Spanish genetic admixture is associated with larger V̇<scp>o</scp><sub>2 max</sub>decrement from sea level to 4,338 m in Peruvian Quechua

Brutsaert, Tom D.; Parra, Esteban J.; Shriver, Mark D.; Gamboa, Alfredo; Palacios, José; Rivera, María M.; Rodriguez, Ivette; León‐Velarde, Fabiola

doi:10.1152/japplphysiol.01088.2002

Cited by 52 publications

(62 citation statements)

References 47 publications

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“…In a relatively large study, Tibetans born and raised at high altitude (Tibetan descent) had higher near-maximal exercise Sa O 2 than Chinese residents at the same altitude (Chinese descent) who were moved there in adulthood and had lived at high altitude for Ͼ1 yr (27). A previously mentioned study (3) from La Paz finding a more efficient V E/V O 2 in residents of Aymara/Quechua than in individuals of European/North American descent also showed that the difference disappeared when the subjects of Indian descent were compared with two groups of European/North American immigrants born or arriving in La Paz before 18 yr of age (3). A potentially confounding factor would be non-Indian gene admixture in the high-altitude natives.…”

Section: Discussionmentioning

confidence: 92%

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

Lundby¹,

Calbet²,

Hall³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

113

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-We aimed to test effects of altitude acclimatization on pulmonary gas exchange at maximal exercise. Six lowlanders were studied at sea level, in acute hypoxia (AH), and after 2 and 8 wk of acclimatization to 4,100 m (2W and 8W) and compared with Aymara high-altitude natives residing at this altitude. As expected, alveolar PO2 was reduced during AH but increased gradually during acclimatization (61 Ϯ 0.7, 69 Ϯ 0.9, and 72 Ϯ 1.4 mmHg in AH, 2W, and 8W, respectively), reaching values significantly higher than in Aymaras (67 Ϯ 0.6 mmHg). Arterial PO 2 (PaO 2 ) also decreased during exercise in AH but increased significantly with acclimatization (51 Ϯ 1.1, 58 Ϯ 1.7, and 62 Ϯ 1.6 mmHg in AH, 2W, and 8W, respectively). Pa O 2 in lowlanders reached levels that were not different from those in high-altitude natives (66 Ϯ 1.2 mmHg). Arterial O 2 saturation (SaO 2 ) decreased during maximum exercise compared with rest in AH and after 2W and 8W: 73.3 Ϯ 1.4, 76.9 Ϯ 1.7, and 79.3 Ϯ 1.6%, respectively. After 8W, Sa O 2 in lowlanders was not significantly different from that in Aymaras (82.7 Ϯ 1%). An improved pulmonary gas exchange with acclimatization was evidenced by a decreased ventilatory equivalent of O2 after 8W: 59 Ϯ 4, 58 Ϯ 4, and 52 Ϯ 4 l⅐ min ⅐ l O2 Ϫ1 , respectively. The ventilatory equivalent of O2 reached levels not different from that of Aymaras (51 Ϯ 3 l⅐ min ⅐ l O2 Ϫ1 ). However, increases in exercise alveolar PO2 and PaO 2 with acclimatization had no net effect on alveolar-arterial PO2 difference in lowlanders (10 Ϯ 1.3, 11 Ϯ 1.5, and 10 Ϯ 2.1 mmHg in AH, 2W, and 8W, respectively), which remained significantly higher than in Aymaras (1 Ϯ 1.4 mmHg). In conclusion, lowlanders substantially improve pulmonary gas exchange with acclimatization, but even acclimatization for 8 wk is insufficient to achieve levels reached by high-altitude natives. chronic hypoxia; acute normoxia; ventilation HIGH-ALTITUDE NATIVES from North America (8), Tibet (27), and South America (19, 25) have unique pulmonary gas transport abilities, maintaining low alveolar-arterial PO 2 difference (A-aPO 2 ) at maximum exercise, thus preserving arterial PO 2 (Pa O 2 ) and saturation (Sa O 2 ). This confers a clear advantage to high-altitude natives compared with the lowlanders during exercise at altitude. Although pulmonary gas exchange in high-altitude natives has been the focus of several studies, only a few reports exist on pulmonary gas exchange during exercise in lowlanders acclimatized to high altitude. The classic study by Dempsey et al. (8) investigated lowlanders acclimatized to 3,100 m for 4, 21, and 45 days and compared these with firstto third-generation high-altitude residents. Despite the limited number of subjects analyzed (4 lowlanders), a comparatively low exercise A-aPO 2 was observed in the natives, whereas the lowlanders seemed to reduce their exercise A-aPO 2 as the altitude exposure was prolonged (8). More recently, Calbet et al. (5, 6) also found reduced exercise A-aPO 2 in seven lowlanders after chronic (9 wk) compared ...

