Evidence from a number of vertebrate taxa suggests that modifications of hemoglobin (Hb) function may often play a key role in mediating an adaptive response to high altitude hypoxia. The respiratory functions of Hb are a product of the protein's intrinsic O-2-binding affinity and its interactions with allosteric effectors such as protons, chloride ions, CO2, and organic phosphates. Here we review several case studies involving high altitude vertebrates where it has been possible to identify specific mechanisms of Hb adaptation to hypoxia. In addition to comparative studies of Hbs from diverse animal species, functional studies of human Hb mutants also suggest that there is ample scope for evolutionary adjustments in Hb-O-2 affinity through alterations of the equilibrium constants of O-2 binding to deoxy- and oxyHb or through changes in the allosteric equilibrium constants for the transition between the deoxy- and oxyHb quaternary structures. It may be the case that certain evolutionary paths are followed more often than others simply because they are subject to less stringent pleiotropic constraints.
Tissot van Patot, Martha C., Guy Leadbetter III, Linda E. Keyes, Kirsten M. Maakestad, Sheryl Olsen, and Peter Hackett. High Alt. Med. & Biol. 9: 289-293, 2008.-Previous studies have shown low-dose acetazolamide to be effective in preventing AMS in persons already at high altitude and then moving higher, a relatively low risk situation. We wished to evaluate prophylactic administration of low-dose acetazolamide for reducing the incidence and severity of AMS in a high-risk setting: rapid ascent from 1600 to 4300 m. We performed a double-blind, randomized, placebo-controlled study with human subjects (n = 44) exposed to 4300 m for 24 h. Subjects were treated for 3 days prior to ascent to 4300 m and during day 1 at altitude with placebo (n = 22) or acetazolamide 250 mg/day (125 mg bid, n = 22). AMS diagnosis required both an AMS-C score from the Environmental Symptom Questionnaire-III >= 0.7 and a Lake Louise Symptom (LLS) questionnaire score >= 3 plus headache. Acetazolamide reduced the incidence of AMS compared to placebo-treated subjects (14% vs. 45%, respectively, p = 0.02), and the number needed to treat was 3. The AMS- C and LLS scores were lower in acetazolamide-treated subjects, indicating less severe AMS. Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting.
Mizuno, Masao, Gabrielle K. Savard, Nils-Holger Areskog, Carsten Lundby, and Bengt Saltin. Skeletal Muscle Adaptations to Prolonged Exposure to Extreme Altitude: A Role of Physical Activity? High Alt. Med. Biol. 9: 311-317, 2008.-This study investigated skeletal muscle adaptations to high altitude and a possible role of physical activity levels. Biopsies were obtained from the m. quadriceps femoris ( vastus) and m. biceps brachii ( biceps) in 15 male subjects, 7 active and 8 less active. Samples were obtained at sea level and after 75 days altitude exposure at 5250 m or higher. The muscle fiber size decreased at an average of 15% in the vastus and biceps, respectively, and to the same extent in both groups. In both muscles, the mean number of capillaries was 2.1-2.2 cap. fiber(-1) before and after the exposure. As mean fiber area was reduced, the mean number of capillaries per unit area increased in all subjects ( from 320 to 405 cap/mm(2)) with no difference between the active and less active groups. The two enzymes selected to reflect mitochondrial capacity, citrate synthase ( CS) and 3-hydroxyl-CoA-dehydrogenase ( HAD), did not change in the leg muscles with altitude exposure, CS: 28.7 (20.7-37.8) vs. 27.8 (23.8-29.4); HAD: 35.2 (20.3-43.1) vs. 30.6 (20.7-39.7) mu mol. min(-1). g(-1) d.w, pre- and post-altitude, respectively. The muscle buffer capacity was elevated in both the vastus; 220 (194-240) vs. 232 (200-277) and the biceps muscles; 233 (190-301) vs. 253 (193-320) after the acclimatization period. In conclusion, mean fiber area was reduced in response to altitude exposure regardless of physical activity which in turn meant that with an unaltered capillary to fiber ratio there was an elevation in capillaries per unit of muscle area. Muscle enzyme activity was unaffected with altitude exposure in both groups, whereas muscle buffer capacity was increased.
