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[High altitude and cardiac disease].

Hypoxia at high altitude is associated with an increase in myocardial work. Cardiovascular effects of high altitude may affect patients suffering from cardiac diseases and raise questions concerning the tolerability of exposure to altitude. In general, altitudes up to 2500 to 3000 meters do not pose a hazard for a patient with stable coronary artery disease and good exercise tolerance. Likewise, a patient suffering from heart failure does not necessarily refrain from these altitude exposures unless exercise capacity and left ventricular ejection fraction are severely impaired. However, cardiac patients have to be informed that symptoms may occur already at lesser efforts at high altitude compared to low altitude. Therefore, patients should be advised to adapt physical activities, particularly during the first 3-4 days of acclimatization. In commercial airplanes pressure conditions are comparable to altitudes of 1500 to 2400 meters. Most cardiac patients tolerante the associated physical stress without difficulty. Contraindications for air travel include unstable cardiac conditions, recent cardiac interventions (2-3 weeks), an uncomplicated myocardial infarction within the last 2 weeks, or a complicated myocardial infarction within the last 6 weeks, respectively. The risk of exposure to altitudes above 3500 meters is not well known for cardiac patients because of a lack of corresponding data. Thus, patients who would like to mountaineer at very high altitudes have to be advised individually based on their physical condition and on the severity of their cardiac illness.

Acclimatization↗

Leptin and altitude in the cardiovascular diseases.

OBJECTIVE: The lower mortality from coronary ischemic disease in populations living at high altitude has been related to an increase of high-density lipoprotein (HDL)-cholesterol at altitude. Leptin has been proposed as a cardiovascular risk factor. We investigated whether leptin varies according to the altitude at which people live. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of the first 889 people enrolled in a cohort study in the Canary Islands, Spain. The relationship among serum leptin, altitude, obesity, and other cardiovascular risk factors was analyzed by bivariate and multivariate tests. RESULTS: Leptin levels showed an inverse correlation to altitude expressed in meters (r = -0.10). Obese subjects had this leptin-altitude association (r = -0.19), but they also had a direct correlation of leptin to HDL-cholesterol (r = 0.27) and an inverse correlation of leptin to the total cholesterol-to-HDL-cholesterol ratio (r = -0.34), triglycerides (r = -0.29), apolipoprotein B (r = -0.21), and glycemia (r = -0.19). Nonobese subjects had only the leptin-altitude association (r = -0.11). The final regression model included altitude as predictor. Other associated variables were gender, physical activity, BMI, age, smoking (reducing leptin independently of BMI), alcohol, heart rate, and income. DISCUSSION: Serum leptin level decreases when altitude increases, and this association could help to explain the lower cardiovascular mortality rate at high altitude. However, because in obese subjects there is a direct association of leptin with HDL-cholesterol and an inverse association with the lipid atherogenic fractions, we suggest the hypothesis of different roles for bound and free leptin, with free leptin being a cardiovascular protective factor in obese people.

Adult↗

Autonomic regulation of heart rate and peripheral circulation: comparison of high altitude and sea level residents.

