Acute Mountain Sickness Research Articles

Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism.

This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on the human intestinal flora and its metabolites. The changes in the intestinal flora, metabolism, and erythropoietin content in the AHAH population under altitude hypoxia conditions were comprehensively analyzed using 16S rRNA sequencing, metabonomics, and erythropoietin content. The results showed that compared with those in the control group (C group), the flora and metabolites in the hypoxemia group (D group) were altered. We found alterations in the flora according to the metabolic marker tyrosine through random forest and ROC analyses. Fecal and serum metabonomics analyses revealed that microbial metabolites could be absorbed into the blood and participate in human metabolism. Finally, a significant correlation between tyrosine and erythropoietin (EPO) content was found, which shows that human intestinal flora and its metabolites can help to confront altitude stress by regulating EPO levels. Our findings provide new insights into the adaptive mechanism and prevention of AHAH.

Quantifying systemic molecular networks affected during high altitude de-acclimatization

High altitude acclimatization and disease have been the centerpiece of investigations concerning human health at high altitude. Almost all investigations have focused on either understanding and ameliorating high altitude disease or finding better methods of acclimatization/training at high altitude. The aspect of altitude de-induction/de-acclimatization has remained clouded despite the fact that it was documented since the first decade of twentieth century. A few recent studies, particularly in China, have stated unanimously that high altitude de-acclimatization involved multiple observable clinical symptoms ranging from headache to abdominal distention. These symptoms have been collectively referred to as “high altitude de-acclimatization syndrome” (HADAS). However, computational omics and network biology centric investigations concerning HADAS are nascent. In this study, we focus on the quantitative proteo-informatics, especially network biology, of human plasma proteome in individuals who successfully descended from high altitude areas after a stay of 120 days. In brief, the protein list was uploaded into STRING and IPA to compute z-score based cut-offs which were used to analyze the directionality and significance of various identified protein networks as well as the proteins within them. Relevant upstream regulators extracted using computational strategies were also validated. Time-points till the 180th day of de-induction have been investigated to comparatively assess the changes in the plasma proteome and protein pathways of such individuals since the 7th day of arrival at altitude. Our investigation revealed extensive effects of de-induction on lipid metabolism, inflammation and innate immune system as well as coagulation system. This novel study provides a conceptual framework for formulating therapeutic strategies to ease the symptoms of HADAS during de-acclimatization. Such strategies should focus on normalization of lipid metabolism, inflammatory signaling and coagulation systems.

High Altitude Cerebral Edema with concomittent rhabdomyolysis: A rare presentation

We report the case of a young gentleman who developed High Altitude Cerebral Edema (HACE) along with rhabdomyolysis whilst on a trip to the northern areas of Pakistan. High Altitude Cerebral Edema (HACE) represents a serious and potentially fatal type of Acute Mountain sickness (AMS). Rhabdomyolysis presenting with HACE is uncommon however cases have been reported. In our patient, clinical presentation with severe bilateral lower limb pain and difficulty walking along with the increased agitation and confusion made it difficult to recognize; however early descent and management allowed for good recovery. MRI findings with microhemorrhages as found in our patient are increasingly being recognized in HACE with improving sensitivity of available imaging modalities. This case highlights the diverse clinical presentations that can exist with HACE and hence the need for medical professionals to maintain a high index of suspicion in anyone with a recent ascent to high altitude regions who develop neurological manifestations.

Analysis of Clinical Characteristics of Stress Response in the Digestive System Caused by Altitude Sickness

Analysis of Clinical Characteristics of Stress Response in the Digestive System Caused by Altitude Sickness

Abstract P129: Cardiovascular Safety Of Severe And Sustained Hypoxia Exposure In Physically Fit Patients Following Myocardial Infarction

