ABSTRACTS VIII World Congress on High Altitude Medicine and Physiology August 8–12,2010 Arequipa,Peru

7. Free Radical Formation in the Hypoxic Human Brain

Introduction: Molecular oxygen (O₂) exists in air as a free radical revealing a more nebulous side to a gas traditionally considered the “elixir of life”. It is a double-edged sword, capable of sustaining life yet fatal in excess or indeed when limited. Methods: The current presentation will focus on the factors that regulate O₂ transport to the exercising human brain with a specific focus on inspiratory hypoxia and its impact on reactive oxygen-nitrogen species (ROS-RNS) metabolism; in essence, how we provide what is provocatively considered the most important “organ” in the Body with the most important “molecule” in the World! Recent advances have been made through the combined application of state-of-the art measurement techniques for the regional detection and characterization of free radicals across the cerebral circulation and diffusion-weighted magnetic resonance imaging. Results: This presentation will integrate and translate the adventures of high-altitude expeditioning with the rigors of laboratory experimentation to reveal how the exercised-hypoxic brain becomes oxidatively-nitrosatively stressed-out, sore and swollen. The notion that redox-regulation of blood-brain barrier function has any bearing on an individual's susceptibility to high-altitude illness, notably acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), will also be examined from a critical perspective. Finally, emerging evidence from our laboratory attests to the potential redox-initiated neuro-protective benefits of intermittent hypoxia as a means of “accelerating” cerebral hemodynamic adaptation to exercise. Conclusion: These findings confirm ROS-RNS as integral components of the signal transduction cascade that are physiologically essential in controlled amounts capable of initiating protective adaptation in the face of hypoxic-exercise stress for the maintenance of homeostasis. Acknowledgments: Prof Peter Bartsch, University of Heidelberg, Germany Profs Niels Secher, Bente Pedersen and Kirsten Moller, University of Copenhagen, Denmark.

9. Mountain Climate and Pulmonary Surfactant System

Introduction. Aim: to investigate injury, reparation and adaptation mechanisms of the pulmonary surfactant system (PSS) in experimental animals and in man under exposure to mountain climate factors and possibilities for drug and physiotherapeutic treatment of related disorders. Methods: Physiological, biochemical (measurement of the phospholipid composition and peroxidation products in bronchoalveolar lavage and plasma), biophysical (surface activity of pulmonary extracts and lavage), computed morphometry (determination of cubic and area density of the respiratory part of the lungs), histochemical (copmputed fluorometry of lipids in Hackney's and Berg's stained sections), electron-microscopic. Study materials: albino rats, rabbits and newborn rabbits, exhaled air condensate and bronchoalveolar lavage fluid from healthy volunteers and patients with bronchial asthma after a month's adaptation to high altitude and permanent high-altitude residents, amniotic fluid from parturient women at high and low elevations. Results: Mountain climate factors (as isolated action in a model and combined action in natural conditions) caused structural and metabolic changes of PSS. In acute exposure to mountain climate factors negative changes leading to respiratory failure were observed. In the long stay of animals and humans in mountain climate conditions, the PSS adapted to the increased functional load. An increased metabolic level of the PSS occurred at the cost of reduced reserve capacities of PSS. Additional physical exercise at high altitude leads to adaptive disruption and development of pulmonary edema. Ambroxol, benzonal, intravascular laser irradiation of blood, extreme high frequency electromagnetic fields, ultrasonic inhalations of copper gumate and linseed was shown to be useful in preventing or correcting hypoxia-related injury of PSS. Conclusion: PSS shows itself to possess lability and compensatory potential. In high altitude climate conditions the synthesis and secretion of surfactant stimulated by Ambroxol and benzonal is able to prevent the development of mountain pulmonary edema.

22. Insulin Response in Healthy Residents in High Altitude

Introduction. Aim: To know the insulin response in normal healthy residents in high altitude (HA) to acute hyperglycemia. Methods: We studied 17 normal men subjects. Group A : 11 residents at sea level (SL) (Lima, 150 m.a.s.l) and Group B : 6 from (HA) (Huancayo, 3200 m.a.s.l). Age ± 28.9 and ± 26 years, Body Mass Index (BMI) ± 23.7 and ± 25.4 kg/m 2 respectively. We used the hyperglycemic clamp at 125 m/dl for two hours. Insulinemia was measured at 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes. Glycemia at 0.6, 12, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 minutes. Results: We observed a significative elevation of insulin concentrations at 10(12.21 ± 1.55 uU/mL;7.38 ± 0.67 uU/mL, P = 0.015),15(15.90 ± 2.25 uU/mL,7.72 ± 0.73 uU/mL, P = 0.005) and 20(16.66 ± 2.62 uU/mL,8.93 ± 0.80 uU/mL, P = 0.016) minutes in residents from SL. Conclusion: The early insulin response to acute hyperglycemia is lower in residents from high altitude. Acknowledgments: This work was supported by Alexander von Humboldt Foundation, Bonn, Germany and Universidad Nacional Mayor de San Marcos, Lima, Perú.

23. Genetics of Mitochondrial Electron Transport Chain in Regulating Oxygen Sensing

Introduction: Physiological hypoxia results in a host of responses that include increased ventilation, constriction of the pulmonary artery, and a cellular transcriptional program that promotes glycolysis, angiogenesis, and erythropoiesis. The biology of hypoxia is also important for understanding diseases such as cancer. At the molecular level, hypoxia-inducible factors (HIF-1 and HIF-2) are the best characterized transcriptional regulators of hypoxic gene expression. In the past decade, my laboratory has elucidated that mitochondrial ROS generated at complex III are required for hypoxic activation of the HIF-1 [Brunelle et al. Cell Metabolism 1:409-414 and Bell et al. Journal of Cell Biology 177(6):1029-36]. Furthermore, we collaborated with Abbott Laboratories in finding small molecules that inhibit HIF transcriptional activity. The small molecules which displayed the greatest efficacy in diminishing HIF transcriptional activity were complex III inhibitors [Lin et al. PNAS 105(1):174-9]. We also demonstrated that a consequence of HIF-1 induction by complex III ROS in primary human cells is extension of replicative lifespan [Bell et al. Mol Cell Biol. 25:4853-62]. These results from my lab demonstrated that increases in ROS levels can be associated with an increase in replicative lifespan. To our knowledge, this is one of the first studies to link increases in ROS with increase in fitness of mammalian cells. The adaptation to hypoxia also involves the activation of AMPK. We genetically showed that mitochondrial complex III ROS are required for hypoxic activation of AMPK activity [Emerling et al. Free Radic Biol Med. 46(10):1386-91]. Recently, we have begun to test whether mitochondrial ROS regulates oxygen sensing in vivo. We have generated mice in which keratinocytes lack mitochondria. These mice do not have hair. We are currently exposing these mice to hypoxia and testing their EPO levels. Collectively our results indicate that mitochondrial complex III generated ROS are required for hypoxic responses [for review see Hamanaka and Chandel Curr. Opin. Cell Biol. 21(6):894-9]. Acknowledgments: This work was supported by a NIH Grant R01CA123067-04.

27. Circadian Variation of Erythropoietin and its Relationship with Arterial Oxygen Saturation at Moderate Altitude: Effect of Gender

Introduction: The aim of this study was to determine the existence of circadian rhythm in the secretion of erythropoietin (EPO) and its relationship with arterial oxygen saturation (SO₂) in subjects living at an altitude of 2600 m (Bogotá, Colombia). Methods: Plasma concentration of EPO was performed by ELISA method using the double antibody sandwich. Continuous measurements of SO₂ were obtained by pulse oximetry in 18 healthy young sedentary (n = 11 women, mean age 18.9 SD 0.2, mean hemoglobin concentration 14.8 SD 0.2 g/dL; men n = 7, mean age 19.4 SD 0.8, mean hemoglobin concentration 16.8 SD 0.4 g/dL) during 24 hours. Plasma concentration of EPO was measured every 4 hours for 24 hours. Results: Circadian rhythm was shown both EPO and SO₂ values. From morning until midnight SO₂ remained stable. From 00:00 to 04:00 hours, there was a decrease of 2.0% in SO₂. EPO plasma concentration increased from 4 to 5 U/L in response to reduced SO₂ at the same period. SO₂ levels and EPO concentrations were significantly different in men and women (ANOVA, P < 0.01). Conclusion: The circadian secretion of EPO was correlated with the SO₂ in a negative way both men and women. Acknowledgments: This study was supported by a grant from Banco de la República, Colombia (F. P. I. T.- 1201).

28. Cardiovascular and Respiratory Responses to High Altitude Exposure in Sea Level And High Altitude Residents

Introduction: High altitude inhabitants have markedly different physiological responses to altitude exposure than sea level residents. Genetics have been reported to play an important role in these responses. This study evaluated the influence of altitude of residence on the cardiovascular and respiratory responses to acute exposure to very high altitude. Methods: Sixty-three subjects participated in the study after giving informed consent. Subjects were recruited and tested at the base refugio at Mount Chimborazo in Ecuador (15,900 ft). This is an ideal location because many Ecuadorians that reside at a variety of altitudes can easily and quickly drive to the refugio. Cardiovascular measurements included systolic and diastolic blood pressure, hemoglobin saturation, hemoglobin concentration and resting heart rate. Vital capacity, chest width and depth were also measured. All measurements were done upon arrival at the refugio. Subjects were then divided into three groups based on their altitude of residence: Low altitude residents - LOW (0-5,000 ft), moderate altitude residents - MOD (5,000- 10,000 ft) and high altitude residents - HIGH(>10,000 ft). Results: Resting heart rate was lower in HIGH (78.2 ± 14.1 bpm) than the MOD (88.3 ± 13.8 bpm) and LOW (95.4 ± 22.6) altitude groups. Hemoglobin saturation was highest in HIGH (83.2 ± 7.9%) as was hemoglobin concentration (16.4 ± 3.5 mg/dL). The highest altitude residents had greater chest widths (38.2 ± 3.6 cm) and depths (23.1 ± 3.7 cm). However, there were no differences in absolute vital capacities between groups. This is probably attributable to the fact that the HIGH residents were shorter (1.64 ± .08 m) and lighter (64.1 ± 8.2 kg) than the MOD or LOW altitude groups. Conclusion: Height of altitude residence plays an important role in the cardiovascular and respiratory responses to acute high altitude exposure. These differences represent favorable adaptations to long-term high altitude residence.