Karinen, Heikki, Juha Peltonen, and Heikki Tikkanen. Prevalence of acute mountain sickness among Finnish trekkers on Mount Kilimanjaro, Tanzania: an observationl study. High Alt. Med. Biol. 9: 301-306, 2008.-The aim of this study was to evaluate the prevalence of acute mountain sickness (AMS) among trekkers on Mount Kilimanjaro during the winter season of 2006-2007. A A total of 130 Finnish trekkers at Marungu route were asked to complete daily a Lake Louise self-report and clinical assessment score questionnaire with the help of a trainee Finnish guide during their trek to Kilimanjaro. A Lake Louise questionnaire score >= 3 indicated AMS. Altogether 112 mountaineers or travelers [54 men, 58 women, mean age 51 +/- 10 (SD) years] were studied. Fifty-nine travelers (53%) reached Gillman's Point or Uhuru Peak. The incidence of AMS among Finnish Kilimanjaro trekkers was 75%. The most common high altitude symptoms were headache, followed by sleeping problems and fatigue or weakness. The incidence of AMS is high among trekkers climbing Mount Kilimanjaro. The main reason for this seems to be rapid ascent. Kilimanjaro treks normally have a fixed timetable, and for commercial reasons there is little opportunity to spend extra days for acclimatization in the camps. Some contributing factors are preventable, so we recommend an educational program for all the trekking agencies that guide on this peak and, in particular, the Tanzania-based guiding agencies, which, typically, are driving these very fast ascent rates.
Chronic mountain sickness (CMS) and high altitude pulmonary hypertension (HAPH) have been well described in different mountainous regions of the world as chronic high altitude (HA) diseases. This review briefly summarizes the available data from some genes known to be regulated by hypoxia-inducible factor 1 (HIF-1) and/or by hypoxia that have been studied in populations from these regions suffering from CMS and/or HAPH. Excessive erythrocytosis, caused by a lower oxygen saturation and hypoxic ventilatory response and/or ventilatory inefficiency, is the outstanding sign of CMS, and right ventricular enlargement, pulmonary hypertension, and remodeling of pulmonary arterioles are hallmarks of HAPH. Familial character and heritability studies have suggested that genetic factors could make a contribution to the pathogenesis of CMS and HAPH. Even though some alleles are more prevalent (G allele of eNOS polymorphism Glu298Asp in Sherpas and ACE I allele in HAPH Kyrgyz) or less prevalent (ACE D allele in HA Andeans) in the different high altitude populations, published data to date are insufficient for a rigorous test of any hypothesis regarding the implications of these gene polymorphims in CMS or HAPH.
The I-allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with performance benefits at high altitude (HA). In n = 142 young males and females of largely Quechua origins in Peru, we evaluated 3 specific hypotheses with regard to the HA benefits of the I-allele: (1) the I-allele is associated with higher arterial oxygen saturation (Sa(O2)) at HA, (2) the I-allele effect depends on the acclimatization state of the subjects, and (3) the putative I-allele effect on Sa(O2) is mediated by the isocapnic hypoxic ventilatory response (HVR, 1/min(-1)/%Sa(O2)(-1)). The subject participants comprised two different study groups including BLA subjects (born at low altitude) who were lifelong sea-level residents transiently exposed to hypobaric hypoxia (<24 h) and BHA subjects (born at HA) who were lifelong residents of HA. To control for the possibility of population stratification, Native American ancestry proportion (NAAP) was estimated as a covariate for each individual using a panel of 70 ancestry-informative molecular markers (AIMS). At HA, resting and exercise Sa(O2) was strongly associated with the ACE genotype, p = 0.008 with similar to 4% of the total variance in Sa(O2) attributed to ACE genotype. Moreover, I/I individuals maintained similar to 2.3 percentage point higher Sa(O2) compared to I/D and D/D. This I-allele effect was evident in both BLA and BHA groups, suggesting that acclimatization state has little influence on the phenotypic expression of the ACE gene. Finally, ACE genotype was not associated with the isocapnic HVR, although HVR had a strong independent effect on Sa(O2) (p = 0.001). This suggests that the I-allele effect on Sa(O2) is not mediated by the peripheral control of breathing, but rather by some other central cardiopulmonary effect of the ACE gene on the renin-angiotensin-aldosterone system (RAAS).
