Effects of a physical exercise program on HIF-1α in people with Chronic Obstructive Pulmonary Disease living at high altitude: study protocol for a clinical trial.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic, noncommunicable disease characterized by hypoxemia, with altered lung function, dyspnea on mild exertion, limited tolerance to physical exertion, and functional impairment. Physical exercise has been recommended worldwide as an efficient strategy to improve the autonomy and quality of life of patients affected by COPD. However, the adaptive molecular mechanisms occurring in these patients after the exposure to the hypoxic stimulus triggered by physical exercise have currently not been described in populations living at high altitude. METHODS: The clinical trial we are presenting here consists of a quasi-experimental design with longitudinal analysis of repeated measures, with intra- and inter-group comparisons, measuring primary and secondary variables in 4 temporal points. Participants will be people with a diagnosis of COPD residing at high altitudes (> 2600 m), without oncological, renal, cardiac, or musculoskeletal comorbidities with a low level of physical activity. The intervention will be an 8-week program of physical exercise of resistance and muscular strength (8-WVP) which will be carried out at home. Primary outcome variables will be the expression of HIF-1α, VEGF, and EPO. As secondary outcome variables, we will consider lung function (measured by spirometry), physical performance (measured by ergospirometry and dynamometry), and hematological parameters. DISCUSSION: The results obtained after the clinical trial proposed here will promote knowledge on the expression of signaling proteins as an adaptive response to hypoxia in people with COPD living at high altitude, which will be relevant because there are not data on this population group. The knowledge generated from the application of this protocol will increase the pathophysiological understanding of the disease and future medical and therapeutic decision-making based on physical exercise prescription. TRIAL REGISTRATION {2A}: NCT04955977 [ClinicalTrials.gov]-NCT04955977 [WHO ICRTP]. First Posted: July 9, 2021.

Effect of hypobaric hypoxia on hematological parameters related to oxygen transport, blood volume and oxygen consumption in adolescent endurance-training athletes.

Objective: To analyze the effect of altitude on hematological and cardiorespiratory variables in adolescent athletes participating in aerobic disciplines. Methods: 21 females and 89 males participated in the study. All were adolescent elite athletes engaged in endurance sports (skating, running and cycling) belonging to two groups: permanent residents in either low altitude (LA, 966 m) or moderate altitude (MA, 2640 m). Hematocrit (Hct), hemoglobin concentration ([Hb]), total hemoglobin mass (Hbt), blood, plasma and erythrocyte volumes (BV, PV and EV), VO2peak and other cardiorespiratory parameters were evaluated. Results: Sex differences were evident both in LA and HA skating practitioners, the males having higher significant values than the females in oxygen transport-related hematological parameters and VO2peak. The effect of altitude residence was also observed in Hct, [Hb], Hbt and EV with increased (14%-18%) values in the hematological parameters and higher EV (5%-24%). These results matched the significantly higher values of VO2peak measured in MA residents. However, BV and PV did not show differences between LA and MA residents in any case. Sports discipline influenced neither the hematological variables nor most of the cardiorespiratory parameters. Conclusions: LA and MA adolescent skaters showed sex differences in hematological variables. Endurance-trained male adolescent residents at MA had an increased erythropoietic response and a higher VO2peak compared to their counterparts residing and training at LA. These responses are similar in the three aerobic sports studied, indicating that the variables described are highly sensitive to hypoxia irrespective of the sports discipline.

Hemoglobin Mass, Blood Volume and VO2max of Trained and Untrained Children and Adolescents Living at Different Altitudes.

Introduction: To a considerable extent, the magnitude of blood volume (BV) and hemoglobin mass (Hbmass) contribute to the maximum O2-uptake (VO2max), especially in endurance-trained athletes. However, the development of Hbmass and BV and their relationships with VO2max during childhood are unknown. The aim of the present cross-sectional study was to investigate Hbmass and BV and their relationships with VO2max in children and adolescents. In addition, the possible influence of endurance training and chronic hypoxia was evaluated. Methods: A total of 475 differently trained children and adolescents (girls n = 217, boys n = 258; untrained n = 171, endurance trained n = 304) living at two different altitudes (∼1,000 m, n = 204, ∼2,600 m, n = 271) and 9-18 years old participated in the study. The stage of puberty was determined according to Tanner; Hbmass and BV were determined by CO rebreathing; and VO2max was determined by cycle ergometry and for runners on the treadmill. Results: Before puberty, there was no association between training status and Hbmass or BV. During and after puberty, we found 7-10% higher values in the trained groups. Living at a moderate altitude had a uniformly positive effect of ∼7% on Hbmass in all groups and no effect on BV. The VO2max before, during and after puberty was strongly associated with training (pre/early puberty: boys +27%, girls +26%; mid puberty: +42% and +45%; late puberty: +43% and +47%) but not with altitude. The associated effects of training in the pre/early pubertal groups were independent of Hbmass and BV, while in the mid- and late pubertal groups, 25% of the training effect could be attributed to the elevated Hbmass. Conclusions: The associated effects of training on Hbmass and BV, resulting in increased VO2max, can only be observed after the onset of puberty.

