Life | Special Issue : Cellular and Functional Response to Hypoxia

Editorial

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Open AccessEditorial

Editorial for Life Special Issue Book Cellular and Functional Response to Hypoxia

by Jean-Paul Richalet

Life 2023, 13(1), 5; https://doi.org/10.3390/life13010005 - 20 Dec 2022

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Abstract

Hypoxia is a current research topic in biology, physiology, and medicine [...] Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

Research

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19 pages, 355 KiB

Open AccessArticle

A Critical Analysis of the Automated Hematology Assessment in Pregnant Women at Low and at High Altitude: Association between Red Blood Cells, Platelet Parameters, and Iron Status

by Ramón Figueroa-Mujica, Luis Angel Ccahuantico, Maycol Suker Ccorahua-Rios, Juan José Sanchez-Huaman, Cinthya Vásquez-Velasquez, Jorge M. Ponce-Huarancca, Rodrigo E. Rozas-Gamarra and Gustavo F. Gonzales

Life 2022, 12(5), 727; https://doi.org/10.3390/life12050727 - 13 May 2022

Cited by 3 | Viewed by 2768

Abstract

The objectives of the study were to determine differences in the parameters of red blood cells (RBC), white blood cells (WBC), and platelets at low altitude (LA) and at high altitude (HA) and with the gestation being advanced, and to determine correlations between [...] Read more.

The objectives of the study were to determine differences in the parameters of red blood cells (RBC), white blood cells (WBC), and platelets at low altitude (LA) and at high altitude (HA) and with the gestation being advanced, and to determine correlations between parameters of RBC and platelets. We also studied the association of RBC and platelets with markers of iron status. In addition, markers of iron status and inflammation were measured and compared at each trimester of gestation in pregnant women at LA and HA. A cross-sectional comparative study was conducted at Lima (150 m above sea level) and Cusco at 3400 m above sea level from May to December 2019. Hematological parameters in pregnant women (233 at LA and 211 at HA) were analyzed using an automated hematology analyzer. Serum ferritin levels, soluble transferrin receptor (sTfR), hepcidin, erythropoietin, testosterone, estradiol, and interleukin-6 (IL6) levels were measured by ELISA. One-way ANOVA supplemented with post hoc test, chi-square test, and Pearson correlation test statistical analyses were performed. p < 0.05 was considered significant. Pregnant woman at HA compared to LA had significantly lower WBC (p < 0.01), associated with higher parameters of the RBC, except for the mean corpuscular volume (MCV) that was no different (p > 0.05). Platelets and mean platelet volume (MPV) were higher (p < 0.01), and platelet distribution width (PDW) was lower at HA than at LA (p < 0.01). A higher value of serum ferritin (p < 0.01), testosterone (p < 0.05), and hepcidin (p < 0.01) was observed at HA, while the concentration of sTfR was lower at HA than at LA (p < 0.01). At LA, neutrophils increased in the third trimester (p < 0.05). RBC parameters decreased with the progress of the gestation, except RDW-CV, which increased. The platelet count decreased and the MPV and PDW were significantly higher in the third trimester. Serum ferritin, hepcidin, and serum testosterone decreased, while sTfR and serum estradiol increased during gestation. At HA, the WBC and red blood cell distribution width- coefficient of variation (RDW-CV), PCT, and serum IL-6 did not change with gestational trimesters. RBC, hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), and platelet count were lower as gestation advanced. MCV, MPV, and PDW increased in the third trimester. Serum ferritin, testosterone, and hepcidin were lower in the third trimester. Serum estradiol, erythropoietin, and sTfR increased as gestation progressed. Direct or inverse correlations were observed between RBC and platelet parameters and LA and HA. A better number of significant correlations were observed at HA. Hb, Hct, and RDW-CV showed a significant correlation with serum ferritin at LA and HA. Of these parameters, RDW-CV and PDW showed an inversely significant association with ferritin (p < 0.05). In conclusion, a different pattern was observed in hematological markers as well as in iron status markers between pregnant women at LA and HA. In pregnant women a significant correlation between several RBC parameters with platelet marker parameters was also observed. Data suggest that pregnant women at HA have adequate iron status during pregnancy as reflected by higher serum ferritin levels, lower sTfR levels, and higher hepcidin values than pregnant women at LA. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

16 pages, 2592 KiB

Open AccessArticle

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

by Zoya O. Serebrovska, Lei Xi, Lesya V. Tumanovska, Angela M. Shysh, Sergii V. Goncharov, Michael Khetsuriani, Taisia O. Kozak, Denis A. Pashevin, Victor E. Dosenko, Sergii V. Virko, Viktor A. Kholin, Oksana N. Grib, Natalie A. Utko, Egor Egorov, Anna O. Polischuk and Tetiana V. Serebrovska

Life 2022, 12(3), 432; https://doi.org/10.3390/life12030432 - 16 Mar 2022

Cited by 11 | Viewed by 3385

Abstract

Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present [...] Read more.

Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% F_IO₂) and 3-min hyperoxia (33% F_IO₂). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aβ expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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9 pages, 2370 KiB

Open AccessArticle

Expiratory Peak Flow and Minute Ventilation Are Significantly Increased at High Altitude versus Simulated Altitude in Normobaria

by Nikolaus C. Netzer, Linda K. Rausch, Matthias Frieß, Kingman P. Strohl, Robert Schilz, Michael Decker and Stephan Pramsohler

Life 2022, 12(2), 306; https://doi.org/10.3390/life12020306 - 17 Feb 2022

Cited by 1 | Viewed by 2010

Abstract

Simulated altitude (normobaric hypoxia, NH) is used to study physiologic hypoxia responses of altitude. However, several publications show differences in physiological responses between NH and hypobaric conditions at altitude (hypobaric hypoxia, HH). The causality for these differences is controversially discussed. One theory is [...] Read more.

Simulated altitude (normobaric hypoxia, NH) is used to study physiologic hypoxia responses of altitude. However, several publications show differences in physiological responses between NH and hypobaric conditions at altitude (hypobaric hypoxia, HH). The causality for these differences is controversially discussed. One theory is that the lower air density and environmental pressure in HH compared to NH lead to lower alveolar pressure and therefore lower oxygen diffusion in the lung. We hypothesized that, if this theory is correct, due to physical laws (Hagen-Poiseuille, Boyle), resistance respectively air compression (Boyle) at expiration should be lower, expiratory flow higher, and therefore peak flow and maximum expiratory flow (MEF) 75–50 increased in hypobaric hypoxia (HH) vs. normobaric hypoxia (NH). To prove the hypothesis of differences in respiratory flow as a result of lower alveolar pressure between HH and NH, we performed spirography in NH at different simulated altitudes and the corresponding altitudes in HH. In a cross over study, 6 healthy subjects (2 f/4 m, 28.3 ± 8.2 years, BMI: 23.2 ± 1.9) performed spirography as part of spiroergometry in a normobaric hypoxic room at a simulated altitude of 2800 m and after a seven-hour hike on a treadmill (average incline 14%, average walking speed 1.6 km/h) to the simulated summit of Mauna Kea at 4200 m. After a two-month washout, we repeated the spirometry in HH on the start and top of the Mauna Kea hiking trail, HI/USA. Comparison of NH (simulated 4200 m) and HH at 4200 m resulted in increased pulmonary ventilation during exercise (VE) (11.5%, p < 0.01), breathing-frequency (7.8%, p < 0.01), peak expiratory flow PEF (13.4%, p = 0.028), and MEF50 (15.9%, p = 0.028) in HH compared to NH, whereas VO_2max decreased by 2%. At 2800 m, differences were only trendy, and at no altitude were differences in volume parameters. Spirography expresses higher mid expiratory flows and peak flows in HH vs. NH. This supports the theory of lower alveolar and small airway pressure due to a lower air density resulting in a lower resistance. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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11 pages, 893 KiB

Open AccessEditor’s ChoiceArticle

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

by Benjamin J. Narang, Giorgio Manferdelli, Katja Kepic, Alexandros Sotiridis, Damjan Osredkar, Nicolas Bourdillon, Grégoire P. Millet and Tadej Debevec

Life 2022, 12(1), 79; https://doi.org/10.3390/life12010079 - 06 Jan 2022

Cited by 4 | Viewed by 3581

Abstract

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), [...] Read more.

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. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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19 pages, 2266 KiB

Open AccessArticle

Physiological Responses at Rest and Exercise to High Altitude in Lowland Children and Adolescents

by Morin Lang, Guillem Vizcaíno-Muñoz, Paulina Jopia, Juan Silva-Urra and Ginés Viscor

Life 2021, 11(10), 1009; https://doi.org/10.3390/life11101009 - 24 Sep 2021

Cited by 1 | Viewed by 2389

Abstract

During the last decades, the number of lowland children exposed to high altitude (HA) has increased drastically. Several factors may influence the development of illness after acute HA exposure on children and adolescent populations, such as altitude reached, ascent velocity, time spent at [...] Read more.

