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PubMed2000

Effects of simulated altitude-induced hypoxia on exercise capacity in patients with chronic heart failure.

PURPOSE: Patients with stable heart failure often wish to spend time at altitudes above those of their residence. However, it is not known whether they can safely tolerate ascent to high altitudes or what its effects on work capacity may be. SUBJECTS AND METHODS: We studied 14 normal subjects and 38 patients with clinically stable heart failure, 12 of whom had normal workload [peak exercise oxygen consumption (VO(2)) greater than 20 mL/min/kg], 14 of whom had slightly diminished workload (peak VO(2) 20 to 15 mL/min/kg), and 12 of whom had markedly diminished workload (peak VO(2) less than 15 mL/min/kg) at baseline. All performed cardiopulmonary exercise tests with inspired oxygen fractions equal to those at 92, 1,000, 1,500, 2,000, and 3,000 m, and maximum achieved work rates (mean +/- SD) were measured. RESULTS: All subjects completed the trial; no test was interrupted because of arrhythmia, angina, or ischemia. Maximum work rate decreased in parallel with increasing simulated altitude. The percentage decrease was greater for patients with heart failure and was most marked among those with the lowest workload at baseline. Maximum achieved work rate declined by 3% +/- 4% per 1,000 m in normal subjects, by 5% +/- 3% (P <0.01) in patients with heart failure with normal workload, by 5% +/- 4% (P <0.01) in patients with slightly diminished workload, and by 11% +/- 5% (P <0.01 vs normal subjects and vs the other patients with heart failure) in patients with markedly reduced workload. CONCLUSION: Patients with stable heart failure who ascend to higher altitudes should expect to have a reduction in maximum physical activity in proportion to their exercise capacity at sea level.

Aged↗

PubMed2000

Low pulse oxygen saturation in post-menopausal women at high altitude is related to a high serum testosterone/estradiol ratio.

OBJECTIVE: The present study was designed to determine if low pulse oxygen saturation (SpO(2)) in post-menopausal women at high altitude was related to high serum testosterone/estradiol (T/E(2)) ratio. METHOD: Studies were carried out in 191 women living in Cerro de Pasco, Peru (4340 m above sea level) and in 56 women living in Lima (150 m asl). Body weight, height, SpO(2), hematocrit, serum follicle stimulating hormone (FSH), T and E(2) levels were measured in all women. Body mass index (BMI), menopausal status and serum T/E(2) ratio were calculated from data. RESULT: At high altitude, the values of SpO(2), serum T, and serum E(2) were significantly lower in post-menopausal than in pre-menopausal women. Hematocrit, serum FSH levels, and serum T/E(2) ratios were significantly higher in post-menopausal women. Serum T and E(2) levels, T/E(2) ratio, SpO(2), and hematocrit levels were not further changed with time after menopause. Women with SpO(2)<85% had lower serum E(2), a higher serum T/E(2) ratio, and higher hematocrit values than women with SpO(2)>90%. At high altitude, multiple regression analysis showed that low SpO(2) was related to menopausal status (-2.6+/-0.83; beta+/-S.E.; P<0.002) and not to chronological age (-0.06+/-0.04; P: NS). Further analysis showed that low SpO(2) was related to high basal serum FSH levels and a high serum T/E(2) ratio in the presence of an interaction between FSH and T/E(2). CONCLUSION: Low values of SpO(2) in women at high altitude were related to a high T/E(2) ratio.

Adult↗

PubMed1989

Atrial natriuretic peptide, altitude and acute mountain sickness.

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide. 2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control. 3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score. 4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.

Acute Disease↗

PubMed1998

Catecholamines, hypoxia and high altitude.

