Abstract

The benefits of intermittent hypobaric hypoxia (IHH) exposure for health and its potential use as a training tool are well-documented. However, since hypobaric hypoxia and cold are environmental factors always strongly associated in the biosphere, additive or synergistic adaptations could have evolved in animals’ genomes. For that reason, the aim of the present study was to investigate body composition and hematological and muscle morphofunctional responses to simultaneous intermittent exposure to hypoxia and cold. Adult male rats were randomly divided into four groups: (1) control, maintained in normoxia at 25°C (CTRL); (2) IHH exposed 4 h/day at 4,500 m (HYPO); (3) intermittent cold exposed 4 h/day at 4°C (COLD); and (4) simultaneously cold and hypoxia exposed (COHY). At the end of 9 and 21 days of exposure, blood was withdrawn and gastrocnemius (GAS) and tibialis anterior muscles, perigonadal and brown adipose tissue, diaphragm, and heart were excised. GAS transversal sections were stained for myofibrillar ATPase and succinate dehydrogenase for fiber typing and for endothelial ATPase to assess capillarization. Hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and glucose transporter 1 (GLUT1) from GAS samples were semi-quantified by Western blotting. COLD and HYPO underwent physiological adjustments such as higher brown adipose tissue weight and increase in blood-related oxygen transport parameters, while avoiding some negative effects of chronic exposure to cold and hypoxia, such as body weight and muscle mass loss. COHY presented an additive erythropoietic response and was prevented from right ventricle hypertrophy. Intermittent cold exposure induced muscle angiogenesis, and IHH seems to indicate better muscle oxygenation through fiber area reduction.

Highlights

  • More than 140 million people worldwide live at high altitude and 40 million people are exposed to altitude environment due to recreational or other reasons (Moore et al, 1998; West et al, 2012)

  • On day 2 of intervention, animals exposed to intermittent hypobaric hypoxia (IHH) (HYPO and cold and hypoxia (COHY)) suffered a significant (p < 0.001 and p < 0.001, respectively) body weight (BW) loss compared to CTRL, whose BW increased slightly respective to its initial values

  • Regarding perigonadal (epididymal) adipose tissue (PAT), no statistical differences were found among the different groups on day 9 of the study, but a significant reduction in PAT/BW ratio was found in hypoxia was applied alone (HYPO) compared with the other three groups after 21 days of IHH sessions

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Summary

Introduction

More than 140 million people worldwide live at high altitude (above 2,500 m) and 40 million people are exposed to altitude environment due to recreational or other reasons (Moore et al, 1998; West et al, 2012). Altitude is characterized by low barometric pressure and, reduced atmospheric oxygen partial pressure (PO2), which in turn results in a decrease in arterial oxygen. Organisms can react with a wide range of responses to low PO2 (Breen et al, 2008; Lundby et al, 2009), but the magnitude of this response to hypoxia is directly related to the dose because the severity of the hypoxemia, the duration of the hypoxic exposure, and its frequency are responsible for the subsequent beneficial or pathological reaction (hormesis) (Navarrete-Opazo and Mitchell, 2014). Intermittent hypoxia is characterized by long periods of normoxia alternated with periods in hypoxia, resulting in a potentially cumulative effect that begins with the first exposure (Neubauer, 2001; Viscor et al, 2018). It has been shown that IHH enhances erythropoiesis and aerobic capacity, improves muscle capillarization and metabolism, controls hypertension, accelerates tissue repair, ameliorates bronchial asthma, regulates metabolic syndrome, and improves altitude acclimatization (see for review Viscor et al, 2018)

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