Excitatory Effects of CNS Hypoxia

Manifestations of Centraiiy Mediated Hypoxic Respiratory Excitation 

In the intact animal, there are a number of phenomena that are thought to represent either direct or indirect CNS-mediated hypoxic excitation of respiratory ouQ)ut. It has been shown in several species, although not in humans, that there is a full recovery of the ventilatory response to acute hypoxia following peripheral chemodenervation in about 21-90 days (41-46). This does not appear to refleet return of peripheral chemoreceptor function but, rather, a considerable reorganization of the central hypoxia chemoreflex pathways (46). 

As noted above, in the unanesthetized animal, acute systemic hypoxia immediately following chemodenervation or inhalation of carbon monoxide (to produce systemic hypoxia without stimulating arterial chemoreceptors) elicits a tachpneic response. Dillon and Waldrop (47), using whole-cell patch recording in tissue slices, have shown that neurons in the caudal hypothalamus depolarize and increase firing rates when exposed to hypoxia. In addition, direct stimulation of this region in the intact animal elicits tachypnea. They propose that this site is the locus of the tachypneic response to hypoxia in the acutely denervated animal. 

In recent years much attention has been paid to the modification of CNS processing of chemoreception (central plasticity ) brought about by repeated short bouts of hypoxia (48-53). Not all findings have been consistent, perhaps owing to the use of different experimental paradigms and because the developmental phase of the experimental animal seems to be an important variable (for recent review see Ref. 54). 

In adult humans and animals, chronic intermittent hypoxia has a facilatory effect manifest by enhanced responses to acute hypoxia (52,53), which appears to involve a serotonin-dependent mechanism (53). Both facilatory and inhibitory effects have been observed in neonatal animals (48,50,51). In addition, state of arousal has been shown to be a factor in the response to repetitive hypoxia in the neonate. In newborn lambs, for example, repetitive hypoxia rapidly became ineffective as a stimulus during active sleep but retained its responses during quiet sleep (49). 

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