scholarly journals Autonomic cardiovascular function in high-altitude Andean natives with chronic mountain sickness

2003 ◽  
Vol 94 (1) ◽  
pp. 213-219 ◽  
Author(s):  
C. Keyl ◽  
A. Schneider ◽  
A. Gamboa ◽  
L. Spicuzza ◽  
N. Casiraghi ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
High Altitude ◽  
Baroreflex Sensitivity ◽  
Cardiovascular Function ◽  
Supplemental Oxygen ◽  
Arterial Oxygen ◽  
Control Group ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness ◽  
Spontaneous Baroreflex

We evaluated autonomic cardiovascular regulation in subjects with polycythemia and chronic mountain sickness (CMS) and tested the hypothesis that an increase in arterial oxygen saturation has a beneficial effect on arterial baroreflex sensitivity in these subjects. Ten Andean natives with a Hct >65% and 10 natives with a Hct <60%, all living permanently at an altitude of 4,300 m, were included in the study. Cardiovascular autonomic regulation was evaluated by spectral analysis of hemodynamic parameters, while subjects breathed spontaneously or frequency controlled at 0.1 and 0.25 Hz, respectively. The recordings were repeated after a 1-h administration of supplemental oxygen and after frequency-controlled breathing at 6 breaths/min for 1 h, respectively. Subjects with Hct >65% showed an increased incidence of CMS compared with subjects with Hct <60%. Spontaneous baroreflex sensitivity was significantly lower in subjects with high Hct compared with the control group. The effects of supplemental oxygen or modification of the breathing pattern on autonomic function were as follows: 1) heart rate decreased significantly after both maneuvers in both groups, and 2) spontaneous baroreflex sensitivity increased significantly in subjects with high Hct and did not differ from subjects with low Hct. Temporary slow-frequency breathing may provide a beneficial effect on the autonomic cardiovascular function in high-altitude natives with CMS.

Erythrocytosis in Chronic Mountain Sickness (CMS) in Andeans

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4873-4873
Author(s):  
Xunde Wang ◽  
David Callacondo ◽  
Jose Rojas ◽  
Jose Quesada-Olarte ◽  
Alan T. Remaley ◽  
...  
Keyword(s):  
High Altitude ◽  
Candidate Genes ◽  
Odds Ratio ◽  
Conflicts Of Interest ◽  
Jak2 V617f ◽  
Control Group ◽  
Chronic Mountain Sickness ◽  
Healthy Group ◽  
Mountain Sickness ◽  
One Way Anova