Hypoxia is a potent activator of the sympathetic nervous system by stimulating arterial chemoreceptors. However, out of 15 laboratory studies on the effects of acute and prolonged hypoxia on catecholamines, 14 failed to show any changes in plasma or urinary noradrenaline and only four studies showed significant increases in plasma or urinary adrenaline. By contrast, six out of eight studies on MSNA showed increased sympathetic nerve activity to the leg. An increased clearance of plasma catecholamines during hypoxia may be a possible explanation. Furthermore, many of the studies had limitations in a number of subjects and catecholamine assays used. Emotional aspects of the study protocols, which could contribute to the increase in adrenaline, was only assessed by sham runs in one chamber study. However, 13 out of 14 reviewed field studies on subjects staying for more than 1 week at high altitude, reported increased plasma or urinary excretion of noradrenaline which may be compatible with increased sympathetic activity. Adrenaline changed to a lesser degree. Out of seven studies on more short-term (4 h to 3 days) exposure to high altitude, only one demonstrated significantly increased plasma noradrenaline. In this study, however, several subjects had been exposed to high altitude less than 1 week before the experiment. In a new study on 12 climbers reported in this paper, a temporary reduction in plasma catecholamines was found 2 days after arrival at 4200 m. There was a steady increase towards normal levels after 1 week. Plasma vasopressin (AVP) increased suggesting a compensatory mechanism. Both plasma noradrenaline and adrenaline were positively correlated with oxygen saturation in these subjects. Thus, in previously unacclimatized subjects, short-term exposure to high altitude does not increase plasma catecholamines, rather plasma levels decreased. In addition to increased clearance, there is some evidence of reduced synthesis of catecholamines during short-term hypoxia. The oxygen sensitivity of tyrosine hydroxylase (TH) activity, may be one possible mechanism.

Acclimatization↗

PubMed2001

High altitude retinal hemorrhages in a Colorado skier.

High altitude retinal hemorrhages are commonly seen at altitudes above 4270 m. While these hemorrhages are generally asymptomatic, macular involvement may result in permanent visual acuity deficit. We present the case of a 29-year-old male recreational skier who traveled to a ski resort at 2930 m, ascended to 3470 m, and developed acute mountain sickness, high altitude pulmonary edema, and bilateral retinal hemorrhages. A funduscopic examination to determine if macular retinal hemorrhage is present may be performed by clinicians in the final assessment of patients following altitude illness.

Adult↗

PubMed2002

Effects of intermittent exposure to high altitude on blood volume and erythropoietic activity.

The purpose of this review is to describe changes in blood volume and erythropoietic activity occurring under different types of intermittent exposure to hypoxia. These hypoxic episodes can vary from a few seconds or minutes to hours, days, or even weeks. Short hypoxic episodes like sleep apnea only lead to a small increase in hemoglobin concentration, which is mainly due to a hormonal-mediated decrease in plasma volume. In most of these cases the cumulative time spent under hypoxia does not exceed the critical threshold of about 90 min. Endurance athletes and mountaineers who voluntarily expose themselves to hypoxia for some hours or during the night while spending the day at normoxia ("sleep high-train low" concept) do improve their physical performance. Despite raising erythropoietic activity, indicated by elevated plasma concentrations of EPO and the transferrin receptor, the postulated increase in red cell volume has not satisfactorily been proved. Frequent changes between low and high altitudes, which are usual in some South American and Asian countries, provoke similar adaptations in red cell mass as occur in high altitude residents. However, the plasma volume decreases at altitude and increases again when staying at sea level. Even after more than 20 yr of regular moving between low and high altitude, the total blood volume, hemoglobin concentration and hematocrit, as well as the plasma EPO concentration, noticeably oscillate during every hypoxic-normoxic cycle. We assume these changes to be an optimal rapid adaptation of the oxygen transport system to the prevailing hypoxic or normoxic environment. However, possible risks for the organism cannot be excluded.

Acclimatization↗

PubMed2002

Delirium at high altitude.

A 35-year-old man on a trek to the Mount Everest region of Nepal presented with a sudden, acute confusional state at an altitude of about 5000 m. Although described at higher altitudes, delirium presenting alone has not been documented at 5000 m or at lower high altitudes. The differential diagnosis which includes acute mountain sickness and high altitude cerebral edema is discussed. Finally, the importance of travelling with a reliable partner and using proper insurance is emphasized in treks to the Himalayas.

Adult↗

PubMed2003

Physiologic response to moderate altitude exposure among infants and young children.