1. To evaluate the activity of the autonomic nervous system on the heart and peripheral circulation in native high-altitude residents, during a Himalayan expedition we studied 12 men (age: 48 +/- 4, mean +/- SEM), life-long resident in a village at 4800 m (Sumdo village, Zanskar, India) and 7 healthy sea-level residents (age: 37 +/- 4) after 7 days of acclimatization (acclimatized lowlanders) at the same altitude. Furthermore 25 sea level residents (age: 46 +/- 2) underwent the same protocol at sea level. 2. R-R interval (RR), respiratory signal, non-invasive blood pressure, and skin arteriolar blood flow were evaluated in three different conditions: during free breathing in supine position and during controlled breathing (at 0.15 Hz), in supine and upright position, and analysed by autoregressive spectral analysis [low- (around 0.1 Hz) and high-frequency (respiratory) fluctuations, LF and HF, markers of sympathetic and vagal activity, respectively]. 3. High-altitude residents showed in supine position a higher RR than acclimatized lowlanders, similar to sea-level residents. RR variability was reduced in acclimatized lowlanders compared to both high-altitude residents and sea level residents. Systolic blood pressure (SBP) did not show significant differences between the three groups. High altitude residents showed in supine lower LF in RR signal compared to sea-level residents, and, compared to acclimatized lowlanders, higher HF and lower LF/HF ratio; high-altitude residents showed a reduction in skin microcirculation variability compared to sea-level residents, but this was eight fold greater than in acclimatized lowlander, thus indicating a much greater vasoconstriction in acclimatized lowlanders than in high-altitude residents. 4. In upright position, high-altitude residents showed the same behaviour as sea-level residents, with increase in LF-RR, and decrease in HF and LF-SBP. Acclimatized lowlanders showed similar directional trends though not significant changes for RR-LF. 5. After one week of acclimatization, lowlanders still manifested sympathetic activation and skin vasoconstriction; high-altitude residents did not show reduced vagal tone compared to sea-level residents, but a mild vasoconstriction appeared to be present. In conclusion, normal or enhanced vagal tone and preserved vasomotion are probably evidence of adaptation at high altitude hypoxia.

Adaptation, Physiological↗

Intermittent altitude exposures reduce acute mountain sickness at 4300 m.

Acute mountain sickness (AMS) commonly occurs at altitudes exceeding 2000-2500 m and usually resolves after acclimatization induced by a few days of chronic residence at the same altitude. Increased ventilation and diuresis may contribute to the reduction in AMS with altitude acclimatization. The aim of the present study was to examine the effects of intermittent altitude exposures (IAE), in combination with rest and exercise training, on the incidence and severity of AMS, resting ventilation and 24-h urine volume at 4300 m. Six lowlanders (age, 23 +/- 2 years; body weight, 77 +/- 6 kg; values are means +/- S.E.M.) completed an Environmental Symptoms Questionnaire (ESQ) and Lake Louise AMS Scoring System (LLS), a resting end-tidal partial pressure of CO2 ( PETCO2) test and a 24-h urine volume collection at sea level (SL) and during a 30 h exposure to 4300 m altitude-equivalent (barometric pressure=446 mmHg) once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h.day(-1), 5 days.week(-1), 4300 m). The previously validated factor score, AMS cerebral score, was calculated from the ESQ and the self-report score was calculated from the LLS at 24 h of altitude exposure to assess the incidence and severity of AMS. During each IAE, three subjects cycled for 45-60 min.day(-1) at 60-70% of maximal O2 uptake (VO2 max) and three subjects rested. Cycle training during each IAE did not affect any of the measured variables, so data from all six subjects were combined. The results showed that the incidence of AMS (%), determined from both the ESQ and LLS, increased (P<0.05) from SL (0 +/- 0) to PreIAE (50 +/- 22) at 24 h of altitude exposure and decreased (P<0.05) from PreIAE to PostIAE (0 +/- 0). The severity of AMS (i.e. AMS cerebral symptom and LLS self-report scores) increased (P<0.05) from SL (0.02 +/- 0.02 and 0.17 +/- 0.17 respectively) to PreIAE (0.49 +/- 0.18 and 4.17 +/- 0.94 respectively) at 24 h of altitude exposure, and decreased (P<0.05) from PreIAE to PostIAE (0.03 +/- 0.02 and 0.83 +/- 0.31 respectively). Resting PETCO2 (mmHg) decreased (i.e. increase in ventilation; P<0.05) from SL (38 +/- 1) to PreIAE (32 +/- 1) at 24 h of altitude exposure and decreased further (P<0.05) from PreIAE to PostIAE (28 +/- 1). In addition, 24-h urine volumes were similar at SL, PreIAE and PostIAE. In conclusion, our findings suggest that 3 weeks of IAE provide an effective alternative to chronic altitude residence for increasing resting ventilation and reducing the incidence and severity of AMS.