During the last decades, the number of lowland children exposed to high altitude (HA) has increased drastically. Several factors may influence the development of illness after acute HA exposure on children and adolescent populations, such as altitude reached, ascent velocity, time spent at altitude and, especially, their age. The main goal of this study was to evaluate the resting cardiorespiratory physiological and submaximal exercise responses under natural HA conditions by means of the six-minute walking test (six MWT). Secondly, we aimed to identify the signs and symptoms associated with acute mountain sickness (AMS) onset after acute HA exposure in children and adolescents. Forty-two children and adolescents, 18 boys and 24 girls aged from 11 to 15 years old, participated in this study, which was performed at sea level (SL) and during the first 42 h at HA (3330 m). The Lake Louise score (LLS) was recorded in order to evaluate the evolution of AMS symptoms. Submaximal exercise tests (six MWT) were performed at SL and HA. Physiological parameters such as heart rate, systolic and diastolic blood pressure, respiratory rate and arterialized oxygen saturation were measured at rest and after ending exercise testing at the two altitudes. After acute HA exposure, the participants showed lower arterial oxygen saturation levels at rest and after the submaximal test compared to SL (p < 0.001). Resting heart rate, respiratory rate and diastolic blood pressure presented higher values at HA (p < 0.01). Moreover, heart rate, diastolic blood pressure and dyspnea values increased before, during and after exercise at HA (p < 0.01). Moreover, submaximal exercise performance decreased at HA (p < 0.001). The AMS incidence at HA ranged from 9.5% to 19%, with mild to moderate symptoms. In conclusion, acute HA exposure in children and adolescent individuals produces an increase in basal cardiorespiratory parameters and a decrement in arterial oxygen saturation. Moreover, cardiorespiratory parameters increase during submaximal exercise at HA. Mild to moderate symptoms of AMS at 3330 m and adequate cardiovascular responses to submaximal exercise do not contraindicate the ascension of children and adolescents to that altitude, at least for a limited period of time. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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14 pages, 2602 KiB

Open AccessEditor’s ChoiceArticle

Sleep Apnea in Idiopathic Pulmonary Fibrosis: A Molecular Investigation in an Experimental Model of Fibrosis and Intermittent Hypoxia

by Liasmine Haine, Juliette Bravais, Céline-Hivda Yegen, Jean-Francois Bernaudin, Dominique Marchant, Carole Planès, Nicolas Voituron and Emilie Boncoeur

Life 2021, 11(9), 973; https://doi.org/10.3390/life11090973 - 15 Sep 2021

Cited by 2 | Viewed by 2336

Abstract

Background: High prevalence of obstructive sleep apnea (OSA) is reported in incident and prevalent forms of idiopathic pulmonary fibrosis (IPF). We previously reported that Intermittent Hypoxia (IH), the major pathogenic element of OSA, worsens experimental lung fibrosis. Our objective was to investigate the [...] Read more.

Background: High prevalence of obstructive sleep apnea (OSA) is reported in incident and prevalent forms of idiopathic pulmonary fibrosis (IPF). We previously reported that Intermittent Hypoxia (IH), the major pathogenic element of OSA, worsens experimental lung fibrosis. Our objective was to investigate the molecular mechanisms involved. Methods: Impact of IH was evaluated on C57BL/6J mice developing lung fibrosis after intratracheal instillation of Bleomycin (BLM). Mice were Pre-exposed 14 days to IH before induction of lung fibrosis or Co-challenged with IH and BLM for 14 days. Weight loss and survival were daily monitored. After experimentations, lungs were sampled for histology, and protein and RNA were extracted. Results: Co-challenge or Pre-exposure of IH and BLM induced weight loss, increased tissue injury and collagen deposition, and pro-fibrotic markers. Major worsening effects of IH exposure on lung fibrosis were observed when mice were Pre-exposed to IH before developing lung fibrosis with a strong increase in sXBP1 and ATF6N ER stress markers. Conclusion: Our results showed that IH exacerbates BLM-induced lung fibrosis more markedly when IH precedes lung fibrosis induction, and that this is associated with an enhancement of ER stress markers. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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15 pages, 2214 KiB