In mice, hypoxia exposure corresponding to 8000 m altitude over several weeks induced myocardial proliferation and improved left ventricular ejection fraction following myocardial infarction. To enable translation of these findings from mice to patients with myocardial infarction, we determined whether exposure to severe sustained hypoxia is limited by right ventricular failure secondary to hypoxia-induced pulmonary hypertension. We enrolled three men who suffered myocardial infarctions 49-126 months prior to the study (left ventricular ejection fraction 47±7 %) but were otherwise healthy and one male, healthy control person. We induced hypoxia by adding nitrogen to ambient air until alveolar oxygen partial pressure decreased to 35 mmHg. Normobaric hypoxia was then maintained for 14 consecutive days (FiO2=0.095) corresponding to 6062- 6224 m altitude. We added 1% oxygen over night to ameliorate sleep and prevent acute mountain sickness. We conducted echocardiography at baseline, during hypoxia in hypoxic conditions and 3 days after reconditioning. Measurements included right ventricular to atrial pressure gradient as surrogate for pulmonary artery systolic pressure (PAPsys), tricuspid annulus systolic excursion (TAPSE) and right ventricular (RV) free wall strain. Hypoxia induced pulmonary hypertension, that rapidly abated in recovery (baseline: 35±3 mmHg, hypoxia: 47±9, recovery: 28±1, p=0.0292). TAPSE was not reduced by hypoxic exposure (baseline: 28±3 mmHg, hypoxia: 26±1 recovery: 29±2, p=0.0693) and right ventricular free wall strain was maintained (baseline: -22.4±3.9 mmHg, hypoxia: -24±5.4 recovery: -22.7±1.5, p=0.8493). The healthy control person showed similar responses. No signs or symptoms of right heart failure occurred throughout the study. In highly selected patients with myocardial infarction, substantial normobaric hypoxia induced pulmonary hypertension, however, right ventricular function was well preserved. These observations pave the way for translational studies on hypoxia-induced cardiovascular regeneration and may have implications for patients traveling to high altitude.

Genome and transcriptome of Ips nitidus provide insights into high-altitude hypoxia adaptation and symbiosis

Ips nitidus is a well-known conifer pest that has contributed significantly to spruce forest disturbance in the Qinghai-Tibet Plateau and seriously threatens the ecological balance of these areas. We report a chromosome-level genome of I.nitidus determined by PacBio and Hi-C technology. Phylogenetic inference showed that it diverged from the common ancestor of I.typographus ∼2.27 mya. Gene family expansion in I.nitidus was characterized by DNA damage repair and energy metabolism, which may facilitate adaptation to high-altitude hypoxia. Interestingly, differential gene expression analysis revealed upregulated genes associated with high-altitude hypoxia adaptation and downregulated genes associated with detoxification after feeding and tunneling in fungal symbiont Ophiostoma bicolor-colonized substrates. Our findings provide evidence of the potential adaptability of I.nitidus to conifer host, high-altitude hypoxia and insight into how fungal symbiont assist in this process. This study enhances our understanding of insect adaptation, symbiosis, and pest management.

Prevention of Acute Mountain Sickness (AMS) with particular emphasis on hydration: a review

Acute mountain sickness (AMS) causes a number of symptoms within the human body, associated with staying at altitudes higher than 2,500 meters above sea level without prior acclimatization. The human body begins to adapt its functioning to the conditions of hypobaric hypoxia in order to maintain homeostasis. Its disturbance can lead to respiratory failure, pulmonary, or cerebral oedema, and, consequently, death. The best method of AMS prevention is slow acclimatization. A high-carbohydrate diet, thermal protection, and pharmacological agents could be listed as additional prevention measures. The development of AMS is influenced by many factors such as ambient temperature, wind speed, altitude, physical preparation of participants, and appropriate protection against adverse effects of these factors. Nevertheless, both dehydration and overhydration may worsen the AMS symptoms. The body’s exposure to altitude and dehydration alone reduces aerobic performance. Appropriate hydration throughout a climb is necessary due to both intense physical exercise and a hypoxic environment.

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

Appetite, Hypoxia, and Acute Mountain Sickness: A 10-Hour Normobaric Hypoxic Chamber Study.

Barclay, Holly, Saptarshi Mukerji, Bengt Kayser, and Jui-Lin Fan. Appetite, hypoxia and acute mountain sickness: A 10-hour normobaric hypoxic chamber study. High Alt Med Biol. 24:329-335, 2023. Background: The effects of hypoxia and acute mountain sickness (AMS) on appetite and food preferences are moot, especially during the early phase of hypoxic exposure. We examined the effects of a 10-hour hypoxic exposure on appetite and food preference. Methods: We assessed appetite (hunger, satisfaction, fullness, perceived appetite, and lost appetite), food preferences (sweet, salty, savory, and fatty), and AMS (Lake Louise score) with questionnaires in 27 healthy individuals (13 women) across 10-hour exposures to normobaric normoxia (fraction of inspired O2 [FiO2]: 0.21) and normobaric hypoxia (FiO2: 0.12, equivalent of 5,000 m) in a randomized, single-blinded manner. Results and Conclusions: Compared with normoxia, hypoxia decreased hunger and appetite (p = 0.040 and <0.001, respectively), which was mediated by a decreased desire for sweet, salty, and fatty foods (p < 0.05 for all). AMS was associated with a decreased desire for sweet (R = -0.438, p = 0.032) and salty foods (R = -0.460, p = 0.024) and greater loss of appetite (R = -0.619, p = 0.018). Our findings suggest that acute hypoxia rapidly suppresses appetite and that AMS development further amplifies anorexia. Clinical Trial Registration Number: ACTRN12618000548235.