Abstract Introduction: Chronic mountain sickness (CMS) was first described as erythrocytosis of high altitude among Andean high altitude dwellers. Later description of this condition quickly implicated increasing age and increasing hematocrit as the main drivers for many physiological changes. Now CMS is a full clinical syndrome, and the severity is based on scoring of symptoms, physical examination signs, and hemoglobin (Hb) levels. Protective alleles in EPAS1 and EGLN1 have been associated with less erythrocytosis in Tibetans. Recently, SNPs in ANP32D and SENP1 leading to increases in their expression have been reported in CMS due to excessive hypoxia response. Fetal hemoglobin (HbF), having higher oxygen affinity than adult Hb, has been tested in small number of participants. There was no difference in those with or without CMS. Thus we tested these genes and laboratory parameters in a larger Andean cohort. Methods: Healthy 153 adults and 32 children age ≥5 years old, born and lived in Cerro de Pasco, Peru (4338 m), enrolled in the study. Native residency was defined as living, eating, and sleeping in households in the study area, with total absences <1 year at lower altitudes (<3000 m), and being > 6 months at high altitude before the study entry. Blood sample for blood counts, hemoglobin electrophoresis, plasma erythropoietin (EPO), and brain natriuretic peptide (pro BNP) were tested. SNP identification was carried out by PCR and Sanger sequencing of the 4 candidate genes (EPAS1, EGLN1, ANP32D, and SENP1). Testing for JAK2 V617F was also performed. Results: 58 adults and no children had CMS. 52% of the participants belonged in the healthy group (CMS score ≤5), 24% in mild CMS (score 6-10), 12% moderate CMS (score 11-15), and 2.2% severe (score >15). The mean Hb level was lower in the healthy group, compared to the CMS groups (P<0.001). The entire group (n= 184) had normal levels of HbF, median value of 0.4% (range 0.2-1.9). There were no differences (P=0.9) between healthy and CMS participants, adults and children, or men and women. In the participants who had sufficient quantity of plasma, EPO and proBNP determinations were performed. Mean plasma EPO levels correlated negatively with increasing CMS score, but none was statistically significant (P=0.24). In contrast, proBNP levels were the lowest levels in healthy group (27.5±3.1 pg/mL) and highest in the mild CMS group (66.5±14.1 pg/mL). TableGroupHb (g/dL)EPO (mIU/mL)Pro BNP (pg/mL)Healthy (N=47)17.1 ± 0.217.7 ± 2.427.5 ± 3.1Mild CMS (N=30)20.6 ± 0.4*12.6 ± 1.666.5 ± 14.1**Moderate CMS (N=15)22.3 ± 0.4*11.2 ± 2.342.0 ± 9.1Severe CMS (N=2)22.5 ± 1.3*10.6 ± 2.747.5 ± 23.5 * P<0.001, compared to healthy group by one way ANOVA ** P=0.005, compared to healthy group by one way ANOVA Previous studies showed that high altitude dwellers in Tibet harbor protective SNPs in the EPAS1 (or HIF 2a) and EGLN1 (or PHD2). Thus we chose 26 men with the highest Hb and 13 individuals with normal Hb, and performed SNP sequencing for these 2 genes. There was no difference between the 2 groups in the EPAS1 gene; all had CC allele. The T content in EGLN1 was 69% in CMS, and 85% in the control group (odds ratio for C vs T, 2.4, P =0.14). Another recent report showed that other candidate genes may be associated with CMS. Sequencing of ANP32D (rs72644851) revealed that G content in 25 CMS participants was 64%, and 96% in 13 controls (odds ratio for G vs A, 14.06, P=0.002). The percent of G content in SENP1 (rs7963934) in CMS was 84%, and 100% in controls (odds ratio for G vs C, 10.6, P=0.045). Additionally, 15 of these participants with CMS had JAK2 V617F mutation analysis; all showed the wildtype allele. Conclusion: Compared to healthy adults, CMS participants had similar and normal HbF levels and statistically insignificant lower plasma EPO levels. Pro BNP levels were higher only in the mild CMS group. We confirmed the association between SNPs in ANP32D and SENP1 and CMS in Andeans. Furthermore, the protective SNPs present in the Tibetan population, EPAS1 or EGLN1, are not present in this population of Andeans, potentially explaining the increased prevalence in Andeans at high altitude. Disclosures No relevant conflicts of interest to declare.

Alveolar-arterial oxygen gradient in Andean natives at high altitude

1964 ◽  
Vol 19 (1) ◽  
pp. 13-16 ◽  
Author(s):  
F. Kreuzer ◽  
S. M. Tenney ◽  
J. C. Mithoefer ◽  
J. Remmers
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Diffusion Barrier ◽  
Pulmonary Ventilation ◽  
Arterial Oxygen Tension ◽  
Normal Subjects ◽  
Arterial Oxygen ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness ◽  
Ventilation Perfusion Ratio

The A-a Do2 (alveolar-arterial oxygen tension difference) was determined at three levels of oxygenation in three groups of subjects: 1) normal persons at sea level, 2) normal Andean natives at high altitude, 3) Andean natives with chronic mountain sickness. The values of A-a Do2 in the Andean natives were uniformly higher than in normal sea-level residents at all levels of oxygenation. These findings were accentuated in patients with chronic mountain sickness. It is concluded that there is no decrease in diffusion barrier for oxygen, and there may be increased veno-arterial shunting in the lung and wider distribution of ventilation-perfusion ratios in the high-altitude residents than in normal subjects at sea level; and that part, at least, of the condition of chronic mountain sickness is an accentuation of these changes. tissue hypoxia; acclimatization; chronic mountain sickness; secondary polycythemia; pulmonary O2 diffusion barrier; pulmonary veno-arterial shunt; pulmonary ventilation perfusion ratio Submitted on April 3, 1963

scholarly journals Importance of Testosterone on Adaptation at High Altitude

2018 ◽  
Vol 2 (4) ◽  
pp. 689-697 ◽  
Author(s):  
Gustavo Gonzales
Keyword(s):  
Androgen Receptor ◽  
High Altitude ◽  
Ventilatory Response ◽  
Arterial Oxygen Saturation ◽  
Serum Testosterone ◽  
Arterial Oxygen ◽  
High Altitudes ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness ◽  
Ventilatory Response To Hypoxia

