Similar hypoxic ventilatory responses in sea-level natives and high-altitude Andean natives living at sea level

Abstract

High-altitude (HA) natives have blunted ventilatory sensitivities to hypoxia, and it is uncertain whether this blunting is reversible on migration to sea level (SL). To study this, the ventilatory sensitivities to hypoxia of HA natives residing near SL were compared with those of SL natives. Two studies were performed. In study A, 24 HA subjects who had lived above 3,000 m for an average of 14 yr and had been resident at SL for an average of 23 yr were compared with 23 SL controls. In study B, 25 HA subjects who had lived above 3,500 m for at least 20 yr and had been resident at SL for no more than 5 yr were compared with 25 SL controls. Hypoxic sensitivities were assessed by breathing seven progressively more hypoxic gas mixtures that contained progressively more CO2 in an attempt to maintain isocapnia throughout. The ventilatory sensitivities to hypoxia (l . min-1 . %-1 . m-2) did not differ significantly (by analysis of variance) between HA and SL natives in either study A (-0.51 +/- 0.25, mean +/- SD) or study B (-0.34 +/- 0. 15), but the ventilatory sensitivities did differ significantly between the two studies for reasons which are not entirely clear. We conclude that HA natives residing at SL, even if previously at HA for >20 yr, do not maintain the severely blunted hypoxic responses that have been reported in such individuals.

Level and duration of developmental hyperoxia influence impairment of hypoxic phrenic responses in rats

“…For example, humans raised at high altitude or born hypoxic because of cardiorespiratory diseases may acquire blunted hypoxic ventilatory responses during development (10,23,33,38,39). There is some debate as to whether this blunting is permanent (10,41), but many of these changes in respiratory control persist long after normoxic conditions are restored. Animal models support the conclusion that perinatal changes in O 2 levels induce developmental plasticity: lasting changes in the respiratory phenotype that can be elicited only during critical periods of development (cf.…”

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

“…There is also conflict on the issue of the reversibility/irreversibility of blunting in adults who have returned to sea level. Older studies showed that chemosensitivity was not reversed by residence at sea level (36,61,64), whereas more recent studies in the Andes show at least partial reversibility of blunting in Peruvians born at HA but migrating to sea level (20,63). Interestingly, the acute HVR may be more reversible than the HVD (20).…”

“…The approach has been used recently to reveal ancestry associations with some complex disease traits in admixed populations (15,23,41,72), although it should be recognized that such associations reveal nothing direct about causal genetic mechanisms or evolutionary origins. Another limitation of this approach is that physiological traits can be sensitive to environmental effects, and it is well known that ventilatory control and pulmonary gas exchange systems are affected by developmental exposure to hypobaric hypoxia (17,10,70,20,63). For this reason, we studied Peruvian subjects who were born and raised at sea level (Lima, Peru).…”

O desafio da altitude. Uma perspectiva fisiológica

“…A exuberância deste processo adaptativo, isto é, do grau da resposta ventilatória ao estímulo hipóxi-co, apresenta grande variabilidade interindividual parecendo estar associada a diversos factores, tais como o fenótipo e genótipo (31,77). Deste modo, alguns estudos com populações nativas de regiões de elevada altitude (14,15,79), nomeadamente andinas e himalaínas, têm demonstrado que, comparativamente a sujeitos caucasianos residentes ao nível do mar, a sua resposta ventilatória à hipóxia não é tão exuberante. Este facto, influenciado por factores ontogenéticos e filogenéticos, parece reflectir um padrão de adaptação ventilatório característico, regulado pela importância da manutenção do equilíbrio ácido-base sanguíneo e por adaptações anatómicas específicas do sistema respiratório (31,55,56).…”