Acclimatization↗

A three-week traditional altitude training increases hemoglobin mass and red cell volume in elite biathlon athletes.

It is well known that altitude training stimulates erythropoiesis, but only few data are available concerning the direct altitude effect on red blood cell volume (RCV) in world class endurance athletes during exposure to continued hypoxia. The purpose of this study was to evaluate the impact of three weeks of traditional altitude training at 2050 m on total hemoglobin mass (tHb), RCV and erythropoietic activity in highly-trained endurance athletes. Total hemoglobin mass, RCV, plasma volume (PV), and blood volume (BV) from 6 males and 4 females, all members of a world class biathlon team, were determined on days 1 and 20 during their stay at altitude as well as 16 days after returning to sea-level conditions (800 m, only males) by using the CO-rebreathing method. In males tHb (14.0 +/- 0.2 to 15.3 +/- 1.0 g/kg, p < 0.05) and RCV (38.9 +/- 1.5 to 43.5 +/- 3.9 ml/kg, p < 0.05) increased at altitude and returned to near sea-level values 16 days after descent. Similarly in females, tHb (13.0 +/- 1.0 to 14.2 +/- 1.3 g/kg, p < 0.05) and RCV (37.3 +/- 3.3 to 42.2 +/- 4.1 ml/kg, p < 0.05) increased. Compared to their sea-level values, the BV of male and female athletes showed a tendency to increase at the end of the altitude training period, whereas PV was not altered. In male athletes, plasma erythropoietin concentration increased up to day 4 at altitude (11.8 +/- 5.0 to 20.8 +/- 6.0 mU/ml, p < 0.05) and the plasma concentration of the soluble transferrin receptor was elevated by about 11 % during the second part of the altitude training period, both parameters indicating enhanced erythropoietic activity. In conclusion, we show for the first time that a three-week traditional altitude training increases erythropoietic activity even in world class endurance athletes leading to elevated tHb and RCV. Considering the relatively fast return of tHb and RCV to sea-level values after hypoxic exposure, our data suggest to precisely schedule training at altitude and competition at sea level.

Adaptation, Physiological↗

Effects of altitude, ambient temperature and solar radiation on fasting heat production in yellow cattle (Bos taurus).

Growing yellow cattle (Bos taurus, n 30, 1.0-3.5 years old and 75-240 kg) from their native altitude (2000-2800 m) were used to evaluate the effects of altitude, ambient temperature (Ta) and solar radiation on the basal energy metabolism in this large mammal. Fasting heat production (FHP) was measured at altitudes of 2260, 3250 and 4270 m on the Tibetan plateau both in the summer and winter respectively, after a 90 d adaptation period at each experimental site. The gas exchanges of the whole animal were determined continuously for 3 (2260 and 3250 m) or 2 (4270 m) d after a 96 (2260 and 3250 m) or 48 (4270 m) h starvation period, using closed-circuit respiratory masks. Increasing altitude from 2260 to 3250 m at similar Ta in the summer significantly elevated FHP for all animals (P<0.01), and from 3250 to 4270 m for young cattle (P<0.05); increasing altitude from 2260 to 3250 m in the winter also significantly elevated FHP (P<0.05), but the increase was mainly due to the decrease of Ta and the increase in wind speed. No results were obtained at 4270 m in the winter, due to the problems of the animals, adapting to the altitude. The magnitude of FHP elevation caused by increasing altitude was greater with summer sunshine or winter wind than without them. Increase of Ta from 10.0 to 22.0 degrees C, in the presence of solar radiation, slightly (2260 m) or significantly (3250 and 4270 m, P<0.01) elevated FHP, but slightly reduced it in the absence of solar radiation; decrease of Ta from 0.0 to -30.0 degrees C linearly increased FHP. At 3250 and 4270 m, FHP at the same Ta was higher with summer sunshine or winter wind (3250 m) than without them, but this did not occur at 2260 m. In conclusion, high altitude elevates FHP in yellow cattle in the warm season, and the summer solar radiation and winter wind at high altitude significantly increase metabolic rate. It may be also concluded that the effects of solar radiation on metabolic rate depend on the altitude and the environmental temperature.