Substantial numbers of children are exposed to moderate altitude while traveling to mountain resorts with their families. Although there has been extensive study of the adult physiologic response to altitude exposure, few studies of infants and young children exist. This investigation examines the acute physiologic responses to moderate altitude exposure among young children and the relationship of these responses to the development of acute mountain sickness (AMS). Children 3 to 36 months old participated in the prospective observational study, which included baseline measurements at 1610 m and measurements after a 24-h exposure to 3109 m. Measurements included pulse and respiratory rate, end-tidal CO(2), arterial oxygen saturation (pulse oximetry), cerebral tissue oxygenation (St(O2)) by near-infrared spectroscopy, middle cerebral artery resistive index by transcranial Doppler, lateral ventricle volumes (ultrasound), and clinical evaluation for the presence of acute mountain sickness (Children's Lake Louise Score). Twenty-four children (13 girls and 11 boys, age 14.5 +/- 10.2 months) participated. After acute exposure to 3109 m, these children showed an increase in respiratory rate from 45 +/- 13 to 51.9 +/- 15 breaths/min (p < 0.008), accompanied by a decrease of end-tidal CO(2) from 31 +/- 3 to 28 +/- 2 mm Hg (p < 0.001) and a reduction of arterial oxygen saturation from 95 +/- 2 to 91 +/- 2% (p < 0.001). St(O2) also decreased from 78 +/- 8 to 67 +/- 13% (p < 0.001), and this reduction appeared to be related to age (r = 0.58, p < 0.05), with lower saturations found in younger children. No evidence of increased intracranial pressure, as assessed by middle cerebral artery resistive index, was seen during ascent. Seven subjects developed symptoms of AMS; however, no relationship was found between the physiologic changes observed and the presence of symptoms. Ascent from 1610 to 3109 m resulted in tachypnea, relative hypoxia, hypocapnia, and a reduction in cerebral tissue oxygenation (St(O2)). The reduction in St(O2) appeared to be related to age, with infants appearing to be the most susceptible to cerebral tissue oxygen desaturation at high altitude. No relationship appears to exist between the presence of AMS and the physiologic measurements.

Age Factors↗

PubMed2003

Going to high altitude with preexisting ocular conditions.

The goal of this paper is to review how preexisting ocular conditions may be affected by altitude exposure. Such preexisting conditions include dry eye problems, monocular visual loss, and potential problems following refractive surgery procedures, as well as the possible changes associated with some forms of retinal and optic nerve diseases. Although most such altitude-related visual difficulties are relatively minor, some have resulted in serious morbidity or even death at high altitude. This review will give the reader background regarding these potentially debilitating conditions in order to better prepare for exposure to high altitude environments.

Altitude↗

PubMed2025

Plasma Proteomic Profiling Reveals ITGA2B as A Key Regulator of Heart Health in High-altitude Settlers.

Myocardial injury is a common disease in the plateau, especially in the lowlanders who have migrated to the plateau, in which the pathogenesis is not well understood. Here, we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteomic profiling. Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude. Notably, integrin alpha-Ⅱb (ITGA2B) emerged as a potential key player in this context. Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6 (IL-6) through the integrin-linked kinase (ILK)/nuclear factor-κB (NF-κB) signaling axis under hypoxic conditions. Moreover, ITGA2B disrupted mitochondrial structure and function, increased glycolytic capacity, and aggravated energy reprogramming from oxidative phosphorylation to glycolysis. Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases, we discovered that tanshinone ⅡA (TanⅡA) effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice, thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.

Animals↗

PubMed2004

Orthostatic tolerance and blood volumes in Andean high altitude dwellers.

Orthostatic tolerance is a measure of the ability to prevent hypotension during gravitational stress. It is known to be dependent on the degree of vasoconstriction and the magnitude of plasma volume, but the possible influence of packed cell volume (PCV) is unknown. High altitude residents have high haematocrits and probably high packed cell volumes. However, it is not known whether plasma volume and blood volume are affected, or whether their orthostatic tolerance is different from low altitude residents. In this study we determined plasma volume, PCV and orthostatic tolerance in a group of high altitude dwellers (HA), including a subgroup of highland dwellers with chronic mountain sickness (CMS) and extreme polycythaemia. Plasma volume and PCV were determined using Evans Blue dye dilution and peripheral haematocrit. Orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilting and lower body suction. All studies were performed at 4338 m. Results showed that plasma volumes were not significantly different between CMS and HA, or in highland dwellers compared to those seen previously in lowlanders. PCV and haematocrit were greater in CMS than in HA. Orthostatic tolerance was high in both CMS and HA, although the heart rate responses to orthostasis were smaller in CMS than HA. Orthostatic tolerance was correlated with haematocrit (r= 0.57, P < 0.01) and PCV (r= 0.54, P < 0.01). This investigation has shown that although high altitude residents have large PCV, their plasma volumes were similar to lowland dwellers. The group with CMS have a particularly large PCV and also have a very high orthostatic tolerance, despite smaller heart rate responses. These results are compatible with the view that PCV is of importance in determining orthostatic tolerance.

Adult↗

PubMed2006

Carotid baroreflex regulation of vascular resistance in high-altitude Andean natives with and without chronic mountain sickness.