Adaptation or natural acclimatization results from the interaction between genetic variations and acclimatization resulting in individuals with ability to live and reproduce without problems at high altitudes. Testosterone is a hormone that increases erythropoiesis and inhibits ventilation. It could therefore, be associated to the adaptation to high altitudes. Excessive erythrocytosis, which in turn will develop chronic mountain sickness is caused by low arterial oxygen saturation and ventilatory inefficiency and blunted ventilatory response to hypoxia. Testosterone is elevated in natives at high altitude with excessive erythrocytosis (>21 g /dl hemoglobin in men and >19 g/dl in women). Natives from the Peruvian central Andes with chronic mountain sickness express gene SENP1 that enhances the activity of the androgen receptor. Results of the current investigations suggest that increase in serum testosterone and hemoglobin is not adequate for adaptation to high altitude.

Global REACH 2018: Volume regulation in high-altitude Andeans with and without chronic mountain sickness

2021 ◽  
Author(s):  
Andrew R. Steele ◽  
Michael M. Tymko ◽  
Victoria L. Meah ◽  
Lydia L Simpson ◽  
Christopher Gasho ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Plasma Renin Activity ◽  
High Altitude ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Plasma Renin ◽  
Renin Activity ◽  
Chronic Mountain Sickness ◽  
Plasma Aldosterone Concentration ◽  
Mountain Sickness

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed N-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP), in Andean males without (n=14; age=39±11) and with (n=10; age=40±12) CMS at 4330 meters (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8±7.9 vs. CMS: 8.7±5.4 ng/ml; p=0.025) and plasma aldosterone concentration (non-CMS: 77.5±35.5 vs. CMS: 54.2±28.9 pg/ml; p=0.018) were lower in highlanders with CMS compared to non-CMS, while NT pro-BNP was not different between groups (non-CMS: 1394.9±214.3 vs. CMS: 1451.1±327.8 pg/ml; p=0.15). Highlanders had similar total blood volume (non-CMS: 90±15 vs. CMS: 103±18 ml • kg-1; p=0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46±10 vs. CMS 66±14 ml • kg-1; p<0.01) and smaller plasma volume (non-CMS 43±7 vs. CMS 35±5 ml • kg-1; p=0.03) compared to non-CMS. There were no differences in ePASP between groups (non-CMS 32±9 vs. CMS 31±8 mmHg; p=0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r=-0.66; p<0.01; non-CMS: r=-0.60; p=0.022; CMS: r=-0.63; p=0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high-altitude, causing potentially greater polycythemia and clinical symptoms.

Acute hypoxia in a simulated high-altitude airdrop scenario due to oxygen system failure

2017 ◽  
Vol 123 (6) ◽  
pp. 1443-1450 ◽  
Author(s):  
William Ottestad ◽  
Tor Are Hansen ◽  
Gaurav Pradhan ◽  
Jan Stepanek ◽  
Lars Øivind Høiseth ◽  
...  
Keyword(s):  
High Altitude ◽  
Acute Hypoxia ◽  
Supplemental Oxygen ◽  
Cerebral Oximetry ◽  
Arterial Oxygen ◽  
Hypoxic Exposure ◽  
System Failure ◽  
Oxygen System ◽  
Simulated High Altitude ◽  
Oxygen Tensions

High-Altitude High Opening (HAHO) is a military operational procedure in which parachute jumps are performed at high altitude requiring supplemental oxygen, putting personnel at risk of acute hypoxia in the event of oxygen equipment failure. This study was initiated by the Norwegian Army to evaluate potential outcomes during failure of oxygen supply, and to explore physiology during acute severe hypobaric hypoxia. A simulated HAHO without supplemental oxygen was carried out in a hypobaric chamber with decompression to 30,000 ft (9,144 m) and then recompression to ground level with a descent rate of 1,000 ft/min (305 m/min). Nine subjects were studied. Repeated arterial blood gas samples were drawn throughout the entire hypoxic exposure. Additionally, pulse oximetry, cerebral oximetry, and hemodynamic variables were monitored. Desaturation evolved rapidly and the arterial oxygen tensions are among the lowest ever reported in volunteers during acute hypoxia. PaO2 decreased from baseline 18.4 (17.3–19.1) kPa, 138.0 (133.5–143.3) mmHg, to a minimum value of 3.3 (2.9–3.7) kPa, 24.8 (21.6–27.8) mmHg, after 180 (60–210) s, [median (range)], N = 9. Hyperventilation with ensuing hypocapnia was associated with both increased arterial oxygen saturation and cerebral oximetry values, and potentially improved tolerance to severe hypoxia. One subject had a sharp drop in heart rate and cardiac index and lost consciousness 4 min into the hypoxic exposure. A simulated high-altitude airdrop scenario without supplemental oxygen results in extreme hypoxemia and may result in loss of consciousness in some individuals. NEW & NOTEWORTHY This is the first study to investigate physiology and clinical outcome of oxygen system failure in a simulated HAHO scenario. The acquired knowledge is of great value to make valid risk-benefit analyses during HAHO training or operations. The arterial oxygen tensions reported in this hypobaric chamber study are among the lowest ever reported during acute hypoxia.