Quantification of testosterone-dependent erythropoiesis during male puberty.

NEW FINDINGS: What is the central question of this study? To what extent does testosterone influence haemoglobin formation during male puberty? What is the main finding and its importance? In boys, testosterone might be responsible for about 65% of the increase in haemoglobin mass during puberty. The underlying mechanisms are assumed to be twofold: (i) indirectly, mediated by the increase in lean body mass, and (ii) directly by immediate testosterone effects on erythropoiesis. Thereby, an increase in testosterone of 1 ng/ml is associated with an increase in haemoglobin mass of ∼65 g. These processes are likely to determine endurance performance in adulthood. ABSTRACT: The amount of haemoglobin during puberty is related to endurance performance in adulthood. During male puberty, testosterone stimulates erythropoiesis and could therefore be used as a marker for later endurance performance. This cross-sectional study aimed to determine the relationship between serum testosterone concentration and haemoglobin mass (Hbmass) in both male and female children and adolescents and to evaluate the possible influences of altitude and training. Three-hundred and thirteen differentially trained boys and girls aged from 9 to 18 years and living at altitudes of 1000 and 2600 m above sea level entered the study. The stage of sexual maturation was determined according to the classification of Tanner. Testosterone was measured by ELISA. Hbmass was determined by CO-rebreathing. Haemoglobin concentration did not change during maturation in girls and was 11% higher during puberty in boys, while Hbmass was elevated by 33% in Tanner stage V compared to stage II in girls (498 ± 77 vs. 373 ± 88 g) and by 95% in boys (832 ± 143 vs. 428 ± 95 g). This difference can most likely be attributed to indirect testosterone influences through an increase in lean body mass (LBM) and to direct testosterone effects on erythropoiesis, which increase the Hbmass by ∼65 g per 1 ng/ml. Altitude and training statuses were not associated with testosterone, but with an increase in Hbmass (altitude by 1.1 g/kg LBM, training by 0.8 g/kg LBM). Changes in Hbmass are closely related to testosterone levels during male puberty. Further studies will show whether testosterone and Hbmass during childhood and adolescence can be used as diagnostic tools for endurance talents.

[BEHAVIOR OF HEMOGLOBIN CONCENTRATION, HEMATOCRIT AND OXYGEN SATURATION IN COLOMBIAN UNIVERSITY POPULATION AT DIFFERENT ALTITUDES]. / COMPORTAMIENTO DE LA CONCENTRACIÓN DE HEMOGLOBINA, EL HEMATOCRITO Y LA SATURACIÓN DE OXÍGENO EN UNA POBLACIÓN UNIVERSITARIA EN COLOMBIA A DIFERENTES ALTURAS.

INTRODUCTION: the development of this research is base on the growing interest in understanding the adaptations to chronic hipoxia mainly in the range of intermediate altitudes (1 500-3 000 m.s.n.m) and the need to establish parameters of normality in the variables [Hb], Hct and SO2 for diagnostic and characterization of the population purposes. OBJECTIVE: to analyze the behavior of the [Hb], Hct and SaO2 at different intermediate altitudes (970 m.s.n.m, 1 520 m.s.n.m, 1 728 m.s.n.m, 1 923 m.s.n.m, 2 180 m.s.n.m and 2 600 m.s.n.m) in order to contribute to the knowledge of the high altitude physiology and the clinical field to support the diagnosis of anemia. METHODS: clinically healthy subjects with low levels of physical activity and food consumption report containing iron. Total of 264 participants of both genders between 18 and 30 years. The blood samples were collected from the antecubital vein and the earlobe and analyzed in a radiometer. A non-parametric statistical analysis was performed. RESULTS: with increasing of altitude, [Hb] and Hct values were increased while the SO2 decreased. Men showed higher values than women in [Hb] and Hct, related to lower values of SO2 than women. DISCUSSION: a threshold variable was not found, perhaps because of the small distance between the altitudes. The values reported were similar but not identical to other studies. This difference could be explained by genetic diversity among populations. CONCLUSIONS: this study allows for the first values of characterization of the study population. All altitudes were above the cutoff for the diagnosis of anemia ([Hb] 12 g/dl).