We investigated carotid baroreflex control of vascular resistance in two groups of high-altitude natives: healthy subjects (HA) and a group with chronic mountain sickness (CMS), a maladaptation condition characterized by high haematocrit values and symptoms attributable to chronic hypoxia. Eleven HA controls and 11 CMS patients underwent baroreflex testing, using the neck collar method in which the pressure distending the carotid baroreceptors was changed by applying pressures of -40 to +60 mmHg to the chamber. Responses of forearm vascular resistance were assessed from changes in the quotient of blood pressure divided by brachial artery blood velocity. Stimulus-response curves were defined at high altitude (4338 m) and within 1 day of descent to sea level. We applied a sigmoid function or third-order polynomial to the curves and determined the maximal slope (equivalent to peak gain) and the corresponding carotid pressure (equivalent to 'set point'). The results showed that the peak gains of the reflex were similar in both groups and at both locations. The 'set point' of the reflex, however, was significantly higher in the CMS patients compared to HA controls, indicating that the reflex operates over higher pressures in the patients (94.4 +/- 3.0 versus 79.6 +/- 4.1 mmHg; P < 0.01). This, however, was seen only when subjects were studied at altitude; after descent to sea level the curve reset to a lower pressure with no significant difference between HA and CMS subjects. These results indicate that carotid baroreceptor control of vascular resistance may be abnormal in CMS patients but that descent to sea level rapidly normalizes it. We speculate that this may be explained by CMS patients having greater vasoconstrictor activity at altitude owing to greater hypoxic stimulation of chemoreceptors.

Adult↗

PubMed1996

Effect of altitude on spirometric parameters and the performance of peak flow meters.

BACKGROUND: Portable peak flow meters are used in clinical practice for measurement of peak expiratory flow (PEF) at many different altitudes throughout the world. Some PEF meters are affected by gas density. This study was undertaken to establish which type of meter is best for use above sea level and to determine changes in spirometric measurements at altitude. METHODS: The variable orifice mini-Wright peak flow meter was compared with the fixed orifice Micro Medical Microplus turbine microspirometer at sea level and at Everest Base Camp (5300 m). Fifty one members of the 1994 British Mount Everest Medical Expedition were studied (age range, 19-55). RESULTS: Mean forced vital capacity (FVC) fell by 5% and PEF rose by 25.5%. However, PEF recorded with the mini-Wright peak flow meter underestimated PEF by 31%, giving readings 6.6% below sea level values. FVC was lowest in the mornings and did not improve significantly with acclimatisation. Lower PEF values were observed on morning readings and were associated with higher acute mountain sickness scores, although the latter may reflect decreased effort in those with acute mountain sickness. There was no change in forced expiratory volume in one second (FEV1) at altitude when measured with the turbine microspirometer. CONCLUSIONS: The cause of the fall in FVC at 5300 m is unknown but may be attributed to changes in lung blood volume, interstitial lung oedema, or early airways closure. Variable orifice peak flow meters grossly underestimate PEF at altitude and fixed orifice devices are therefore preferable where accurate PEF measurements are required above sea level.

Adult↗

PubMed1994

Control of erythropoiesis in humans during prolonged exposure to the altitude of 6,542 m.

Altitude hypoxia induces an increase in erythropoiesis. Some of the factors involved in the control of altitude polycythemia were studied. Ten subjects (4 women, 6 men) were exposed for 3 wk to extreme altitude (6,542 m). Blood was withdrawn in normoxia (N) and after 1 wk (H1), 2 wk (H2), or 3 wk (H3) at 6,542 m for the measurement of serum erythropoietin (EPO), blood hemoglobin (Hb), hematocrit (Hct), intraerythrocyte folate (Fol), and plasma ferritin (Fer) concentrations. Renal blood flow (RBF) and absolute proximal reabsorption rate (APR) were measured by the p-aminohippuric acid and lithium clearance, respectively, in N and H2 conditions. O2 supply to the kidneys was calculated using RBF and arterial O2 content (CaO2). After an initial sharp increase in EPO, it decreased at H2 and H3. Hct and Hb increased from N to H1 and H2 and then unexpectedly decreased from H2 to H3. Mean corpuscular Hb content (MCHC = Hb/Hct) was lower in all H than in N conditions. Increase in EPO at H1 varied from 3- to 134-fold among individuals. Women showed a smaller increase in Hct and Hb and a greater decrease in MCHC. Two women showed a large increase in EPO without increase in Hb. Fol was not modified by altitude hypoxia. Fer showed a marked decrease in H1 and H3 compared with N. Hb was positively related to Fer in hypoxia. Iron intake in food was markedly decreased during the 2-wk ascent to 6,542 m. EPO was inversely related to CaO2 and positively related to APR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1977

Urinary catecholamine excretion on induction to high altitude (3,658 m) by air and road.

