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PubMed1975

Sleep physiology at high altitude.

All night sleep EEG, EKG, and respiration were recorded from six young men during 2 nights at sea level and 4 nonconsecutive nights at high altitude (14.110 ft., 4301 m). Sleep at high altitude was chraacterized initially by a significant decrease in Stages 3 and 4, a significant increase in the number of arousals, and a trend towards more time spent awake. In terms of actual time spent sleep, however, a relatively good night's sleep was obtained, which suggests that the objective sleep disturbance was not commensurate with the marked subjective complaints of sleeplessness. Periodic respiration during sleep was frequent at high altitude, was quickly terminated by oxygen administration, was not clearly related to the increased number of arousals, and usually was not seen during REM periods. Heart rate was increased during sleep at high altitude. All measures tended to return towards sea level means during 12 days at altitude. We suggest that the marked increase in the number of arousals may account for the disparity between the subjective reports and objective measures of sleep disturbance at high altitude. Although the objective sleep disruption is probably related in some fashion to hypoxemia, it is unclear whether hypoxemia itself or the alkalosis commonly present shortly after arrival at altitude is the major factor.

Adult↗

PubMed1982

2,3-diphosphoglycerate in high- and low-altitude populations of the deer mouse.

Erythrocyte DPG concentrations were studied in populations of Peromyscus maniculatus native to different altitudes. Deer mice native to, and resident at, high altitude showed higher DPG/Hb ratios than did deer mice native to, and resident at, low altitude. However, after prolonged acclimation to low altitude, the high-altitude natives showed lower DPG/Hb ratios than did low-altitude natives. The differences in baseline DPG levels appear to be determined primarily by genetic factors. The heritability (h2) of DPG/Hb ratios was estimated by two independent methods to be 0.51 and 0.66, but those values are inflated to an unknown extent by environmental correlations between relatives. Mild cold stress did not elicit an increase in DPG/Hb ratios. DPG levels tended to decrease with age, but the aging effect was not consistently observed in all samples. Neither sex nor alpha-globin genotype influenced DPG levels. The adaptive significance of the genetic differences in DPG metabolism between high- and low-altitude populations remains problematic.

2,3-Diphosphoglycerate↗

PubMed1989

Arterial blood gas status in rats exposed to chronic CO at low and high altitude.

Arterial blood gases were measured in 52 unanesthetized Sprague-Dawley rats following six weeks exposure to either room air at ambient altitude (950 m), room air containing 100 ppm CO at ambient altitude, room air at 4575 m simulated high altitude, or room air containing 100 ppm CO at 4575 m simulated high altitude. PaCO2 was significantly higher in animals exposed to CO both at ambient altitude (38.2 vs 34.5 Torr) and simulated high altitude (28.3 vs 23.6 Torr). The data show that chronic exposure to low concentrations of CO depresses ventilatory drive at both ambient and simulated high altitude. This depression could be related to changes in brain blood flow and the acidity of the central medullary chemosensitive area or to changes in peripheral chemoreceptor activity.

Altitude↗

PubMed1988

The effect of altitude on adolescent growth and development.

To evaluate the effect of altitude on adolescent growth and development, three groups of healthy, well-nourished youth of similar socioeconomic status and ethnic grouping who resided at sea level (n = 1262 subjects), mid-altitude (n = 1743 subjects), and high altitude (n = 1137 subjects) were studied. The following parameters were evaluated: weight and height in all subjects; genital and pubic hair development in the males; and the initiation of breast development and age of menarche in the females. At mid-altitude, puberty appears to start at a similar age, but lasts longer, than at sea level. At high altitude, puberty starts significantly later and is more prolonged than at sea level and mid-altitude. Our data reveal relatively little effect of altitude upon growth and weight-gain patterns or final attained heights and weights.

Adolescent↗

PubMed2006

[Characteristics of mepivacaine axillary brachial plexus block performed at 2800 m of altitude].