31. General Considerations, Organization and Equipment in Mountain Rescue

Introduction: This practical workshop will highlight the fundamental areas that need to be addressed when operating an organized mountain rescue service Methods: A short presentation will be followed by discussion and sharing of ideas between participants and members of the International Commission for Mountain Emergency Medicine. Results: Many service models can provide an effective mountain rescue service. Despite enormous differences, fundamental topics, such as scope of the service, command and control, communication and rescue equipment, and integration and co-operation with other emergency services require addressing. Safety must be considered at all stages. Conclusion: The quality of a mountain rescue service depends on many factors; as medical practitioners performing mountain emergency medicine, we need to appreciate the complete picture.

38. High Altitude Pulmonary Edema (HAPE) Clinical Presentation

Introduction: Objectives: To highlight and recognize HAPE as an entity and pathology peculiar to the region of high mountain. Methods: Material and Method: A retrospective study was made of patients hospitalized with confirmed diagnosis of HAPE, in the past 5 years, in hospitals located more than 3500 m above sea level (North-Argentina). Results: 26 children were included in a period from 2004 to 2009. The mean age was 7.5 years; its relationship male- female was 1.4/1.0. The month of highest incidence was in March, coinciding with the holiday period for children. Its clinical presentation was characterized by: 99% were positive for epidemiology HAPE reentry, 100% had dyspnea and cyanosis, 10 patients were found in pulse oximetry below 70%, more than 90% had tachycardia and tachypnea, and in 32% was found fever over 38 degrees centigrade. Their complementary methods showed: signs of overload of right ventricle by ECG in 67%; the chest X-ray showed: 42% unilateral infiltrated and bilateral 26%. By Echocardiogram Color Doppler were observed pulmonary pressures exceeding 40 mmHg. In 100% of the patients began treatment with oxygen therapy and 80% required to be transferred (Using the decline as a therapy). In 37% diuretics were used, and steroids only in one case. In 5 patients of HAPE reentry, all of them had shown the same clinic characteristics in previous years. The average placement was 3.9 days with full recovery. Conclusion: Conclusions: Reentry epidemiology of HAPE is the basis of diagnosis. Its treatment is oxygen therapy and the descent.

39. Neural Crest-Derived Stem Cells are Responsible for Carotid Body Growth in Chronic Hypoxia

Introduction: The carotid body (CB) is an arterial chemoreceptor organ responsible for the acute ventilatory response to hypoxemia. Unlike other neuronal crest-derived organs, the adult CB grows several-fold its normal size upon exposure to sustained hypoxia, an adaptive response that participates in ventilatory acclimatization to high altitude. The mechanisms underlying this fundamental homeostatic CB function are poorly known. The CB is formed during fetal life by migration of sympathoadrenal progenitors from the superior cervical ganglion. We hypothesized that a population of these progenitors might remain quiescent in the developed organ, thus they could be re-activated by hypoxia in adult life. Methods: Experiments were performed in rats and mice maintained in low O₂ tension. CB morphology was studied by standard histological techniques. Proliferation and differentiation of dispersed rat CB cells were analyzed by immunocytochemical methods. The functional properties of the cells were studied by patch clamp and amperometric techniques. Results: In animals exposed to hypoxia, CB growth was paralleled by increase in the number of neuron-like, tyrosine-hydroxylase positive (TH+), glomus cells. Although glomus cells retain some capacity for proliferation, most newly generated TH + cells appeared only after two-three days in hypoxia thus suggesting that they derived from precursors. Indeed, neurosphere assays performed with CB cells demonstrated the appearance of clonal colonies of nestin + progenitors that proliferate for a few days and subsequently differentiate into TH + glomus cells. These in vitro generated glomus cells had normal neurochemical, electrophysiological, and chemoreceptive properties. In vivo and in vitro cell fate mapping assays have suggested that the CB stem/progenitor cells are the glia-like, sustentacular, or type II cells. These are converted to nestin + , highly proliferative, intermediate progenitors, which, in turn, give rise to glomus cells. Conclusion: The data show that the CB is a neurogenic niche in the peripheral nervous system that resembles in many aspects the neurogenic centers in the mammalian brain.

40. Peripheral and Cerebrovascular Responses in High Altitude Residents

Methods: We have compared cardiovascular adaptations to high altitude living in three populations of long-term altitude residents: Andeans (4338 m), Ethiopian highlanders (3622 m) and Ladakhis on the Tibetan plateau (4606 m). Peruvians and Ladakhis showed more erythrocytosis than Ethiopians and some showed evidence of chronic mountain sickness (CMS). All groups had high normalised blood volumes. In Peruvians and Ladakhis with CMS this was mainly due to the large packed cell volumes, whereas in Ethiopians both plasma and packed cell volumes were large. End-tidal carbon dioxide tension was higher in Ethiopians than in Peruvians or Ladakhis (37.1 ± 0.8 versus 27.3 ± 1.2 and 27.0 ± 0.6 mmHg) implying a smaller respiratory drive. Because the high end-tidal CO₂ levels of the Ethiopians was unexpected, in our latest study we determined arterial blood gas values in Ethiopians living in the highlands in both the Bale and the Simien mountains. These results supported the earlier end-tidal data. PaCO₂ values were 32.2 ± 0.82 and 33.0 ± 0.75 mmHg respectively. Cardiovascular control was assessed using an orthostatic stress test. This showed effective vasoconstriction in all groups although it was less in the Peruvians with CMS. Results: Despite this, orthostatic tolerance was greatest in the Peruvians (P < 0.01), most of whom (60%) did not develop presyncope despite a very high orthostatic stress. We determined cerebral blood flow velocity by transcranial Doppler and found it to be significantly less in Peruvians, especially those with CMS, than in Ethiopians. Ethiopians also showed better autoregulation of cerebral blood flow than the other groups and flow was insensitive to changes in oxygen tension but more sensitive to changes in CO₂, both during normoxia and hypoxia. Conclusion: We suggest that Ethiopians are best adapted to hypoxia. Their blood volumes were large but they were not excessively polycythaemic and none had CMS. CO₂ levels were little different from those of lowlanders. Cerebral autoregulation was good and the large vasodilatation to CO₂ would favor better cerebral perfusion and oxygenation.

41. Mechanisms and Limits of Hypoxemia Tolerance in Diving Birds and Mammals

Introduction: Bio-logging instruments capable of continuously measuring PO₂ in the blood while diving have recently revealed exceptional hypoxemic tolerance and highly efficient O₂ utilization in the consummate avian and pinniped divers, the emperor penguin and elephant seal. Methods: Minimum PaO₂ values as low as 12-23 mmHg have been documented in diving elephant seals, corresponding to routine SaO₂ of 8-26%, the lowest values ever measured in a freely diving seal. This is well below limits of other animals, and is nearly equivalent to “critical PaO₂” (10 mmHg) of seals in forced submersions, defined by EEG marking the threshold of cerebral dysfunction. Characterization of the O₂-hemoglobin dissociation curves of these species revealed biochemical adaptations relevant to dive capacity. Results: Emperor penguin hemoglobin has significantly higher affinity for O₂ as compared to other birds, allowing more complete utilization of respiratory O₂ stores and increased blood O₂ content when PO₂ is low. Application of the dissociation curve to PO₂ profiles also indicates differing blood O2 store management strategies. In emperor penguins, arterial SO₂ remains near 100% for much of the dive, preserving high O₂ content in the arterial system for critical organs like the brain. Arterial SO₂ does not decrease significantly until final ascent, consistent with the decline in ambient pressure and decrease in air sac and arterial PO₂. These profiles demonstrate the significance of the respiratory O₂ store and high affinity hemoglobin of the emperor penguin. In contrast, although there is a transient rise and peak near 100% arterial SO₂ in the initial dive phase of elephant seals, these values decreased rapidly after this point. Venous SO₂ profiles demonstrate highly efficient and near complete utilization of the venous blood O₂ store during dives of both species. Conclusion: These findings reflect differences in the magnitude of the respiratory O₂ store and maintenance of gas exchange during diving between this bird and mammal, and depict attributes that undoubtedly contribute to their extraordinary dives. Acknowledgments: Paul J. Ponganis, M.D., Ph.D.

Funding: NSF grants OPP-0538594, IOS-0641801.

42. The Effect of Living in the High Plateau on Cardiovascular System

Introduction: Place: “Dr. Pablo Soria” Hospital, San Salvador de Jujuy, Argentina. Town of La Quiaca, Province of Jujuy, Argentina. Purpose: To determine heart and lung hemodynamic changes seen in 12 years old children, in the town of La Quiaca, placed at 3500 m (about 10,000 feet) above sea level, as compared to normal standards. Methods: Method and Materials: A transversal descriptive study was performed. A school in La Quiaca was selected in which one hundred children, 12 years old, were chosen at random. The inclusion criteria were: Be a resident in that town for at least one year, be healthy at the moment of the research, to be 12 years old. The variables analyzed were: sex, weight, height, body mass index, pulse oximetry, systemic arterial tension, electrocardiogram, color Doppler echocardiogram. By means of the operationalization of variables it was attempted to determine some values to measure degrees of hypoxia and lung pressure. Results: Results: The study included 100 children of twelve years old; 53 boys and 47 girls. Their average weight was 30.34 kg. Their average height was 134 cm tall. Their average index of body mass was 18.9. Their average arterial tension was 96/63 mmHg. Among these values there were no important changes as compared to normal values. Pulse oximetry showed a saturation of 89,66%. The result of the electrocardiogram is the following: Only 5% was normal; 7% showed left pattern; and 87% showed an electric axis deviated to the right, being the mean of these children of+ 108°. By means of color Doppler echocardiography it was observed the following: 93% showed tricuspid insufficiency that helped to determine the pressure in the VD that was an average of 22 mmHg. The changes detected in the pulse oximetry, the electrocardiogram, and the VD pressure measured by color Doppler echocardiography, were statistically meaningful as compared to the normal standards. Conclusion: Children who live in the high plateau (3,500 m above sea level) developed hemodynamic changes in order to adapt to that geographic condition. This is influenced by low oxygen pressure at that level, causing an answer of adaptation that modifies the values of normal control. Therefore, they develop some degree of “lung hypertension”. Acknowledgments: Hypothesis: At 3500 m above sea level there is a low pressure of oxygen (hypoxia). This is the case of the Puna high plateau, where the town of La Quiaca is located (Province of Jujuy, Argentina). This geographic condition generates important heart and lung hemodynamic changes as compared to children who live at sea level with normal standard measurements.