Bengt, Kayser, Ronald Hulsebosch, and Frank Bosch. Low-dose acetylsalicylic acid analog and acetazolamide for prevention of acute mountain sickness. High Alt. Med. Biol. 9:15-–23, 2008.-—Analgesic drugs like acetylsalicylic acid, paracetamol, and ibuprofen are frequently used by subjects suffering from headache of acute mountain sickness (AMS). It is not clear if the effect is due to analgesia or prevention of AMS. We performed a randomized controlled clinical trial comparing a low dose of an acetylsalicylic acid analog, calcium carbasalate (380 mg /day), to placebo in a cohort of altitude-naïïve subjects attempting a fast climb of Mt. Kilimanjaro (5896 m). A third noncontrolled open arm was proposed-—the usual recommended preventive treatment of acetazolamide 500 mg/day. Of 93 potential participants, 44 chose prevention with acetazolamide, 18 refused participation, 15 received calcium carbasalate, and 16 received placebo. Mean age was 39 ±± 9 (SD) yr and 15%% were female. AMS was quantified by the Lake Louise Symptom Score and physician assessment. Calcium carbasalate at 380 mg/day did not have any preventive effect on AMS and did not have any effect on the prevalence and intensity of headache. Event rate of AMS in the pooled carbasalate placebo group was 84%% and 55%% in the acetazolamide group. The number needed to treat (NNT) at 500 mg/day of acetazolamide was 3. One subject on acetazolamide developed high altitude cerebral edema and was treated with dexamethasone, oxygen, and descent by evacuation. In conclusion, low-dose calcium carbasalate is not effective for prevention of AMS. In addition, these results corroborate the contention that in typical steep climbing profile settings, such as used by commercial enterprise on Mt. Kilimanjaro, acetazolamide 500 mg/day may not be sufficient to prevent AMS or to sufficiently reduce symptom intensity in almost half of subjects.
Long-term exposure of humans and many mammals to hypoxia leads to the activation of several cellular mechanisms within skeletal muscles that compensate for a limited availability of cellular oxygen. One of these cellular mechanisms is to increase the expression of a subset of hypoxia-inducible genes, including the expression of vascular endothelial growth factor (VEGF). The VEGF promoter contains a hypoxic response element (HRE) that can bind the transcription factor, hypoxia-inducible factor-1 alpha; (HIF-1 alpha), and initiate transcriptional activation of the VEGF gene. VEGF gene expression is critically important for skeletal muscle angiogenesis and VEGF gene deletion in the mouse has been shown to greatly reduce skeletal muscle capillarity. However, HIF-1 alpha-dependent transcriptional activation of the VEGF gene may not be the only signaling pathway that leads to increased or maintained VEGF levels under conditions of acute or long-term hypoxia. Additional mechanisms, induced during hypoxic exposure that could signal skeletal muscle VEGF activation include inflammation, possibly linked to reactive O-2 species generation, or a change in cellular energy status as reflected by AMP kinase activity. These pathways may provide quite different mechanisms for VEGF upregulation in the context of muscular activity during long-term exposure to a hypoxic environment such as occurs at high altitude. This review will accordingly discuss the potential cellular signals or stimuli resulting from hypoxic exposure that could increase myocyte VEGF expression. These cellular signals include 1) a decrease in intracellular P-O2, 2) skeletal muscle inflammation, associated cytokines and oxidative stress, and 3) an increase in AMP kinase activity and adenosine accompanying a reduction in cellular energy potential.