Open AccessArticle

Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude

by Kavita Sharma, Neha Chanana, Ghulam Mohammad, Tashi Thinlas, Mohit Gupta, Mansoor Ali Syed, Rajat Subhra Das, Qadar Pasha and Aastha Mishra

Life 2021, 11(9), 893; https://doi.org/10.3390/life11090893 - 29 Aug 2021

Cited by 5 | Viewed by 2314

Abstract

Thrombospondin-1 (THBS1) levels elevate under hypoxia and have relevance in several cardiovascular disorders. The association of THBS1 with endothelial dysfunction implies its important role in hypertension. To establish the hypothesis, we screened patients with hypertension and their respective controls from the two different [...] Read more.

Thrombospondin-1 (THBS1) levels elevate under hypoxia and have relevance in several cardiovascular disorders. The association of THBS1 with endothelial dysfunction implies its important role in hypertension. To establish the hypothesis, we screened patients with hypertension and their respective controls from the two different environmental regions. Cohort 1 was composed of Ladakhis, residing at 3500 m above sea level (ASL), whereas Cohort 2 was composed of north-Indians residing at ~200 m ASL. Clinical parameters and circulating THBS1 levels were correlated in the case–control groups of the two populations. THBS1 levels were significantly elevated in hypertension patients of both cohorts; however, the levels were distinctly enhanced in the hypertensive patients of HA as compared to normoxia (p < 0.002). The observation was supported by the receiver operating curve analysis with an area under curve of 0.7007 (0.627–0.774) demonstrating the discriminatory effect of hypobaric hypoxia on the levels as compared to normoxia (p < 0.011). Significant correlation of THBS1 and mean arterial pressure was observed with upraised positive correlations in the hypertensive highlanders as compared to the hypertensive patients from sea-level. The prevalence of differential distribution of THBS1 and CD47 genes variants, their interactions, and association with the THBS1 levels were also determined. Genotype-interactions between THBS1 rs2228263 and CD47 rs9879947 were relevant and the regression analysis highlighted the association of risk genotype-interactions with increased THBS1 levels in hypertension. Genetic studies of additional thrombospondin pathway-related genes suggest the complex role of THBS1 in the presence of its family members and the related receptor molecules at HA. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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9 pages, 1416 KiB

Open AccessArticle

Clinical Markers of Chronic Hypoxemia in Respiratory Patients Residing at Moderate Altitude

by Rosario Fernández-Plata, Ireri Thirion-Romero, Karol J. Nava-Quiroz, Gloria Pérez-Rubio, Sebastián Rodríguez-Llamazares, Midori Pérez-Kawabe, Yadira Rodríguez-Reyes, Selene Guerrero-Zuñiga, Arturo Orea-Tejeda, Ramcés Falfán-Valencia, Rogelio Pérez-Padilla and on behalf of the Mexican Translational Research Hypoxemia Working Group

Life 2021, 11(5), 428; https://doi.org/10.3390/life11050428 - 10 May 2021

Cited by 6 | Viewed by 2228

Abstract

Supplemental oxygen (SO) increases survival in hypoxemic patients. In hypoxia, mammals respond by modulating O₂-sensitive transducers that stabilize the transcription factor hypoxia-inducible factor-1-alpha (HIF-1α), which transactivates the genes that govern angiogenesis and metabolic pathways. Residing at high altitudes exposes millions of [...] Read more.

Supplemental oxygen (SO) increases survival in hypoxemic patients. In hypoxia, mammals respond by modulating O₂-sensitive transducers that stabilize the transcription factor hypoxia-inducible factor-1-alpha (HIF-1α), which transactivates the genes that govern angiogenesis and metabolic pathways. Residing at high altitudes exposes millions of people to hypoxemia with potential adverse consequences on their health. We aimed to identify markers of hypoxemia that can be used in the evaluation of patients in addition to pulse oximetry and arterial blood gases, especially those that could respond after 1 month of oxygen use. We performed a prospective pilot study at 2240 m above sea level, with repeated measurements before and after (b/a) 1-month home oxygen therapy in 70 patients with lung diseases, of which 24/20 have COPD, 41/39 obstructive sleep apnea (OSA), and 5/2 with interstitial lung diseases (ILD), all of them having chronic hypoxemia, as well as 70 healthy subjects as controls. Proteins evaluated included HIF-1α, vascular endothelial growth factor (VEGF), and erythropoietin (EPO). Among the main results, we found that hypoxemic patients had normal levels of HIF-1α but increased EPO compared with healthy controls. VEGF levels were heterogeneous in the sample studied, similar to the control group in COPD, slightly increased in OSA, and decreased in fibrosis. With oxygen treatment, the HIF-1α and EPO decreased in COPD and OSA but not in fibrosis, and VEGF remained constant over time. In conclusion, erythropoietin and HIF-1α identified hypoxemia initially and responded to oxygen. In pulmonary fibrosis, HIF-1α, EPO, and VEGF increased with oxygen therapy, which is likely linked to the disease’s pathogenesis and clinical course rather than hypoxemia. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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11 pages, 740 KiB