Altitude↗

Exercise at low altitude (Jordan Valley) causes changes in serum levels of ACTH, insulin, cortisol and lactate.

This study was designed to examine the effects of exercise on adrenocorticotropic hormone (ACTH) and cortisol at low altitude (350 meters below sea level) and to compare these effects with those at a moderate level altitude (620 meters above sea level). Ten male trained athletes participated in a 21-K(m) non-competitive race. Serum levels of ACTH, luteinizing hormone (LH), growth hormone and cortisol were measured before and after the race at each of the altitudes. A significant increase in serum levels of ACTH was observed in response to this exercise only at low altitude. Serum levels of growth hormone were increased at both altitudes. Those of LH were not affected. Serum cortisol levels were increased following exercise at both altitudes. It is proposed here that ACTH may play a role in acclimatization to exercise at low altitudes. The role of growth hormone and LH in this conditioning process seems to be insignificant. Additionally, serum levels of insulin and lactate were also measured in these experiments. Exercise caused a decrease in serum insulin levels at both altitudes. Serum levels of lactate were decreased only at low altitude. These changes of serum levels of insulin and lactate suggest a type of metabolic adjustment to meet energy requirements. Changes in energy metabolism can be correlated by changes in the ratio of insulin to serum cortisol levels and those of other counter-regulatory hormones in response to exercise at both altitudes.

Acclimatization↗

Is elbow breadth a measure of frame size in non-Caucasian populations? A study in low- and high-altitude Central-Asia populations.

UNLABELLED: The concept of frame size has not undergone a thorough evaluation in non-Caucasian populations. Using data from the Central Asia High Altitude Population (CAHAP) study, we tested whether: (1) the relationship between frame size and body composition is different in high-, medium- and low-altitude populations; (2) elbow breadth is a better index of frame size than biacromial and biiliac breadth; and (3) measures of frame size are associated with blood pressure, cholesterol and triglycerides. A number of 334 male subjects aged 33 +/- 10 years (mean +/- standard deviation) were selected from the CAHAP population (n = 384) on the basis of the availability of breadth measurements. The subjects were 85 high-altitude Kirghizs, 105 medium-altitude Kazakhs, 79 low-altitude Kirghizs and 65 low-altitude Uighurs. A detailed anthropometric evaluation and blood pressure, cholesterol and trygliceride measurements were performed on all individuals. Among breadths, elbow had the lowest correlation with arm fat area, thigh fat area, calf fat area and the sum of trunk skinfolds (r < or = 0.196, P < 0.01). Even if elbow breadth did not have the highest correlation with muscularity indexes, its constantly lower association with adiposity indexes shows that it is a better measure of frame size than biacromial breadth and biiliac breadth. The relationship between frame size and body composition did not differ in high-, medium- and low-altitude subjects (P = not significant, analysis of co-variance). Only a weak association was present between breadths, blood pressure, cholesterol and triglycerides (r < or = 0.230, P < 0.01) and it was not influenced by altitude (P = not significant, analysis of co-variance). Elbow breadth was significantly correlated only with diastolic blood pressure (r = 0.121, P < 0.05). IN CONCLUSION: (1) the relationship between frame size and body composition is similar in high- and low-altitude populations; (2) elbow breadth is an index of frame size independent of altitude; and (3) elbow breadth is correlated with diastolic blood pressure, but this correlation is of doubtful biological relevance.

Adult↗

Cold-induced peripheral vasodilation at high altitudes--a field study.