McIntosh, Scott E., Aaron D. Campbell, Jennifer Dow, and Colin K. Grissom. Mountaineering fatalities on Denali. High Alt. Med. Biol. 9:89-–95, 2008.-—Mount McKinley, or Denali, is the tallest mountain in North America and attracts over 1000 climbers annually from around the world. Since Denali is located within a national park, the National Park Service (NPS) manages mountaineering activities and attempts to maintain a balance of an adventurous experience while promoting safety. We retrospectively reviewed the fatalities on Denali from 1903 to 2006 to assist the NPS, medical personnel, and mountaineers improve safety and reduce fatalities on the mountain. Historical records and the NPS climber database were reviewed. Demographics, mechanisms, and circumstances surrounding each fatality were examined. Fatality rates and odds ratios for country of origin were calculated. From 1903 through the end of the 2006 climbing season, 96 individuals died on Denali. The fatality rate is declining and is 3.08/1000 summit attempts. Of the 96 deaths, 92%% were male, 51%% occurred on the West Buttress route, and 45%% were due to injuries sustained from falls. Sixty-one percent occurred on the descent and the largest number of deaths in 1 year occurred in 1992. Climbers from Asia had the highest odds of dying on the mountain. Fatalities were decreased by 53%% after a NPS registration system was established in 1995. Although mountaineering remains a high-risk activity, safety on Denali is improving. Certain groups have a significantly higher chance of dying. Registration systems and screening methods provide ways to target at-risk groups and improve safety on high altitude mountains such as Denali.
Shrivastava, Kalpana, M. Sai Ram, Anju Bansal, S. S. Singh, and G. Ilavazhagan. Cobalt supplementation promotes hypoxic tolerance and facilitates acclimatization to hypoxia in rat brain. High Alt. Med. Biol. 9:63-–75, 2008.-—In the present study, we report the molecular mechanisms of action by cobalt in facilitating acclimatization to hypobaric hypoxia using male Sprague Dawley rats as the model system. We determined hypoxic gasping time and survival time as a measure to assess the degree of tolerance of animals to hypobaric hypoxia by exposing the animals to an altitude of 10,668 m. Oral administration of cobalt chloride (12.5 mg Co/kg body weight, BW, for 7 days) increased gasping time and hypoxic survival time by 3 to 4 times compared to the control animals. This could be attributed to an increased expression and the DNA binding activity of hypoxia inducible transcriptional factor (HIF-1αα) and its regulated genes, that is, erythropoietin (EPO), vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), and nitric oxide synthase (NOS) levels. This in turn leads to better oxygenation, oxygen delivery, glucose transport, and maintenance of vascular tone, respectively, under oxygen-limited conditions. This was further confirmed by lower levels of lactate dehydrogenase (LDH) activity and lactate in the brain of cobalt ++ hypoxia group compared with animals exposed to hypoxia. Glucose levels also increased after cobalt supplementation. The findings of the study provide a basis for the possible use of cobalt for facilitating acclimatization to hypoxia and other conditions involving oxygen deprivation.
There are numerous publications on altitude-related diseases in adults. In addition, an International Consensus Statement published in 2001 deals with altitude-related illnesses occurring in lowland children who travel to high altitudes. However, despite the millions of children living permanently at high altitudes around the world, there are few publications on altitude-related diseases and pulmonary hemodynamics in this pediatric population. In this paper, we review the published literature on this subject. First, the pulmonary hemodynamics of healthy children (newborns, infants, children, and adolescents) residing at altitudes above 4000 m are summarized. Asymptomatic pulmonary hypertension, which slowly declines with increasing age, is found in these children. This is followed by a discussion of the functional closure of ductus arteriosus, which is delayed at high altitude. Then, the high prevalence of patent ductus arteriosus (PDA) in highland children and the pulmonary hemodynamics in these patients are described. Next, the pulmonary hemodynamics in highland children who suffer high altitude pulmonary edema (HAPE) after a short stay at lower levels is discussed, and the possible reasons for susceptibility to reentry HAPE in this pediatric population are postulated. The pulmonary hemodynamics in children with subacute mountain sickness (SMS) are then described. Moderate to severe pulmonary hypertension is a common finding in all these altitude-related diseases. Finally, the management of these clinical conditions is outlined.