44. Maternal Hemoglobin Level and Fetal Outcome at Low and High Altitude

Introduction: Both, low (<7 g/dL) and high (>14.5 g/dL) maternal hemoglobin (Hb) levels have been related to poor fetal outcome (stillbirths, preterm deliveries and/or small for gestational age). At high altitude, the Hb cutoff to define anemia is increased as altitude increases. There is no evidence demonstrating that this correction is needed. The objective of the present study was to determine the association of maternal hemoglobin level and fetal outcome at low and at high altitudes. The study is based in a retrospective multicenter analysis of 293,158 pregnancies occurred in 33 Peruvian Public hospitals located in altitudes from sea level to 4340 m during the period between 2002 and 2010. In analyses of all women at both LA and HA, those with Hb < 9 g/dL had odds ratios (ORs) and 95% confidence intervals (CI) of 3.26 (CI:2.8-3.8), 1.87 (CI:1.71-2.03), and 1.16 (CI:1.06-1.27) for stillbirths, pre-term, and small for gestational age (SGA) births respectively, compared to women with 11-12.9 g/dL of Hb, after adjustment for confounders. From 0-1999 m optimal Hb values for low risk of stillbirths, pre-term deliveries and SGA were 9-12.9 g/dL, > 9 g/dL and 9-12.9 g/dL respectively. From 2000-2999 m, optimal Hb values were 11-14.4 g/dL fpr stillbirth and pre-terms and 9-12.9 g/dL for SGA. From altitudes between 3000 and 3999 m, 11-15.5 g/dL for stillbirths, > 11 g/dL for preterm and 9-12.9 g/dL for SGA respectively, whereas at 4000-4500 m, low risks for stillbirths were observed at Hb values > 9 g/dL; for preterm deliveries at > 9 g/dL and 9-14.4 g/dL for SGA. Data suggest that no correction of the definition of anemia is necessary for women at HA. Women living at altitude increases risks of stillbirths, pre-terms and SGA independent of the Hb effect. The risk for stillbirths increases significantly since 2000 m, for pre-terms since 3000 m and SGA from 3000 m. Conclusions: Both, high and low maternal hemoglobin levels were related to poor pregnancy outcome, with similar effect of low hemoglobin in both LA and HA. Our data suggest that maternal hemoglobin above 11 g/dL but below 13 g/dL is the area of minimal risk of poor adverse perinatal outcomes. Living at HA over 3000 m associated with Hb > 13 g/dL increases significantly the risk for SGA. The, it is important the monitoring of women with iron supplementation when they are living over 3000 m.

47. Consequences of EPO-Induced Excessive Erythrocytosis

Introduction: Application of erythropoietin (Epo) increases hematocrit (Htc) and, consequently, arterial O₂ content thereby increasing exercise performance. However, since elevated blood viscosity associated with increasing Htc levels may limit cardiac performance, it was suggested that the highest attainable Htc may not necessarily be associated with the highest attainable exercise capacity. To test the proposed hypothesis that an optimal Htc in acute and chronic Epo-treated mice exists, i.e. the Htc that facilitates the greatest O₂ flux during maximal exercise, Htc levels of wild type (wt) mice were acutely elevated by administering novel erythropoiesis stimulating protein (NESP; wtNESP). Furthermore, in the transgenic mouse line tg6 that reaches Htc levels of up to 0.9 due to constitutive overexpression of human Epo, the Htc was gradually reduced by application of the hemolysis-inducing compound phenylhydrazine (PHZ; tg6PHZ). Maximal cardiovascular performance was measured using telemetry in all exercising mice. Highest exercise intensities were reached at Htc values of 0.58 and 0.57 for wtNESP, and 0.68 and 0.66 for tg6PHZ, respectively. Blood viscosity correlated with O₂ max. Apart from enhancing erythropoiesis, non-erythroid functions of Epo enhancing performance such as improved ventilation or cognitive functions at hypoxia will be presented.

48. Developmental Programming of Cardiovascular Disease by Prenatal Hypoxia: Lessons from High Altitude

Introduction: In addition to traditional risks, such as smoking and obesity, the quality of our prenatal development plays a role in determining the risk of suffering disease in later life. In turn, the quality of the intrauterine environment is largely determined by the available nutrient and oxygen supply to the growing young. As such, the association between poor conditions in utero and increased risk of disease in adulthood has exploded a number of studies investigating the effects of changes in materno-fetal nutrition on programming of disease. In contrast to this international research effort, the contribution of fetal hypoxia, of the type that can occur during pre-eclampsia, placental insufficiency or pregnancy at high altitude, to developmental programming has been comparatively ignored. Further, the mechanisms underlying the early programming of disease in complicated pregnancy remain unknown, preventing the identification of potential therapeutic targets for clinical intervention. Methods: Here, we put forward the hypothesis that oxidative stress in the fetus underlies the molecular basis via which prenatal hypoxia alters fetal growth and contributes to the developmental programming of cardiovascular disease. Results: Observations in human pregnancy at high altitude and experiments in chick and rat embryos show that developmental hypoxia independent of changes in maternal nutrition not only alters the trajectory of fetal growth, but it also induces changes in the cardiovascular and metabolic systems, which are normally associated with disease states in later life. Treatment with antioxidants of animal pregnancies complicated with reduced oxygen delivery to the fetus prevents the alterations in fetal growth and the fetal cardiovascular and metabolic remodelling. Conclusion: Combined, the human and experimental data support the hypothesis tested and the work offers both insight into mechanisms and possible therapeutic targets for clinical intervention against the early origin of disease in hypoxic pregnancy. Acknowledgments: The Bristish Heart Foundation, The BBSRC, The Royal Society.

52. Clinical Evaluation of a New Non-Invasive Sensor for Continuous Core Body Temperature Measurement in Humans

Introduction: Accurate measurement of the core body temperature (cbt) is fundamental to the study of human temperature regulation. Recently, we developed a non-invasive cbt heat flux sensor (Double Sensor) (1,2). Two investigations are presented showing the applicability of this sensor under physical strain, extreme environmental conditions and in a clinical setting. Methods: The first study, evaluated the sensor in a laboratory study in 20 male subjects (39.5 ± 10.2 years, height 1.80 ± 0.06 m, 83.8 ± 11.0 kg). Thermal (rectal, nasopharyngeal, skin, Double Sensor temperatures) and cardiovascular data were collected continuously before, during and after different experimental set-ups (25-55% maximal intensity work load at 10, 25, and 40°C environmental temperatures). In the second study, we determined the cbt of 24 patients during cardiac operations and compared it to the vesical or rectal temperature. The patients were cooled to 14-16°C (deep hypothermia). After surgery the patients were heated up to normal body core temperature. Statistical methods: general linear model, paired t-Test (significant level: P < 0.05.), Bland-Altman diagrams (3), and Li and Chow(4), and Lin's(5) Concordance Correlation Coefficients (CCC). Results: The first study revealed that i) the device under test differed between –0.16 to 0.1°C from the average of the rectal temperature and the Double Sensor, ii) showed with increasing ambient temperatures increasing Li and Chow CCC (10°C: 0.49; 25°C: 0.69; 40°C: 0.75), and iii) exhibited a faster temperature decrease at all resting periods at all ambient conditions as compared to rectal temperature (P < 0.01). In the second study the sensor showed great accuracy to vesical and rectal temperature (Lin's CCC = 95%). Conclusion: The device under test seems to be a reliable method of assessing cbt during clinical settings as well as in emergency care in the field, e.g. avalanche victims.

Acknowledgements: Funding: Draegerwerke AG and DLR/BMWi.

62. Cardioventilatory Acclimatization Induced by Intermittent Hypoxia: The Role of Oxidative Stress

Introduction: It is well recognized that sustained hypoxia due to high altitude exposure enhances the hypoxic ventilatory response, a phenomenon known as ventilatory acclimatization. At the sea level, the most usual pattern of hypoxia in humans is the chronic intermittent hypoxia (CIH) resulting from the obstructive sleep apnea (OSA). The OSA syndrome, a growing health problem that affects 5% of the worldwide population, is recognized as an independent risk factor for hypertension. Sympathetic activation, oxidative stress and inflammation have been proposed as potential pathogenic mechanisms involved in the progression of hypertension. A major contributing mechanism to the sympathetic activation is the potentiation of the carotid body (CB) chemosensory response to hypoxia, which is responsible for the augmented ventilatory, and cardiovascular responses induced by hypoxia in OSA patients and animals exposed to CIH. Since hypoxic-reoxygenation cycles produce oxidative stress, we study if the treatment with an antioxidant may prevent the cardioventilatory acclimatization and the hypertension induced by CIH. Methods: We studied the effects of ascorbic acid supplemented in drink water (1.25 mg/mL) on the oxidative stress, CB chemosensory and cardioventilatory responses to acute hypoxia in male Sprague-Dawley rats exposed to CIH (5% O₂, 12 times/hr for 8 hrs) or sham condition during 21 days. Results: CIH increased plasma lipid peroxidation and nitrotyrosine formation in the CB, enhanced CB chemosensory and ventilatory hypoxic responses, modified the heart rate variability (HRV) power spectrum and produced hypertension. Ascorbic acid treatment prevented the increases in plasma lipid peroxidation and nitrotyrosine formation within the CB, the enhanced CB chemosensory and ventilatory responses to hypoxia, as well as HRV alterations and hypertension. Conclusion: Present results support a crucial role for oxidative stress in the potentiation of CB chemosensory and systemic cardiorespiratory acclimatization induced by CIH. Acknowledgments: Funding source: FONDECYT Grants 1070584 and 1100542.