OBJECTIVE: We evaluated the feasibility and pharmacodynamic profile of axillary brachial plexus nerve blocks performed in high altitude. STUDY DESIGN: A prospective study was performed in healthy volunteers. PATIENTS AND METHODS: Ten male volunteers received 20 ml of 1.5% mepivacaine on radial and median nerves (total 40 ml), first at altitude of 150 then at 2877 m. Onset and offset times for sensory, motor and sympathetic blocks were recorded. Blood was sampled up to 60 min after injection to measure plasma concentrations of mepivacaine. RESULTS: At 150 and 2877 m of altitude, onset times for blocks were similar. Duration of sensory and motor blocks was not different at low and high altitude (193+/-35 min and 180+/-47 min; and 237+/-32 min and 217+/-44 min, respectively). Plasma mepivacaine concentrations were significantly lower at 20 minutes in high altitude (p<0.05). At higher altitude, one patient showed clinical signs of neurological toxicity, with plasma concentrations of mepivacaine ranging from 0.94 to 1.21 mug/ml. CONCLUSION: At altitude of 2877 m, axillary brachial plexus block with 1.5% mepivacaine is feasible, with onset and offset times for sensory and motor effects similar to those performed at 150 m.

Adult↗

PubMed2004

High-altitude illness.

Travel to a high altitude requires that the human body acclimatize to hypobaric hypoxia. Failure to acclimatize results in three common but preventable maladies known collectively as high-altitude illness: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Capillary leakage in the brain (AMS/HACE) or lungs (HAPE) accounts for these syndromes. The morbidity and mortality associated with high-altitude illness are significant and unfortunate, given they are preventable. Practitioners working in or advising those traveling to a high altitude must be familiar with the early recognition of symptoms, prompt and appropriate therapy, and proper preventative measures for high-altitude illness.

Acclimatization↗

PubMedDate not supplied

High-altitude-related disorders--Part II: prevention, special populations, and chronic medical conditions.

This second section of a 2-part review on high-altitude-related disorders focuses on strategies for prevention of high-altitude illness, identification of populations at increased risk for high-altitude illness, and effects of high altitude on selected chronic medical conditions. Practical aspects of advising and educating patients traveling to high altitude will be discussed, with special reference to pregnant women, infants and young children, healthy elders, and chronic medical conditions that may place persons at greater risk for high-altitude illness. The special concerns of pre-verbal children will be covered relative to the risks of high altitude for those too young to voice symptoms of illness and, thus, at-risk for potential serious consequences caused by delay in diagnosis and treatment.

Age Factors↗

PubMed2002

Maternal serum insulin-like growth factor binding protein-1 in pregnancy at high altitude.

OBJECTIVE: To investigate the effect of environmental hypoxia at 4300-m altitude on the maternal serum concentration of insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: We conducted a cross-sectional study of 108 pregnant women in Peru, 62 from high altitude (4300 m, 14100 ft) and 46 from sea level at 14-42 weeks' gestation. For comparison, 20 healthy nonpregnant women (ten from high altitude and ten from sea level) were also examined. Total and nonphosphorylated IGFBP-1 were measured in maternal serum. RESULTS: Both total and nonphosphorylated IGFBP-1 were higher at high altitude than at sea level in the pregnant groups (ratio = 1.28, P =.008, and ratio = 1.45, P =.003, respectively), and there was significant interaction between high altitude and sea level (P =.037 and P =.043, respectively). The threshold model showed that the difference became significant from 25 weeks' gestation onwards. CONCLUSION: Before 25 weeks of pregnancy, there was no significant difference in IGFBP-1 between women living at high or low altitude, suggesting that the increased IGFBP-1 at high altitude is unlikely to be related to inadequate trophoblast invasion resulting in placental hypoxia. In the second half of pregnancy, the maternal and fetal demands increase dramatically, and low atmospheric oxygen with resulting maternal systemic hypoxemic hypoxia may cause placental hypoxia. This stimulates increased production of IGFBP-1, which in turn restricts the insulin-like growth factor-mediated fetal growth as an adaptive mechanism to prevent worsening of the fetoplacental hypoxia.

Adult↗

PubMed1997

Term ovine placental vasculature: comparison of sea level and high altitude conditions by corrosion cast and histomorphometry.