Introducción: el desarrollo de la presente investigación se basa en el creciente interés por comprender las adaptaciones a la hipoxia crónica, principalmente en el rango altitudinal denominado de alturas intermedias (1.500- 3.000 m.s.n.m), con la necesidad de establecer parámetros de normalidad en las variables [Hb], Hct y SO2 con fines diagnósticos y de caracterización de la población. Objetivos: analizar el comportamiento de la [Hb], el Hct y la SaO2 a diferentes alturas intermedias (970 m.s.n.m, 1.520 m.s.n.m, 1.728 m.s.n.m, 1.923 m.s.n.m, 2.180 m.s.n.m y 2.600 m.s.n.m) con el fin de aportar conocimiento sobre la fisiología de la altura y al campo clínico para apoyar el diagnóstico de anemia. Métodos: sujetos clínicamente sanos, con nivel bajo de actividad física y reporte de consumo de alimentos con contenido de hierro. Total de 264 participantes de ambos géneros entre 18 y 30 años. Las muestras se obtuvieron de sangre de la vena antecubital y del lóbulo de la oreja y fueron analizadas en un radiómetro. Se realizó un análisis estadístico no paramétrico. Resultados: con el incremento de la altitud los valores de [Hb] y Hct se incrementaron, mientras la SO2 descendió. Los hombres presentaron valores más altos que las mujeres en [Hb] y Hct, relacionado con valores más bajo de SO2 que las mujeres. Discusión: no se evidenció un umbral de las variables, quizás por la pequeña distancia entre las alturas. Los valores reportados fueron similares pero no iguales a otros estudios, lo que podría deberse a la diversidad genética entre poblaciones. Conclusiones: este estudio permite obtener los primeros valores de caracterización de la población estudiada. Todas las alturas estuvieron por encima del punto de corte para el diagnóstico de anemia ([Hb] 12 g/dl).

Comportamiento de la concentración de hemoglobina, el hematocrito y la saturación de oxígeno en una población universitaria en Colombia a diferentes alturas / Behavior of hemoglobin concentration, hematocrit and oxygen saturation in colombian university population at different altitudes

Introducción: el desarrollo de la presente investigación se basa en el creciente interés por comprender las adaptaciones a la hipoxia crónica, principalmente en el rango altitudinal denominado de alturas intermedias (1.500- 3.000 m.s.n.m), con la necesidad de establecer parámetros de normalidad en las variables [Hb], Hct y SO2 con fines diagnósticos y de caracterización de la población. Objetivos: analizar el comportamiento de la [Hb], el Hct y la SaO2 a diferentes alturas intermedias (970 m.s.n.m, 1.520 m.s.n.m, 1.728 m.s.n.m, 1.923 m.s.n.m, 2.180 m.s.n.m y 2.600 m.s.n.m) con el fin de aportar conocimiento sobre la fisiología de la altura y al campo clínico para apoyar el diagnóstico de anemia. Métodos: sujetos clínicamente sanos, con nivel bajo de actividad física y reporte de consumo de alimentos con contenido de hierro. Total de 264 participantes de ambos géneros entre 18 y 30 años. Las muestras se obtuvieron de sangre de la vena antecubital y del lóbulo de la oreja y fueron analizadas en un radiómetro. Se realizó un análisis estadístico no paramétrico. Resultados: con el incremento de la altitud los valores de [Hb] y Hct se incrementaron, mientras la SO2 descendió. Los hombres presentaron valores más altos que las mujeres en [Hb] y Hct, relacionado con valores más bajo de SO2 que las mujeres. Discusión: no se evidenció un umbral de las variables, quizás por la pequeña distancia entre las alturas. Los valores reportados fueron similares pero no iguales a otros estudios, lo que podría deberse a la diversidad genética entre poblaciones. Conclusiones: este estudio permite obtener los primeros valores de caracterización de la población estudiada. Todas las alturas estuvieron por encima del punto de corte para el diagnóstico de anemia ([Hb] 12 g/dl) (AU)

