Hypoxic ventilatory decline

A much-studied respiratory depressant effect of hypoxia that is either directly or indirectly mediated by the CNS has been termed hypoxic ventilatory decline. That the ventilatory deeline with arterial hypoxia in carotid sinus nerve (CSN) denervated anesthetized eats with maintained arterial Pco2 could be reversed by electrical stimulation of the eut CSN suggests that the CSN input maintained ventilation with eoneomitant central nervous system (CNS) hypoxic depression (19a). This evidenee also suggests that hypoxic CNS inhibition is an active process (see later. Refs. 2,4,11). In adult humans and some animals, when isocapnic hypoxia is produced in a square-wave fashion, the initial enhancement of respiratory output is followed, in about 5-7 min, by a decline to approximately 50% of the peak level (20-22). The phenomenon is best observed in the imanaesthetized state, but may be seen in anesthetized animals as well. It is far more prominent in the early neonate (1-5 days in humans) where the decline in respiratory output may be to baseline or below the initial level of respiratory output. Recent studies in the neonate have demonstrated a significant genetic variation to expression of this phenomenon (23). 

In the developing rat, the facilatory effect of intermittent hypoxia has been shown to be manifest as a reduction in hypoxic ventilatory decline observed with continuous hypoxia. This phenomenon was abolished by administrations of 7-nitroindazole, an antagonist of neuronal nitric oxide (NO) synthase, leading to the conclusion that this manifestation of the facilatory effect of chronic intermittent hypoxia is mediated by enhanced expression of neuronal NO (50). On the other hand, mutant mice deficient in neuronal nitric oxide synthase manifest augmented hypoxic responses (55). Whether the locus of this modulation is peripheral or central is unclear. 

Tabata M, Kurosawa H, Kikuchi Y, Hida W, Ogawa H, Okabe S, Tun Y, Hattori T, Shirato K. Role of GABA within the nucleus tractus solitarii in the hypoxic ventilatory decline of awake rats. Am J Physiol Regul Integr Comp Physiol 2001 281 R1411-R1419. 

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