Shea, Meredith G.

Many individuals travel to high altitude each year. Acclimatization to altitude occurs over the course of several days as the body adequately adapts to function in an environment with reduced partial pressure of oxygen. However, with a faster accent to attitude, comes an increased potential for maladaptations to occur, leading to the development of acute mountain sickness (AMS). Each year scientists and support workers are transported by plane from McMurdo Station in Antarctica (sea level) to the Amundsen‐Scott South Pole Station (2835m). This uniform and rapid deployment to altitude provides a unique opportunity to study the effects of hypobaric hypoxia on gene expression, which may help to illustrate the body’s ability to acclimatize to these environmental conditions. Purpose To detect pathway specific gene expression changes associated with the development of AMS and help identify potential targets that may aid in the prediction of risk in the development of AMS symptoms due to rapid exposure to high altitude. Methods Venous blood samples were collected from 53 (height 176.65±8.91cm, weight: 80.49±14.36kg) healthy subjects (38 (27 males; 11 females) that did not develop AMS and 15 (10 males; 5 females) that did develop AMS, as defined by the Lake Louis symptom questionnaire, collected at 2 different time points, with the first being at sea level and the second being after 48hr of altitude exposure). Microarray analysis was performed on the peripheral blood mononuclear cells (PBMCs) from the collected samples, and a logistic regression was performed to determine probe set association with AMS. Results There was a total of 178 significant (p<0.05) probe sets, with 156 of the probe sets being associated with AMS and 22 of the probe sets being associated with no AMS. The probe sets were entered into the Reactome Pathway Database (reactome.org). Pathways identified in association with AMS involved immune system pathways (interleukin signaling) and cellular responses to stimuli pathways (oxidative stress induced senescence signaling), and gene transcription pathways (mitochondrial biogenesis signaling, differentiation of hematopoietic stem cells). Interestingly, pathways identified in association with no development of AMS involved cell cycling pathways (mitotic signaling), chromatin organization pathways (chromatin modifying enzymes), metabolism pathways (utilization of ketone bodies) and the circadian clock pathway (circadian gene expression signaling). Conclusion These findings indicate potential maladaptive responses within the immune system and mitochondrial function, may play a key role in why some individuals develop AMS symptoms. An individual’s ability to sufficiently utilize different metabolic fuel sources and adapt their circadian rhythm may also prevent the development of AMS symptoms.

Introduction: Heart failure (HF) is associated with limited blood flow reserve due to reduced cardiac output (Q). HF is also associated with generalized respiratory muscle weakness, despite patients being exposed to an increased work and cost of breathing due primarily to increased flow resistive work from an altered breathing pattern. We hypothesized that the use of a respiratory training device during aerobic exercise training would positively impact patients with HF by training the inspiratory muscles and modifying their respiratory response to exercise. Methods: 15 subjects completed all study visits (age 67.5±10.0 yr, Ht 179.3±6.1cm, BMI 28.8±5.7 m/cm 2 ). Patients diagnosed with HF and currently enrolled in cardiac rehabilitation (CR) completed the Minnesota living with heart failure questionnaire (MLHFQ), pulmonary function testing, and measures during exercise that included Q (soluble gas method), ventilation (V E ) and respiratory gas exchange. Measures were made at baseline and after completion of CR. Participants were randomized to no respiratory resistance (NR) or mild-moderate inspiratory resistance (MR, 15 to 20 cmH 2 O) provided by a respiratory resistance mask (Training Mask Co., Cadillac, MI) worn during aerobic portions of CR. Results: Participants completed on average 23.9 ± 2.5 CR sessions with 10 subjects in the MR group and 5 in the NR group. The MR group had a decrease on the MLHFQ score of 19.9±26.9 and the NR group had a decrease of 6.0±23.4 (p=0.330). At a matched workload of 30 Watts (W), V E declined by 4.0±7.0 L/min and increased by 2.2±13.1 L/min for subjects in the MR and NR groups, respectively (p=0.06). Respiratory rate (RR) decreased in MR by 1.2± 4.9 and decreased in NR by 0.67± 5.9 (p>0.05). Heart rate at 30W decreased with time in both the MR and NR groups 10.4±12.4 and 3.9±8.9 respectively (p=0.036, no difference between groups). Stroke volume at 30W tended to increase for both MR and NR (p>0.05, no difference between groups). Conclusion: The addition of moderate inspiratory resistance to the aerobic training during CR was well tolerated by HF patients and preliminarily suggests trends toward improved ventilatory responses when assessed during submaximal exercise.