Cardiac Acclimatization at High Altitude in Two Different Ethnicity Groups.

Gaur, Priya, Meerim Sartmyrzaeva, Abdirashit Maripov, Kubatbek Muratali Uulu, Supriya Saini, Koushik Ray, Krishna Kishore, Almaz Akunov, Akpay Sarybaev, Bhuvnesh Kumar, Shashi Bala Singh, and Praveen Vats. Cardiac acclimatization at high altitude in two different ethnicity groups. High Alt Med Biol. 22:58-69, 2021. Introduction: High altitude (HA) exposure causes substantial increase in pulmonary artery pressure (PAP) and resistance. However, the effects of HA hypoxia exposure on cardiac function remain incompletely understood. Studies evaluating interethnic differences in cardiac functions in response to HA exposure are lacking. We aimed to compare the cardiac performance in Indian versus Kyrgyz healthy lowland subjects over the course of a 3-week HA exposure at 4,111 m. Methodology: Ten Indians and 20 Kyrgyz subjects were studied to assess cardiac acclimatization noninvasively by echocardiography in two different ethnic groups for 3 weeks of stay at HA. Pulmonary hemodynamics, right and left ventricular functions were evaluated at basal and on days 3, 7, 14, and 21 of HA exposure and on day 3 of deinduction. Results: HA exposure significantly increased PAP, pulmonary vascular resistance, cardiac output (CO), and heart rates (HRs) in both groups. Tricuspid regurgitant gradient increased significantly in both the group at day 3 versus basal; 38.9 mmHg (31.8, 42.9) versus 21.9 mmHg (19.5, 22.6) in Kyrgyz; and 34.1 mmHg (30.2, 38.5) versus 20.4 mmHg (19.7, 21.3) in Indians. HR increased significantly in Indians at day 3 and 7, whereas in Kyrgyz throughout exposure. CO increased significantly in both groups at day 3 versus basal with 5.9 L/min (5.5, 6.4) versus 5.1 L/min (4.4, 5.9) in Kyrgyz, and 5.7 L/min (5.56, 5.98) versus 4.9 L/min (4.1, 5.3) in Indians. Both groups exhibited preserved right ventricular diastolic and systolic functions at HAs. HA exposure changed the left ventricular diastolic parameters only in Kyrgyz subjects with impaired mitral inflow E/A, but not in Indian subjects. All cardiac changes induced at HAs have been recovered fully upon deinduction in both, except lateral-septal A', which remained low in Indians. Conclusion: Although pulmonary hemodynamics responses were similar in both groups, there were differences in cardiac functional parameters between the two in response to HA exposure that may be accounted to ethnic variation.

Temporal transcriptome analysis suggest modulation of multiple pathways and gene network involved in cell-cell interaction during early phase of high altitude exposure.

High altitude (HA) conditions induce several physiological and molecular changes, prevalent in individuals who are unexposed to this environment. Individuals exposed towards HA hypoxia yields physiological and molecular orchestration to maintain adequate tissue oxygen delivery and supply at altitude. This study aimed to understand the temporal changes at altitude of 4,111m. Physiological parameters and transcriptome study was conducted at high altitude day 3, 7, 14 and 21. We observed changes in differentially expressed gene (DEG) at high altitude time points along with altered BP, HR, SpO2, mPAP. Physiological changes and unsupervised learning of DEG's discloses high altitude day 3 as distinct time point. Gene enrichment analysis of ontologies and pathways indicate cellular dynamics and immune response involvement in early day exposure and later stable response. Major clustering of genes involved in cellular dynamics deployed into broad categories: cell-cell interaction, blood signaling, coagulation system, and cellular process. Our data reveals genes and pathways perturbed for conditions like vascular remodeling, cellular homeostasis. In this study we found the nodal point of the gene interactive network and candidate gene controlling many cellular interactive pathways VIM, CORO1A, CD37, STMN1, RHOC, PDE7B, NELL1, NRP1 and TAGLN and the most significant among them i.e. VIM gene was identified as top hub gene. This study suggests a unique physiological and molecular perturbation likely to play a critical role in high altitude associated pathophysiological condition during early exposure compared to later time points.

A Temporal Study on Learning and Memory at High Altitude in Two Ethnic Groups.

