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Muscle Fn14 gene expression is associated with fat-free mass retention during energy deficit at high altitude.
Pasiakos, SM, Berryman, CE, Carbone, JW, Murphy, NE, Carrigan, CT, Bamman, MM, Ferrando, AA, Young, AJ, Margolis, LM
Physiological reports. 2018;(14):e13801
Abstract
Intramuscular factors that modulate fat-free mass (FFM) loss in lowlanders exposed to energy deficit during high-altitude (HA) sojourns remain unclear. Muscle inflammation may contribute to FFM loss at HA by inducing atrophy and inhibiting myogenesis via the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible protein 14 (Fn14). To explore whether muscle inflammation modulates FFM loss reportedly developing during HA sojourns, muscle inflammation, myogenesis, and proteolysis were assessed in 16 men at sea level (SL) and following 21 days of energy deficit (-1862 ± 525 kcal/days) at high altitude (HA, 4300 m). Total body mass (TBM), FFM, and fat mass (FM) were assessed using DEXA. Gene expression and proteolytic enzymatic activities were assessed in muscle samples collected at rest at SL and HA. Participants lost 7.2 ± 1.8 kg TBM (P < 0.05); 43 ± 30% and 57 ± 30% of the TBM lost was FFM and FM, respectively. Fn14, TWEAK, TNF alpha-receptor (TNFα-R), TNFα, MYOGENIN, and paired box protein-7 (PAX7) were upregulated (P < 0.05) at HA compared to SL. Stepwise linear regression identified that Fn14 explained the highest percentage of variance in FFM loss (r2 = 0.511, P < 0.05). Dichotomization of volunteers into HIGH and LOW Fn14 gene expression indicated HIGH lost less FFM and more FM (28 ± 28% and 72 ± 28%, respectively) as a proportion of TBM loss than LOW (58 ± 26% and 42 ± 26%; P < 0.05) at HA. MYOGENIN gene expression was also greater for HIGH versus LOW (P < 0.05). These data suggest that heightened Fn14 gene expression is not catabolic and may protect FFM during HA sojourns.
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Association between body water status and acute mountain sickness.
Gatterer, H, Wille, M, Faulhaber, M, Lukaski, H, Melmer, A, Ebenbichler, C, Burtscher, M
PloS one. 2013;(8):e73185
Abstract
PURPOSE The present study determined the association between body fluid variation and the development of acute mountain sickness (AMS) in adults. METHODS Forty-three healthy participants (26 males and 17 females, age: 26 ± 6 yr, height: 174 ± 9 cm, weight: 68 ± 12 kg) were passively exposed at a FiO2 of 12.6% (simulated altitude hypoxia of 4500 m, PiO2 = 83.9 mmHg) for 12-h. AMS severity was assessed using the Lake Louise Score (LLS). Food and drink intakes were consumed ad libitum and measured; all urine was collected. Before and after the 12-h exposure, body weight and plasma osmolality were measured and whole-body bioimpedance analysis was performed. RESULTS The overall AMS incidence was 43% (38% males, 50% females). Participants who developed AMS showed lower fluid losses (3.0 ± 0.9 vs. 4.5 ± 2.0 ml/kg/h, p = 0.002), a higher fluid retention (1.9 ± 1.5 vs. 0.6 ± 0.8 ml/kg/h, p = 0.022), greater plasma osmolality decreases (-7 ± 7 vs. -2 ± 5 mOsm/kg, p = 0.028) and a larger plasma volume expansion (11 ± 10 vs. 1 ± 15%, p = 0.041) compared to participants not developing AMS. Net water balance (fluid intake--fluid loss) and the amount of fluid loss were strong predictors whether getting sick or not (Nagelkerkes r(2) = 0.532). The LLS score was related to net water balance (r = 0.358, p = 0.018), changes in plasma osmolality (r = -0.325, p = 0.033) and sodium concentration (r = -0.305, p = 0.047). Changes in the impedance vector length were related to weight changes (r = -0.550, p<0.001), fluid intake (r = -0.533, p<0.001) and net water balance (r = -0.590, p<0.001). CONCLUSIONS Participants developing AMS within 12 hours showed a positive net water balance due to low fluid loss. Thus measures to avoid excess fluid retention are likely to reduce AMS symptoms.
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Effects of acute hypobaric hypoxia on resting and postprandial superior mesenteric artery blood flow.