A significant reduction in cold-induced vasodilation (CIVD) is observed at high altitudes. No agreement is found in the literature about acclimatization effects on CIVD. Two studies were performed to investigate the effect of altitude acclimatization on CIVD. In the first study 13 male subjects immersed the distal phalanx of the left middle finger in water of 0 degrees C for 30 min to evoke CIVD. Five subjects were exposed to altitudes of 5,100 to 7,000 m for 45 days (A). Eight subjects were exposed to an altitude of 5,100 m for <3 days (NA). The groups did not differ in age, weight, and stature. No significant differences were observed between A and NA. However, the maximum finger skin temperature of group A tended to return to sea level values (6.9 +/- 3.2 degrees C at sea level vs. 6.0 +/- 0.7 degrees C at altitude), while a strong reduction was observed for the NA group (7.7 +/- 4.3 degrees C vs. 3.7 +/- 3.1 degrees C). This indicates that the CIVD response at altitude tended to be stronger for the acclimatized subjects. In a second study, nine males were followed in a longitudinal study. CIVD was measured before, during and after 7 days of exposure to 4,350 m. Maximum finger skin temperature before and after exposure did not differ (8.5 +/- 2.6 degrees C vs. 7.8 +/- 1.6 degrees C), and was reduced at altitude. There was no difference in maximum finger skin temperature between the 7 days at altitude (e.g., 5.3 +/- 2.7 degrees C at day 2 and 4.7 +/- 1.1 degrees C at Day 7). It can be concluded that no acclimatization effects of CIVD occur during the first 7 days of altitude exposure, but that differences may occur after altitude exposure of several weeks.

Acclimatization↗

Analysis of the myoglobin gene in Tibetans living at high altitude.

Myoglobin, a protein with an important role in muscle oxidative metabolism, is increased in high altitude residents. In the closely related hemoglobins, mutations cause or contribute to human disease. Furthermore, heme-containing proteins may be involved in oxygen sensing. We therefore tested the hypotheses that myoglobin allele frequencies differed in Tibetans, a long-resident human high-altitude population, compared with sea-level residents, and varied in relation to altitude among Tibetans. We obtained the sequence of exon 2 of the myoglobin gene in 146 Tibetans with greater than three generations of stable residence at altitude in rural Tibet. We compared the frequency of known polymorphic sites in this gene among Tibetans living at altitudes of 3000, 3700, and 4500 m and to allele frequencies previously obtained in 525 residents of Dallas, Texas. We also examined the association between different myoglobin genotypes and hemoglobin concentration, used as an index of myoglobin levels. The frequency of the myoglobin 79A allele was higher in the high altitude compared with the sea-level residents, but unchanged with increasing altitude among Tibetans. There was no significant deviation from Hardy-Weinberg equilibrium in any of the Tibetan altitude groups, nor was there any association between myoglobin genotype and hemoglobin concentration. Screening of exon 2 of the myoglobin gene in high altitude Tibetans does not show novel polymorphism or selection for specific myoglobin alleles as a function of altitude of residence or hypoxic challenge.

Altitude↗

Short-term altitude mountain living improves glycemic control.

The aim of this study was to investigate the effect of mountain living conditions and high altitude hiking activities on glucose tolerance. In study I, we performed an oral glucose tolerance test on nine untrained subjects before and after 3 days of mountain living. In study II, the same measurement was used to determine the effect of high altitude hiking in two distinct geographic environments; participants included 19 professionally trained mountaineers. We found that trained mountaineers displayed significantly better sea-level glucose tolerance than sedentary subjects of a similar age (p < 0.05). This result suggests that mountaineering training could produce a beneficial effect on glucose tolerance. More importantly, in study I we demonstrated that 3 days of high altitude living (altitude approximately 2400 m) was sufficient to improve glucose tolerance. Furthermore, hiking in a relatively flat plateau area (Pamirs highland area, China, altitude approximately 4000 m) generated significantly better improvement in glucose tolerance than hiking in a mountain that contained many rough hills at a similar altitude (Mountain Snow, Taiwan, altitude approximately 3800 m). In conclusion, we found that living at a high altitude for the short term can significantly improve glucose tolerance. Additionally, the improving effect of hiking at high altitudes on glucose tolerance appears to be influenced by the geographic environment. These preliminary results suggest that high altitude living conditions and activities may possibly be developed as potential natural medicines for the prevention and treatment of type II diabetes in the future.

Adolescent↗

The placenta at high altitude.

The influence of oxygen pressure on placental and villous vascular development is reviewed and considered relative to the natural experiment afforded by residence at high altitude. Data obtained from normal high altitude pregnancies are compared with those from IUGR and preeclampsia, conditions believed to be caused by placental hypoxia. High altitude placentas are characterized by increased villous vascularization, thinning of the villous membranes, proliferation of the villous cytotrophoblast, and reduced perisyncytial fibrin deposition relative to low altitude placentas. The significance of reduced fibrin deposition is unknown; it could be explained by less apoptosis along the barrier membrane, less syncytiotrophoblast turnover, or altered ratios of local proversus anticoagulant production. Increased villous capillary density and thinning of the villous membranes increases oxygen diffusion capacity and is generally considered a beneficial adaptation. Nonetheless, there is evidence that hypoxia and/or reduced blood flow reduce placental nutrient transporter densities, and this may act in additive or synergistic fashion to reduce birth weight at high altitude. The available literature on high altitude placentas derives from less than 100 pregnancies from three different continents and six different ethnic groups, and were acquired in pregnancies ranging from 2500 to 4300 m in altitude. Thus differences between studies are likely to be due to variation in altitude and/or to ethnic variation, which in turn may be due to differences in population history of residence at high altitude (e.g., Andeans vs. Europeans). Nonetheless, systematic examination of human placental development under conditions of lowered maternal arterial oxygen pressure (high altitude > 2700 m) may provide useful insights into the etiology of pathological conditions believed to be associated with placental hypoxia.

Altitude↗

Blood volume and hemoglobin mass in endurance athletes from moderate altitude.

PURPOSE: To determine whether total hemoglobin (tHb) mass and total blood volume (BV) are influenced by training, by chronic altitude exposure, and possibly by the combination of both conditions. METHODS: Four groups (N = 12, each) either from locations at sea level or at moderate altitude (2600 m) were investigated: 1) sea-level control group (UT-0 m), 2) altitude control group (UT-2600 m), 3) professional cyclists from sea level (C-0 m), and 4) professional cyclists from altitude (C-2600 m). All subjects from altitude were born at about 2600 m and lived all their lives (except during competitions at lower levels) at this altitude. tHb and BV were determined by the CO-rebreathing method. RESULTS: VO2max (mL x kg(-1) x min(-1)) was significantly higher in UT-0 m (45.3 +/- 3.2) than in UT-2600 m (39.6 +/- 4.0) but did not differ between C-0 m (68.2 +/- 2.7) and C-2600 m (69.9 +/- 4.4). tHb (g x kg(-1)) was affected by training (UT-0 m: 11.0 +/- 1.1, C-0 m: 15.4 +/- 1.3) and by altitude (UT-2600 m: 13.4 +/- 0.9) and showed both effects in C-2600 m (17.1 +/- 1.4). Because red cell volume showed a behavior similar to tHb and because plasma volume was not affected by altitude but by training, BV (mL x kg(-1)) was increased in C-0 m (UT-0 m: 78.3 +/- 7.9; C-0 m: 107.0 +/- 6.2) and in UT-2600 m (88.2 +/- 4.8), showing highest values in the C-2600 m group (116.5 +/- 11.4). CONCLUSION: In endurance athletes who are native to moderate altitude, tHb and BV were synergistically influenced by training and by altitude exposure, which is probably one important reason for their high performance.

Adult↗

The response of leaf morphology to irradiance depends on altitude of origin in Nothofagus cunninghamii.

Leaf morphology varies reliably with increasing altitude in many species, and this is generally considered to be related to temperature. Changes in irradiance with elevation may confound any relationships between a morphological character and altitude, particularly if altitude of origin affects the response to irradiance. Here we describe the interaction between irradiance and altitude of origin on leaf morphology of Southern beech, Nothofagus cunninghamii. Cuttings from each of four altitudes were grown in a glasshouse under full sunlight or 50% shade, and leaf morphology was related to irradiance, altitude of origin and accession. There was a significant interaction between irradiance and altitude of origin for leaf length, width, thickness, area, weight, specific leaf area and stomatal density. There was no effect of altitude on leaf length to width ratio or stomatal index, nor was there an interaction between irradiance and altitude of origin for these variables. These results show that the altitude of origin of a plant has an overriding impact on the leaf morphological response to irradiance. This must be considered in climatic reconstructions.

Altitude↗

Blood gases in pregnancy at sea level and at high altitude.

OBJECTIVE: 1. To measure blood gases and minute ventilation in healthy women with normal pregnancies, compare with non-pregnant women both at sea level and at high altitude; 2. to relate the results at altitude with duration of residence there. DESIGN: Cross-sectional study. SETTING: Antenatal clinics at sea level in Lima, Peru and at high altitude 4300m in Cerro de Pasco, Peru. POPULATION: A total of 304 normal pregnant women between 7 and 41 weeks of gestation were studied, including 112 who lived at sea level and 192 at high altitude (4300m). For comparison 38 non-pregnant women (19 at sea level and 19 at high altitude) were also studied. METHODS: Arterialised blood gases, haemoglobin, pulse oximetry and minute ventilation were measured once in each woman. MAIN OUTCOME MEASURES: PO2, PCO2, pH, haemoglobin, oxygen saturation, arterial oxygen content and minute ventilation and their relationship to gestation. RESULTS: PO2, PCO2, bicarbonate, base excess and oxygen saturation were lower in pregnancies at high altitude compared with sea level; pH, haemoglobin, arterial oxygen content and minute ventilation were higher. At high altitude oxygen saturation and haemoglobin decreased towards term resulting in a fall in arterial oxygen content at the end of pregnancy. Women whose family had lived at high altitude for at least three generations maintained their oxygenation throughout pregnancy better than women whose family had lived there for less than three generations. CONCLUSIONS: In pregnancy at high altitude maternal adaptation appeared adequate in the first trimester but declined towards term. However, maternal oxygenation was maintained in those whose family had lived longest at high altitude suggesting a beneficial adaptation to a hypoxic environment, occurring over generations.

Adult↗

Individual variation in the erythropoietic response to altitude training in elite junior swimmers.

OBJECTIVES: Inter-individual variations in sea level performance after altitude training have been attributed, at least in part, to an inter-individual variability in hypoxia induced erythropoiesis. The aim of the present study was to examine whether the variability in the increase in total haemoglobin mass after training at moderate altitude could be predicted by the erythropoietin response after 4 h exposure to normobaric hypoxia at an ambient Po(2) corresponding to the training altitude. METHODS: Erythropoietin levels were measured in 16 elite junior swimmers before and after 4 h exposure to normobaric hypoxia (Fio(2) 0.15, approximately 2500 m) as well as repeatedly during 3 week altitude training (2100-2300 m). Before and after the altitude training, total haemoglobin mass (CO rebreathing) and performance in a stepwise increasing swimming test were determined. RESULTS: The erythropoietin increase (10-185%) after 4 h exposure to normobaric hypoxia showed considerable inter-individual variation and was significantly (p<0.001) correlated with the acute erythropoietin increase during altitude training but not with the change in total haemoglobin mass (significant increase of approximately 6% on average). The change in sea level performance after altitude training was not related to the change in total haemoglobin mass. CONCLUSIONS: The results of the present prospective study confirmed the wide inter-individual variability in erythropoietic response to altitude training in elite athletes. However, their erythropoietin response to acute altitude exposure might not identify those athletes who respond to altitude training with an increase in total haemoglobin mass.