The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia

The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia

Eleutheroside E from pre-treatment of Acanthopanax senticosus (Rupr.etMaxim.) Harms ameliorates high-altitude-induced heart injury by regulating NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 pathway.

Eleutheroside E, a major natural bioactive compound in Acanthopanax senticosus (Rupr.etMaxim.) Harms, possesses anti-oxidative, anti-fatigue, anti-inflammatory, anti-bacterial and immunoregulatory effects. High-altitude hypobaric hypoxia affects blood flow and oxygen utilisation, resulting in severe heart injury that cannot be reversed, thereby eventually causing or exacerbating high-altitude heart disease and heart failure. The purpose of this study was to determine the cardioprotective effects of eleutheroside E against high-altitude-induced heart injury (HAHI), and to study the mechanisms by which this happens. A hypobaric hypoxia chamber was used in the study to simulate hypobaric hypoxia at the high altitude of 6000m. 42 male rats were randomly assigned to 6 equal groups and pre-treated with saline, eleutheroside E 100mg/kg, eleutheroside E 50mg/kg, or nigericin 4mg/kg. Eleutheroside E exhibited significant dose-dependent effects on a rat model of HAHI by suppressing inflammation and pyroptosis. Eleutheroside E downregulated the expressions of brain natriuretic peptide (BNP), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH). Moreover, The ECG also showed eleutheroside E improved the changes in QT interval, corrected QT interval, QRS interval and heart rate. Eleutheroside E remarkably suppressed the expressions of NLRP3/caspase-1-related proteins and pro-inflammatory factors in heart tissue of the model rats. Nigericin, known as an agonist of NLRP3 inflammasome-mediated pyroptosis, reversed the effects of eleutheroside E. Eleutheroside E prevented HAHI and inhibited inflammation and pyroptosis via the NLRP3/caspase-1 signalling pathway. Taken together, eleutheroside E is a prospective, effective, safe and inexpensive agent that can be used to treat HAHI.

Effect of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults: the Shigatse CARdiorespiratory fitness study design.

Cardiorespiratory function influences exercise capacity and is an important determinant of high-altitude adaptation. Some studies have investigated the characteristics of changes in cardiorespiratory fitness during high-altitude acclimatization. However, studies on changes in cardiorespiratory fitness during high-altitude de-acclimatization are still lacking and have not yet been elucidated. Furthermore, few drugs have been studied to improve cardiorespiratory function during both processes. The Shigatse CARdiorespiratory Fitness (SCARF) study is a single-center, randomized, double-blind, placebo-control clinical trial to explore the effects of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults. Participants will be randomly assigned 1:1 to ubiquinol 200 mg daily or a placebo for 14 days before departure until the end of data collection after return in 7 days. Cardiorespiratory fitness is the primary outcome, while acute mountain sickness and high-altitude de-acclimatization symptoms are secondary endpoints. In addition, laboratory measurements, including routine blood tests and serological measurements, will be performed. To the best of our knowledge, the SCARF study will be the first to reveal the changes in the cardiorespiratory fitness characteristics during high-altitude acclimatization and de-acclimatization. Furthermore, the results of this study will contribute to exploring whether ubiquinol supplementation could be beneficial for endurance exercise capacity at different altitudes and help improve adaptation to acute hypoxia and de-acclimatization. Clinical Trial Registration: This study has been registered in the Chinese Clinical Trial Register (www.chictr.org.cn) as ChiCTR2200059900 and ChiCTR2200066328.

Comparative study of Heart Rate variability in pregnant women living in conditions of High-mountain Hypoxia of the Pamirs and the steppe zone of Central Kazakhstan

A comparative analysis of the main indicators of heart rate variability was carried out in 72 women aged 25-35 with a normal course of pregnancy, 90-30 days and 10-5 days before delivery, living in different geographical areas: high-mountainous region of Tajikistan (Pamir, Murghab village, 3600-4200m above sea level) and the steppe region of Central Kazakhstan (546m above sea level). The mechanism of compensatory-adaptive reactions, which is not typical for other regions, was revealed in pregnant women living in conditions of high-altitude hypoxia. In women living in the territory of Central Kazakhstan, at 90-30 days before delivery, pregnancy proceeded against the background of increased activity of the sympathetic division of the autonomic nervous system (SD of ANS). Recovery of heart rate variability (HRV) began 10–5 days before term birth, which is the result of a decrease in the effectiveness of adrenergic effects and an increase in the effectiveness of M-cholinergic effects on heart rate, according to some authors1,2. These changes in HRV can be successfully used as a biological marker of a mother’s readiness for childbirth, taking into account the availability and safety of the HRV method. In Pamir women, an increase in the activity of the parasympathetic division (PD) of ANS was noted 90-30 days before childbirth, and persisted until delivery. Starting from the third trimester of pregnancy, the dynamics of the values of such parameters as AMo (amplitude mode), ARI (autonomic rhythm index), RMSD (root mean square deviation), VR (variation range) showed a optimal functional state of regulatory systems before childbirth. This was also evidenced by the value of the stress index, which was in the range of 194-197 units. This mechanism of regulation in the conditions of high-altitude hypoxia ensures the normal development of the fetus and the mobilization of the functional reserves of newborns during childbirth and after birth.

High-altitude cerebral hypoxia promotes mitochondrial dysfunction and apoptosis of mouse neurons.

Neuronal cell death is an important factor in the pathogenesis of acute high-altitude cerebral hypoxia; however, the underlying molecular mechanism remains unclear. In this study, we tested if high-altitude hypoxia (HAH) causes neuronal death and mitochondrial dysfunction using various in vivo and in vitro approaches. Acute high-altitude cerebral hypoxia was induced by hypobaric hypoxia chamber in male mice. we explored the mechanisms of neuronal cell death using immunofluorescence, western blotting, transmission electron microscopy, and flow cytometry. Next, mitochondrial function and morphology were observed using Jc-1 staining, seahorse assay, western blotting, MitoTracker staining, and transmission electron microscopy. Moreover, open field test, elevated plus test, and Morris water maze were applied for animal behavior. Results revealed that HAH disrupted mitochondrial function and promoted neuronal apoptosis and necroptosis both in HT-22 cells and in mouse hippocampal neurons. Moreover, the mitochondrial membrane potential and adenosine triphosphate production decreased in neurons after HAH, while oxidative stress and mitochondrial fission increased. Behavioral studies suggested that HAH induced anxiety-like behavior and impaired spatial memory, while it had no effect on athletic ability. These findings demonstrated that HAH promotes mitochondrial dysfunction and apoptosis of mouse neurons, thus providing new insights into the role of mitochondrial function and neuronal cell death in acute high-altitude cerebral hypoxia.

A comprehensive review of natural products with anti-hypoxic activity.

Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.

Energy metabolic mechanisms for high altitude sickness: Downregulation of glycolysis and upregulation of the lactic acid/amino acid-pyruvate-TCA pathways and fatty acid oxidation

Hypobaric hypoxia is often associated with the plateau environment and can lead to altitude sickness or death. The underlying cause is a lack of oxygen, which limits energy metabolism and leads to a compensatory stress response. Although glycolysis is commonly accepted as the primary energy source during clinical hypoxia, our preliminary experiments suggest that hypobaric hypoxia may depress glycolysis. To provide a more comprehensive understanding of energy metabolism under short-term hypobaric hypoxia, we exposed mice to a simulated altitude of 5000 m for 6 or 12 h. After the exposure, we collected blood and liver tissues to quantify the substrates, enzymes, and metabolites involved in glycolysis, lactic acid metabolism, the tricarboxylic acid cycle (TCA), and fatty acid β-oxidation. We also performed transcriptome and enzymatic activity analyses of the liver. Our results show that 6 h of hypoxic exposure significantly increased blood glucose, decreased lactic acid and triglyceride concentrations, and altered liver enzyme activities of mice exposed to hypoxia. The key enzymes in the glycolytic, TCA, and fatty acid β-oxidation pathways were primarily affected. Specifically, the activities of key glycolytic enzymes, such as glucokinase, decreased significantly, while the activities of enzymes in the TCA cycle, such as isocitrate dehydrogenase, increased significantly. Lactate dehydrogenase, pyruvate carboxylase, and alanine aminotransferase were upregulated. These changes were partially restored when the exposure time was extended to 12 h, except for further downregulation of phosphofructokinase and glucokinase. This study demonstrates that acute high altitude hypoxia upregulated the lactic acid/amino acid-pyruvate-TCA pathways and fatty acid oxidation, but downregulated glycolysis in the liver of mice. The results obtained in this study provide a theoretical framework for understanding the mechanisms underlying the pathogenesis of high-altitude sickness in humans. Additionally, these findings have potential implications for the development of prevention and treatment strategies for altitude sickness.

