Human hypoxia acute responses

Figure 5.1. The interplay between time and adaptational options occurs in human as well as in animal evolution of physiological systems. The acute and acclimation effects on human hypoxia response physiology can be readily evaluated. However, adaptations requiring generations of time of course cannot be studied by direct manipulations in humans. All workers in this area therefore rely upon comparing human lineages adapted to hypobaric hypoxia in different regions of the world and for different time periods. Two such groups that have extensively studied in this manner are Quechuas and Aymaras from the Andes, and Sherpas and Tibetans from the Himalayas. See chapter 1 for further discussion of time and adaptation options.

Acute high-altitude studies of both human and animal models indicate that hypoxia defenses are initiated by several oxygen sensing, signal transduction pathways. For convenience, these have been summarized as five general hypoxia response systems (figure 5.2(A)-(E) ... 

Pialoux V, Hanly PJ, Foster GE, et al. Effects of exposure to intermittent hypoxia on oxidative stress and acute hypoxic ventilatory response in humans. Am /Respir Crit Care Med. 2009 180(10) 1002-1009. 

Epoetin alpha (e.g., Epogen) Epoetin alpha is recombinant human erythropoietin. Erythropoetin, which is synthesized in the kidney in response to hypoxia or anemia, stimulates erythropoiesis. Epoetin alpha is indicated for anemia in patients with chronic renal failure, because these patients are unable to synthesize erythropoetin to correct the anemia. Additional uses include correcting zidovudine (AZT)-induced anemia in HIV-infected patients and chemotherapy-induced anemia in cancer patients (unlabelled use). Several weeks of therapy are required before the hematocrit levels rise, therefore, this drug cannot replace transfusions for the acute treatment of severe anemia. Epoetin alpha should not be used in patients with uncontrolled hypertension because the elevation in hematocrit may exacerbate hypertension. 

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). 

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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