Introduction: the development of this research is base on the growing interest in understanding the adaptations to chronic hipoxia mainly in the range of intermediate altitudes (1 500-3 000 m.s.n.m) and the need to establish parameters of normality in the variables [Hb], Hct and SO2 for diagnostic and characterization of the population purposes. Objective: to analyze the behavior of the [Hb], Hct and SaO2 at different intermediate altitudes (970 m.s.n.m, 1520 m.s.n.m, 1 728 m.s.n.m, 1 923 m.s.n.m, 2 180 m.s.n.m and 2600 m.s.n.m) in order to contribute to the knowledge of the high altitude physiology and the clinical field to support the diagnosis of anemia. Methods: clinically healthy subjects with low levels of physical activity and food consumption report containing iron. Total of 264 participants of both genders between 18 and 30 years. The blood samples were collected from the antecubital vein and the earlobe and analyzed in a radiometer. A non-parametric statistical analysis was performed. Results: with increasing of altitude, [Hb] and Hct values were increased while the SO2 decreased. Men showed higher values than women in [Hb] and Hct, related to lower values of SO2 than women. Discussion: a threshold variable was not found, perhaps because of the small distance between the altitudes. The values reported were similar but not identical to other studies. This difference could be explained by genetic diversity among populations. Conclusions: this study allows for the first values of characterization of the study population. All altitudes were above the cutoff for the diagnosis of anemia ([Hb] 12 g/dl) (AU)

Efectos de la exposición a la altura sobre los indicadores de la eritropoyesis y el metabolismo del hierro / Effects of high altitude exposure on erythropoiesis and iron metabolism

Antecedentes. La investigación sobre los efectos de la exposición a la altura sobre la eritropoyesis y el metabolismo de hierro ha permitido conocer el comportamiento y las adaptaciones que se presentan en poblaciones residentes o expuestas a diversas alturas sobre el nivel del mar. Objetivo. El presente artículo de revisión tiene como objetivo analizar la información científica disponible y actualizar al lector respecto al efecto de la altura sobre los indicadores de la eritropoyesis y el metabolismo del hierro. Materiales y métodos. Se realizó una búsqueda de artículos de diferentes bases de datos como PubMed, MEDLINE, Scielo, EBSCO y OVID, la cual se hizo con base en los títulos médicos MeSH (Medical Subjects Headings) y DeCS Bireme (descriptores de la salud). Resultados. A nivel de la eritropoyesis se puede observar un incremento de la eritropoyetina y de los reticulocitos con el incremento en la altura. En el metabolismo del hierro se puede apreciar un descenso de las reservas del hierro (ferritina) y un incremento de la transferrina y del receptor soluble de transferrina con ascenso en la altitud. Conclusión. La magnitud de estos incrementos depende del tiempo de exposición a la hipoxia, el género y la población, ya que se han encontrado diferencias entre etnias que viven a la misma altura pero presentan diferencias en las adaptaciones. Las investigaciones existentes están referidas a grandes alturas, pero en alturas intermedias por debajo de los 2600 m s. n. m. todavía existen grandes interrogantes.

Background. Research on the effects of high altitude exposure on erythropoiesis and iron metabolism has revealed the behavior and adaptations that occur in populations that visit or live at different altitudes above sea level. Objective. To analyze the scientific information available and to give an update to the reader regarding the effects of high altitude exposure on erythropoiesis and iron metabolism. Materials and Methods. A research of articles in different databases such us PubMed, MEDLINE, Scielo, EBSCO and OVIDm was performed. This research was based on the MeSH (Medical Subject Headings) and DeCS Bireme (Health Descriptors) descriptors lists. Results. Regarding erythropoiesis, an increase of erythropoietin and reticulocytes have been observed when the altitude increases. Regarding iron metabolism a decline in reserves of iron (ferritin) and an increase of transferrin and soluble transferrin receptor can be noted when the altitude increases. Conclusion. The magnitude of these increases depends on the time of exposure to hypoxia, the individual's gender and the population, since differences between ethnic groups living at the same altitude have been found. Existing research is related to great altitudes, but at intermediate altitudes, below 2600m s. n. m., there is not enough research.