Partial Pressure of Arterial Oxygen in Healthy Adults at High Altitudes

With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao2 decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown. To calculate an effect size estimate for the decrease in Pao2 with each kilometer of vertical gain among healthy unacclimatized adults and to identify factors associated with Pao2 at high altitude (HA). A systematic search of PubMed and Embase was performed from database inception to April 11, 2023. Search terms included arterial blood gases and altitude. A total of 53 peer-reviewed prospective studies in healthy adults providing results of arterial blood gas analysis at low altitude (<1500 m) and within the first 3 days at the target altitude (≥1500 m) were analyzed. Primary and secondary outcomes as well as study characteristics were extracted from the included studies, and individual participant data (IPD) were requested. Estimates were pooled using a random-effects DerSimonian-Laird model for the meta-analysis. Mean effect size estimates and 95% CIs for reduction in Pao2 at HA and factors associated with Pao2 at HA in healthy adults. All of the 53 studies involving 777 adults (mean [SD] age, 36.2 [10.5] years; 510 men [65.6%]) reporting 115 group ascents to altitudes between 1524 m and 8730 m were included in the aggregated data analysis; 13 of those studies involving 305 individuals (mean [SD] age, 39.8 [13.6] years; 185 men [60.7%]) reporting 29 ascents were included in the IPD analysis. The estimated effect size of Pao2 was -1.60 kPa (95% CI, -1.73 to -1.47 kPa) for each 1000 m of altitude gain (τ2 = 0.14; I2 = 86%). The Pao2 estimation model based on IPD data revealed that target altitude (-1.53 kPa per 1000 m; 95% CI, -1.63 to -1.42 kPa per 1000 m), age (-0.01 kPa per year; 95% CI, -0.02 to -0.003 kPa per year), and time spent at an altitude of 1500 m or higher (0.16 kPa per day; 95% CI, 0.11-0.21 kPa per day) were significantly associated with Pao2. In this systematic review and meta-analysis, the mean decrease in Pao2 was 1.60 kPa per 1000 m of vertical ascent. This effect size estimate may improve the understanding of physiological mechanisms, assist in the clinical interpretation of acute altitude illness in healthy individuals, and serve as a reference for physicians counseling patients with cardiorespiratory disease who are traveling to HA regions.

Active ascent accelerates the time course but not the overall incidence and severity of acute mountain sickness at 3,600 m.

Acute mountain sickness (AMS) typically peaks following the first night at high altitude (HA) and resolves over the next 2-3 days, but the impact of active ascent on AMS is debated. To determine the impact of ascent conditions on AMS, 78 healthy Soldiers (means ± SD; age = 26 ± 5 yr) were tested at baseline residence, transported to Taos, NM (2,845 m), hiked (n = 39) or were driven (n = 39) to HA (3,600 m), and stayed for 4 days. AMS-cerebral (AMS-C) factor score was assessed at HA twice on day 1 (HA1), five times on days 2 and 3 (HA2 and HA3), and once on day 4 (HA4). If AMS-C was ≥0.7 at any assessment, individuals were AMS susceptible (AMS+; n = 33); others were nonsusceptible (AMS-; n = 45). Daily peak AMS-C scores were analyzed. Ascent conditions (active vs. passive) did not impact the overall incidence and severity of AMS at HA1-HA4. The AMS+ group, however, demonstrated a higher (P < 0.05) AMS incidence in the active vs. passive ascent cohort on HA1 (93% vs. 56%), similar incidence on HA2 (60% vs. 78%), lower incidence (P < 0.05) on HA3 (33% vs. 67%), and similar incidence on HA4 (13% vs. 28%). The AMS+ group also demonstrated a higher (P < 0.05) AMS severity in the active vs. passive ascent cohort on HA1 (1.35 ± 0.97 vs. 0.90 ± 0.70), similar score on HA2 (1.00 ± 0.97 vs. 1.34 ± 0.70), and lower (P < 0.05) score on HA3 (0.56 ± 0.55 vs. 1.02 ± 0.75) and HA4 (0.32 ± 0.41 vs. 0.60 ± 0.72). Active compared with passive ascent accelerated the time course of AMS with more individuals sick on HA1 and less individuals sick on HA3 and HA4.NEW & NOTEWORTHY This research demonstrated that active ascent accelerated the time course but not overall incidence and severity of acute mountain sickness (AMS) following rapid ascent to 3,600 m in unacclimatized lowlanders. Active ascenders became sicker faster and recovered quicker than passive ascenders, which may be due to differences in body fluid regulation. Findings from this well-controlled large sample-size study suggest that previously reported discrepancies in the literature regarding the impact of exercise on AMS may be related to differences in the timing of AMS measurements between studies.