The placental vascular architecture differs significantly at high altitude from that at sea level in the human and guinea-pig. Four sheep between 137 and 140 days of gestation, kept near sea level throughout gestation, were used as a normoxic control group for comparison of the placental vasculature with 10 other ewes, kept at high altitude (3820 m above sea level; Barcroft Laboratory, White Mountain Research Station, CA, USA). Placentomes from both groups were prepared for histology and scanning electron microscopy of vascular corrosion casts. Singular perfusion of fetal placentae, as well as combined maternal/fetal injection was performed. The influence of long-term hypoxaemia was determined by qualitative and semi-quantitative evaluation of corrosion casts and histological sections. The fetal vessel casts show a distinct difference in the arrangement of vessels of all sizes in response to long-term hypoxaemia. In the control group, stem arteries and veins are straight and parallel. In contrast, this is much less evident in the hypoxaemic group because arterioles and venules branch off the stem vessels more frequently and in an irregular manner. This leads to a capillary bed that is much more dense due to increased branching and capillary coiling. These observations are confirmed by histomorphometry. In the fetal vessels of high altitude sheep placentomes, we observed a decreased number of vascular cross sections (21.6 +/- 4.7 SEM versus 27.7 +/- 4.0 SEM; P = 0.02). However, the average luminal size per cross section (77.9 +/- 10.5 microns2 SEM versus 59.4 +/- 7.4 microns2 SEM; P = 0.004) was increased at high altitude and the percentage of lumina of the total area (5.7 +/- 0.5 SEM versus 5.3 +/- 0.3 SEM; P = 0.09) indicated a trend towards an increase. In maternal vessels of high altitude placentomes, the number of vessel cross sections (6.5 +/- 0.7 SEM versus 6.0 +/- 0.5 SEM; P = 0.2) remained unchanged, whereas the average luminal size (1108 +/- 122 microns2 SEM versus 844 +/- 77 microns2 SEM; P < 0.001) and the percentage of lumina out of the total area (20.9 +/- 1.8 SEM versus 17.5 +/- 1.7 SEM; P < 0.001) were increased. The interhaemal distance appeared to be slightly but not significantly increased at high altitude. These findings indicate that at high altitude the sheep placenta develops an increased materno-fetal absorptive surface to help guarantee substance exchange.

Altitude↗

PubMedDate not supplied

Ovine placentome morphology: effect of high altitude, long-term hypoxia.

The effect of high altitude, long-term hypoxaemia on placentome morphology in the sheep was examined using singleton and twin pregnant ewes. Normoxic twins had lower fetal and placental weights (3.7+/-0.2 kg and 215+/-26 g, respectively) than normoxic singleton fetuses (4.3+/-0.2 kg and 336+/-17 g, respectively). Fetal and placental weights were similar in normoxic singleton and high altitude (3820 m) hypoxic singleton fetuses (4.3+/-0.2 and 4.4+/-0.4 kg, 336+/-17 and 342+/-62 g, respectively). The distribution of placentome types was classified into four major categories (A-D) and for normoxic singletons was as follows: A=76+/-4, B=22+/-3, C=1+/-2, and D=1+/-1. Normoxic twins tended to have more type B (type A=63+/-10, B=33+/-8, C=2+/-1, and D=2+/-1). High altitude hypoxic singletons had significantly fewer type A (33+/-4) and more type B (50+/-3), C (10+/-7), D (7+/-1) placentomes than normoxic singletons. In addition, in the sea-level control group, five animals were found to be spontaneously hypoxic with a placentome distribution similar to that of the high altitude hypoxic fetuses. In conclusion, both high altitude, long-term hypoxia and low altitude spontaneous hypoxia lead to a significant change in placentome distribution with less type A and increases in types B, C and D. Physiologically, the change in the several placentome types with high altitude hypoxia suggests an acclimatization response to optimize transplacental exchange efficiency.

Altitude↗

PubMedDate not supplied

Carbon monoxide studies at high altitude.

In high altitude areas, ambient carbon monoxide (CO) concentrations are rising because of the increasing number of new residents and tourists, and their concomitant use of motor vehicles and heating appliances. There are, however, comparatively few studies of the acute or chronic physiological effects that may be caused by inhaling CO at high altitude. There are data supporting the concept that the effects of breathing CO at high altitude are additive, and data suggesting that the effects may be more than additive. Visual sensitivity and flicker fusion frequency are reduced in humans inhaling CO at high altitude. One provocative study suggests that the increase in coronary capillarity seen with chronic altitude exposure may be blocked by CO. We exposed male, laboratory rats for 6 weeks to 100 ppm CO, 4676 m (15,000 ft) simulated high altitude (SHA), and CO at SHA. SHA increase hematocrit ratio (Hct) and right ventricle weight, but decreased body weight. CO increased Hct and left ventricle weight. Our results indicate that 100 ppm CO does not exacerbate the effects produced by exposure to 4676 m altitude.

Altitude↗

PubMed2005

Sea-level performance in runners using altitude tents: a field study.