64. Analysis of Perinatal Birth Defects on Plateau

Introduction: Birth defects are an important factor that seriously affects the quality of the population, the deformed children suffers pain, and bring burden to families and society. Birth defect is the result of certain factors leading to developmental disorders in embryos in the womb, including the structural deformity, dysfunction, metabolic disorder or behavioral abnormalities of fetus before birth. Methods: According to the Monitoring Program of Birth Defects, 14,531 cases of perinatal birth in 10 years were analyzed retrospectively in our hospital and compare to the sea level area. Results: there are 141 children with perinatal birth defects in 14,531 cases, the incidence of perinatal birth defects is 9.69 ‰. Incidence of congenital heart disease is the highest in all perinatal birth defects, it is closely related to environmental factors such as altitude-related hypoxia, while only 5.23‰ in sea level. Conclusion: In order to reduce perinatal birth defects at high altitude, especially birth of children with congenital heart disease, we should take healthcare educations for all married couples, including to the pre-marital medical check-ups, and pre-marital, pre-pregnancy healthcare, and raise the awareness of environmental protection, especial for living in the high altitude areas.

65. The Relationship between Perinatal Hypoxia and Sleep-Disordered Breathing in Preclinical Chronic Mountain Sickness

Introduction: Chronic intermittent hypoxia due to sleep-disordered breathing is implicated as a potential etiological factor for chronic mountain sickness (CMS). Whether sleep-disordered breathing precedes or results from CMS is not known. Likewise, factors responsible for sleep-disordered breathing in CMS are not well understood. Based on our preliminary data that perinatal hypoxia increases susceptibility to excessive erythrocytosis (EE, Hb ≥ 18.3 g/dL), a preclinical phase of CMS, we sought to determine whether respiratory characteristics during wakefulness or sleep differ between EE subjects and controls and, if so, to determine the relationship of this variation with perinatal hypoxia. Methods: Respiratory characteristics during sleep and wakefulness, and the incidence of perinatal hypoxia were compared in 28 EE and 25 control subjects selected from a survey of 820 young men (18-25 yrs) residing in La Paz, Bolivia ≥3600 m), and matched by age- and altitude of residence. Respiratory characteristics during wakefulness and sleep were assessed by standard spirometry and polysomnography, respectively. Perinatal conditions were assessed by medical record review and maternal interview. EE and control groups were compared using independent t-tests or appropriate. Results: FVCs, FEV1, FEV1/FVC and HVR were similar between EE and controls. EE subjects had lower FEF25-75 than controls (<0.05), suggesting alterations in the peripheral airways. EE subjects had more central apneas and hyponeas (P < 0.05), as well as lower nadir and average noctural SaO₂. Perinatal hypoxia [i.e., premature delivery, oxygen supplementation at delivery or preeclamptic mother] was more common in EE than controls, and was associated with altered respiratory function during wakefulness or sleep. Preeclampsia showed the strongest relationship to sleep-disordered breathing and EE, and was positively associated with hypopneas, central sleep apneas, and Hb. Conclusion: Perinatal hypoxia may contribute to impaired respiratory function during sleep at high altitude, and consequently EE and/or CMS. Acknowledgments: We would like to thank the generous participation of our research subjects, Dr. Rob Roach (ARC); Dra. Diva Bellido, Cristina Gonzales, Ana Maria Alarcón, Marta Aguillar, Catherine Romero, Yvonne Contreras (IBBA); Lic. Javier Fuentes (INSEF); Dra. Maritza Vargas and Lic. Walter Amezaga (Normal Superior Simon Bolivar); and financial support provided by NIH (R03TW007957-01A2).

67. Characterization of Presenilin Function in the Oxygen-Sensing Pathway

Introduction: Presenilin 1 and 2 (PS1 and PS2) are the core components of the g-secretase complex which cleaves a variety of proteins such as the amyloid precursor protein (APP) and Notch. The proteolysis of APP leads to the formation of amyloid beta (Ab) that is crucially involved in the pathogenesis of Alzheimer's disease (AD). The cleavage of Notch leads to the generation of the Notch intracellular domain (NICD) which is involved in the control of cell fate and stem cells maintenance. Hypoxia plays an important role both in the progression of neurological disorders as well as in the maintenance of the undifferentiated cell state. The central activators of oxygen-dependent gene transcription are the heterodimeric hypoxia-inducible factors (HIFs). In normoxia, a family of prolyl-4-hydroxylase domain (PHD) proteins hydroxylate the HIF-a subunits which leads to their degradation via the ubiquitin-proteasome pathway. In hypoxia, prolyl hydroxylation is inhibited, HIF-a protein is stabilized and dimerizes with its constitutive counterpart HIF-b. Results: To study PS function in the oxygen sensing pathway, we analyzed PS1/PS2 wild-type (wt) and knock-out (ko) mouse embryonic fibroblasts (MEFs). HIF-1a transcript levels, hypoxic HIF-1a protein accumulation and HRE-dependent reporter gene activity were found to be decreased in PS1/2 ko MEFs. Hif1a promoter activity of both HIF-1a isoforms was lower in PS1/2 ko MEFs but not regulated by hypoxia as determined by reporter gene experiments. Reconstitution of either PS1 or PS2 (or both) partially rescued these effects, indicating a role of both PSs in the hypoxia pathway. Specific g-secretase inhibition led to a decrease of hypoxic HIF-1a protein levels, suggesting that the observed results are dependent on g-secretase function. Interestingly, PHD2 protein levels were also found to be decreased in PS1/2 ko MEFs. Given the fact that PHD2 itself is regulated by HIF, this finding might result from an absent PHD2 induction. Conclusion: Current research focuses on unravelling the mechanism by which presenilins regulate HIF-1a transcript levels and the hypoxic response. Acknowledgments: This work is supported by the Swiss National Foundation (SNF 3100A_129962/1).

78. Evolution of Height and Nutritional Status in School Children Between 1997 and 2010 in Antofagasta De La Sierra, Catamarca, Puna Argentina

Introduction: The aim of this work was to analyze the evolution of height and nutritional status in schoolchildren from Antofagasta de la Sierra, Catamarca, Argentina, over a period of 14 years. The town of Antofagasta de la Sierra has 656 inhabitants; the eponymous department has an area of 28,260 km² and a population density of 0.045 inhabitants per km². It is one of the most depopulated places in the planet, with altitudes above 3000 m above the sea level, extreme desert climate, and a daily temperature reaching up to 30 ° C. It remained isolated for many years. In the '80s a road that linked it to the north of the province was opened. The new political system was applied and improved social programs and the development of tourism-related activities, public offices, as well as the income of money and economic movement. All this is demonstrated by the drastic decline of households with unsatisfied basic needs (NBI). Methods: In 2010, the weight (W), height (H) and body mass index (BMI) calculated for all school children between 6 and 14 years old were obtained. Nutritional indicators W / age, H / age, BMI / age were determined through the 2007 WHO standards. Height and nutritional indicators were compared with those from prior assessment in 1997. Results: In all age groups an increase in height is revealed. In turn the prevalence of underweight and stunting decreased, overweight was doubled and obesity was quadrupled between 1997 and 2010. Conclusion: In conclusion, this population has shown a secular change in height, which can be interpreted as a result of lifestyles changes in a relatively short period. On the other hand, the influence of globalization together with the participation of private companies and government agencies impacted the decline in the prevalence of low weight and low height and the increase in overweight and obesity for each age. Acknowledgments: This work was funded by the ANPCYT under the project PICTO 32 451 of FONCYT and UNCA.

80. Patients with Chronic Cardiac Diseases at High Altitude

Introduction: With the growing interest in adventure travel, increasing numbers of individuals are venturing to high altitude. As medical care for many common conditions improves, it is likely that many of these travelers will have underlying medical problems that may be adversely affected by acute high altitude exposure. Given that many of the primary physiologic responses to acute hypoxia, including hypoxic pulmonary vasoconstriction, and increased sympathetic nervous system activity involve the cardio-respiratory system, patients with chronic cardiac diseases are one group that deserves particular attention prior to any planned high altitude travel. In this talk, we review the effects of acute high altitude exposure on patients with coronary artery disease, chronic heart failure, congenital heart disease and pulmonary hypertension. Although the literature on such patients at high altitude are limited at this time, it is possible to draw on an understanding of the main physiologic responses to high altitude and how those responses will interact with the underlying pathophysiology in each of these disease states and draw tentative conclusions about how these patients will do in acute hypoxia. Theoretical concerns with each patient group will be explored, the available data reviewed and recommendations made about how to evaluate the safety of planned high altitude travel in these groups.

87. Hemoglobin Polymorphism in Andean Ducks

Introduction: Theory predicts that parallel evolution should be common when the number of beneficial mutations is limited by selective constraints on protein structure. However, confirmation is scarce in natural populations. Methods: We studied the major hemoglobin genes of eight Andean duck lineages and compared them to 115 other waterfowl species, including the bar-headed goose (Anser indicus) and Abyssinian blue-winged goose (Cyanochen cyanopterus), two additional species living at high altitude. Results: One to five amino acid replacements were significantly overrepresented or derived in each highland population, and parallel substitutions were more common than in simulated sequences evolved under a neutral model. Two substitutions evolved in parallel in the α A subunit of two (Ala-α 8) and five (Thr-α 77) taxa, and five identical βA subunit substitutions were observed in two (Ser-β4, Glu-β94, Met-β133) or three (Ser-β13, Ser-β116) taxa. Substitutions at adjacent sites within the same functional protein region were also observed. Five such replacements were in exterior, solvent-accessible positions on the A helix and AB corner of the α A subunit. Five others were in close proximity to inositolpentaphosphate binding sites, and two pairs of independent replacements occurred at two different α β intersubunit contacts. More than half of the substitutions in highland lineages resulted in the acquisition of serine or threonine (18 gains vs. 2 losses), both of which possess a hydroxyl group that can hydrogen bond to a variety of polar substrates. Conclusion: The patterns of parallel evolution observed in these waterfowl suggest that adaptation to high-altitude hypoxia has resulted from selection on unique but overlapping sets of one to five amino acid substitutions in each lineage. Acknowledgments: Funding was provided by the National Science Foundation (DEB-0444748).