Open AccessEditor’s ChoiceArticle

Pro-Oxidant/Antioxidant Balance during a Prolonged Exposure to Moderate Altitude in Athletes Exhibiting Exercise-Induced Hypoxemia at Sea-Level

by Antoine Raberin, Elie Nader, Jorge Lopez Ayerbe, Gauthier Alfonsi, Patrick Mucci, Chantal L. Rytz, Vincent Pialoux and Fabienne Durand

Life 2021, 11(3), 228; https://doi.org/10.3390/life11030228 - 11 Mar 2021

Cited by 4 | Viewed by 2314

Abstract

This study examined to what extent athletes exhibiting exercise-induced hypoxemia (EIH) possess an altered redox status at rest, in response to exercise at sea level (SL) and during moderate altitude exposure. EIH was defined as a fall in arterial O₂ saturation of [...] Read more.

This study examined to what extent athletes exhibiting exercise-induced hypoxemia (EIH) possess an altered redox status at rest, in response to exercise at sea level (SL) and during moderate altitude exposure. EIH was defined as a fall in arterial O₂ saturation of at least 4% during exercise. Nine endurance athletes with EIH and ten without (NEIH) performed a maximal incremental test under three conditions: SL, one (H1) and five (H2) days after arrival to 2400 m. Gas exchange and peripheral capillary oxygen saturation (SpO₂) were continuously monitored. Blood was sampled before exercise and after exercise cessation. Advanced oxidation protein products (AOPP), catalase, ferric-reducing antioxidant power, glutathione peroxidase, superoxide dismutase (SOD) and nitric oxide metabolites (NOx) were measured in plasma by spectrophotometry. EIH athletes had higher AOPP and NOx concentrations at pre- and post-exercise stages compared to NEIH at SL, H2 but not at H1. Only the EIH group experienced increased SOD activity between pre- and post-exercise exercise at SL and H2 but not at H1. EIH athletes had exacerbated oxidative stress compared to the NEIH athletes at SL and H2. These differences were blunted at H1. Oxidative stress did not alter the EIH groups’ aerobic performance and could lead to higher minute ventilation at H2. These results suggest that higher oxidative stress response EIH athletes could be involved in improved aerobic muscle functionality and a greater ventilatory acclimatization during prolonged hypoxia. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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Review

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14 pages, 3623 KiB

Open AccessReview

Early Endothelial Signaling Transduction in Developing Lung Edema

by Giuseppe Miserocchi

Life 2023, 13(6), 1240; https://doi.org/10.3390/life13061240 - 24 May 2023

Cited by 2 | Viewed by 806

Abstract

The lung promptly responds to edemagenic conditions through functional adaptations that contrast the increase in microvascular filtration. This review presents evidence for early signaling transduction by endothelial lung cells in two experimental animal models of edema, hypoxia exposure, and fluid overload (hydraulic edema). [...] Read more.

The lung promptly responds to edemagenic conditions through functional adaptations that contrast the increase in microvascular filtration. This review presents evidence for early signaling transduction by endothelial lung cells in two experimental animal models of edema, hypoxia exposure, and fluid overload (hydraulic edema). The potential role of specialized sites of the plasma membranes considered mobile signaling platforms, referred to as membrane rafts, that include caveolae and lipid rafts, is presented. The hypothesis is put forward that early changes in the lipid composition of the bilayer of the plasma membrane might trigger the signal transduction process when facing changes in the pericellular microenvironment caused by edema. Evidence is provided that for an increase in the extravascular lung water volume not exceeding 10%, changes in the composition of the plasma membrane of endothelial cells are evoked in response to mechanical stimuli from the interstitial compartment as well as chemical stimuli relating with changes in the concentration of the disassembled portions of structural macromolecules. In hypoxia, thinning of endothelial cells, a decrease in caveolae and AQP-1, and an increase in lipid rafts are observed. The interpretation of this response is that it favors oxygen diffusion and hinder trans-cellular water fluxes. In hydraulic edema, which generates greater capillary water leakages, an increase in cell volume and opposite changes in membrane rafts were observed; further, the remarkable increase in caveolae suggests a potential abluminal–luminal vesicular-dependent fluid reabsorption. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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25 pages, 869 KiB