Introduction: Cognitive function has been compromised during high-altitude (HA) exposure due to slowing of mental processing. Materials and Methods: A total of 20 Indian and 20 Kyrgyz soldiers were studied at 4111 m to assess cognitive function in two different ethnic groups. Paired associate learning, pattern recognition memory, spatial span (SSP), spatial working memory (SWM), choice reaction time (CRT), and simple reaction time (SRT) were evaluated at sea level and on days 3, 7, 14, and 21 of HA stay and on day 3 of deinduction. Results: All the parameters were significantly affected at HA. Indian soldiers were acclimatized by 7 days but Kyrgyz soldiers required 21 days for acclimatization. A slow impairment in SWM, CRT, and SRT was observed in Kyrgyz soldiers than in Indian soldiers and it continues throughout 21 days of HA stay, but for Indian soldiers the deterioration was maximum on day 7 and improvement in SWM, CRT, and SRT was observed on day 14 and close to baseline value on day 21. After deinduction, although Indian soldiers attained the normal value, Kyrgyz soldiers had higher value than baseline in SSP, SWM, CRT, and SRT. Conclusion: Difference in the cognitive performances of Indian and Kyrgyz soldiers may be due to the ethnogenetic diversity of these two groups.

Global expression profiling and pathway analysis in two different population groups in relation to high altitude.

High altitude (HA) is associated with number of stresses. Response of these stresses may vary in different populations depending upon altitude, duration of residency, ancestry, geographical variation, lifestyle, and ethnicities. For understanding population variability in transcriptome, array-based global gene expression profiling was performed on extracted RNA of male volunteers of two different lowland population groups, i.e., Indians and Kyrgyz, at baseline and day 7 of HA exposure (3200 m). A total of 97 genes were differentially expressed at basal in Kyrgyz as compared to Indians (82 downregulated and 15 upregulated), and 196 were differentially expressed on day 7 of HA (118 downregulated and 78 upregulated). Ingenuity Pathway Analysis and gene ontology highlighted eIF2 signaling with most significant negative activation z score at basal in Kyrgyz compared to Indians with downregulation of various L- and S-ribosomal proteins indicating marked translational repression. On day 7, cAMP-mediated signaling is most enriched with positive activation z score in Kyrgyz compared to Indians. Plasma cAMP levels were higher in Kyrgyz on day 7 compared to Indians. Extracellular adenosine levels were elevated in both the groups upon HA, but higher in Kyrgyz compared to Indians. Valedictory qRT-PCR showed upregulation of ADORA2B and CD73 along with downregulation of ENTs in Kyrgyz compared to Indians indicating elevated levels of extracellular nucleotides mainly adenosine and activation of extracellular cAMP-adenosine pathway which as per literature triggers endogenous protective mechanisms under stress conditions like hypoxia. Thus, transcriptome changes at HA are population-specific, and it may be necessary to take care while interposing similar results in different populations.

Hemoglobin Changes After Long-Term Intermittent Work at High Altitude.

Chronic high altitude hypoxia leads to an increase in red cell numbers and hemoglobin concentration. However, the effects of long-term intermittent hypoxia on hemoglobin concentration have not fully been studied. The aim of this study was to evaluate hemoglobin levels in workers commuting between an elevation of 3,800 m (2-week working shift) and lowland below 1,700 m (2 weeks of holiday). A total of 266 healthy males, aged from 20 to 69 years (mean age 45.9 ± 0.6 years), were included into this study. The duration of intermittent high altitude exposure ranged from 0 to 21 years. Any cardiac or pulmonary disorder was excluded during annual check-ups including clinical examination, clinical lab work (blood cell count, urine analysis, and biochemistry), ECG, echocardiography, and pulmonary function tests. The mean hemoglobin level in workers was 16.2 ± 0.11 g/dL. Univariate linear regression revealed an association of the hemoglobin levels with the years of exposure. Hemoglobin levels increased 0.068 g/dL [95% CI: 0.037 to 0.099, p < 0.001] for every year of intermittent high altitude exposure. Further, after adjusting for other confounding variables (age, living at low or moderate altitude, body mass index, and occupation) using multivariable regression analysis, the magnitude of hemoglobin level changes decreased, but remained statistically significant: 0.046 g/dL [95% CI: 0.005 to 0.086, p < 0.05]. Besides that, a weak linear relationship between hemoglobin levels and body mass index was revealed, which was independent of the years of exposure to high altitude (0.065 g/dL [95% CI: 0.006 to 0.124, p < 0.05]). We concluded that hemoglobin levels have a linear relationship with the exposure years spent in intermittent hypoxia and body mass index.

