Johnson, Jacob

Objective To identify novel genes and pathways associated with acute mountain sickness (AMS). Background The uniform, rapid transfer of adults from McMurdo Station (sea level, SL) in Antarctica to the South Pole (SP, 2835m) provides a unique opportunity to study changes in gene expression related to the body's adaptation to hypobaric hypoxia. Methods Venous blood was drawn at SL and after 2 d at SP in 98 subjects (age 37±9 y, 70% male). Peripheral blood mononuclear cells (PBMCs) were isolated and microarray analysis of the mRNA isolated from these cells was performed (Affymetrix HG U133 Plus 2 microarray chip). Analysis and the computation of expression fold changes and phenotypic regression were performed using the Bioconductor package in R. Pathway analysis was performed using MetaCore™. Results ~3200 probe sets with sig. p‐values (p<0.05) and fold changes for each subject were used in a binary logistic regression with the presence or absence of AMS during the 2 d at altitude. Corresponding p‐values and z‐values were entered into MetaCore™ for pathways analysis. Identified pathways included smooth muscle contraction, calcium signaling, and acetylcholine regulation of nerve impulses. Conclusions Probe sets associated with the presence of AMS had a significant representation in pathways involving aspects of the autonomic nervous system including smooth muscle contraction and nerve signaling. NSF B‐179‐M.

Objective To identify novel genes that change expression in healthy adults exposed to hypobaric hypoxia. Background The uniform and rapid transfer of adults from McMurdo Station (sea level, SL) in Antarctica to the South Pole (2835m, SP) provides a unique opportunity to study the changes in gene expression related to the body's adaptation to high altitude. We hypothesized that a large number of genes would change expression and that many of these genes would be associated with inflammatory processes. Methods Peripheral venous blood was drawn at SL and after 2 d at SP in 98 subjects (age 37±9 y, 70% male). Peripheral blood mononuclear cells (PBMCs) were isolated and microarray analysis of the mRNA isolated from these cells was performed (Affymetrix HG U133 Plus 2 microarray chip). Analysis and the computation of expression fold changes was performed using the Bioconductor package in R. Pathway analysis was performed using MetaCore™. Results 1118 probe sets with significant p‐values (p<0.05) and fold changes were identified and entered into MetaCore™. Several pathways including oxidative phosphorylation, cytoskeletal remodeling, and platelet aggregation were identified as having significant representation in the restricted data set. Conclusion Several pathways indicating significantly increased activity in PBMCs were identified. This is indicative of an increased inflammatory response. NSF B‐179‐M.

Maximal expiratory flows (MEF) are dependent on gas density, lung volume, subject effort and airway characteristics. Variable changes in MEF occur after ascent to altitude which may represent an interaction between gas density changes, catecholamine stimulation and mild interstitial edema. Hypoxia induced catecholamine up‐regulation has also been associated with acute mountain sickness (AMS). This study examined the association between MEF variability and AMS symptoms in United States Antarctic Program personnel (n=198, age 37±1 yrs, 3% asthma) rapidly transported to the South Pole (SP, 9302 ft). Spirometric parameters, epinephrine (Epi), norepinepherine (NE) and SaO2 levels were recorded at sea level (SL, McMurdo Station) and after the 2 nd night at SP. AMS was assessed using Lake Louise questionnaires (score ≥ 3). FVC, FEV 1 , FEF 25 , FEF 75 and FEF 25–75 increased by 0, 3, 17, 10 and 14% from SL to SP, respectively. On day 2, AMS incidence was 31% and Epi and NE increased by 44 and 71%. Changes in MEF ranged from −64 to +93% in FEF 25–75 and −63 to +70% in FEF 75 . Subjects with the greatest increase in MEF had higher incidence of AMS (24 vs 41%) and higher NE levels, while the subjects with the greatest decrease in MEF had lower SaO2 values (88 vs 90%). Subjects with increased MEF had increased AMS and bronchodilation while subjects with decreased MEF displayed values consistent with mild interstitial edema.

AbstractThis study aimed to evaluate the influence of physical activity on incidence of acute mountain sickness (AMS) by continuous activity monitoring in a free-living sample of South Pole workers over the initial 72 h at altitude exposure of 2,840 m (9,318 ft). Body Media activity monitors were worn by 47 healthy participants. AMS was defined by the Lake Louise symptom questionnaire. Venous blood samples were taken at sea level and approximately 48 h after high altitude exposure. AMS incidence was 34% (n=16/47) over the first 48 h and 40% (n=19/47) over 72 h. On day 2 at high altitude, individuals with AMS demonstrated a significantly greater increase in the percent change in physical activity metrics from baseline: total energy expenditure 19±13 vs. 5±7%, total steps 65±51 vs. 10±18%, metabolic equivalent of tasks 21±13 vs. 7±13%, and time spent performing moderate to vigorous physical activity 114±79 vs. 26±27% for individuals with AMS vs. no AMS, respectively, p<0.05. In addition, erythropoietin and vascular endothelial growth factor were 1.69 and 1.75 times higher, respectively, in those with AMS. In conclusion, workers who engaged in increased physical activity and activity intensity during initial exposure to the South Pole were more susceptible to developing AMS.

Introduction Each year, the US Antarctic Program rapidly transports scientists and support personnel from sea level (SL) to the South Pole (SP, 2835 m) providing a unique natural laboratory to quantify the incidence of acute mountain sickness (AMS), patterns of altitude related symptoms and the field effectiveness of acetazolamide in a highly controlled setting. We hypothesized that the combination of rapid ascent (3 hr), accentuated hypobarism (relative to altitude), cold, and immediate exertion would increase altitude illness risk. Methods Medically screened adults (N = 246, age = 37 ± 11 yr, 30% female, BMI = 26 ± 4 kg/m 2 ) were recruited. All underwent SL and SP physiological evaluation, completed Lake Louise symptom questionnaires (LLSQ, to define AMS), and answered additional symptom related questions (eg, exertional dyspnea, mental status, cough, edema and general health), during the 1st week at altitude. Acetazolamide, while not mandatory, was used by 40% of participants. Results At SP, the barometric pressure resulted in physiological altitudes that approached 3400 m, while T ° C averaged -42, humidity 0.03%. Arterial oxygen saturation averaged 89% ± 3%. Overall, 52% developed LLSQ defined AMS. The most common symptoms reported were exertional dyspnea-(87%), sleeping difficulty-(74%), headache-(66%), fatigue-(65%), and dizziness/lightheadedness-(46%). Symptom severity peaked on days 1-2, yet in >20% exertional dyspnea, fatigue and sleep problems persisted through day 7. AMS incidence was similar between those using acetazolamide and those abstaining (51 vs. 52%, P = 0.87). Those who used acetazolamide tended to be older, have less altitude experience, worse symptoms on previous exposures, and less SP experience. Conclusion The incidence of AMS at SP tended to be higher than previously reports in other geographic locations at similar altitudes. Thus, the SP constitutes a more intense altitude exposure than might be expected considering physical altitude alone. Many symptoms persist, possibly due to extremely cold, arid conditions and the benefits of acetazolamide appeared negligible, though it may have prevented more severe symptoms in higher risk subjects.