Loshbaugh, JE, Loeppky, JA, Greene, ER
High altitude medicine & biology. 2006;(1):47-53
Abstract
Reduced blood flow to the gut may contribute to weight loss and gastrointestinal symptoms of acute mountain sickness (AMS) at altitude. A study in humans tested the hypothesis that acute hypobaric hypoxia (ALT) would attenuate the normal postprandial hyperemia in the superior mesenteric artery (SM). Blood pressure, cardiac output (CO), and (SM) were measured with previously validated noninvasive Doppler ultrasonic flowmetry in 9 (3 women) healthy young adults (mean age: 23; range: 18-33 yr) residing at 1700 m. Baseline measurements were made after 2 h at ALT in a chamber at 430 mmHg (asymptotically equal to 4800 m = 15,750 ft) after 10-12-h fasting, and the next day the control (CON) measurements were made at 615 mmHg (1850 m). Postprandial measurements were made 45 to 60 min after ingesting a 1000-cal liquid meal under both conditions. At ALT, 5 of the 9 subjects had AMS by the Lake Louise score criteria of headache > or =1 and total score > or =3. ALT significantly reduced fasting, baseline SM relative to CON by 15%, and increased CO by 16%. The postprandial CO increase was not different between ALT and CON, but (SM) increased 115% at CON, but only 75% at ALT, the attenuation being significant (p < 0.006). Neither the diminution of fasting (SM) at ALT nor the attenuation of the postprandial increase in (SM) correlated significantly with AMS symptom scores. These results suggest that baseline and postprandial gut blood flow are altered during acute altitude exposure because of increased intestinal sympathetic tone, inferred from increased local resistance, and may be related to reduced energy intake if sustained during prolonged exposure.
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Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema.
Berger, MM, Hesse, C, Dehnert, C, Siedler, H, Kleinbongard, P, Bardenheuer, HJ, Kelm, M, Bärtsch, P, Haefeli, WE
American journal of respiratory and critical care medicine. 2005;(6):763-7
Abstract
RATIONALE High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung. OBJECTIVES We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature. METHODS During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects. MAIN RESULTS Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). CONCLUSIONS Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.
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Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT).
Gertsch, JH, Basnyat, B, Johnson, EW, Onopa, J, Holck, PS
BMJ (Clinical research ed.). 2004;(7443):797
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Abstract
OBJECTIVE To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness. DESIGN Prospective, double blind, randomised, placebo controlled trial. SETTING Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002. PARTICIPANTS 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent. MAIN OUTCOME MEASURES Incidence measured by Lake Louise acute mountain sickness score > or = 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores > or = 5), incidence of headache, and severity of headache. RESULTS Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70). CONCLUSIONS When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.
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Acute mountain sickness; prophylactic benefits of antioxidant vitamin supplementation at high altitude.
Bailey, DM, Davies, B
High altitude medicine & biology. 2001;(1):21-9
Abstract
Acute mountain sickness; prophylactic benefits of Free-radical-mediated damage to the blood-brain barrier may be implicated in the pathophysiology of acute mountain sickness (AMS). To indirectly examine this, we conducted a randomized double-blind placebo-controlled trial to assess the potentially prophylactic benefits of enteral antioxidant vitamin supplementation during ascent to high altitude. Eighteen subjects aged 35 +/- 10 years old were randomly assigned double-blind to either an antioxidant (n = 9) or placebo group (n = 9). The antioxidant group ingested 4 capsules/day(-1) (2 after breakfast/2 after evening meal) that each contained 250 mg of L-ascorbic acid, 100 IU of dl-a-tocopherol acetate and 150 mg of alpha-lipoic acid. The placebo group ingested 4 capsules of identical external appearance, taste, and smell. Supplementation was enforced for 3 weeks at sea level and during a 10-day ascent to Mt. Everest base camp (approximately 5,180 m). Antioxidant supplementation resulted in a comparatively lower Lake Louise AMS score at high altitude relative to the placebo group (2.8 +/- 0.8 points versus 4.0 +/- 0.4 points, P = 0.036), higher resting arterial oxygen saturation (89 +/- 5% versus 85 +/- 5%, P = 0.042), and total caloric intake (13.2 +/- 0.6 MJ/day(-1) versus 10.1 +/- 0.7 MJ/day(-1), P = 0.001); the latter is attributable to a lower satiety rating following a standardized meal. These findings indicate that the exogenous provision of water and lipid-soluble antioxidant vitamins at the prescribed doses is an apparently safe and potentially effective intervention that can attenuate AMS and improve the physiological profile of mountaineers at high altitude.
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Exercise exacerbates acute mountain sickness at simulated high altitude.
Roach, RC, Maes, D, Sandoval, D, Robergs, RA, Icenogle, M, Hinghofer-Szalkay, H, Lium, D, Loeppky, JA
Journal of applied physiology (Bethesda, Md. : 1985). 2000;(2):581-5
Abstract
We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, approximately 4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (VE), pulmonary function, arterial oxygen saturation (Sa(O(2))), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors.