Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood.

Sleep-disordered breathing and oxidative stress in preclinical chronic mountain sickness (excessive erythrocytosis).

Chronic mountain sickness (CMS) is considered to be a loss of ventilatory acclimatization to high altitude (>2500m) resulting in marked arterial hypoxemia and polycythemia. This case-control study explores the possibility that sleep-disordered breathing (SDB) and associated oxidative stress contribute to the etiology of CMS. Nocturnal respiratory and [Formula: see text] patterns were measured using standard polysomnography techniques and compared between male high-altitude residents (aged 18-25) with preclinical CMS (excessive erythrocytosis (EE), n=20) and controls (n=19).

Potential role for elevated maternal enzymatic antioxidant status in Andean protection against altitude-associated SGA.

Oxidative stress has been implicated in the uteroplacental ischemia characteristic of preeclampsia and small-for-gestational-age (SGA) birth, both of which are more common at high (>2500 m) vs low altitude. Since Andeans are protected relative to Europeans from the altitude-associated rise in SGA, we asked whether alterations in maternal antioxidant status or oxidative stress contributed to their protection. Enzymatic antioxidant (erythrocyte catalase and superoxide dismutase [SOD]) activity and a plasma marker of lipid peroxidation (8-iso-PGF2α) were measured during pregnancy and in the non-pregnant state in Andean or European residents of low (400 m) or high altitude (3600-4100 m).

Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study.

The pathophysiology of acute mountain sickness (AMS) is unknown. One hypothesis is that hypoxia induces biochemical changes that disrupt the blood-brain barrier (BBB) and, subsequently, lead to the development of cerebral edema and the defining symptoms of AMS. This study explores the relationship between AMS and biomarkers thought to protect against or contribute to BBB disruption.

High altitude during pregnancy.

One of the greatest physiologic challenges during pregnancy is to maintain an adequate supply of oxygenated blood to the uteroplacental circulation for fetal development. This challenge is magnified under conditions of limited oxygen availability. High altitude impairs fetal growth, increases the incidence of preeclampsia, and, as a result, significantly increases the risk of perinatal and/or maternal morbidity and mortality.

Identifying positive selection candidate loci for high-altitude adaptation in Andean populations.

High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano.

Evolutionary adaptation to high altitude: a view from in utero.

A primary focus within biological anthropology has been to elucidate the processes of evolutionary adaptation. Frisancho helped to move anthropology towards more mechanistic explanations of human adaptation by drawing attention to the importance of the functional relevance of human variation. Using the natural laboratory of high altitude, he and others asked whether the unique physiology of indigenous high-altitude residents was the result of acclimatization, developmental plasticity, and/or genetic adaptation in response to the high-altitude environment.

Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth.

The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.

Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude.

Reduced uteroplacental blood flow is hypothesized to play a key role in altitude-associated fetal growth restriction. It is unknown whether reduced blood flow is a cause or consequence of reduced fetal size. We asked whether determinants of uteroplacental blood flow were altered prior to reduced fetal growth and whether vasoactive and/or angiogenic factors were involved.

High-altitude ancestry protects against hypoxia-associated reductions in fetal growth.

Objective: The chronic hypoxia of high-altitude (>/=2500 m) residence has been shown to decrease birth weight in all populations studied to date. However, multigenerational high-altitude populations appear protected relative to newcomer groups. This study aimed to determine whether such protection exists independently of other factors known to influence fetal growth and whether admixed populations (ie, people having both high- and low-altitude ancestry) show an intermediate level of protection.