Open AccessEditor’s ChoiceReview

Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation

by Katie A. O’Brien, Andrew J. Murray and Tatum S. Simonson

Life 2022, 12(3), 437; https://doi.org/10.3390/life12030437 - 16 Mar 2022

Cited by 8 | Viewed by 5995

Abstract

Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O₂) homeostasis, adjusting convective O₂ delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural [...] Read more.

Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O₂) homeostasis, adjusting convective O₂ delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural selection of multiple gene regions supporting adaptive traits. Some of the strongest selection signals identified in highland populations emanate from hypoxia-inducible factor (HIF) pathway genes. The HIF pathway is a master regulator of the cellular hypoxic response, but it is not the only regulatory pathway under positive selection. For instance, regions linked to the highly conserved Notch signaling pathway are also top targets, and this pathway is likely to play essential roles that confer hypoxia tolerance. Here, we explored the importance of the Notch pathway in mediating the cellular hypoxic response. We assessed transcriptional regulation of the Notch pathway, including close cross-talk with HIF signaling, and its involvement in the mediation of angiogenesis, cellular metabolism, inflammation, and oxidative stress, relating these functions to generational hypoxia adaptation. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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12 pages, 831 KiB

Open AccessReview

Effects of Altitude on Chronic Obstructive Pulmonary Disease Patients: Risks and Care

by Thomas Georges, Camille Le Blanc, Sophie Ferreol, Pierre Menu, Marc Dauty and Alban Fouasson-Chailloux

Life 2021, 11(8), 798; https://doi.org/10.3390/life11080798 - 07 Aug 2021

Cited by 2 | Viewed by 5032

Abstract

Air travel and altitude stays have become increasingly frequent within the overall population but also in patients suffering from chronic obstructive pulmonary disease (COPD), which is the most common respiratory disease worldwide. While altitude is well tolerated by most individuals, COPD patients are [...] Read more.

Air travel and altitude stays have become increasingly frequent within the overall population but also in patients suffering from chronic obstructive pulmonary disease (COPD), which is the most common respiratory disease worldwide. While altitude is well tolerated by most individuals, COPD patients are exposed to some serious complications, that could be life-threatening. COPD patients present not only a respiratory illness but also frequent comorbidities. Beyond oxygen desaturation, it also affects respiratory mechanics, and those patients are at high risk to decompensate a cardiac condition, pulmonary hypertension, or a sleep disorder. Recently, there has been considerable progress in the management of this disease. Nocturnal oxygen therapy, inhaled medications, corticosteroids, inspiratory muscle training, and pulmonary rehabilitation are practical tools that must be developed in the comprehensive care of those patients so as to enable them to afford altitude stays. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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15 pages, 4163 KiB

Open AccessReview

Exercising in Hypoxia and Other Stimuli: Heart Rate Variability and Ventilatory Oscillations

by Eric Hermand, François J. Lhuissier, Aurélien Pichon, Nicolas Voituron and Jean-Paul Richalet

Life 2021, 11(7), 625; https://doi.org/10.3390/life11070625 - 28 Jun 2021

Cited by 7 | Viewed by 2280

Abstract

Periodic breathing is a respiratory phenomenon frequently observed in patients with heart failure and in normal subjects sleeping at high altitude. However, until recently, periodic breathing has not been studied in wakefulness and during exercise. This review relates the latest findings describing this [...] Read more.