Role of sex hormones in development of chronic mountain sickness in rats

1994 ◽  
Vol 77 (1) ◽  
pp. 427-433 ◽  
Author(s):  
L. C. Ou ◽  
G. L. Sardella ◽  
J. C. Leiter ◽  
T. Brinck-Johnsen ◽  
R. P. Smith
Keyword(s):  
Gender Differences ◽  
Pulmonary Hypertension ◽  
High Altitude ◽  
Sex Hormones ◽  
Systolic Pressure ◽  
Female Rats ◽  
Hypoxic Exposure ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness

After chronic exposure to hypoxia, Hilltop Sprague-Dawley rats developed excessive polycythemia and severe pulmonary hypertension and right ventricular (RV) hypertrophy, signs consistent with human chronic mountain sickness; however, there were gender differences in the magnitude of the polycythemia and susceptibility to the fatal consequence of chronic mountain sickness. Orchiectomy and ovariectomy were performed to evaluate the role of sex hormones in the gender differences in these hypoxic responses. After 40 days of exposure to simulated high altitude (5,500 m; barometric pressure of 370 Torr and inspired Po2 of 73 Torr), both sham-gonadectomized male and female rats developed polycythemia and had increased RV peak systolic pressure and RV hypertrophy. The hematocrit was slightly but significantly higher in males than in females. Orchiectomy did not affect these hypoxic responses, although total ventricular weight was less in the castrated high-altitude rats. At high altitude, the mortality rates were 67% in the sham-operated male rats and 50% in the castrated animals. In contrast, ovariectomy aggravated the high-altitude-associated polycythemia and increased RV peak systolic pressure and RV weight compared with the sham-operated high-altitude female rats. Both sham-operated control and ovariectomized females suffered negligible mortality at high altitude. The present study demonstrated that 1) the male sex hormones play no role in the development of the excessive polycythemia, pulmonary hypertension, and RV hypertrophy during chronic hypoxic exposure or in the associated high mortality and 2) the female sex hormones suppressed both the polycythemic and cardiopulmonary responses in vivo during chronic hypoxic exposure.

scholarly journals Effect of Hypoxia in the Pharmacological Treatment of Chronic Mountain Sickness (monge sickness) in Native Residents of High Altitude

2020 ◽  
Vol 5 (12) ◽  
pp. 3-3
Author(s):  
Aquino Lopez Tatiana; Aylas Aylas ◽  
Lucero; Brian Talledo Flores; Correa ◽  
Munoz; Mishel Loayza Miranda Jesus Alexander; Mendoza Chuquillanqui ◽  
Lenin; Mercado Baltazar Maria de los Angeles; Quispe Hidalgo ◽  
Natalia; Quispe Tovar Consuelo Milagros; Ramos Lucas ◽  
...  
Keyword(s):  
High Altitude ◽  
Pharmacological Treatment ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness

scholarly journals Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude

2021 ◽  
Author(s):  
Benjamin James Talks ◽  
Catherine Campbell ◽  
Stephanie J Larcombe ◽  
Lucy Marlow ◽  
Sarah Louise Finnegan ◽  
...  
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Acute Mountain Sickness ◽  
Symptom Burden ◽  
Control Group ◽  
Physiological Changes ◽  
Symptom Experience ◽  
Psychological Traits ◽  
Bodily Sensations ◽  
Mountain Sickness

Background: Interoception refers to an individuals ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesised that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods and Material: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at two-week intervals. The control group remained in Birmingham (140m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2624m, and test 3 at 2728m after an 11-day trek at high altitude (up to 4800m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea-level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike.

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