Percent of oxygen saturation of arterial hemoglobin among Bolivian Aymara at 3,900-4,000 m.

A range of variation in percent of oxygen saturation of arterial hemoglobin (SaO2) among healthy individuals at a given high altitude indicates differences in physiological hypoxemia despite uniform ambient hypoxic stress. In populations native to the Tibetan plateau, a significant portion of the variance is attributable to additive genetic factors, and there is a major gene influencing SaO2. To determine whether there is genetic variance in other high-altitude populations, we designed a study to test the hypothesis that additive genetic factors contribute to phenotypic variation in SaO2 among Aymara natives of the Andean plateau, a population geographically distant from the Tibetan plateau and with a long, separate history of high-altitude residence. The average SaO2 of 381 Aymara at 3,900-4,000 m was 92+/-0.15% (SEM) with a range of 84-99%. The average was 2.6% higher than the average SaO2 of a sample of Tibetans at 3,800-4,065 m measured with the same techniques. Quantitative genetic analyses of the Aymara sample detected no significant variance attributable to genetic factors. The presence of genetic variance in SaO2 in the Tibetan sample and its absence in the Aymara sample indicate there is potential for natural selection on this trait in the Tibetan but not the Aymara population.

Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara.

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives.

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9-82 years of age and 542 Bolivian Aymara 13-94 years of age, native residents at 3,800-4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2-7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara.

Salivary testosterone concentration of Aymara men native to 3600 m.

This paper explores the possibility that variation in the normal physiological range of testosterone concentration modulates men's adaptation to hypobaric high-altitude hypoxia through stimulating haemoglobin production and/or causing respiratory disturbances and exacerbated hypoxaemia during sleep. These effects of testosterone are observed clinically at sea level and have potentially opposing consequences at high altitude, the former perhaps enhancing and the latter diminishing the effectiveness of adaptations to hypoxia. Seventeen young (average age 27 years) and 22 older (average age 57 years) healthy adult high altitude native Aymara men tested at 3600 m have average morning salivary testosterone concentrations of 282 and 241 pmol/l, respectively. The 31 urban men of both age groups have higher testosterone concentrations than the eight rural men and have mean haemoglobin concentrations significantly 0.7-1.0 g/dl higher within the normal high-altitude range, consistent with known effects of testosterone at sea level. Older urban men have slightly more frequent respiratory disturbances during sleep, associated with significantly greater hypoxaemia. There appear to be modest benefits to testosterone concentrations in the upper end of the observed range; however, the direction of these responses towards more haemoglobin production and more hypoxaemia during sleep of older men suggests the hypothesis that very high testosterone concentrations such as those in the upper ranges of sea level values could compromise adaptation to high altitude, particularly among older men.

Effect of maturation on oral breathing in sleeping premature infants.

To evaluate the influence of postnatal maturation on oral breathing, we measured nasal and oral ventilation during sleep and the ventilatory response to nasal occlusion in 11 preterm infants. Studies were repeated at 31-32, 33-34, and 35-36 weeks postconceptional age. Premature infants had rare episodes of spontaneous oronasal breathing during sleep. The frequency of oral breathing in response to nasal occlusion increased with advancing postconceptional age, from 8% +/- 8% at 31-32 weeks to 26% +/- 18% at 33-34 weeks and 28% +/- 33% at 35-36 weeks. Oral breathing in preterm infants, unlike that in term infants, was characterized by intermittent airway obstruction leading to a significant decrease in respiratory rate, tidal volume, minute ventilation, and tcpo2 (P less than 0.005). When inspiratory (Rl) and expiratory (RE) resistances during nasal and oral breathing were compared, Rl increased from 41 +/- 30 to 234 +/- 228 (P less than 0.004) and RE from 62 +/- 16 to 145 +/- 43 cm H2O X L-1 X sec (P less than 0.004). The ability of preterm infants to use the oral route of breathing thus increases with advancing postnatal maturation, but its effectiveness may remain limited by high oral airway resistance.

Oral breathing in newborn infants.

Newborn infants are considered obligate nasal breathers, hence dependent on a patent nasal airway for ventilation. The conditions under which oral breathing could occur and the contribution of oral ventilation to total ventilation were studied in 30 healthy term infants (aged 1 to 3 days). Nasal and oral airflow were measured using two resistance-matched pneumotachometers, and heart rate, tcPO2, etCO2, and sleep state were continuously recorded. In three of 10 infants studied in undisturbed sleep, spontaneous oronasal breathing was noted during both active and quiet sleep (mean duration 19 +/- 25 minutes), the distribution of tidal volume being 70% +/- 12% nasal and 30% +/- 12% oral. Episodes of oronasal breathing were also observed after crying in six infants (mean duration 21 +/- 19 seconds). In an additional 20 infants, multiple 15-second end-expiratory nasal occlusions were performed; eight (40%) of these infants initiated and sustained oral breathing in response to nasal occlusion. Respiratory rate, tidal volume, heart rate, and tcPO2 did not change when oral breathing occurred in response to nasal occlusion, although minute ventilation decreased from 265 to 199 ml/min/kg (P less than 0.05). These results demonstrate that newborn infants may use the oral airway for ventilation, both spontaneously and in response to complete nasal occlusion.