In this randomized, double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema (HAPE) in trekkers traveling between 4250 m (Pheriche)\4350 m (Dingboche) and 5000 m (Lobuje) in Nepal; to determine if acetazolamide decreases pulmonary artery systolic pressures (PASP) at high altitude; and to determine if there is an association with PASP and signs and symptoms of HAPE. Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje. The Lake Louise Consensus Criteria were used for the diagnosis of HAPE, and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP. Complete measurements were performed on 339 of the 364 subjects (164 in the placebo group, 175 in the acetazolamide group). No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups. Mean PASP values did not differ significantly between the acetazolamide and placebo groups (31.3 and 32.6 mmHg, respectively). An increasing number of signs and symptoms of HAPE was associated with elevated PASP (p < 0.01). The efficacy of acetazolamide against acute mountain sickness, however, was significant with a 21.9% incidence in the placebo group compared to 10.2% in the acetazolamide group (p < 0.01). Given the lack of cases of HAPE in either group, we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE, but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 m.
Loeppky, Jack A., Milton V. Icenogle, Gerald A. Charlton, Carole A. Conn, Damon Maes, Katrina Riboni, Lee Gates, Marcos F. Vidal Melo, and Robert A. Roach. Hypoxia and AMS: which comes first? High Alt. Med. Biol. 9: 271-279, 2008.-Hypoxemia is usually associated with acute mountain sickness ( AMS), but most studies have varied in time and magnitude of altitude exposure, exercise, diet, environmental conditions, and severity of pulmonary edema. We wished to determine whether hypoxemia occurred early in subjects who developed subsequent AMS while resting at a simulated altitude of 426 mmHg (approximate to 16,000 ft or 4880 m). Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of 16 subjects having the lowest AMS scores (nonAMS: mean LL = 1.0, range = 0-2.5) were compared with the 16 having the highest scores (+ AMS: mean LL = 7.4, range = 5-11). Total and alveolar ventilation responses to altitude were not different between groups. + AMS had significantly lower PaO2 (4.6 mmHg) and SaO(2) (4.8%) at A1 and 3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and A12 reduced vital capacity ( VC) and increased breathing frequency suggested interstitial pulmonary edema in + AMS. The early hypoxemia in + AMS appears to be the result of diffusion impairment or venous admixture, perhaps due to a unique autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful to predict AMS susceptibility.
The goal of this review is to highlight the underlying genetics that may explain complex traits associated with high altitude adaptation. The review covers the traditional candidate gene approach for identifying molecular variants having a functional role and associating with high altitude adaptation and disorders. We review some of the salient features of these candidate genes, debating their potential role in high altitude fitness. The advancement in high-throughput techniques in molecular genetics and the availability of large-scale catalogs of genetic variation in the public domain have provided a better platform for genome-wide scans for identifying genetic components for many traits. Current techniques such as whole-genome scans, admixture mapping using powerful tag SNPs, and the vast data available from human genome sequencing and the HapMap project may aid in a comprehensive understanding of genomic patterns of high altitude adaptation as well as disease-related research.
Shatilo, Valeriy B., Oleg V. Korkushko, Vadim A. Ischuk, H. Fred Downey, and Tatiana V. Serebrovskaya. Effects of intermittent hypoxia training on exercise performance, hemodynamics, and ventilation in healthy senior men. High Alt. Med. Biol. 9:43-–52, 2008.-—The efficacy and safety of intermittent hypoxia training (IHT) were investigated in healthy, 60- to 74-yr-old men. Fourteen men (Gr 1) who routinely exercised daily for 20 to 30 min were compared with 21 (Gr 2) who avoided exercise. Their submaximal work-load power values before the IHT training were 94 ±± 3.7 and 66 ±± 3.1, respectively. Before and after 10 days of IHT, the ventilatory response to sustained hypoxia (SH; 12%% O 2 for 10 min), work capacity (bicycle ergometer), and forearm cutaneous perfusion (laser Doppler) were determined. During SH, no negative electrocardiogram (ECG) changes were observed in either group, and the ventilatory response to SH was unaltered by IHT. In Gr 1, IHT (normobaric rebreathing for 5 min, final Sa O 2 == 85%% to 86%%, followed by 5 min normoxia, 4/day) produced no changes in hemodynamic indixes and work capacity. In Gr 2, IHT decreased blood pressure (BP) by 7.9 ±± 3.1 mmHg ( p < 0.05) and increased submaximal work by 11.3%% ( p < 0.05) and anaerobic threshold by 12.7%% ( p < 0.05). The increase in HR and BP caused by a 55 W-work load was reduced by 5%% and 6.5%%, respectively ( p < 0.05). Cutaneous perfusion increased by 0.06 ±± 0.04 mL/min/100 g in Gr 1 and by 0.11 ±± 0.04 mL/min/100 g in Gr 2 ( p < 0.05). Hyperemia recovery time increased significantly by 15.3 ±± 4.6 sec in Gr 1 and by 25.2 ±± 11.2 sec in Gr 2. Thus, healthy senior men well tolerate IHT as performed in this investigation. In untrained, healthy senior men, IHT had greater positive effects on hemodynamics, microvascular endothelial function, and work capacity.