Adolescent↗

Effects of high altitude hypoxia on left ventricular systolic time intervals in man.

Effects of high altitude hypoxia on systolic time intervals were examined in 34 healthy men: 20 sea level residents studied at rest and at the end of 3 minutes steady isometric (handgrip) exercise at sea level and then serially for the first 5 days and on the tenth day, at an altitude of 3658 m, and I4 permanent residents at high altitude studied at high altitude. In the sea level residents there was a significant increase in the pre-ejection period (PEP), abbreviation of the left ventricular ejection time (LVET), both corrected for heart rate, and prolongation of the PEP/LVET ratio at high altitude. The maximum changes were seen on days 2 and 3; these parameters tended to approach sea level control values by the tenth day. The systolic time interval values of high altitude residents were similar to the control values of the sea level residents obtained at sea level but significantly different from the changes in the sea level values seen in the first 4 days at high altitude. It thus appears that while the high altitude residents do not show any left ventricular dysfunction as determined by systolic time intervals, healthy sea level residents when exposed to high altitude hypoxia show a significant depression of the left ventricular function for at least the first 4 days. This might be a contributing factor in the genesis of high altitude pulmonary oedema.

Adult↗

Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude.

In pulmonary hypertension right ventricular pressure overload leads to abnormal left ventricular (LV) diastolic function. Acute high-altitude exposure is associated with hypoxia-induced elevation of pulmonary artery pressure particularly in the setting of high-altitude pulmonary edema. Tissue Doppler imaging (TDI) allows assessment of LV diastolic function by direct measurements of myocardial velocities independently of cardiac preload. We hypothesized that in healthy mountaineers, hypoxia-induced pulmonary artery hypertension at high altitude is quantitatively related to LV diastolic function as assessed by conventional and TDI Doppler methods. Forty-one healthy subjects (30 men and 11 women; mean age 41 +/- 12 yr) underwent transthoracic echocardiography at low altitude (550 m) and after a rapid ascent to high altitude (4,559 m). Measurements included the right ventricular to right atrial pressure gradient (DeltaP(RV-RA)), transmitral early (E) and late (A) diastolic flow velocities and mitral annular early (E(m)) and late (A(m)) diastolic velocities obtained by TDI at four locations: septal, inferior, lateral, and anterior. At a high altitude, DeltaP(RV-RA) increased from 16 +/- 7 to 44 +/- 15 mmHg (P < 0.0001), whereas the transmitral E-to-A ratio (E/A ratio) was significantly lower (1.11 +/- 0.27 vs. 1.41 +/- 0.35; P < 0.0001) due to a significant increase of A from 52 +/- 15 to 65 +/- 16 cm/s (P = 0.0001). DeltaP(RV-RA) and transmitral E/A ratio were inversely correlated (r(2) = 0.16; P = 0.0002) for the whole spectrum of measured values (low and high altitude). Diastolic mitral annular motion interrogation showed similar findings for spatially averaged (four locations) as well as for the inferior and septal locations: A(m) increased from low to high altitude (all P < 0.01); consequently, E(m)/A(m) ratio was lower at high versus low altitude (all P < 0.01). These intraindividual changes were reflected interindividually by an inverse correlation between DeltaP(RV-RA) and E(m)/A(m) (all P < 0.006) and a positive association between DeltaP(RV-RA) and A(m) (all P < 0.0009). In conclusion, high-altitude exposure led to a two- to threefold increase in pulmonary artery pressure in healthy mountaineers. This acute increase in pulmonary artery pressure led to a change in LV diastolic function that was directly correlated with the severity of pulmonary hypertension. However, in contrast to patients suffering from some form of cardiopulmonary disease and pulmonary hypertension, in these healthy subjects, overt LV diastolic dysfunction was not observed because it was prevented by augmented atrial contraction. We propose the new concept of compensated diastolic (dys)function.

Acute Disease↗