Baroreflex sensitivity is blunted in hypoxia independently of changes in inspired carbon dioxide pressure in prematurely born male adults.

Premature birth may result in specific cardiovascular responses to hypoxia and hypercapnia, that might hamper high-altitude acclimatization. This study investigated the consequences of premature birth on baroreflex sensitivity (BRS) under hypoxic, hypobaric and hypercapnic conditions. Seventeen preterm born males (gestational age, 29 ± 1 weeks), and 17 age-matched term born adults (40 ± 0 weeks) underwent consecutive 6-min stages breathing different oxygen and carbon dioxide concentrations at both sea-level and high-altitude (3375 m). Continuous blood pressure and ventilatory parameters were recorded in normobaric normoxia (NNx), normobaric normoxic hypercapnia (NNx + CO2 ), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO2 ), and hypobaric hypoxia with end-tidal CO2 clamped at NNx value (HHx + clamp). BRS was assessed using the sequence method. Across all conditions, BRS was lower in term born compared to preterm (13.0 ± 7.5 vs. 21.2 ± 8.8 ms⋅mmHg-1 , main group effect: p < 0.01) participants. BRS was lower in HHx compared to NNx in term born (10.5 ± 4.9 vs. 16.0 ± 6.0 ms⋅mmHg-1 , p = 0.05), but not in preterm (27.3 ± 15.7 vs. 17.6 ± 8.3 ms⋅mmHg-1 , p = 0.43) participants, leading to a lower BRS in HHx in term born compared to preterm (p < 0.01). In conclusion, this study reports a blunted response of BRS during acute high-altitude exposure without any influence of changes in inspired CO2 in healthy prematurely born adults.

Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2 days at high altitude (3375 m), 16 young preterm-born (gestational age, 29 ± 1 weeks) and 15 age-matched term-born (40 ± 0 weeks) adults were exposed to two consecutive 4 min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P = 0.036), but not in preterm-born (-4 ± 27%, P = 0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P = 0.026) but not in preterm-born adults (-21 ± 107%, P = 0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P < 0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P = 0.012) and lower hypercapnic (P = 0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidence.

GOALS: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. METHODS: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. RESULTS: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. CONCLUSION: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.

Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre-term-born adults.

Pre-term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre-term birth per se causes these effects remains unclear. Therefore, we aimed to assess pulmonary ventilation and blood gases under various environmental conditions, comparing 17 healthy prematurely born individuals (mean ± SD; gestational age, 28 ± 2 weeks; age, 21 ± 4 years; peak oxygen uptake, 48.1 ± 11.2 ml kg-1  min-1 ) with 16 well-matched adults born at term (gestational age, 40 ± 1 weeks; age, 22 ± 2 years; peak oxygen uptake, 51.2 ± 7.7 ml kg-1  min-1 ). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO2 ), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O2 and CO2 were similar in pre-term and full-term individuals under all conditions. Higher ventilation in hypoxia compared to normoxia was only observed at terrestrial altitude, despite an equivalent (normobaric) hypoxic stimulus administered at sea level (0.138 F i O 2 ${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Assessment of oscillations in key variables revealed that combined hypoxic hypercapnia induced greater underlying fluctuations in ventilation in pre-term individuals only. In general, higher pulse oxygen saturation fluctuations were observed with hypoxia, and lower fluctuations in end-tidal CO2 with hypercapnia, despite similar ventilatory oscillations observed between conditions. These findings suggest that healthy prematurely born adults display similar overall ventilation to their term-born counterparts under various environmental stressors, but that combined ventilatory stimuli could induce an irregular underlying ventilatory pattern. Moreover, barometric pressure may be an important factor when assessing ventilatory responsiveness to moderate hypoxic stimuli. KEY POINTS: Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre-term birth. Whether pre-term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term-born individuals. According to the present data, there is no difference between healthy pre-term and well-matched term-born individuals in the magnitude of pulmonary ventilation or arterial blood gases during independent and combined hypobaria, hypoxia and hypercapnia. Terrestrial altitude (hypobaria) was necessary to induce differences in ventilation between normoxia and a hypoxic stimulus equivalent to ∼3375 m of altitude. Furthermore, peak power in pulse oxygen saturation was similar between hypobaric normoxia and normobaric hypoxia. The observed similarities between groups suggest that ventilatory regulation under various environmental stimuli is not impaired by pre-term birth per se. Instead, an integrated combination of neonatal treatment strategies and cardiorespiratory fitness/disease status might underlie previously observed chemosensitivity impairments.

Microvascular and oxidative stress responses to acute high-altitude exposure in prematurely born adults.

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. -15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. -13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm.

End-tidal carbon dioxide tension is a reliable surrogate of arterial carbon dioxide tension across different oxygen, carbon dioxide and barometric pressures.

End-tidal CO2 tension provides an accurate estimation of P aCO2 in healthy awake individuals over an extensive range of CO2 pressures induced by 17 environmental conditions combining different O2, CO2 and barometric pressures https://bit.ly/3YuKPAY.