100. Sleep in Hypoxia: Impact on High Altitude Sickness

Introduction: The aim of this study was to investigate sleep in simulated altitude in patients with recurrent life-threatening altitude intolerance (AI i.e. severe acute mountain sickness and/or pulmonary or cerebral oedema), in comparison with paired controls with a good tolerance to altitude (similar age, gender, physical fitness, altitude experience). Methods: 12 AI subjects recruited for the study and 12 paired controls underwent two full night polysomnography (i) in hypoxia (FiO₂ = 14.5%) versus (ii) normoxia in a similar normoxic tent. Poïkilocapnic and isocapnic ventilatory response to hypoxia (pHVR and iHVR) were determined as well as the hypercapnic ventilatory response (HCVR). Results: There was no difference of sleep in normoxia. None of the subjects displayed any sleep disorders. In hypoxia significant differences were observed: (i) mean and minimal oxygen saturation (SpO₂) were lower in AI (81.6 ± 2.2% vs. 86.3 ± 2.06%, P = 0.003; 73.8 ± 3.12% vs. 78.4 ± 2.59%, P = 0.008, in AI and controls respectively). Conversely, Apnea/Hypopnea Index (AHI) was higher in controls (39.4 ± 20 vs. 19.9 ± 18.4/h, P = 0.04). Sleep structure was also modified: stage I was reduced in AI (9.8 ± 4.6 % vs. 16.1 ± 7.9 % of Total Sleep Time (TST) in AI and controls respectively, P = 0.03) with a greater sleep stage III/IV (19.7 ± 7.2 vs. 14.0 ± 6.6 % TST, P = 0.02). AI subjects had a lower iHVR (iHVR5: 0.40 ± 0.51 vs. 0.90 ± 0.49 vs. l/min/%SpO₂, P = 0.01). There was no difference in pHVR. HCVR showed a higher central chemosensitivity in control vs AI (slope: 4.30 ± 1.86 vs 2.60 ± 1.49 l/min/mmHg, P < 001; ventilatory threshold 45.1 ± 3.5 mmHg vs. 49.9 ± 2.8 mmHg, P = 0.01). Spontaneous eucapnic PETCO₂ was lower in control than in AI subjects (35.9 ± 2.5 mmHg vs. 40.2 ± 2.5 mmHg, P < 0.001). Conclusion: These findings indicate that in spite a higher AHI, tolerance to altitude is associated with a better preserved mean SpO₂. Peripheral response to hypoxia, as well as central chemosensitivity to CO₂ are higher in well adapted subjects. Collectively, our findings provide new insights into physiological mechanisms of high altitude sickness. Acknowledgments: This research was supported by the Grenoble University Hospital Research Clinic Administration. Thanks to all who made this study possible.

101. Non-Hematopoietic Activity of Endogenous Erythropoietin

Introduction: Erythropoietin (EPO), the principle regulator of erythropoiesis, is upregulated in response to hypoxic stress resulting in increased red blood cell production to increase oxygen delivery. However, EPO receptor (EpoR) is also expressed in other tissue including high level in embryonic brain of wild type (WT) mice. Methods: Deletion of endogenous EpoR in mice is used to determine EPO activity beyond hematopoietic tissue. Results: Mice that lack EpoR die in utero of severe anemia and also exhibit increased brain apoptosis. Selective rescue of EpoR to restore expression in erythroid tissue but not in brain results in viable mice with decreased neurogenesis and increased susceptibility to insult, suggesting neural activity of endogenous Epo. Unexpectedly, mice expressing EpoR only in erythroid cells (Tg mice) also exhibit glucose intolerance and increased fat mass accumulation. At 6 months Tg mice had 25%-30% more body mass and were insulin resistant. No differences in food intake were observed, but Tg mice exhibited increased energy efficiency and decreased energy expenditure. EPO treatment in WT mice stimulated erythropoiesis and also decreased fat mass accumulation and blood glucose. EPO treatment in Tg mice increased hematocrit, but the change in fat mass accumulation compared with saline treatment observed in WT mice was not evident. In contrast to other non-hematopoietic tissue, we observed high EpoR expression in white adipose tissue (WAT). To study this further, we examined an in vitro model of adipogenesis using primary mouse embryonic fibroblasts (MEF). In cultures of differentiating MEF cells, EPO inhibited adipogenesis, activated signal transduction pathways and increased PPARgamma phosphorylation, a transcription factor required for adipogenesis. Conclusion: These data indicate that in addition to erythroid tissue, EPO signaling is functional in select non-hematopoietic tissue such as brain and WAT, and contributes to development, maintenance or stress response. Acknowledgments: Support for this work was provided by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program.

108. Physiological Responses to Intermittent Hypoxia in Healthy Humans: Implications For Obstructive Sleep Apnea and Periodic Breathing

Introduction: We have recently shown in a small group of patients with obstructive sleep apnea (OSA) a negative association between the severity of OSA and associated hypoxemia, and the cerebral blood flow response to hypoxia (Foster, G.E. et al., Am. J Resp. Crit. Care Med. 175:720-25, 2007). Our data indicated that cerebrovascular sensitivity to hypoxia, which determines the capacity of the cerebral vessels to respond and compensate for reduced oxygen supply, is reduced in patients with OSA but increases to normal levels after treatment of OSA with continuous positive airway pressure. Methods: More recently, we have developed a novel experimental human model of intermittent hypoxia to investigate the mechanisms underlying this association. Our human model represents a substantial improvement relative to previous animal and human models that have been used to evaluate potential mechanisms for the association between OSA and cardiovascular disease. The objective of this presentation is to review the physiological responses that are elicited by our model of intermittent hypoxia. Results: Data obtained from our model reveal adaptive cerebrovascular, cardiovascular, and respiratory responses to intermittent hypoxia that resemble those observed in OSA, and are reversible within days after termination of exposure to intermittent hypoxia. Moreover, new data emerging from our group and others will be presented to describe some of the molecular changes that take place in response to intermittent hypoxia (i.e., erythropoiesis, angiogenesis, oxidative stress, endothelial dysfunction), and the mechanisms that may underlie these adaptive processes in healthy humans will be examined. Conclusion: Finally, the implications for patients with OSA and periodic breathing will be discussed. Acknowledgments: Funding Sources: This project was funded by the Alberta Heritage Foundation for Medical Research (AHFMR), the Canadian Institutes of Health Research (CIHR) and the R. Samuel McLaughlin Travelling Medical Education Fund (University of Calgary).

112. Determine the Effect of GGA on the Survival of Mice and Brain Damage Under Acute Hypobaric Hypoxia

Introduction: It has been shown that induction of HSP70 by administration of geranylgeranylacetone (GGA) leads to protection against ischemia/reperfusion injury. Methods: The present study was performed to determine the effect of GGA on the survival of mice and brain damage under acute hypobaric hypoxia. Results: The data showed that the mice injected with GGA survived significantly longer than control animals (survival time of 9.55 ± 3.12 min, n = 16 vs. controls at 4.28 ± 4.29 min, n = 15, P < 0.005). Accordingly, the cellular necrosis or degeneration of hippocampus and cortex induced by sublethal hypoxia for 6 h could be attenuated by pre-injection with GGA, especially in the CA2 and CA3 regions of hippocampus. In addition, the activity of NOS of hippocampus and cortex was increased after exposure of sublethal hypoxia for 6 h, but could be inhibited by the pre-injection of GGA. Furthermore, the expression of HSP 70 was significantly increased at 1 h after GGA injection. Conclusion: These results suggest that administration of GGA improved survival rate and prevents brain from acute hypoxia damage, the underlying mechanism was involved in inducing HSP70 expression and inhibiting the NOS activity. Acknowledgments: This work was supported by a grant from the National Basic Research Program of China (No. 2006CB504100).

121. Flying Across the Himalayas: the Unique Physiology of Bar-Headed Geese

Introduction: Bar-headed geese reach altitudes of up to 9000 m during their biannual migration over the Himalayas. The ability of this species to maintain O₂ supply in the severe hypoxia at these elevations is impressive when considering the high metabolic costs of flight in birds. Methods: We examined how the O₂ transport pathway has evolved in this species to help determine the physiological basis for this feat. Results: Bar-headed geese can breathe much more than low-altitude birds during hypoxia, largely due to alterations in the pattern and chemosensitivity of breathing. This species also has larger lungs and a higher haemoglobin-O₂ affinity. As a result of these characteristics, pulmonary O₂ uptake during hypoxia is markedly improved. Evolutionary changes in the heart, such as a higher capillarity, also improve circulatory O₂ delivery. Oxygen diffusion capacity in the flight muscle is improved by an enhanced capillarity and a redistribution of mitochondria towards the cell membrane. These unique characteristics exist without prior exercise or hypoxia exposure. However, mitochondria isolated from bar-headed goose muscle are equally sensitive to reductions in O₂ tension to those from other geese. Conclusion: High-altitude adaptations that enhance O₂ supply, and sustain O₂ tensions at the mitochondria, therefore appear to be essential for the exceptional ability of bar-headed geese to fly high.

Acknowledements: Supported by NSERC of Canada.

125. Are UK Commercial Expeditions Complying with WMS Guidelines?

Introduction: Trekking is becoming an increasingly popular tourist activity, and three of the most popular areas for commercial expeditions are Kilimanjaro, Aconcagua, and Everest Base Camp (EBC). However, with this, comes the risk of acute mountain sickness (AMS), which is believed to be due to the rapid rate of ascent offered by many commercial companies. In an attempt to minimize AMS, the Wilderness Medicine Society (WMS) has recommended that once above 3000 m, the gain in sleeping altitude should be no more than 500 m, and in addition, a rest day should be taken after three or four days of ascent. The aim of this study was to ascertain whether treks to these popular areas, offered by commercial companies in the UK, satisfied the guidelines stated by the WMS. Methods: A search of the World Wide Web was conducted in order to identify those UK-based companies that offer treks to the summit of Kilimanjaro and Aconcagua, and to EBC between January 2010 and December 2011. For each route on offer, the ascent profile was compared with the ascent profile recommended by the WMS. Results: 10 UK-based companies offering climbs of Aconcagua, and 16 offering treks to EBC were identified. 30 companies offering 90 treks on nine different routes on Kilimanjaro were identified. The average ascent rate on Aconcagua was 250 m/day, and to EBC was 275 m/day. On Kilimanjaro, the ascent rate ranged from 513 m/day to 566 m/day, depending on which route was offered. The ascent rate recommended by the WMS is 400 m/day, and of the companies identified in this study, 10 complied on Aconcagua (100%), 13 complied on EBC (81%), and none complied on Kilimanjaro.

