Chronic hypoxia intermittent

Savransky V, Nanayakkara A, Vivero A, et al. Chronic intermittent hypoxia predisposes to liver injury. Hepatology. 2007 45(4) 1007-1013. 

Savransky V, Reinke C, Jun J, et al. Chronic intermittent hypoxia and acetaminophen induce synergistic liver injury in mice. Exp Physiol. 2009 94(2) 228-239. 

Di Giulio C, Bianchi G, Cacchio M, Artese L, Piccirilli M, et al. 2006. Neuroglobin, a new oxygen binding protein is present in the carotid body and increases after chronic intermittent hypoxia. Berlin Springer-Verlag pp. 15-19. 

Numerous physiological and clinical conditions are associated with hypoxemia, ranging from acute episodes of hypoxia (asthma) to chronic sustained hypoxia (ascent to high altitude, COPD) or chronic intermittent hypoxia (OSA). During these episodes of hypoxia, activation of both peripheral and central sites likely occurs, with the net response refiecting a coordination of these drives by the pattern-generating network. 

In addition to the potential for adaptations in the eentral oxygen sensors during chronic sustained hypoxia, it is likely that adaptations occur in these central cardiorespiratory oxygen sensors during chronic intermittent hypoxia as well. Of particular interest is understanding what the impact of chronic intermittent hypoxia is on the cardiorespiratory responses and the particular adaptive or maladaptive changes in the cellular processing of the hypoxic stimulus (128-130). For example, how much of the clinical sequalae associated with OSA can be attributed to the responses to hypoxia ... 

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). 

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. 

Ling L, Fuller DD, Bach KB, Kinkead R, Olson EB, Jr, Mitchell GS. Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. JNeurosci 2001 21 5381-5388. 

Lahiri S, DiGiulio C, Roy A. Lessons from chronic intermittant and sustained hypoxia at high altitudes. Respir Physiol 2002 130 223-233. 

---