Physiological Responses to Exercise in Hypoxia in Preterm Adults: Convective and Diffusive Limitations in the O 2 Transport.

PURPOSE: Premature birth induces long-term sequelae on the cardiopulmonary system, leading to reduced exercise capacity. However, the mechanisms of this functional impairment during incremental exercise remain unclear. Also, a blunted hypoxic ventilatory response was found in preterm adults, suggesting an increased risk for adverse effects of hypoxia in this population. This study aimed to investigate the oxygen cascade during incremental exercise to exhaustion in both normoxia and hypobaric hypoxia in prematurely born adults with normal lung function and their term born counterparts. METHODS: Noninvasive measures of gas exchange, cardiac hemodynamics, and both muscle and cerebral oxygenation were continuously performed using metabolic cart, transthoracic impedance, and near-infrared spectroscopy, respectively, during an incremental exercise test to exhaustion performed at sea level and after 3 d of high-altitude exposure in healthy preterm ( n = 17; gestational age, 29 ± 1 wk; normal lung function) and term born ( n = 17) adults. RESULTS: At peak, power output, oxygen uptake, stroke volume indexed for body surface area, and cardiac output were lower in preterm compared with term born in normoxia ( P = 0.042, P = 0.027, P = 0.030, and P = 0.018, respectively) but not in hypoxia, whereas pulmonary ventilation, peripheral oxygen saturation, and muscle and cerebral oxygenation were similar between groups. These later parameters were modified by hypoxia ( P < 0.001). Hypoxia increased muscle oxygen extraction at submaximal and maximal intensity in term born ( P < 0.05) but not in preterm participants. Hypoxia decreased cerebral oxygen saturation in term born but not in preterm adults at rest and during exercise ( P < 0.05). Convective oxygen delivery was decreased by hypoxia in term born ( P < 0.001) but not preterm adults, whereas diffusive oxygen transport decreased similarly in both groups ( P < 0.001 and P < 0.001, respectively). CONCLUSIONS: These results suggest that exercise capacity in preterm is primarily reduced by impaired convective, rather than diffusive, oxygen transport. Moreover, healthy preterm adults may experience blunted hypoxia-induced impairments during maximal exercise compared with their term counterparts.

Respiratory responses to hypoxia during rest and exercise in individuals born pre-term: a state-of-the-art review.

The pre-term birth survival rate has increased considerably in recent decades, and research investigating the long-term effects of premature birth is growing. Moreover, altitude sojourns are increasing in popularity and are often accompanied by various levels of physical activity. Individuals born pre-term appear to exhibit altered acute ventilatory responses to hypoxia, potentially predisposing them to high-altitude illness. These impairments are likely due to the use of perinatal hyperoxia stunting the maturation of carotid body chemoreceptors, but may also be attributed to limited lung diffusion capacity and/or gas exchange inefficiency. Aerobic exercise capacity also appears to be reduced in this population. This may relate to the aforementioned respiratory impairments, or could be due to physiological limitations in pulmonary blood flow or at the exercising muscle (e.g. mitochondrial efficiency). However, surprisingly, the debilitative effects of exercise when performed at altitude do not seem to be exacerbated by premature birth. In fact, it is reasonable to speculate that pre-term birth could protect against the consequences of exercise combined with hypoxia. The mechanisms that underlie this assertion might relate to differences in oxidative stress responses or in cardiopulmonary morphology in pre-term individuals, compared to their full-term counterparts. Further research is required to elucidate the independent effects of neonatal treatment, sex differences and chronic lung disease, and to establish causality in some of the proposed mechanisms that could underlie the differences discussed throughout this review. A more in-depth understanding of the acclimatisation responses to chronic altitude exposures would also help to inform appropriate interventions in this clinical population.

Effects of Pre-Term Birth on the Cardio-Respiratory Responses to Hypoxic Exercise in Children.

Pre-term birth is associated with numerous cardio-respiratory sequelae in children. Whether these impairments impact the responses to exercise in normoxia or hypoxia remains to be established. Fourteen prematurely-born (PREM) (Mean ± SD; gestational age 29 ± 2 weeks; age 9.5 ± 0.3 years), and 15 full-term children (CONT) (gestational age 39 ± 1 weeks; age 9.7 ± 0.9 years), underwent incremental exercise tests to exhaustion in normoxia (FiO2 = 20.9%) and normobaric hypoxia (FiO2 = 13.2%) on a cycle ergometer. Cardio-respiratory variables were measured throughout. Peak power output was higher in normoxia than hypoxia (103 ± 17 vs. 77 ± 18 W; p < 0.001), with no difference between CONT and PREM (94 ± 23 vs. 86 ± 19 W; p = 0.154). VO2peak was higher in normoxia than hypoxia in CONT (50.8 ± 7.2 vs. 43.8 ± 9.9 mL·kg-1·min-1; p < 0.001) but not in PREM (48.1 ± 7.5 vs. 45.0 ± 6.8 mL·kg-1·min-1; p = 0.137; interaction p = 0.044). Higher peak heart rate (187 ± 11 vs. 180 ± 10 bpm; p = 0.005) and lower stroke volume (72 ± 13 vs. 77 ± 14 mL; p = 0.004) were observed in normoxia versus hypoxia in CONT, with no such differences in PREM (p = 0.218 and >0.999, respectively). In conclusion, premature birth does not appear to exacerbate the negative effect of hypoxia on exercise capacity in children. Further research is warranted to identify whether prematurity elicits a protective effect, and to clarify the potential underlying mechanisms.