Periodic breathing is a respiratory phenomenon frequently observed in patients with heart failure and in normal subjects sleeping at high altitude. However, until recently, periodic breathing has not been studied in wakefulness and during exercise. This review relates the latest findings describing this ventilatory disorder when a healthy subject is submitted to simultaneous physiological (exercise) and environmental (hypoxia, hyperoxia, hypercapnia) or pharmacological (acetazolamide) stimuli. Preliminary studies have unveiled fundamental physiological mechanisms related to the genesis of periodic breathing characterized by a shorter period than those observed in patients (11~12 vs. 30~60 s). A mathematical model of the respiratory system functioning under the aforementioned stressors corroborated these data and pointed out other parameters, such as dead space, later confirmed in further research protocols. Finally, a cardiorespiratory interdependence between ventilatory oscillations and heart rate variability in the low frequency band may partly explain the origin of the augmented sympathetic activation at exercise in hypoxia. These nonlinear instabilities highlight the intrinsic “homeodynamic” system that allows any living organism to adapt, to a certain extent, to permanent environmental and internal perturbations. Full article

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Other

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12 pages, 1593 KiB

Open AccessSystematic Review

Weight Loss and Fat Metabolism during Multi-Day High-Altitude Sojourns: A Hypothesis Based on Adipocyte Signaling

by Stephan Pramsohler, Martin Burtscher, Linda Rausch and Nikolaus C. Netzer

Life 2022, 12(4), 545; https://doi.org/10.3390/life12040545 - 06 Apr 2022

Cited by 4 | Viewed by 3108

Abstract

Several publications and random observations have reported weight loss in high-altitude sojourners of both sexes. This could be a result of multiple adaptations, which hypoxia and mountaineering provoke on a cellular and organic level. Several publications have discussed the effect on appetite-regulating hormones [...] Read more.

Several publications and random observations have reported weight loss in high-altitude sojourners of both sexes. This could be a result of multiple adaptations, which hypoxia and mountaineering provoke on a cellular and organic level. Several publications have discussed the effect on appetite-regulating hormones to be one of the main contributing factors. We aimed to review the available data and show the current state of knowledge regarding nutritional aspects in high altitude with a special focus on fatty dietary forms. To reach this aim we conducted a literature search via PubMed according to the PRISMA 2020 protocol to identify relevant studies. We found that very few studies cover this field with scientifically satisfying evidence. For final analysis, reviews as well as papers that were not clearly related to the topic were excluded. Six articles were included discussing hormonal influences and the impact of exercise on appetite regulation as well as genetic factors altering metabolic processes at altitude. Leptin expression seems to be the biggest contributor to appetite reduction at altitude with an initial increase followed by a decrease in the course of time at high altitude. Its expression is greatly dependent on the amount of white adipose tissue. Since the expression of leptin is associated with an increased β-oxidation of fatty acids, a high-fat diet could be advantageous at a certain time point in the course of high-altitude sojourns. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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11 pages, 726 KiB

Open AccessEditor’s ChoiceSystematic Review

Contribution of Hypoxic Exercise Testing to Predict High-Altitude Pathology: A Systematic Review

by Thomas Georges, Pierre Menu, Camille Le Blanc, Sophie Ferreol, Marc Dauty and Alban Fouasson-Chailloux

Life 2022, 12(3), 377; https://doi.org/10.3390/life12030377 - 05 Mar 2022

Cited by 4 | Viewed by 2591

Abstract

Altitude travelers are exposed to high-altitude pathologies, which can be potentially serious. Individual susceptibility varies widely and this makes it difficult to predict who will develop these complications. The assessment of physiological adaptations to exercise performed in hypoxia has been proposed to help [...] Read more.

Altitude travelers are exposed to high-altitude pathologies, which can be potentially serious. Individual susceptibility varies widely and this makes it difficult to predict who will develop these complications. The assessment of physiological adaptations to exercise performed in hypoxia has been proposed to help predict altitude sickness. The purpose of this review is to evaluate the contribution of hypoxic exercise testing, achieved in normobaric conditions, in the prediction of severe high-altitude pathology. We performed a systematic review using the databases PubMed, Science Direct and Embase in October 2021 to collect studies reporting physiological adaptations under hypoxic exercise testing and its interest in predicting high-altitude pathology. Eight studies were eligible, concerning 3558 patients with a mean age of 46.9 years old, and a simulated mean altitude reaching of 5092 m. 597 patients presented an acute mountain sickness during their altitude travels. Three different protocols of hypoxic exercise testing were used. Acute mountain sickness was defined using Hackett’s score or the Lake Louise score. Ventilatory and cardiac responses to hypoxia, desaturation in hypoxia, cerebral oxygenation, core temperature, variation in body mass index and some perceived sensations were the highlighted variables associated with acute mountain sickness. A decision algorithm based on hypoxic exercise tests was proposed by one team. Hypoxic exercise testing provides promising information to help predict altitude complications. Its interest should be confirmed by different teams. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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