Diagnosis and prophylaxis for high-altitude acclimatization: Adherence to molecular rationale to evade high-altitude illnesses (original) (raw)
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Plasma protein(s)–based conceptual diagnostic tool for assessing high-altitude acclimation in humans
Functional & Integrative Genomics, 2019
Exposure to high altitude above 3000 m leads to two outcomes-acclimation or high-altitude maladies. To reach a particular outcome, the plasma proteome is modified differentially, either in context of an acclimation response or mal-acclimation response leading to disease. This ensures that hypoxia-responsive plasma protein trends reflect acclimation in acclimated individuals when compared with their levels prior to acclimation. Such protein trends could be used to assess acclimation in an individual and any significant deviation from this trend may indicate non-acclimation, thereby preventing high-altitude illnesses before they manifest. In this study, we investigate and statistically evaluate the trendlines of various hypoxia-responsive plasma protein levels, reported significantly perturbed in our previous studies, in individuals (male; n = 20) exposed to 3520 m at high-altitude day 1 (HAD1), HAD4, and HAD7L and to 4420 m at HAD7H, HAD30, and HAD120. We observe that thioredoxin (Trx), glutathione peroxidase 3 (GPx-3), and apolipoprotein AI (Apo-AI) are statistically robust markers to assess acclimation across the exposure duration while sulfotransferase 1A1 (ST1A1) is a capable negative control whose levels increase only in cases of HAPE. We also observe exposure day-specific and resident altitude-specific proteins capable of accurately assessing acclimation when compared with baseline levels or the lower altitude zone.
Deciphering Molecular Cascades In A Novel Acclimatization Strategy For Rapid Ascent To High Altitude
The repercussions of hypobaric hypoxia are dependent upon two factors: time and intensity of exposure. The effects of intensity i.e. variation of altitude are yet unknown although it is a significant factor in terms of acclimatization protocols. In this study we present the effects of acute (24 h) exposure to high (10,000 ft), very high (15,000 ft) and extreme altitude (25,000 ft) zones on lung and plasma using semi-quantitative redox specific transcripts and quantitative proteo-bioinformatics workflow in conjunction with redox stress assays. Our findings indicate that very high altitude exposure elicits systemic redox homeostatic processes due to failure of lung redox homeostasis without causing mortality. We also document a rapid acclimatization protocol causing a shift from 0 to 100% survival at 25,000 ft in male SD rats upon rapid induction. Finally we posit the various processes involved and the plasma proteins that can be used to ascertain the acclimatization status of an indi...
Physiology of high-altitude acclimatization
Resonance, 2014
Travel to high altitude exposes the human body to a variety of stresses, the most prominent being reduced available oxygen with increase in altitude due to reduced partial pressure of oxygen. Several physiological responses are initiated in the human body to promote faster acclimatization to these adverse environmental conditions. These physiological and molecular readjustments encompassing acclimatization, namely, hypoxic ventilatory response, diuresis, increased cardiac output, improved oxygen carrying capacity and cerebral blood flow, Hypoxia inducible factor 1 stabilization, etc., converge to a single outcome, ensuring optimal bioavailability of oxygen. In this article, we describe the basic acclimatization framework mentioned above. RESONANCE June 2014 GENERAL ARTICLE The state of suboptimal O 2 availability due to decreased ambient barometric pressure is termed as hypobaric hypoxia.
Journal of Clinical Medicine
High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the mai...
2021
Rapid induction of soldiers to high altitude under emergency situation may lead to higher incidence of acute mountain sickness (AMS) and other high altitude illness. Intermittent Hypoxia Training (IHT) at sea level before going to high altitude is an approach for rapid acclimatisation. This approach may be helpful to reduce the occurrence of AMS and leads to better acclimatisation at high altitude in shorter duration. The present study evaluates the role of biochemical markers of acclimatisation after IHT before induction to actual high altitude. The study participants were Indian Army Personnel (n=30) and they were divided into two groups of control (n=16) and IHT exposed (n=14). The intermittent hypoxia training was administered at 12 per cent Oxygen for 4h/day for 4 days at sea level using normobaric hypoxia chamber and within 24 hrs 48 hrs the subjects were airlifted to Leh, Ladakh, India at 11,700 ft. Preconditioning with IHT may be beneficial in maintaining antioxidant levels ...
Pflügers Archiv - European Journal of Physiology, 2019
Intermittent hypoxic training (IHT) is a discrete cost-effective method for improving athletic performance and high altitude acclimatization. Unfortunately, IHT protocols widely vary in terms of hypoxia severity, duration, and number of cycles affecting physiological outcomes. In the present study, we evaluated the efficacy of a moderate normobaric IHT protocol (12% FiO 2 for 4 h, 4 days) on acclimatization to high altitude (3250 m). Global plasma proteomics studies revealed that IHT elicited acute-phase response proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and alpha-1-acid glycoprotein 2 (AGP 2) as well as altered levels of several apolipoproteins. On subsequent exposure to high altitude, the IH trained volunteers exhibited significant higher arterial oxygen saturation with concomitant lower incidences of acute mountain sickness (AMS) as compared to controls. Interestingly, IH trained subjects exhibited lower levels of positive acute-phase proteins like C-reactive protein (CRP), serum amyloid A-1 protein (SAA), and fibrinogen (FGA, FGB, and FGG) both after days 4 and 7 of high altitude ascent. High altitude exposure also decreased the levels of HDL, LDL, and associated proteins as well as key enzymes for assembly and maturation of lipoprotein particles like lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). In contrast, IHT curtailed hypoxia-induced alterations of HDL, LDL, Apo-AI, Apo-B, LCAT, CETP, and PLTP. Further validation of results also corroborated attenuation of hypoxia-induced inflammation and dyslipidemia by IHT. These results provide molecular evidences supporting the use of moderate IHT as a potential nonpharmacological strategy for high altitude acclimatization.
Hypoxia Conditioning for High-Altitude Pre-acclimatization
Journal of Science in Sport and Exercise, 2022
Purpose Main purposes of pre-acclimatization by hypoxia conditioning (HC) are the prevention of high-altitude illnesses and maintenance of aerobic exercise performance. However, robust evidence for those effects or evidence-based guidelines for exposure strategies, including recommendations to ensure safety, are largely lacking. Therefore, we summarize the current knowledge on the physiology of acclimatization to hypoxia and HC with the aim to derive implications for pre-acclimatization strategies before going on high-altitude treks and expeditions. Methods Based on the literature search and personal experience, core studies and important observations have been selected in order to present a balanced view on the current knowledge of high-altitude illnesses and the acclimatization process, specifically focusing on pre-acclimatization strategies by HC. Results and Conclusions It may be concluded that in certain cases even short periods (e.g., 7 h) of pre-acclimatization by HC are effe...