Pretreatment with Notoginsenoside R1 attenuates high-altitude hypoxia-induced cardiac injury via activation of the ERK1/2-P90RSK-Bad signaling pathway in rats.

High-altitude cardiac injury (HACI) is one of the common tissue injuries caused by high-altitude hypoxia that may be life threatening. Notoginsenoside R1 (NG-R1), a major saponin of Panax notoginseng, exerts anti-oxidative, anti-inflammatory, and anti-apoptosis effects, protecting the myocardium from hypoxic injury. This study aimed to investigate the protective effect and molecular mechanism of NG-R1 against HACI. We simulated a 6000 m environment for 48 h in a hypobaric chamber to create a HACI rat model. Rats were pretreated with NG-R1 (50, 100 mg/kg) or dexamethasone (4 mg/kg) for 3 days and then placed in the chamber for 48 h. The effect of NG-R1 was evaluated by changes in Electrocardiogram parameters, histopathology, cardiac biomarkers, oxidative stress and inflammatory indicators, key protein expression, and immunofluorescence. U0126 was used to verify whether the anti-apoptotic effect of NG-R1 was related to the activation of ERK pathway. Pretreatment with NG-R1 can improve abnormal cardiac electrical conduction and alleviate high-altitude-induced tachycardia. Similar to dexamethasone, NG-R1 can improve pathological damage, reduce the levels of cardiac injury biomarkers, oxidative stress, and inflammatory indicators, and down-regulate the expression of hypoxia-related proteins HIF-1α and VEGF. In addition, NG-R1 reduced cardiomyocyte apoptosis by down-regulating the expression of apoptotic proteins Bax, cleaved caspase 3, cleaved caspase 9, and cleaved PARP1 and up-regulating the expression of anti-apoptotic protein Bcl-2 through activating the ERK1/2-P90RSK-Bad pathway. In conclusion, NG-R1 prevented HACI and suppressed apoptosis via activation of the ERK1/2-P90RSK-Bad pathway, indicating that NG-R1 has therapeutic potential to treat HACI.

Recurrence Rate of High-altitude Pulmonary Edema in Lowlanders Inducted Temporarily to High-altitude Areas

Abstract Background: Some section of the Indian population resides in high-altitude areas of the mighty Himalayas. In addition to the residents who inhabit mountainous areas, there is also a group of lowlanders who occasionally visit these regions temporarily for work-related purposes or vacations. These individuals are prone to high-altitude illnesses, including acute mountain sickness and high-altitude pulmonary edema (HAPE). This cohort study was undertaken, among acclimatized and nonacclimatized lowlanders based on 3 years of data at a tertiary care hospital, to study the recurrence rate of HAPE in lowlanders. Materials and Methods: The inception cohort consisted of consecutive cases of HAPE among lowlanders, temporarily posted to these high-altitude regions, over 3 years. This cohort was followed up for at least 1 year. The recurrence rate of HAPE in terms of incidence density in person-months and cumulative incidence was calculated, and variables, including clinical features, altitudes at which the symptoms occurred, mode of induction to the high-altitude area, and time of onset of HAPE episodes postinduction altitudes, were studied. Results: The study revealed the recurrence of HAPE as an incidence density of 88.7 per 1000 person-months (95% confidence limit 66.1–115.9 per 1000 person-months). The cumulative incidence was 125 per 1000, over an average follow-up of 22.54 months (95% confidence limit 26–323 per 1000). The study revealed that the recurrence was found to occur at similar altitudes as the previous episode even after following strict acclimatization protocols and slow induction to the high-altitude area by road route with the onset of symptoms within 72 h of entry into the high-altitude area. Conclusion: This study brought out that there is a risk of recurrence of HAPE in lowlanders temporarily inducted to high-altitude areas, with previous episodes of HAPE at similar altitudes as previous episodes, even when acclimatization protocols are followed.