In a preliminary pilot study we had reported a significant difference in urinary catecholamine excretion between symptomatic and asymptomatic individuals inducted to high altitude by air. The present study covers slower induction by road; 25 lowlanders ascended from 1,800 to 3,658 m in 50 h and 33 similar subjects covered the journey in 6 h. They were studied according to the protocal used in the initial study. None of the 58 subjects inducted by road developed symptoms of high-altitude illness. Their urinary catecholamine excretion remained normal during the 10 days' stay at high altitude. These findings lend support to our earlier contention that there might be a relationship between increased sympathoadrenal activity and high-altitude illnesses.

Adult↗

PubMed1996

Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema.

Individuals with a prior history of (susceptible to high altitude pulmonary edema (HAPE-S) have high resting pulmonary arterial pressures, but little data are available on their vascular response to exercise. We studied the pulmonary vascular response to exercise in seven HAPE-S and nine control subjects at sea level and at 3,810 m altitude. At each location, both normoxic (inspired PO2 = 148 Torr) and hypoxic (inspired PO2 = 91 Torr) studies were conducted. Pulmonary hemodynamic measurements included pulmonary arterial and pulmonary arterial occlusion pressures. A multiple regression analysis demonstrated that the pulmonary arterial pressure reactivity to exercise was significantly greater in the HAPE-S group. This reactivity was not influenced by altitude or oxygenation, implying that the response was intrinsic to the pulmonary circulation. Pulmonary arterial occlusion pressure reactivity to exercise was also greater in the HAPE-S group, increasing with altitude but independent of oxygenation. These findings suggest an augmented flow-dependent pulmonary vasoconstriction and/or a reduced vascular cross-sectional area in HAPE-S subjects.

Adult↗

PubMed1996

Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema.

Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise, especially in hypoxia. A possible explanation is subclinical interstitial edema due to high pulmonary capillary pressures. We hypothesized that this may be pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE-susceptible people with higher vascular pressures would develop more exercise-induced VA/Q mismatch. To examine this, seven healthy people with a history of HAPE and nine with similar altitude exposure but no HAPE history (control) were studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We measured cardiac output and respiratory and inert gas exchange. In both groups, VA/Q mismatch (assessed by log standard deviation of the perfusion distribution) increased with exercise. At sea level, log standard deviation of the perfusion distribution was slightly higher in the HAPE-susceptible group than in the control group during heavy exercise. At altitude, these differences disappeared. Because a history of HAPE was associated with greater exercise-induced VA/Q mismatch and higher pulmonary capillary pressures, our findings are consistent with the hypothesis that exercise-induced mismatch is due to a temporary extravascular fluid accumulation.

Adult↗

PubMed1999

Appetite at "high altitude" [Operation Everest III (Comex-'97)]: a simulated ascent of Mount Everest.

We hypothesized that progressive loss of body mass during high-altitude sojourns is largely caused by decreased food intake, possibly due to hypobaric hypoxia. Therefore we assessed the effect of long-term hypobaric hypoxia per se on appetite in eight men who were exposed to a 31-day simulated stay at several altitudes up to the peak of Mt. Everest (8,848 m). Palatable food was provided ad libitum, and stresses such as cold exposure and exercise were avoided. At each altitude, body mass, energy, and macronutrient intake were measured; attitude toward eating and appetite profiles during and between meals were assessed by using questionnaires. Body mass reduction of an average of 5 +/- 2 kg was mainly due to a reduction in energy intake of 4.2 +/- 2 MJ/day (P < 0.01). At 5,000- and 6,000-m altitudes, subjects had hardly any acute mountain sickness symptoms and meal size reductions (P < 0.01) were related to a more rapid increase in satiety (P < 0.01). Meal frequency was increased from 4 +/- 1 to 7 +/- 1 eating occasions per day (P < 0. 01). At 7,000 m, when acute mountain sickness symptoms were present, uncoupling between hunger and desire to eat occurred and prevented a food intake necessary to meet energy balance requirements. On recovery, body mass was restored up to 63% after 4 days; this suggests physiological fluid retention with the return to sea level. We conclude that exposure to hypobaric hypoxia per se appears to be associated with a change in the attitude toward eating and with a decreased appetite and food intake.

Adult↗