In this study of effects of simulated altitude exposure on sea-level performance, 10 competitive runners slept in a hypoxic environment achieved with tents for 9.8+/-1.3 h.d(-1) (mean+/-standard deviation) for 24 days-30 days at 2500-3500 m (PIO2=117-103 mmHg) above sea level. The altitude group and a control group of 10 runners performed usual training (PIO2=149 mmHg). At approximately 4-wk intervals before and after exposure both groups performed an incremental test for lactate threshold. The altitude group performed an additional test, a treadmill run to exhaustion lasting approximately 5 min. One week following exposure lactate threshold speed of the altitude group relative to the control group increased by 1.2% (90% likely limits +/-3.1%), but the effect became slightly negative after controlling for baseline differences in running speed between the groups. A 16% increase in time to exhaustion was observed in the altitude group, equivalent to a 1.9% (+/-1.4%) increase in speed in a time trial. Change in performance had an unclear relationship to total altitude exposure, genotype for angiotensin converting enzyme, and change in haemoglobin concentration. Our findings are consistent with little or no effect of use of altitude tents on sea-level performance.

Adult↗

PubMed2002

Bioenergetics of the heart at high altitude: environmental hypoxia imposes profound transformations on the myocardial process of ATP synthesis.

The low concentration of O2 in the thin air at high altitude is undoubtedly the reason for the remarkable modifications in the structure and function of the heart, lung, and blood of humans permanently living under these conditions. The effect of natural hypoxia on the energy metabolism of the cell is however not well understood. Here we study the proces of ATP synthesis in the heart of guinea pigs native to high altitude (4500 m) as compared with those native to sea level. The following are the novel findings of this study. (1) The rates and extents of ATP synthesis in the presence of low concentrations of ADP (<30 microM) are significantly higher at high altitude than at sea level. (2) The Hill coefficient, i.e. the degree of cooperativity between the three catalytic sites of the ATP synthase, is lower at high altitude (n = 1.36) than at sea level (n = 1.94). (3) Both, the affinity for ADP and the fractional occupancy of the catalytic sites by ATP, are higher at high altitude than at sea level but the P50, i.e. the concentration of ADP at which 50% of the catalytic sites are filled with ADP and/or ATP, is the same (approximately 74.7 microM). (4) In the physiological range of ADP concentrations, the phosphorylation potential deltaGp is significantly higher at high altitude than at sea level. It is concluded that the molecular mechanism of energy transduction is profoundly modified at high altitude in order to readily and efficiently generate ATP in the presence of low concentrations of O2 and ADP.

Adenosine Diphosphate↗

PubMed2004

Poor nutritional status of younger Tibetan children living at high altitudes.

BACKGROUND: The growth, development and nutrition of children in Tibet with high-altitude and unique traditional culture have recently gained attention. However, few researches are available on the nutritional status of younger children of Tibet. OBJECTIVE: The objective of the study was to evaluate the nutritional status of children below 36 months old in Tibet by means of anthropometry. DESIGN: The cross-sectional survey was conducted between August and September in 1999 and a sample of 1655 children below 36 months old was obtained using a stratified multistage cluster random sampling method from a total of seven districts of Tibet. Height, weight and hemoglobin concentration were measured and at the same time related sociodemographic and environmental information were collected. NCHS/CDC/WHO reference data were used to evaluate the nutritional status of the entire study children population and estimate the prevalence of stunting, underweight and wasting. RESULTS: Compared with the reference of NCHS/CDC/WHO, the distributions of HAZ and WAZ shifted to the left significantly and the means of HAZ and WAZ were -1.53 and -1.05, respectively, which were significantly lower than the reference value. The distribution of WHZ, however, was close to that of the reference. The reduction of Z-scores for height and weight occurred very early in life and was greatest in the second year after birth. The prevalence of malnutrition of children was 39.0% for stunting, 23.7% for underweight and 5.6% for wasting, respectively. Rural children had prevalence of stunting of 41.4% and underweight of 24.7%, as compared with prevalence of stunting of 25.3% and underweight of 18.1% for urban children. Stunting and underweight were associated with altitudes. The mean of hemoglobin (Hb) of children was 120.4 g/l and rural children had a significantly lower Hb concentration (119.9 g/l) than urban children (123.3 g/l). The prevalence of anemia seemed higher when using different altitude corrections for Hb to estimate the prevalence, but the consequences were uneven. CONCLUSIONS: For Tibetan young children, the nutritional status of the entire population is poor and the prevalence of malnutrition is higher, especially for stunting. Malnutrition is related to high altitudes. Although the Hb concentration is higher induced by high altitude, there must be quite a lot of anemic children at high altitudes. The relationship between altitude and Hb for children on the Tibetan plateau requires further study in order to determine correctly the magnitude of anemia of children.

