Hypoxia-induced pulmonary hypertension-Utilizing experiments of nature.

An increase in pulmonary artery pressure is a common observation in adult mammals exposed to global alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest in understanding pulmonary vascular homeostasis. There is an expectation that identifying the key molecules in the integrated vascular response to hypoxia will inform potential drug targets. One strategy is to take advantage of experiments of nature, specifically, to understand the genetic basis for the inter-individual variation in the pulmonary vascular response to acute and chronic hypoxia. To date, detailed phenotyping of highlanders has focused on haematocrit and oxygen saturation rather than cardiovascular phenotypes. This review explores what we can learn from those studies with respect to the pulmonary circulation. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

Residential Altitude Associates With Endurance but Not Muscle Power in Young Swiss Men.

INTRODUCTION: Physical fitness benefits health. However, there is a research gap on how physical fitness, particularly aerobic endurance capacity and muscle power, is influenced by residential altitude, blood parameters, weight, and other cofactors in a population living at low to moderate altitudes (300-2100 masl). MATERIALS AND METHODS: We explored how endurance and muscle power performance changes with residential altitude, Body Mass Index (BMI), hemoglobin and creatinine levels among 108,677 Swiss men aged 18-22 years (covering >90% of Swiss birth cohorts) conscripted to the Swiss Armed Forces between 2007 and 2012. The test battery included a blood test of about 65%, a physical evaluation of about 85%, and the BMI of all conscripts. RESULTS: Residential altitude was significantly associated with endurance (p < 0.001) but not with muscle power performance (p = 0.858) after adjusting for all available cofactors. Higher BMI showed the greatest negative association with both endurance and muscle power performance. For muscle power performance, the association with creatinine levels was significant. Elevated C-reactive protein (CRP) and hemoglobin levels were stronger contributors in explaining endurance than muscle power performance. CONCLUSION: We found a significant association between low to moderate residential altitude and aerobic endurance capacity even after adjustment for hemoglobin, creatinine, BMI and sociodemographic factors. Non-assessed factors such as vitamin D levels, air pollution, and lifestyle aspects may explain the presented remaining association partially and could also be associated with residential altitude. Monitoring the health and fitness of young people and their determinants is important and of practical concern for disease prevention and public health implications.

The increase in hemoglobin concentration with altitude varies among human populations.

Decreased oxygen availability at high altitude requires physiological adjustments allowing for adequate tissue oxygenation. One such mechanism is a slow increase in the hemoglobin concentration ([Hb]) resulting in elevated [Hb] in high-altitude residents. Diagnosis of anemia at different altitudes requires reference values for [Hb]. Our aim was to establish such values based on published data of residents living at different altitudes by applying meta-analysis and multiple regressions. Results show that [Hb] is increased in all high-altitude residents. However, the magnitude of increase varies among the regions analyzed and among ethnic groups within a region. The highest increase was found in residents of the Andes (1 g/dL/1000 m), but this increment was smaller in all other regions of the world (0.6 g/dL/1000 m). While sufficient data exist for adult males and females showing that sex differences in [Hb] persist with altitude, data for infants, children, and pregnant women are incomplete preventing such analyses. Because WHO reference values were originally based on [Hb] of South American people, we conclude that individual reference values have to be defined for ethnic groups to reliably diagnose anemia and erythrocytosis in high-altitude residents. Future studies need to test their applicability for children of different ages and pregnant women.

Pregnancy at high altitude in the Andes leads to increased total vessel density in healthy newborns.

The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea-level controls. Pre- and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre- and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level (P < 0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P < 0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm(2); P ≤ 0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.