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Section: Discussionmentioning

confidence: 92%

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

Lundby¹,

Calbet²,

Hall³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

113

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“…Exercise differences in pulmonary gas exchange between altitude natives and lowlanders are also the result of genetic selection over millennia, since secondgeneration Tibetan lowlanders acclimatize to high altitude more quickly than Caucasians (Marconi et al, 2004). Thus both genetic and developmental adaptations contribute to the enhanced pulmonary gas exchange efficiency in altitude natives, with a likely predominance of the genetic over the developmental component (Brutsaert et al, 2003;Marconi et al, 2004).…”

Section: Effects Of Altitude Acclimatization On Pulmonary Gas Exchangementioning

confidence: 99%

Air to Muscle O₂Delivery during Exercise at Altitude

Calbet

Lundby

2009

High Altitude Medicine & Biology

106

100

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Calbet, José, and Carsten Lundby. High Alt. Med. & Biol. 10.123-134, 2009.-Hypoxia-induced hyperventilation is critical to improve blood oxygenation, particularly when the arterial Po 2 lies in the steep region of the O 2 dissociation curve of the hemoglobin (ODC). Hyperventilation increases alveolar Po 2 and, by increasing pH, left shifts the ODC, increasing arterial saturation (Sao 2 ) 6 to 12 percentage units. Pulmonary gas exchange (PGE) is efficient at rest and, hence, the alveolar-arterial Po 2 difference (Pao 2 ÀPao 2 ) remains close to 0 to 5 mm Hg. The (Pao 2 ÀPao 2 ) increases with exercise duration and intensity and the level of hypoxia. During exercise in hypoxia, diffusion limitation explains most of the additional Pao 2 ÀPao 2 . With altitude, acclimatization exercise (Pao 2 ÀPao 2 ) is reduced, but does not reach the low values observed in high altitude natives, who possess an exceptionally high DLo 2 . Convective O 2 transport depends on arterial O 2 content (Cao 2 ), cardiac output (Q), and muscle blood flow (LBF). During whole-body exercise in severe acute hypoxia and in chronic hypoxia, peak Q and LBF are blunted, contributing to the limitation of maximal oxygen uptake (Vo 2max ). During small-muscle exercise in hypoxia, PGE is less perturbed, Cao 2 is higher, and peak Q and LBF achieve values similar to normoxia. Although the Po 2 gradient driving O 2 diffusion into the muscles is reduced in hypoxia, similar levels of muscle O 2 diffusion are observed during small-mass exercise in chronic hypoxia and in normoxia, indicating that humans have a functional reserve in muscle O 2 diffusing capacity, which is likely utilized during exercise in hypoxia. In summary, hypoxia reduces Vo 2max because it limits O 2 diffusion in the lung.

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“…Exercise studies were conducted in Cerro de Pasco. Previously published maximal oxygen consumption data from Lima are also presented here to demonstrate that cardiorespiratory fitness was not a confounding factor relative to the respiratory control studies (5). Again, subjects were tested in Cerro de Pasco after 10 -12 h of exposure to 4,338 m. To begin, V O2 and SaO 2 were measured at rest (5 min) with the subject seated.…”

Section: Methodsmentioning

confidence: 94%

“…This approach has been used recently to reveal ancestry associations with some complex disease traits in admixed populations (15,23,41,72), as well as ancestry associations with the V O 2 max decrement in Quechua (5). Admixture may also be exploited in future studies to map genes involved in complex traits or diseases that have a genetic basis and are known to differ significantly between parental populations using an approach known as admixture mapping (28,48).…”

Section: Discussionmentioning

confidence: 99%

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives

Brutsaert

Parra

Shriver

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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-Andean highaltitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O 2 saturation (SaO 2 ). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10 -12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r ϭ Ϫ0.36, P ϭ 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r ϭ Ϫ0.50, P ϭ 0.005) and ventilatory equivalent (VE/V O2, r ϭ Ϫ0.51, P ϭ 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the wellknown blunted HVR (10,35,36,57,62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua. genetic markers; admixture; arterial saturation; Andes THE HYPOXIC VENTILATORY RESPONSE (HVR) is the increase in ventilation (VE) that occurs when arterial blood oxygen partial pressure PO 2 decreases (60). Typically, on acute exposure to hypoxia, VE increases to a peak in the first few minutes and thereafter declines somewhat to a level higher than control depending on the level of hypoxia (13,49). This attenuation of VE has been termed the hypoxic ventilatory decline (HVD), and it is usually assessed by protocols that give a sustained hypoxic exposure greater than ϳ10 min. The sustained vs. acute response has not been systematically evaluated in Andean highland natives, but groups from this region appear to have a lower or "blunted" acute HVR and a lower effective alveolar ventilation compared with high altitude (HA)-acclimatized control groups from the lowlands (10,35,36,43,57,61,62). Andeans also have lower VE during exercise at HA compared with acclimatized lowland controls (7,32,55,66). These traits may be unique to Andeans, as many studies show normal HVR and higher VE in natives of the Himalayan plateau (2,21,25,29,75). However, little is known about the underlying genetic and/or environmental basis for ventilatory trait differences between populations. One possibility is that there are genes at which allele frequencies differ ...

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Spanish genetic admixture is associated with larger V̇o_{2 max}decrement from sea level to 4,338 m in Peruvian Quechua

Cited by 52 publications

References 47 publications

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

Air to Muscle O₂Delivery during Exercise at Altitude

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives

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Spanish genetic admixture is associated with larger V̇o2 maxdecrement from sea level to 4,338 m in Peruvian Quechua

Cited by 52 publications

References 47 publications

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

Air to Muscle O2Delivery during Exercise at Altitude

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives

Contact Info

Product

Resources

About

Spanish genetic admixture is associated with larger V̇o_{2 max}decrement from sea level to 4,338 m in Peruvian Quechua

Air to Muscle O₂Delivery during Exercise at Altitude