Altitude↗

PubMed1997

Hypoxia, hypocapnia and spirometry at altitude.

1. Both hypoxia and hypocapnia can cause broncho-constriction in humans, and this could have a bearing on performance at high altitude or contribute to altitude sickness. We studied the relationship between spirometry, arterial oxygen saturation and end-tidal carbon dioxide (ETCO2) concentration in a group of healthy lowland adults during a stay at high altitude, and then evaluated the response to supplementary oxygen and administration of a beta 2 agonist. 2. We collected spirometric data from 51 members of the 1994 British Mount Everest Medical Expedition at sea level (barometric pressure 101.2-101.6 kPa) and at Mount Everest Base Camp in Nepal (altitude 5300 m, barometric pressure 53-54.7 kPa) using a pocket turbine spirometer. A total of 205 spirometric measurements were made on the 51 subjects during the first 6 days after arrival at Base Camp. Further measurements were made before and after inhalation of oxygen (n = 47) or a beta 2 agonist (n = 39). ETCO2 tensions were measured on the same day as spirometric measurements in 30 of these subjects. 3. In the first 6 days after arrival at 5300 m, lower oxygen saturations were associated with lower forced expiratory volume in 1 s (FEV1; P < 0.02) and forced vital capacity (FVC; P < 0.01), but not with peak expiratory flow (PEF). Administration of supplementary oxygen for 5 min increased oxygen saturation from a mean of 81%-94%, but there was no significant change in FEV1 or FVC, whilst PEF fell by 2.3% [P < 0.001; 95% confidence intervals (CI) -4 to -0.7%]. After salbutamol administration, there was no significant change in PEF, FEV1 or FVC in 35 non-asthmatic subjects. Mean ETCO2 at Everest Base Camp was 26 mmHg, and a low ETCO2 was weakly associated with a larger drop in FVC at altitude compared with sea level (r = 0.38, P < 0.05). There was no correlation between either ETCO2 or oxygen saturation and changes in FEV1 or PEF compared with sea-level values. 4. In this study, in normal subjects who were acclimatized to hypobaric hypoxia at an altitude of 5300 m, we found no evidence of hypoxic broncho-constriction. Individuals did not have lower PEF when they were more hypoxic, and neither PEF nor FEV1 were increased by either supplementary oxygen or salbutamol. FVC fell at altitude, and there was a greater fall in FVC for subjects with lower oxygen saturations and probably lower ETCO2.

Administration, Inhalation↗

PubMed2004

Evidence against redox regulation of energy homoeostasis in humans at high altitude.

The present study examined if free radicals and associated inflammatory sequelae influenced metabolic biomarkers involved in the neuro-endocrinological regulation of energy homoeostasis at high altitude. Sixteen mountaineers (11 males/five females) were matched for physical fitness and caloric intake and assigned in a double-blind manner to either antioxidant (n=8) or placebo (n=8) supplementation, which was enforced for 7 days at sea level and during an 11-day ascent to 4780 m. Enteral prophylaxis incorporated a daily bolus dose of 1 g of L-ascorbate, 400 international units of D,L-alpha-tocopherol acetate and 600 mg of alpha-lipoic acid. EPR (electron paramagnetic resonance) spectroscopic detection of PBN (alpha-phenyl-tert-butylnitrone) adducts confirmed an increase in the venous concentration of carbon-centred radicals at high altitude in the placebo group, whereas a decrease was observed in the antioxidant group (P<0.05 compared with that at sea level). EPR detection of DMSO/A*- (DMSO-supplemented ascorbate free radical) demonstrated that the increase in carbon-centred radicals at high altitude was associated with a decrease in ascorbate (r2=0.63; P<0.05). Ascent to high altitude (pooled placebo+antioxidant groups) also increased the expression of pro-inflammatory cytokines (P<0.05 compared with that at sea level) and biomarkers of skeletal tissue damage (P<0.05). Despite a general decrease in leptin, insulin and glucose at high altitude (pooled placebo+antioxidant groups; P<0.05 compared with that at sea level), persistent anorexia resulted in a selective loss of body fat (P<0.05). In conclusion, antioxidant prophylaxis decreased the concentration of carbon-centred radicals at high altitude (P<0.05 compared with the placebo group), but did not influence markers of inflammation, appetite-related peptides, ad libitum nutrient intake or body composition. Thus free radicals do not appear to be involved in the inflammatory response and subsequent control of eating behaviour at high altitude.

