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Resilience and Survival in Extreme Environments 147

who developed HAPE. These individuals were more likely to be positive for

the antigens HLA-DR6 and HLA-DQ4 compared with their non-HAPE
counterparts. Mairbaurl et al. (2003) considered the hypothesis that
HAPE susceptibility is related to a diminished expression of transporters
involved in alveolar fluid clearance. Mairbaurl et al. observed signifi cant

decreases in several factors that control fluid clearance (mRNA of Na-K-

ATPase, cystic fibrosis transmembrane regulator [CFTR], and β-actin)
among individuals who developed HAPE during a 2-day exposure to
4559 m altitude. However, the authors were unable to take measures that
might have defi nitively established these factors as relevant to the patho-
physiology of HAPE.

The renin–angiotensin system is certainly involved in the pathophysi-
ology of pulmonary hypertension and in the development of HAPE. Hotta
et al. (2004) measured angiotensin-converting enzyme (ACE) and angioten-
sin II type 1 receptors in climbers who did and did not develop HAPE. Con-

sistent with earlier findings (Dehnert et al., 2002), climbers who suff ered from

HAPE did not diff er significantly from their healthy counterparts in terms
of the polymorphism of the ACE gene. However, investigators observed sig-
nifi cant differences in single nucleotide polymorphisms of the angiotensin II

type 1 receptor gene (Hotta et al., 2004).
Populations that have lived at high altitudes for many generations dem-

onstrate genetic adaptations. These adaptations have been observed and
studied for decades among Andean Quechua Indians. Parallel but diff erent
adaptations have been observed in Himalayan Sherpas (Howald & Hoppeler,

2003). There is still much yet to discover about the genomic basis of adapta-
tion to altitude. Moore, Armaza, Villena, and Vargas (2000) identifi ed sev-
eral differences in Tibetans, including better neonatal oxygenation, greater

ventilation and hypoxic ventilatory response, lower hemoglobin concentra-
tions, and reduced susceptibility to chronic altitude sickness. Beall (2000)
speculates that such diff erences reflect a “microevolutionary” process

whereby geographically separate populations responded diff erently when
they ascended on altitude for permanent residence. The primary fi nding

of importance here is that highland natives adapt to altitude by decreasing
oxidative capacity, rather than by increasing oxidative capacity to manage
reduced oxygen availability. As a result, highland natives have an excep-
tional ability to perform at high altitudes. Sherpas may also be protected by
intrinsic antioxidant mechanisms (Howald & Hoppeler, 2003).

With or without the benefit of acclimatization or adaptation, the human
body is simply unable to tolerate hypoxia at altitudes higher than 8000 m.
Lasting neurological damage has been reported in highly motivated moun-
taineers who have pushed to the limits of human tolerance (Silber, 2000;
West, 1989).

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