Gupta, Noopur, Indira Prasad, G. Himashree, and Pamela D'Souza. Prevalence of dry eye at high altitude: a case controlled comparative study. High Alt. Med. Biol. 9: 327-333, 2008.-High altitude is associated with physiological as well as pathological changes in the eye related to adverse environmental conditions that result in increased tear evaporation and contribute to a higher incidence of dry eye in these regions. We aimed to study the difference in prevalence of dry eye at high altitude and at low altitude. The prevalence of dry eye among the natives and the army soldiers who were recently posted at high altitude was also studied and compared. 200 adults above 20 years of age were enrolled. 100 subjects were recruited at a high altitude region (study group), of which 50 were native Ladakhis and 50 were soldiers recently posted at Leh, Ladakh, India (height; 3300 m above sea level; temperature: 18 degrees C to 24 degrees C). 100 subjects, age and sex matched, were screened at a low altitude region, New Delhi, India (218 m above sea level; temperature: 19 degrees C to 24 degrees C) to serve as the control group. Prevalence of dry eye was assessed through standard questionnaires (McMonnies' Questionnaire (MMI), Ocular Surface Disease Index Questionnaire (OSDI), and Schirmer's basic secretion test. On the basis of the parameters studied (symptoms, MMI, OSDI and Schirmer's test), dry eye was diagnosed in 20% of subjects screened at high altitude and in 9% of subjects in the control group screened at low altitude. In the study group, the prevalence of dry eye was significantly higher amongst the native population (54%) than in the army soldiers who were recently posted at that region (26%). The difference was statistically significant (p < 0.005). In conclusion, dry eye is more common at high altitude, particularly in the native population. Awareness among people residing at high altitude and the treating medical personnel needs to be created for early detection and treatment of dry eye to prevent vision-threatening complications.
The efficacy and safety of intermittent hypoxia training (IHT) were investigated in healthy, 60- to 74-yr-old men. Fourteen men (Gr 1) who routinely exercised daily for 20 to 30 min were compared with 21 (Gr 2) who avoided exercise. Their sub maximal work-load power values before the IHT training were 94 +/- 3.7 and 66 +/- 3.1, respectively. Before and after 10 days of IHT, the ventilatory response to sustained hypoxia (SH; 12% O-2 for 10 min), work capacity (bicycle ergometer), and forearm cutaneous perfusion (laser Doppler) were determined. During SH, no negative electrocardiogram (ECG) changes were observed in either group, and the ventilatory response to SH was unaltered by IHT. In Gr 1, IHT (normobaric rebreathing for 5 min, final SaO(2) = 85% to 86%, followed by 5 min normoxia, 4/day) produced no changes in hemodynamic indixes and work capacity. In Gr 2, IHT decreased blood pressure (BP) by 7.9 +/- 3.1 mmHg (p < 0.05) and increased submaximal work by 11.3% (p < 0.05) and anaerobic threshold by 12.7% (p < 0.05). The increase in HR and BP caused by a 55 W-work load was reduced by 5% and 6.5%, respectively (p < 0.05). Cutaneous perfusion increased by 0.06 +/- 0.04 mL/min/100 g in Gr I and by 0.11 +/- 0.04 mL/min/100 g in Gr 2 (p < 0.05). Hyperemia recovery time increased significantly by 15.3 +/- 4.6 sec in Gr 1 and by 25.2 +/- 11.2 sec in Gr 2. Thus, healthy senior men well tolerate IHT as performed in this investigation. In untrained, healthy senior men, IHT had greater positive effects on hemodynamics, microvascular endothelial function, and work capacity.