Right Ventricular Remodeling and Dysfunction in Obstructive Sleep Apnea: A Systematic Review of the Literature and Meta-Analysis.

BACKGROUND: Recent studies have reported that obstructive sleep apnea (OSA) patients present alterations in right ventricular (RV) structure and function. However, large randomized controlled trials evaluating the impact of OSA on the right ventricle are lacking. METHODS: A comprehensive electronic database (PubMed, Web of Science, and Google Scholar) and reference search up to October 30, 2016, was performed. A systematic review and meta-analysis were performed to assess RV structure and function in OSA patients based on conventional echocardiography and tissue Doppler imaging. RESULTS: Twenty-five studies with 1,503 OSA patients and 796 controls were included in this study. OSA patients exhibited an increase in RV internal diameter (weighted mean difference (WMD) (95% confidence intervals (CIs)) 2.49 (1.62 to 3.37); p = 0.000) and RV wall thickness (WMD (95% CIs) 0.82 (0.51 to 1.13); p = 0.000). Furthermore, OSA patients had a significantly elevated RV myocardial performance index (WMD (95% CI) 0.08 (0.06 to 0.10); p = 0.000), decreased RV S' (WMD (95% CI) -0.95 (-1.59 to -0.32); p = 0.003), tricuspid annular plane systolic excursion (WMD (95% CI) -1.76 (-2.73 to -0.78); p = 0.000), and RV fractional area change (WMD (95% CI) -3.16 (-5.60 to -0.73); p = 0.011). CONCLUSION: OSA patients display RV dilatation, increased wall thickening, and altered RV function.

High Altitude Pulmonary Edema in a Mining Worker With an Abnormal Rise in Pulmonary Artery Pressure in Response to Acute Hypoxia Without Prior History of High Altitude Pulmonary Edema.

High altitude pulmonary edema (HAPE) is a potentially life-threatening form of noncardiogenic pulmonary edema that may develop in otherwise healthy individuals upon ascent to high altitude. A constitutional susceptibility has been noted in some individuals, whereas others appear not to be susceptible at all. In our report, we present a case of HAPE triggered by concurrent respiratory tract infection and strenuous exercise in a mining worker with an abnormal rise in pulmonary artery pressure in response to acute hypoxia, without a prior history of HAPE during almost a year of commuting between high altitude and lowland areas.

Changes in cardiovascular functions, lipid profile, and body composition at high altitude in two different ethnic groups.

High altitude (HA) presents inhospitable environmental conditions that adversely affects human physiology and metabolism. Changes in physiological functions are reported during high altitude exposure, but the changes vary with physical state, culture habits, geographical locations, and genetic variation of individual. The present study was carried out to explore the variation in acclimatization pattern of two different ethnic groups in relation to cardiovascular functions, lipid profile and body composition. The study was carried out on 30 human volunteers (20 Indian and 10 Kyrgyz) initially at Bishkek for basal recording and on day 3, 7, 14, and 21 of high altitude (3200 m) induction and again on day 3 of de-induction. On altitude exposure significant decrease in body weight was observed both in Indian (day 14, p<0.001) and Kyrgyz (day 3, p<0.01) subjects. Decreased levels of total body water, extra cellular and intra cellular body water were also observed in both the groups. Significant reduction in body mass index (p<0.01), fat free mass (p<0.01), body cell mass (p<0.01) and body volume (p<0.01) was also observed in Kyrgyz subjects, whereas in Indian subjects the changes were not significant in these variables on high altitude exposure. Diastolic blood pressure and heart rate increased significantly on day 3 (p<0.001 and p<0.01, respectively) of induction in Indian subjects; whereas in Kyrgyz significant increase was observed on day 14 (p<0.05) in both the cases. High density lipoprotein (HDL) cholesterol levels increased significantly on day 7 of HA exposure in both the groups. Results indicate that the Indian and Kyrgyz groups report differently, in relation to changes in cardiovascular functions, lipid profiles, and body composition, when exposed to HA. The difference observed in acclimatization pattern in the two groups may be due to ethnic/genetic variation of two populations.