Ji-hang Zhang

Inhaled budesonide prevents acute mountain sickness in young Chinese men.

BACKGROUND Oral glucocorticoids can prevent acute mountain sickness (AMS). Whether inhaled budesonide (BUD) can prevent AMS remains unknown. OBJECTIVE Our aim was to investigate the effectiveness of BUD in AMS prevention. METHODS Eighty subjects were randomly assigned to receive budesonide (BUD, inhaled), procaterol tablet (PT), budesonide/formoterol (BUD/FM, inhaled), or placebo tablet (n = 20 in each group). Subjects were treated for 3 days before ascending from 500 m to 3700 m within 2.5 h by air. Lake Louis AMS questionnaire, blood pressure, heart rate, and oxygen saturation (SpO2) were examined at 20, 72, and 120 h after high-altitude exposure. Pulmonary function was measured at 20 h after exposure. RESULTS Compared with placebo, BUD significantly reduced the incidence of AMS (70% vs. 25% at 20 h, p < 0.05; both 10% vs. 5% at 72 and 120 h, both p > 0.05) without side effects. The relative risk was 0.357, and the risk difference was 0.45. Mean SpO2 was higher in BUD, BUD/FM, and PT groups than in the placebo group at 20 h (p < 0.05). SpO2 in all 80 subjects dropped after ascent (98.1% to 88.12%, p < 0.01) and increased gradually, but it was still lower at 120 h than at baseline (92.04% vs. 98.1%, p < 0.01). Pulmonary function did not differ among the four groups at 20 h. CONCLUSION BUD can prevent AMS without side effects. The alleviation of AMS may be related to increased blood oxygen levels rather than pulmonary function.

Anxiety correlates with somatic symptoms and sleep status at high altitudes

High altitude exposure results in many physical and psychological discomforts, with anxiety and sleep disturbances being the most common ones. This cross-sectional study was performed to explore the relationship between anxiety, somatic symptoms, and sleep status at high altitude. A sample of 426 young males between 18 and 24 years old ascended from low-level land to 3600 m, where they acclimated for 40 days, before ascending to 4400 m. Questionnaires including the Louise Lake Score (LLS, for diagnosis of acute mountain sickness [AMS]), the Self-rating Anxiety Scale (SAS), the Epworth Sleepiness Scale (ESS), and the Athens Insomnia Scale (AIS) were administered immediately before departure from 3600 m (40th day) and the day after arrival at 4400 m (20 days after the first data collection). Physiological parameters were also measured. We observed that 49 of 426 and 51 of 329 people were diagnosed with anxiety according to SAS at 3600 and 4400 m, respectively. Physical symptoms were more severe in subjects with anxiety, and the severity of anxiety was significantly positively correlated to the severity of insomnia and increased heart rate (HR). Overall, these data indicate that after 40 days acclimatization in 3600 m, anxious persons have more severe somatic symptoms. When ascending to higher altitudes, these individuals are more likely to develop AMS, show more severe symptoms, and are prone to insomnia and more serious daytime sleepiness. Insomnia and elevated HR are indicators of anxiety severity.

Store-operated calcium entry-activated autophagy protects EPC proliferation via the CAMKK2-MTOR pathway in ox-LDL exposure

ABSTRACT Improving biological functions of endothelial progenitor cells (EPCs) is beneficial to maintaining endothelium homeostasis and promoting vascular re-endothelialization. Because macroautophagy/autophagy has been documented as a double-edged sword in cell functions, its effects on EPCs remain to be elucidated. This study was designed to explore the role and molecular mechanisms of store-operated calcium entry (SOCE)-activated autophagy in proliferation of EPCs under hypercholesterolemia. We employed oxidized low-density lipoprotein (ox-LDL) to mimic hypercholesterolemia in bone marrow-derived EPCs from rat. Ox-LDL dose-dependently activated autophagy flux, while inhibiting EPC proliferation. Importantly, inhibition of autophagy either by silencing Atg7 or by 3-methyladenine treatment, further aggravated proliferative inhibition by ox-LDL, suggesting the protective effects of autophagy against ox-LDL. Interestingly, ox-LDL increased STIM1 expression and intracellular Ca2+ concentration. Either Ca2+ chelators or deficiency in STIM1 attenuated ox-LDL-induced autophagy activation, confirming the involvement of SOCE in the process. Furthermore, CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, β) activation and MTOR (mechanistic target of rapamycin [serine/threonine kinase]) deactivation were associated with autophagy modulation. Together, our results reveal a novel signaling pathway of SOCE-CAMKK2 in the regulation of autophagy and offer new insights into the important roles of autophagy in maintaining proliferation and promoting the survival capability of EPCs. This may be beneficial to improving EPC transplantation efficacy and enhancing vascular re-endothelialization in patients with hypercholesterolemia.

Reduction of Store-Operated Ca2+ Entry Correlates with Endothelial Progenitor Cell Dysfunction in Atherosclerotic Mice

The dysfunction of endothelial progenitor cells (EPCs) has been shown to prevent endothelial repair during the development of atherosclerosis (AS). Previous studies have revealed that store-operated calcium entry (SOCE) is an important factor in regulating EPC functions. However, whether this is also the mechanism in AS has not been elucidated. Therefore, we evaluated the role of SOCE in EPCs isolated from an atherosclerotic mouse model. Atheromatous plaques were more frequent in the aortas of ApoE(-/-) mice fed a high-fat diet for 16 weeks compared with controls, and the proliferative and migratory activities of atherosclerotic EPCs were significantly decreased. Accordingly, SOCE amplitude, as well as spontaneous or VEGF-induced Ca(2+) oscillations, decreased in atherosclerotic EPCs. These results may be associated with the downregulated expression of Stim1, Orai1, and TRPC1, which are major mediators of SOCE. In addition, eNOS expression and phosphorylation at Ser(1177), which are critical regulators of EPC function, were markedly reduced in the atherosclerotic EPCs. The impairment of eNOS activity could also be induced by using an SOCE inhibitor or by Stim1 gene silencing, indicating a link between the activities of eNOS and SOCE in AS. Furthermore, decreased SOCE function inhibited EPC proliferation and migration in vitro. In conclusion, our results showed that the reduction of SOCE induced EPC dysfunction during AS, potentially through downregulation of store-operated calcium channel (SOCC) components and impaired eNOS activity. Approaches aimed at reestablishing SOCE activity may thus improve the function of EPCs during AS.

Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men

Background The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude. Methods A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured. Results Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01–1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28–1.51, P<0.001). Conclusion The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects.

Principal Component Analysis and Risk Factors for Acute Mountain Sickness upon Acute Exposure at 3700 m.

Objective We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors. Methods The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses. Results The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS. Conclusions Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS.

High altitude-induced borderline pulmonary hypertension impaired cardiorespiratory fitness in healthy young men

OBJECTIVE High altitude exposure has been suggested to cause borderline elevation of pulmonary artery pressure (PAP) in quite a few healthy individuals. This cohort study was to investigate the impact of altitude induced borderline pulmonary hypertension (PH) on cardiorespiratory fitness in healthy subjects. METHODS 299 healthy Chinese young men with normal PAP were consecutively studied between July 2011 and September 2013. Among these subjects 114 kept living at low altitude (450m), 91 ascended to high altitude (3700m) from low altitude within 24h (acute exposure), and 94 resided at 3700m for more than 1year (chronic exposure). Mean PAP and cardiac function were examined by echocardiography, and cardiorespiratory fitness was determined by predicted work capacity at a heart rate of 170beats per minute (PWC170). RESULTS Mean PAP remained within normal range (<20mmHg) in 113 of 114 participants (99%) at low altitude. In contrast, the incidence of borderline PH (mPAP between 20 and 25mmHg) was 29% and 37% for respective acute and chronic exposures. Compared to the subjects with normal mPAP within each of the exposure groups, the subjects with borderline PH had increased right ventricular Tei index (RV-Tei), which correlated with the decline of PWC170 (acute exposure: r=-0.296, p=0.004; chronic exposure: r=-0.247, p=0.016). However, these changes were relatively milder than those with confirmed PH (mPAP>25mmHg). CONCLUSION Borderline PH compromised cardiorespiratory fitness in healthy young men. The decline of cardiorespiratory fitness was related at least in part with the impaired right ventricular function, which was correlated with the elevated mPAP.

Physiological and psychological factors associated with onset of high-altitude headache in Chinese men upon acute high-altitude exposure at 3700 m.

Aim We aimed to identify clinical characteristics and risk factors associated with onset of high-altitude headache (HAH) after acute exposure at 3700 m. Method In two hours, 163 individuals ascended by plane to 3700 m. Demographic information, physiological and psychological measurements, cognitive function, physical work capacity tests and profile of mood states within one week prior to the departure and within 24 hours after arrival were examined. Results HAH patients featured significantly higher vertebral artery diastolic velocity (Vd), heart rate (HR) and pulmonary artery diameter. HAH was also associated with a more negative mood state, including scores for tension anxiety, depression, hostility, fatigue and confusion, as well as lower vigor (all p values <0.05). Furthermore, negative emotions were positively related to HAH severity. HAH slightly decreased cognitive functioning. HR, Vd, lack of vigor, confusion and self-reported anxiety (all p values <0.05) were independent risk factors for HAH. We have identified three independent baseline predictors for HAH including internal diameter of the left ventricle (LVD), Athens Insomnia Scale (AIS) and confusion score. Conclusions Higher HR, Vd, confusion and self-reported anxiety and insufficient vigor were independent risk factors for HAH. Furthermore, higher baseline LVD, AIS and confusion score are independent predictors of HAH.

Smoking is associated with the incidence of AMS: a large-sample cohort study.

BackgroundIn recent years, the number of people visiting high altitudes has increased. After rapidly ascending to a high altitude, some of these individuals, who reside on plains or other areas of low altitude, have suffered from acute mountain sickness (AMS). Smoking interferes with the bodys oxygen metabolism, but research about the relationship between smoking and AMS has yielded controversial results.MethodsWe collected demographic data, conducted a smoking history and performed physical examinations on 2000 potential study participants, at sea level. Blood pressure (BP) and pulse oxygen saturation (SpO2) were measured for only some of the patients due to time and manpower limitations. We ultimately recruited 520 smokers and 450 nonsmokers according to the inclusion and exclusion criteria of our study. Following acute high-altitude exposure, we examined their Lake Louise Symptom (LLS) scores, BP, HR and SpO2; however, cerebral blood flow (CBF) was measured for only some of the subjects due to limited time, manpower and equipment.ResultsBoth the incidence of AMS and Lake Louise Symptom (LLS) scores were lower in smokers than in nonsmokers. Comparing AMS-related symptoms between nonsmokers and smokers, the incidence and severity of headaches and the incidence of sleep difficulties were lower in smokers than in nonsmokers. The incidences of both cough and mental status change were higher in smokers than in nonsmokers; blood pressure, HR and cerebral blood flow velocity were lower in smokers than in nonsmokers.ConclusionOur findings suggest that the incidence of AMS is lower in the smoking group, possibly related to a retardation of cerebral blood flow and a relief of AMS-related symptoms, such as headache.

Left Ventricular Function during Acute High-Altitude Exposure in a Large Group of Healthy Young Chinese Men

Objective The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males. Methods A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points. Results Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude. Conclusion Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function.