Wilson, Mark H., Mark Edsell, Chris Imray, Alex Wright, and the Birmingham Medical Research Expeditionary Society. Changes in pupil dynamics at high altitude-an observational study using a handheld pupillometer. High Alt. Med. Biol. 9: 319-325, 2008. Gross pupil dynamics are used as an indirect measure of brain function. Changes in hypoxia and intracranial pressure are thought to alter pupil responses to light. This study assessed a portable handheld pupil measuring device ( pupillometer) in the field investigating the changes in pupil size, speed of reaction, and rate of constriction/dilatation with hypoxia induced by changes in altitude. A correlation between pupil dynamics and acute mountain sickness was sought. Seventeen volunteers were studied following acute exposure to 3450 m and then during a trek to 4770 m in Ladakh, India. The pupillometer was used to record maximum and minimum pupil diameter in response to a standard light source with calculation of latency, constriction and dilatation velocities. Acute mountain sickness (AMS) was recorded using Lake Louise self completed questionnaires both in the morning and afternoon on each day. Acute altitude exposure resulted in a significant reduction of percentage change in pupil size (36.5% to 24.1% p = <0.001), significant delay in pupillary contraction ( latency; 0.208 to 0.223 seconds p = 0.015) and a significant slowing of the rate of contraction (constriction velocity; -2.77 mm/s to -1.75 mm/s p = 0.012). These changes reverted to normal during a period of acclimatization. A significant diurnal variation in pupil size was also observed. There was no significant difference between subjects with and without AMS. The handheld pupillometer is a suitable robust tool for monitoring changes in pupil dynamics in the field. With acute exposure to hypobaric hypoxia associated with an ascent to a moderate altitude, there is a general slowing of pupil function which reverts to normal within a few days of acclimatization. There appears to be a marked diurnal variation in pupil size. The measurements clearly demonstrated an effect of hypoxia on cerebral function, but these changes did not relate to moderate AMS.
Toshner, Mark R., A. A. Roger Thompson, John B. Irving, J. Kenneth Bailie, J. J. Morton, and Andrew J. Peacock. NT-proBNP does not rise on acute ascent to high altitude. High Alt. Med. & Biology 9: 307-310, 2008.-The response of brain natriuretic peptide (BNP) to acute ascent to altitude is of interest as a surrogate for ventricular function and because BNP is involved in the normal homeostasis of the pulmonary vasculature. The structurally related hormone atrial natriuretic pressure (ANP) has been demonstrated to be elevated at altitude and implicated in natriuresis. We measured plasma concentrations of ANP and NT-proBNP (a more stable BNP precursor) in 10 healthy non-HAPE-susceptible lowlanders during acute exposure to 5200 m on the Apex 2 expedition to Bolivia. Systolic pulmonary artery pressure (PASP) was measured using tricuspid regurgitant jet estimation by echocardiography. Despite a significant rise in the PASP, NT-proBNP did not rise. A small decrease in NT-pro BNP occurred after 7 days at high altitude. There was no significant change in ANP levels. The lack of any increase in NT-proBNP in healthy resting subjects supports the view that ventricular function is well preserved and suggests that BNP is not playing a significant role in altered pulmonary artery pressure.
Yaron, Michael, and Susan Niermeyer. Travel to high altitude with young children: An approach for clinicians. High Alt. Med. Biol. 9: 265-269, 2008. - As more families travel to mountainous destinations, clinicians are frequently asked for advice regarding children at altitude. We briefly review the principles of altitude illness in children, offer a management plan for the clinician, and highlight the gaps in current evidence. Planning for ascent, altitude illness management, and diagnostic follow-up are discussed.