128. Oxygen Supplementation Effects on AMS Symptoms and Functional Capacity of a 2 km Walk Test on Chajnantor Plateau (5050 m, Northern Chile)

Introduction: We evaluated the effects of oxygen supplementation on the functional capacity and acute mountain sickness (AMS) symptoms in 26 young healthy subjects that performed a test of 2 km fast walk at sea level and at Chajnantor plateau at 5050 m of altitude. Methods: The 16 men and 11 ladies were randomLy distributed into four groups according the following arrangement: M1: 8 men who received by mask supplementary oxygen at a rate of 1LO₂ min-1; group M3: 7 men who received 3LO₂ min-1. W1: 5 ladies who received 1LO₂ min-1 and W3: 6 ladies receiving 3LO₂ min-1. A previous walk test at sea level was carried out in a flat land track of 100 m of length that was covered in 10 U-returns. First walk at altitude was made carrying the supplementary oxygen system but without functioning. Second test was performed in the following day with actual oxygen supply through a facemask. Results: Our results showed that supplementary oxygen administration in a 2 km walk test significantly improved the walking time at 5050 m in men but not in women groups.

Also we observed a significant improvement in AMS symptoms in men groups. The women had bad tolerance to breathe as mask; three of them left the test for bad tolerance the mask. Nevertheless, instead of supplementary oxygen in men, a reduced performance persists in comparison to the test values at sea level. Conclusion: This study has practical application in people who develop specific tasks at high altitude, during a whole working day (6-8 hours). Our findings indicate that they could benefit from the administration of supplementary oxygen, in continuous or intermittent form, with the objective of diminish the AMS incidence and to improve its working physical condition. In the same way, our results could be applied to improve the performance in workers who must develop static activities at altitude, but requiring great concentration capacity, such as vehicle driving, decision making, or fine manipulation, in which the speed of reaction is vital and a mechanism guarantying a suitable brain oxygen supply it can be a key safety factor not only during the ascent and altitude stay as in the descent to lower altitude. Acknowledgments: Authors are grateful to Chiledeportes II Region by their sponsorship to research projects in the area of the Altitude Physiology and Medicine through the modality of Sports Sciences; and to ALMA Project (European Southern Observatory) authorities for their support to the present study.

131. Acute High Altitude Illness in Patients Urgently Transferred to Sea Level Private Hospital. Lima, Peru

Introduction: With globalization, Peru is becoming an increasingly important attraction for international tourism. Medical problems as Acute High Altitude Illness can arise, especially when tourists visit the Peruvian highlands. The aim of the present study was to describe the clinical characteristics of acute high altitude illness in patients who required urgent transfer to a sea level Private Hospital in Lima-Peru. Methods: The medical records of 69 patients with diagnosis of High Altitude Pulmonary Edema (HAPE) and/or High Altitude Cerebral Edema (HACE) who were urgently transferred to the British American Hospital (Clinica Anglo Americana) from 2000 to 2007 were retrospective evaluated. Results: The mean age was 51.53 + /- 15.47 years, 47 (72.3%) were males, 65 (98.5%) were tourists. Twenty nine patients come from 3990 m (Cuzco) and 17 from 3918 m (Puno). The most common nationalities were 19 French, 12 Americans, 8 British and 6 Japanese. Sixty three percent of patients started symptoms 1 day after arrival. Fifteen (28.8%) had past medical history and 8 patients had prior acute medical problems before altitude symptoms. Only 5 patients needed intensive care unit. Regarding symptoms 52(75.3%) reported dyspnea, 23 (33.3%) headaches, 22 (31.8%) coughs, and 11 (16%) mental status changes. Fifty five patients (75.3%) developed HAPE, 9 (13%) HACE and 8 (11.6%) HACE and HAPE. Twenty one patients also developed additional acute medical problems. In four patients were necessary oxygen and medical support to discharge. No fatal events related to acute high altitude illnesses were reported during the time of our study. None of the patients took preventive medication. Conclusion: HAPE was the most common acute high altitude illness in our study and dyspnea was the most frequent symptom. Acute high altitude illness is a preventable disease, our data suggests that proper advice and prophylaxis will be provided to people who travel to high altitude places. Acknowledgments: British American Hospital (Clinica Anglo Americana).

133. Mechanisms of Hemoglobin Adaptation to Hypoxia in High-Altitude Rodents

Introduction: In high-altitude vertebrates, adaptive changes in blood-oxygen affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic oxygen affinity and/or responsiveness to allosteric effectors that modulate Hb-oxygen affinity. This mode of genotypic specialization is considered typical of mammalian species that are high-altitude natives. Here we investigate genetically based differences in Hb-oxygen affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal.: We used a combined genetic and proteomic approach to characterize Hb isoform diversity, and we measured oxygen-binding properties of purified hemoglobins from mice with known genotypes. We also conducted a multilocus population genetic analysis to assess the role of natural selection in shaping altitudinal patterns of nucleotide variation at two tandemLy duplicated alpha-globin genes on Chromsome 8 and two tandemLy duplicated beta-globin genes on Chromosome 1. Results: Results revealed that deer mice harbor an extremely high level of Hb isoform diversity which translates into a correspondingly high level of interindividual variation in Hb functional properties. Results of functional experiments revealed that, on average, the Hbs of highland mice exhibit slightly higher intrinsic oxygen affinities and lower chloride sensitivities relative to the Hbs of lowland mice. The experiments also revealed distinct biochemical properties of deer mouse Hb related to the allosteric regulation of oxygen affinity. Combined evolutionary and functional analyses suggest that genetic differences in Hb function between highland and lowland deer mice evolved under the influence of positive directional selection that favors different blood-oxygen affinities in different elevational zones. Conclusion: In conjunction with previous findings, our results demonstrate that modifications of Hb structure and regulatory adjustments in the intracellular concentrations of erythrocytic anions both play a role in the adaptive fine-tuning of blood-oxygen affinity. Acknowledgments: This work was funded by grants from NIH and NSF.

138. Placental Adaptation to High Altitude

Introduction: The placenta is integral to the development of preeclampsia, its incidence being 3-4 fold greater in high altitude populations. Thus, placentas from healthy and preeclamptic high altitude pregnancies provide an excellent in vivo human model for investigating mechanisms of successful and failed adaptation to hypoxia. Methods: Our recent work suggests that placental adaptation to reduced oxygen supply is not accomplished by improving vascularization, rather it involves modification of mitochondrial-mediated response to hypoxia. The goal of our current investigations is to determine mechanisms by which mitochondrial density and activity are altered in placentas from pregnancies that have successfully adapted to high altitude and those that have not (preeclampsia). Results: Specifically, acute hypoxic activation of HIF can lead to mitochondrial autophagy (mitophagy) via BNIP3, thus reducing mitochondrial density during chronic hypoxia and mitochondrial density is lower in adapted high altitude placentas. Furthermore, expression of mitochondrial uncoupling proteins (UCP), which act to reduce oxidative phosphorylation and oxygen radical production are also lower in healthy placentas. However, mitochondrial density and UCP expression do not appear to be lowered in preeclamptic placentas at high altitude. Conclusion: Further details of mitophagy and mitochondrial activity in relation to placental adaptation to high altitude will be presented and discussed.

140. Auscultatory and Echocardiographic Findings in Dogs with “Lone” Tricuspid Regurgitation, and Responses to Changing Pulmonary Arterial Pressure

Introduction: Three large, male dogs had multiple catheters placed via a jugular vein through the tricuspid orifice. These produced “lone and pure” tricuspid regurgitation (TR) with systolic murmurs and jugular pulsations. We sought to describe the murmur intensity (mi), and to determine if increasing (with hypoxia) or decreasing (with sildenafil) peak pulmonary arterial pressure (PAP) would affect the mi. Methods: Dogs were narcotized lightly and examinations were performed without alterations in PAP, and after PAP was increased as dogs breathed 11% 02, or decreased in response to the PDE5-inhibitor, sildenafil. Mi and point of maximal intensity (PMI) of the murmur on the thorax was recorded by 4 persons who penciled the PMI on a sketch of the left and right sides of the torso. Echocardiograms with Doppler interrogations of the tricuspid orifice quantified severity of TR, and PAP was estimated by the modified Bernoulli's equation. Results: All dogs had jugular venous pulsations, and systolic murmurs heard, in general loudest on the right hemithorax at the 3rd intercostal space approximately ¼ of the ventrodorsal distance from the sternum. PAP increased from an average ∼35 mmHg to ∼54 mmHg during hypoxia and decreased to an average ∼30 mmHg after sildenafil. Because the number of dogs included was small, statistical analysis was not performed, but the possibility of these directional changes occurring by chance is 1:6. TR changed ∼10%, increasing with hypoxia and decreasing with sildenafil; Mi changed approximately I/VI, decreasing with sildenafil, however Mi could not be quantified due to hypoxic dyspnoea. Conclusion: In summary, TR and Mi increased with increased PAP produced by hypoxia and decreased with decreased PAP produced by sildenafil. It suggests that directional changes in PAP may be predicted by mi. However this study must be repeated in dogs with naturally-occurring TR, but will be more complicated since TR occurs most often with mitral regurgitation the murmur of which might obfuscate that of TR. Acknowledgments: The Ohio State University Medical Center, Department of Cardiovascular Medicine.

141. Pulmonary Hypertension (PH) Occurs Because of Increased Arteriolar and/or Arterial Hindrance of Flow From Right Ventricle to Left Atrium

Introduction: To determine the location of the increased resistance to pulmonary arterial flow hindrance in dogs subjected to FiO₂'s of 12% and 10%. Methods: Nine dogs were anesthetized with acepromazine-butorphanol-propofol. Pulmonary peak systolic, mean, diastolic, and pulse pressures were monitored continuously using Millar catheters. Dogs ventilated with 21%, 12%, and 10% FiO₂'s, and differences in pulmonary arterial pressures and rates of increase and decrease were measured. Results: Although we observed the expected hypoxia-induced increase in pulmonary arterial pressure, interesting observations were: (1) the rate of elevation of pressure to decreased FiO₂ appears linear, but the rate of fall in pressure after return to normal FiO₂ is exponential, and (2) the pulse pressure changed more for 10% than for 12%. Conclusion: Historesis in differences in “on “ and “off” of pulmonary arterial pressure, and differences between pulse pressures for 10% and 12% FiO₂'s may indicate that the causative increase in hindrances may be pulmonary arteriolar (i.e., increased pulmonary vascular resistance) or pulmonary arterial (i.e., increased impedance) and depend upon the FiO₂. Acknowledgments: We appreciate the support of QTest Labs and Facultad de Medicina Veterinaria, Universidad Nacional de Colombia.