Long-Term Effects of Prematurity on Resting Ventilatory Response to Hypercapnia.

Manferdelli, Giorgio, Benjamin J. Narang, Mathias Poussel, Damjan Osredkar, Grégoire P. Millet, and Tadej Debevec. Long-term effects of prematurity on resting ventilatory response to hypercapnia. High Alt Med Biol. 22:420-425, 2021. Background: This study investigated the resting ventilatory response to hypercapnia in prematurely born adults. Materials and Methods: Seventeen preterm and fourteen full-term adults were exposed to normoxic hypercapnia (two 5-minute periods at 3% and 6% carbon dioxide [CO2] interspersed by 5-minute in normoxia). Pulmonary ventilation ([Formula: see text]) and end-tidal partial pressure of CO2 (Petco2) were measured continuously. Results: No difference in lung function was observed between preterm and full-term adults. Petco2 was lower in preterm than in full-term adults (p < 0.05) during normoxia. During exposure to 3% CO2, both [Formula: see text] and Petco2 increased in a similar way in preterm and full-term adults. However, at the end of the 6% CO2 period, there was a significantly higher [Formula: see text] in preterm compared with full-term adults (30.2 ± 7.5 vs. 23.7 ± 4.5 L/min, p < 0.0001), whereas no difference was observed for Petco2 (46.9 ± 2.1 vs. 50.6 ± 2.1 L/min, p = 0.99). Breath frequency was higher in preterm than in full-term adults (17.9 ± 4.0 vs. 12.8 ± 3.5 b/min, p < 0.01) during 6% CO2 exposure. Conclusions: Although data suggest that prematurity results in resting hypocapnia, the exact underlying mechanisms remain to be elucidated. Moreover, preterm adults seem to have increased chemosensitivity to hypercapnia.

Interactive effects of acute exercise and carbohydrate-energy replacement on insulin sensitivity in healthy adults.

This study investigated whether carbohydrate-energy replacement immediately after prolonged endurance exercise attenuates insulin sensitivity the following morning, and whether exercise improves insulin sensitivity the following morning independent of an exercise-induced carbohydrate deficit. Oral glucose tolerance and whole-body insulin sensitivity were compared the morning after 3 evening conditions, involving (1) treadmill exercise followed by a carbohydrate replacement drink (200 or 150 g maltodextrin for males and females, respectively; CHO-replace); (2) treadmill exercise followed by a non-caloric, taste-matched placebo (CHO-deficit); or (3) seated rest with no drink provided (Rest). Treadmill exercise involved 90 minutes at ∼80% age-predicted maximum heart rate. Seven males and 2 females (aged 23 ± 1 years; body mass index 24.0 ± 2.7 kg·m-2) completed all conditions in a randomised order. Matsuda index improved by 22% (2.2 [0.3, 4.0] au, p = 0.03) and HOMA2-IR improved by 10% (-0.04 [-0.08, 0.00] au, p = 0.04) in CHO-deficit versus CHO-replace, without corresponding changes in postprandial glycaemia. Outcomes were similar between Rest and other conditions. These data suggest that improvements to insulin sensitivity in healthy populations following acute moderate/vigorous intensity endurance exercise may be dependent on the presence of a carbohydrate-energy deficit. Novelty: Restoration of carbohydrate balance following acute endurance exercise attenuated whole-body insulin sensitivity. Exercise per se failed to enhance whole-body insulin sensitivity. Maximising or prolonging the post-exercise carbohydrate deficit may enhance acute benefits to insulin sensitivity.

A Tool to Explore Discrete-Time Data: The Time Series Response Analyser.

The analysis of time series data is common in nutrition and metabolism research for quantifying the physiological responses to various stimuli. The reduction of many data from a time series into a summary statistic(s) can help quantify and communicate the overall response in a more straightforward way and in line with a specific hypothesis. Nevertheless, many summary statistics have been selected by various researchers, and some approaches are still complex. The time-intensive nature of such calculations can be a burden for especially large data sets and may, therefore, introduce computational errors, which are difficult to recognize and correct. In this short commentary, the authors introduce a newly developed tool that automates many of the processes commonly used by researchers for discrete time series analysis, with particular emphasis on how the tool may be implemented within nutrition and exercise science research.