with increasing postnatal age are primarily due to postnatal development and appear to be unrelated to mass or changes in levels of tissue oxygenation.