142. The Role of Perinatal Hypoxia in The Development of Preclinical CMS

Introduction: Chronic mountain sickness (CMS) is a significant public health problem for the more than 140 million persons living at high altitudes (>2500 m) yet its etiology remains incompletely understood, in part, because the effects of normal aging obscure the identification of causal factors. Excessive erythrocytosis (EE, Hb ≥ 18.3 g/dL) is considered to be a preclinical form of CMS. We hypothesized that perinatal hypoxia increases susceptibility to CMS by impairing development of pulmonary structure and/or respiratory control. Methods: 30 EE and 29 controls were selected for detailed physiological study from a survey of 820 young (18-25 yr) male residents of La Paz/El Alto (3600-4100 m). Results: Of the 820 males surveyed, 8% had EE. The majority of the 30 EE subjects studied presented with arterial hypoxemia (SaO₂ < 2 SD altitude-specific mean) and/or pulmonary hypertension (>35 mmHg, systolic) in the absence of underlying disease. 63% of EE cases experienced perinatal hypoxia as manifested either by being preterm (29%), born to a preeclamptic mother (38%), or neonatal hypoxia diagnosis (38%). In contrast, the frequency of these conditions in controls was 24%, 11% and 6%, respectively. Although EE subjects weighed 378 g less at birth than controls, this difference was not statistically significant. All 59 subjects were normal in terms of body weight, height, and body mass index. Alveolar ventilation and FEF75% values were lower in EE than control subjects, whereas lung diffusion capacity, HVR, FVC, FEV1 and % of FEV1/FVC were equivalent. The majority of EE subjects showed evidence of pulmonary hypertension (62%), and/or right ventricular hypertrophy (67%). Conclusion: We concluded that exaggerated perinatal hypoxia may increase the susceptibility to CMS via alterations in pulmonary development and/or respiratory control. Impaired growth in utero has been shown to raise susceptibility to adult disease; these are the first data from a well-controlled study to demonstrate a possible influence of exaggerated perinatal hypoxia on increased the susceptibility to CMS. Acknowledgments: We would like to thank the generous participation of our research subjects; Dr. Rob Roach (ARC); Dra. Diva Bellido, Cristina Gonzales, Ana Maria Alarcón, Marta Aguillar, Catherine Romero, Yvonne Contreras (IBBA); Lic. Javier Fuentes (INSEF); Dra. Maritza Vargas and Lic. Walter Amezaga (Normal Superior Simon Bolivar); and financial support provided by NIH (R03TW007957-01A2).

143. Vasodilators Effects of P-Hydroxyacetophenone Isolated From Senecio Nutans From Northern Chile

Introduction: The species Senecio nutans (Chachacoma) plant endemic of the altiplane of northern of Chile is widely used by communities altiplanic of Chile, Bolivia, Peru and Argentina as a medicinal tea for acute mountain sickness (AMS). The aim of this study is to determine the vasodilator effects of p-hydroxyacetofenona obtained from Senecio nutans. Methods: We obtained aqueus and hydroalcholic extracts from leaves and stems of Senecio nutans. Subsequently, a secondary metabolite was purified from hydroalcholic extract through column chromatography (silica gel) which was eluted with n-hexane-ethyl acetate (10-70%). The purity of the compound isolated was verified by nuclear magnetic resonance spectroscopic and infrared spectroscopy analysis. The vasodilator effects was evaluated through myography in rat aortic rings maintained in Krebs solution (95% O₂, 5% CO₂, pH 7.4, 37 ° C) connected to isometric tension transducers and BIOPAC system. Results: The intravenous administration of aqueous and hydroalcoholic extract in rats induce a significant decrease in mean arterial pressure (MAP) from 5 to 10 mg/kg rat, respectively. Also induce dosis-dependent vasodilation in rat aortic rings pre-contracted with phenylephrine (10-6 M). The EC50 determined for aqueous and hydroalcoholic extracts were 56 and 558 ug/mL, respectively. The compound purified from the hydroalcoholic extracts were run in thin layer chromatoghaphy (TLC) in aluminum film with different standards. The retention factor (Rf) was 0.28 similar to the compound 4-hydroxy-3-(2′-isopentenyl) acetophenone. The purified compound (10-4 m) induces a relaxation ∼80% in rat aortic rings pre-contracted with phenylephrine. Conclusion: Our results suggest that derivatives of p-hydroxyacetophenone obtained from Senecio nutans could be drug with potent vasodilator effects. Future experiments must be conducted to determine effects on blood pressure and the mechanism of action of these compounds. Acknowledgments: Supported by FONDECYT 1040294, DI-1339-07, Paredes A and Kuzmicic hold PhD Felowship.

146. Effects of Globalization on Living Habits in an Argentina High Altitude Population

Introduction: In order to study growth and nutritional condition of schoolchildren from Antofagasta de la Sierra, a village in height, located at 3223 m in the Puna Argentina, anthropometric measurements were obtained and dietary surveys were applied. In this paper we analyze the results of dietary surveys. Methods: 59 ad hoc surveys were conducted and applied to mothers and guardians of all school-age children from Antofagasta de la Sierra (204 individuals). The data obtained as to do with main meals per day, from Monday to Friday and on weekends separately; frequency of consumption of dairy products, meat, vegetables, water, sugary foods, fried foods and with physical activity. Results: Results show that approximately two thirds of children had the four main meals, either from Monday to Friday or weekends. As regards frequency, the findings show relatively low percentages of “healthy food groups” daily consumption, in particular dairy products, fruit and vegetables; high consumption of sugary foods and drinks on a daily basis - more than 58% replacing water intake-, since a third of children do not prefer water as the main beverage. In this group, only 50% of the children exercise physical activity regularly. Conclusion: As a conclusion, we found that the surveyed population maintain ancient cultural patterns ingrained in relation to food and recipes consumed because they have lived far from urban centers for centuries until two decades ago. Due to better access roads to this community, there is now a burst in of new food and technologies, Depending on that situation, the results are interpreted as a nutritional, epidemiological, food access and availability transition context. Acknowledgments: This work was funded by ANPCYT in the context of the project PICTO 32451 of FONCYT and UNCA.

148. Peripheral Oxygen Delivery Adjustments After Intermittent Hypobaric Hypoxia Exposure

Introduction: In recent years our group has studied adaptive responses at the level of myocardial and skeletal muscles to intermittent hypobaric hypoxia exposure (IHHE) programs. Although it is clear that the laboratory rat has a lower tolerance to hypoxia than people do, a rat experimental model allows us to perform studies that, for technical or ethical reasons, cannot be performed on humans. Methods: Tissue hypoxia is a stressful situation for most animals. To cope with oxygen requirements, organisms are able to make physiological and morphological adjustments to maintain a minimum level of aerobic metabolism under conditions of poor oxygen delivery to the tissues. Intermittent hypoxia exposure patterns follow the training theory; a series of stressful sessions, followed by sufficient recuperation periods, elicit a better adaptive response. Moreover, according to the symmorphosis principle, structural elements are formed to satisfy functional requirements without excess. As a consequence, it can be expected that some corresponding morphological and metabolic changes in heart and skeletal muscle must be associated with the increase in blood oxygen transport capacity elicited by the hypoxia-induced erythropoiesis. Results: Our results showed a significant increase in capillary myocardial density after IHHE, whereas in skeletal muscles these effects seemed to be dependent of the level of activity as well. Associated changes were also detected after IHHE in some muscular enzymes that are markers of oxidative and anaerobic metabolism. In addition, blood viscosity did not increase in proportion with the rise in hematocrit, indicating that some adjustment occurred to maintain adequate blood flow despite the increased corpuscular fraction. Lower plasma protein content and also probably microrheological erythrocyte changes may be the main causes of this phenomenon. We recently demonstrated a significantly increased stem cell (CD34+) proportion in circulating blood after IHHE plus muscle activity. Conclusion: These findings provide a basis for future applications of IHHE in potentially fast-growing new biomedical fields.

149. Acute Mountain Sickness (AMS): Some Ideas for Unraveling the Puzzle

AMS was first described and classified as one of the high altitude illnesses in Peru nearly 100 years ago by Ravenhill. Since then scientists have struggled to understand what causes AMS. In the process, good options have been discovered for treatment and prevention. Yet the underlying pathophysiology remains uncertain. Since the early descriptions of a 'nervous puna' the focus in AMS pathophysiology studies has shifted to investigations of the role of the brain in AMS. We will review a number of factors that may be at play in the pathophysiology of AMS. Some of these factors are clearly described, and others which are 'thought' to be at play, and still others remain completely untested. We will also review procedures to experimentally test AMS and how those procedures, utilized or not, may influence the outcome of studies into the pathophysiology of AMS. In our opinion, to move the study of the fundamental causes of AMS forward, the field needs to consider these issues to formulate advanced studies with potential to reveal the remaining pieces of the puzzle that is the pathophysiology of AMS.

150. Sports Training at Altitude

Introduction: This research was conducted in Arequipa, the second largest city of Peru located at 2360 m, in the High Performance Sports Center in Peru, a space created to enhance physical functional capacity of Sprint, Track and Field, Middle Distance and Long Distance Athletes based on competitive performance. The main research objective was to determine the hematological changes, medical and sports performance training at medium altitude. Methods: In terms of methodology, we evaluated the levels of hemoglobin and hematocrit, clinical histories and sports results in a period of 12 months. The sample was consisted 20 elite athletes with an average age of 14 years of both sexes. Results: The main results showed that the Centre was home to the best athletes in motion, short and middle distance from across the country, 90% came from the mountains (3500- 4500 m). During the first days of adaptation to altitude of Arequipa, tests were made which included the baselines of hemoglobin and hematocrit. These tests were repeated for the first 15 days and then monthly, to see the trend in a year. At the beginning of the training, athletes from the mountains had an average level of hemoglobin by 18.5 g/dL, while the average for athletes from the coast was 14.0 g/dL. After a month of training in Arequipa, these levels changed the levels of the athletes from the mountains decreased by 1.5 of hemoglobin and athletes from the coast increased by 2 points. After a year, the average hemoglobin level for the group stabilized on 17 g/dL for males and 14.8 g/dL for females, and also their performance and physical capacity of endurance, strength and speed were improved. Regarding the most common medical problems in the early days of adaptation were: headache, fatigue and digestive problems, which were resolved within 10 days. Conclusions: An increased hemoglobin level between 1 and 3 g/dL is responsible for a higher uptake of oxygen and improves the capabilities of sports.

