Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m)

Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m).

Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m

Bloch, Konrad E., Alexander J. Turk, Marco Maggiorini, Thomas Hess, Tobias Merz, Martina M. Bosch, Daniel Barthelmes, Urs Hefti, Jacqueline Pichler, Oliver Senn, and Otto D. Schoch. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. High Alt. Med. Biol. 10:25-32, 2009.-Data on acclimatization during expedition-style climbing to > 5000 m are scant. We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness (AMS) symptoms and mountaineering success in climbers to Muztagh Ata (7546 m), Western China. We performed a randomized, controlled trial during a high altitude medical research expedition to Muztagh Ata. Thirty-four healthy mountaineers (mean age 45 yr, 7 women) were randomized to follow one of two protocols, ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m, respectively. The main outcome measures, AMS symptom scores and the number of proceeding climbers, were assessed daily. Mean +/- SD AMS-C scores of 16 climbers randomized to slow ascent were 0.06 +/- 0.18, 0.26 +/- 0.08, 0.41 +/- 0.45, 0.53 +/- 0.77 at camps I (5533 m), II (6265 m), III (6865 m), and the summit (7546 m), respectively. Corresponding values in 18 climbers randomized to fast ascent were significantly higher: 0.17 +/- 0.23, 0.43 +/- 0.75, 0.49 +/- 0.36, and 0.69 +/- 0.54 (p < 0.008, vs. slow ascent in regression analysis accounting for weather-related protocol deviation). Climbers randomized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers randomized to fast ascent (p = 0.04, Kaplan-Meier analysis). More climbers randomized to slow ascent were successful in reaching the highest camp at 6865 m without AMS (odds ratio 9.5; 95% confidence interval 1.02 to 89). In climbers ascending to very high altitudes, differences of a few days in acclimatization have a significant impact on symptom severity, the prevalence of AMS, and mountaineering success. ClinicalTrials.gov Identifier NCT00603122.

Acclimatization improves submaximal exercise economy at 5533m

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6–7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (Wmax) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6–7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6–7 (5533 m), VO2 at 75% Wmax (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO2 was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO2 to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5–6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions.

Periodic breathing during ascent to extreme altitude quantified by spectral analysis of the respiratory volume signal

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value < 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value < 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value < 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Glomerular filtration rate estimates decrease during high altitude expedition but increase with Lake Louise acute mountain sickness scores

AIM: Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited. METHODS: Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests. RESULTS: eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01). CONCLUSIONS: Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.

High incidence of optic disc swelling at very high altitudes

OBJECTIVES: To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema. METHODS: This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores. RESULTS: Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001). CONCLUSION: Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Oxidative Stress in Hypobaric Hypoxia and Influence on Vessel-Tone Modifying Mediators

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.

Cognitive performance in high-altitude climbers: a comparative study of saccadic eye movements and neuropsychological tests

Impairment of cognitive performance during and after high-altitude climbing has been described in numerous studies and has mostly been attributed to cerebral hypoxia and resulting functional and structural cerebral alterations. To investigate the hypothesis that high-altitude climbing leads to cognitive impairment, we used of neuropsychological tests and measurements of eye movement (EM) performance during different stimulus conditions. The study was conducted in 32 mountaineers participating in an expedition to Muztagh Ata (7,546 m). Neuropsychological tests comprised figural fluency, line bisection, letter and number cancellation, and a modified pegboard task. Saccadic performance was evaluated under three stimulus conditions with varying degrees of cortical involvement: visually guided pro- and anti-saccades, and visuo-visual interaction. Typical saccade parameters (latency, mean sequence, post-saccadic stability, and error rate) were computed off-line. Measurements were taken at a baseline level of 440 m and at altitudes of 4,497, 5,533, 6,265, and again at 440 m. All subjects reached 5,533 m, and 28 reached 6,265 m. The neuropsychological test results did not reveal any cognitive impairment. Complete eye movement recordings for all stimulus conditions were obtained in 24 subjects at baseline and at least two altitudes and in 10 subjects at baseline and all altitudes. Measurements of saccade performances showed no dependence on any altitude-related parameter and were well within normal limits. Our data indicates that acclimatized climbers do not seem to suffer from significant cognitive deficits during or after climbs to altitudes above 7,500 m. We demonstrated that investigation of EMs is feasible during high-altitude expeditions.

Polydnavirus DNA of the braconid wasp Chelonus inanitus is integrated in the wasp's genome and excised only in later pupal and adult stages of the female

Many endoparasitic wasps inject, along with the egg, polydnavirus into their insect hosts, the virus being a prerequisite for successful parasitoid development. The genome of polydnaviruses consists of multiple circular dsDNA molecules of variable size. We show for a 12 kbp segment of the braconid Chelonus inanitus (CiV12) that it is integrated into the wasp genome. This is the first direct demonstration of integration for a bracovirus. PCR data indicated that the integrated form of CiV12 was present in all male and female stages investigated while the excised circular virus DNA only appeared in females after a specific stage in pupal-adult development. The data also indicated that after excision of virus DNA the genomic DNA was rejoined. This has not yet been reported for any polydnavirus. Sequence analyses in the junction regions revealed the presence of an imperfect consensus sequence of 15 nucleotides in CiV12, in each terminus of the integrated virus DNA and in the rejoined genomic DNA. Within these repeats two sequence types (ATA, TAC) were observed in the various virus clones and in the clones encompassing the rejoined genomic DNA; they corresponded to the sequence type in the right and left junction, respectively. To explain this, we propose a model of virus DNA replication in which the genomic DNA is folded to juxtapose the direct repeat of the left with that of the right junction; recombination at specific sites would then yield the two types of virus and rejoined genomic DNA.

Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude.

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.