Altitude↗

PubMed2001

Fetal Doppler velocimetry at high altitude.

OBJECTIVES: To determine impedance and velocity characteristics of the fetal circulation using Doppler ultrasound, at extremely high altitude (4300 m) in the Peruvian Andes compared to an ethnically similar population at sea level. METHODS: This was a cross-sectional study of 196 women resident at high altitude (Cerro de Pasco, 4300 m above sea level) and 196 women resident at sea level (Lima) with normal singleton pregnancies. Pulsatility index (PI), maximum velocity (Vmax) and minimum velocity (Vmin) in the umbilical artery, the descending aorta, the middle cerebral artery and the ductus venosus were compared between the two populations using fractional polynomial regression analysis. RESULTS: The PI was higher at high altitude than at sea level in the umbilical artery (regression coefficient = 0.112, P < 0.001), and not significantly different in the descending aorta, middle cerebral artery and ductus venosus. Vmax was lower at high altitude than at sea level in all three arterial vessels assessed; Vmin was lower in two: the umbilical artery and the descending aorta. The high-altitude/sea-level ratios for umbilical artery Vmax and Vmin were 0.93 and 0.82, respectively (P < 0.001 for each), the ratios for descending aorta Vmax and Vmin were 0.93 and 0.89, respectively (P = 0.003 and P < 0.001, respectively), and the regression coefficient for the middle cerebral artery Vmax was -2.844 (P = 0.003). There was no significant difference in the middle cerebral artery Vmin or in the ductus venosus Vmax and Vmin. CONCLUSIONS: Despite the lower ambient oxygen at high altitude and an increase in umbilical artery PI, the fetal circulation does not exhibit a 'brain sparing effect'. This and the overall decrease in blood flow velocities in the fetal circulation at high altitude may be due to the increased fetal hematocrit, which will result in increased blood viscosity.

Adult↗

PubMedDate not supplied

Hypobaric hypoxia and villous trophoblast: evidence that human pregnancy at high altitude (3600 m) perturbs epithelial turnover and coagulation-fibrinolysis in the intervillous space.

Spatial relationships between fibrin-type fibrinoid and regions of villous trophoblast were examined in order to address two main questions: [1] is high-altitude pregnancy accompanied by changes in the sizes of trophoblast compartments (cytotrophoblast, syncytiotrophoblast, denudation sites)?, and [2] do highland placentae differ in the amounts and distribution patterns of perivillous fibrin-type fibrinoid? Placentae were collected from two ethnic groups completing term pregnancies at low (400 m above sea level; n=25) and high (3600 m; n=45) altitude in Bolivia. Masson trichrome-stained sections were sampled randomly and analysed stereologically to estimate compartment volumes and surfaces. Comparisons were drawn using variance, Chi-squared and contingency table analyses. At high altitude, birthweights were 265 g lower and placentas had a larger intervillous space (270 cf 181 cm(3)), less fibrin-type fibrinoid (4.1 cf 8.4 cm(3) by volume; 2570 cf 4430 cm(2) by surface area), less villous trophoblast (50 cf 73 cm(3)) and a smaller villous surface (5.6 cf 7.0 m(2)). Volumes were reduced in all syncytiotrophoblast compartments (with and without nuclear aggregations). Cytotrophoblast was maintained and its relative volume increased significantly (from 2.7 to 3.6 per cent of trophoblast volume). Decreases in villous surface area affected primarily thinner (nuclear aggregate-free) regions of syncytium. Regardless of altitude, fibrin-type fibrinoid was deposited non-randomly: it was preferentially located at sites of trophoblast denudation. Although no altitudinal differences in fibrin-type fibrinoid patterns were detected, absolute surfaces were diminished on denuded and thinner regions of trophoblast but not on syncytial knots or bridges. Ethnic differences at low altitude (relatively greater deposits on denudations in Amerindians) were minimized at high altitude. We conclude that pregnancy at high altitude alters the epithelial steady state (towards cytotrophoblast and away from syncytiotrophoblast) and the coagulation-fibrinolysis steady state in the intervillous space (to favour fibrinolysis over coagulation). Thinner regions of syncytiotrophoblast may be the main sites of greater fibrinolytic or anticoagulatory activity. The findings are partly consistent with results from in vitro studies which indicate that hypoxia stimulates proliferation of cytotrophoblast but impairs fusion into syncytium.

Adult↗