153. Blood and Body Composition Changes Before and After Ascents of Aconcagua and Everest

Introduction: Both Mt. Aconcagua (6962 m) and Mt. Everest (8850 m) are highly prized summits by mountaineers. Ascents of these peaks place a physiological strain on the human body resulting in adaptation. The purpose of this case study was to compare the pre- and post- blood chemistry and body composition of a mountaineer who ascended both peaks. Methods: The male subject was 41 y during the Aconcagua ascent (February 2008) and 43 y during the Everest ascent (May 2009). He was moderately fit (VO_2max = 54 mL/kg/min), residing at 1382 m, and had a history of more than a dozen ascents above 6000 m over the previous 10 years. Baseline blood draws and body composition measurements were done within a couple days of departure for both expeditions. The blood draw consisted of a complete blood count (CBC), and body composition was assessed by air displacement plethysmography (Bod Pod^®). Results: The post-Aconcagua measurements were taken 10 d after reaching the summit. They revealed a 2.0 kg drop in body mass and a reduction in body fat (15.5% to 12.1%). Blood chemistry remained largely unchanged (RBC = 5.09 million/mL to 4.95 million/mL, Hgb = 15.6 g/dL to 15.4 g/dL, Hct = 46.4% to 45.7%, MCHC = 33.7 g/dL to 33.8 g/dL). The post-Everest measurements were taken 14 d after reaching the summit. Body mass was reduced from 65.0 kg to 60.5 kg with a drop in body fat from 17.3% to 10.2%. Despite no change in RBCs (4.90 million/mL to 4.86 million/mL) there were increases in Hgb (15.7 g/dL to 17.7 g/dL), Hct (45.8% to 48.0%), and MCHC (34.3 g/dL to 37.0 g/dL). Conclusion: It took the subject 12 d to reach the summit of Aconcagua whereas it took 50 d to reach the summit of Everest. The longer duration at higher altitude resulted in more dramatic physiological changes.

156. Observation of Bone Mineral Density in Perimenopausal Women at Different Altitudes

Introduction: Osteoporosis is the world's intractable diseases, more and more attention, and the many factors that lead to osteoporosis has also been more in-depth research. At different altitudes on the plateau, whether bone mineral density in Han women with perimenopausal have different with one in plain areas, it has not been reported in China. we would observe and compare bone mineral density in perimenopausal women at different altitudes, to study a correlation between bone mineral density in perimenopausal women and altitude. Methods: The perimenopausal women who living in different altitude were divided into two groups: perimenopausal women with 180 cases at high altitude (elevation 4200 m) for the A group. perimenopausal women with 180 cases moderate altitude (elevation 2260 m) for the B group. The two groups were all Han Chinese with a mean age (46 ± 1.5) years old, not yet menopausal, with an average age of menarche (14.01 ± 1.60) years, and exclude hereditary and bone metabolism diseases.The reference of 180 cases data that published in Chinese Osteoporosis in 2002 as plain control group. Age, body mass index of perimenopausal women at moderate altitude groups have not different with high-altitude group (P > 0.05). Bone mineral density of lumbar spine, greater trochanter and femoral neck in two group were determind by CHRONOS French dual energy x-ray absorptiometry. Results: Bone mineral density of 2-4th lumbar spines, trochanter, femoral neck in A group have no significant difference with B group (P > 0.05), two compared with the plain P > 0.05, there was no significant difference in. Conclusion: The plateau regions at different altitudes of perimenopausal women with bone mineral density and the plain areas without distinction. Conclusion: We believe this phenomenon and adapt to the highland environment, habits related to the plateau of living longer, the body has to adapt to high altitude environment, nutrition intake and metabolism is basically balanced.

157. Measurement of Body Core Temperature by Heat Flux Double Sensor in Hypothermic Pigs During Artificial Avalanche Burial

Introduction: If an avalanche victim is completely buried by snow prolonged survival is only possible if breathing is possible due to an air pocket surrounding his airways. Hence, two thirds of buried victims die from obstructive asphyxia within 35 min (10-11, 15), but one third will survive for more than 35 min depending on the size of an air pocket and snow density (2). Therefore, in victims with an air pocket hypothermia becomes an important co-morbidity. It is known that hypothermia can have a protective effect on highly oxygen dependent brain and heart in reducing oxygen metabolism by ∼6% per °C body core temperature (13), but it may also provoke cardiac arrest below the critical level of 32°C (4, 6, 12, 15-16). Deep hypothermia has a mortality rate between 30 and 80% (1, 5). Previous studies found core temperature cooling rates of 1.2°C/hour (7) in contrast to some recent case reports with ≈ 9°C/hour (15). To this day, onsite temperature measurement is still unreliable with epitympanic, not practicable with rectal probes, and semi-invasive method with an esophageal or invasive with pulmonary artery probe, which are only applicable in intubated patients (3). Core temperature is predictive of survival and hence essential in guiding on-site treatment (11). Thus, a reliable, fast and non-invasive method for body core temperature measurement is warranted to optimize onsite treatment of avalanche victims. Methods: In a prospective, randomized study, officially approved by the Veterinary Study Committee of the Science Ministry of Austria, and conducted in the Oetz Valley, Austria, at 1,900 m of altitude, avalanche burial was simulated by burying intubated, continuously anesthetized and spontaneous breathing pigs (weight 25-42 kg) beneath avalanche snow. From a total of eight pigs, randomized in group A (n = 3) and B (n = 2) having a closed air pocket of 1L and 2L respectively, the control group C (n = 3) with an open air pocket to the outside permitting to breath into ambient air was used to assess agreement between the different methods of core temperature measurement. Pigs were monitored continuously and body core temperature (Tc) was measured and recorded manually by pulmonary artery (TcPA) and esophageal probes (TcOE). In comparison to those, Tc was measured with the non-invasive, heat flux Double Sensor (8-9), placed on the head (submandibular; Tchead) and sternum (Tcster) and recorded continuously every 2sec by HealthLab-System (Koralewski, Hambühren, Germany). Statistical analyses were done with PASW statistics 18.0 and Matlab 2009, significance level P < 0.05. Results: Because survival times in group A and B were short and we could not find a correlation between TcPA/OE and Tchead/ster temperature due to concomitant hypoxia, we present only results of group C to demonstrate long term temperature sequences without hypoxia. Survival in the control group ranged from78 to 178 min with a mean survival of 137 min (±48.8 min). Mean decrease in body core temperature from baseline to the endpoint per piglet was − 10.5°C (±3.9) with TcPA, − 11.5°C (±3.9) with TcOE, − 14.12°C (±6.2) with Tcster, and-17.3°C (±2.0) with Tchead. A Bland-Altman analysis revealed significant negative correlations between the difference and mean of TcPA to TcOE (r = − .58, p < .001) as well as Tcster (r = − .87, p < .001) and Tchead (r = − .76, p < .001), indicating that TcOE, Tcster and Tchead are lower than TcPA with lower core temperatures. After correcting for this measurement bias mean decrease in body core temperature was, − 10.7°C (±3.7) with TcOE,-9.3°C (±4.1) with Tcster, and − 10.6°C (±1.2) with Tchead. Using those corrected values 95% confidence intervals for agreement are ± .75°C for TcOE, ± 1.73°C for Tcster and ± 3.1°C for Tchead with intraclass correlation coefficients (ICC(3,1)) of .99, .97 and .92 respectively. Conclusion: Brain temperature, cerebral cooling rate and absolute temperatures are decisive for the outcome of avalanche victims (14). Various techniques have been developed to measure body core temperature but an optimal method has not been found yet. This study shows a possibility to measure Tc non-invasively by heat flux DoubleSensor with a quick response rate and in good agreement as compared to standard pulmonary artery or esophageal methods. Although mean Tcster was not statistically significant different from Tchead it seems to produce better results than Tchead possibly related to the location of the sensor. Moreover, with DoubleSensor we did notice in two pigs an initial increase in Tchead followed by a steep drop thereafter not seen in PA or OE. The same could be observed in one pig with Tcster. It has to be figured out if it is related to physiological or methodological reasons. Nevertheless, our results on three piglets do suggest that DoubleSensor measurement will most probably be reliable for the on-site as well as in hospital measurement of core temperature in avalanche and other hypothermic patients.

158. Strategies for Improving Human Performance at High Altitude

Introduction: Increasingly, people are ascending to high altitude to work. How can their performance be improved in this hypoxic environment? The advantages obtained by gradual ascent and the resulting acclimatization are well known. However many people have misconceptions about acclimatization. Although it reduces the incidence of high altitude diseases such as Acute Mountain Sickness, it certainly does not return the body to the sea level state. As Barcroft noted in 1925 “all dwellers at high altitudes are persons of impaired physical and mental powers.” Incidentally this statement apparently incensed the eminent Peruvian physician Carlos Monge Medrano. One strategy for working at high altitude is to commute, spending for example a week at altitude and a subsequent week at sea level. Partial acclimatization occurs and this pattern is employed in some mines in Chile. Another strategy for improving performance at high altitude involves pre-exposure to an intermediate altitude for several days. For example continuous residence for 6 days at an altitude of 2200 m improves work performance after a rapid ascent to 4300 m (Muza et al., 2010). Interestingly this regime also resulted in a lower pulmonary artery pressure when the subjects ascended to a simulated altitude of 4300 m (Baggish et al, 2010). A major advance in improving human performance at high altitude has been oxygen-enrichment of room air. This is a relatively simple procedure to carry out and is remarkably effective. For example every 1 percent of oxygen enrichment, for example from 21 to 22 percent, decreases the effective altitude by about 300 m. The technique is now extensively used in mines and telescope facilities, and is a critical feature in the success of the new Chinese train to Lhasa which passes through an altitude of over 5000 m. An alternative to adding oxygen to room air is supplying it with nasal cannulas. A new mine at 4500 m has plans to do this on a large scale to improve sleep but it remains to be seen how well the cannulas will be tolerated.