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Item Effects of aerobic exercise training on diaphragm muscle metabolism in a rat model of Pulmonary Arterial Hypertension(Office of the Vice Chancellor for Research, 2014-04-11) Pittman, Angela DPulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance that leads to right ventricular (RV) overload and eventually RV failure and death. PAH is associated with diaphragm muscle dysfunction and increased work of breathing which contributes to the exercise intolerance that is hallmark in this patient population. Our lab and others have described a shift in substrate utilization toward non-oxidative (glycolytic) metabolism in the RV and skeletal muscle of PAH rodent models as well as in patients. This project will determine if ‘glycolytic shift’ also occurs in the diaphragm muscle which may contribute to exercise intolerance and dyspnea. Since regular aerobic exercise is well-known to promote adaptations enhancing oxidative metabolism in cardiac muscle and skeletal muscle of the extremities, this project will also investigate the impact of exercise training on diaphragm muscle metabolism. Diaphragm muscles were harvested upon completion of a 6 week, 4x/wk. treadmill training program that consisted of 60 min runs at a relative intensity of 50% of aerobic capacity (VO2max). Abundance of glucose transporter Glut-1, a marker of glycolytic metabolism, is being evaluated by Immunoflourescent (IF) staining at the cell membrane of diaphragm myocytes. We expect to find that PAH rats have greater abundance of diaphragm Glut-1 and that exercise training at least partially ameliorates this PAH-induced ‘glycolytic shift’.Item A prescribed walking regimen plus arginine supplementation improves function and quality of life for patients with pulmonary arterial hypertension: a pilot study(SAGE, 2017-12-04) Brown, Mary Beth; Kempf, Attie; Collins, Catherine M.; Long, Gary M.; Owens, Matthew; Gupta, Shikha; Hellman, Yaron; Wong, Vincent; Farber, Mark; Lahm, Tim; Physical Therapy, School of Health and Rehabilitation SciencesCurrent evidence suggests that exercise training is beneficial in pulmonary arterial hypertension (PAH). Unfortunately, the standard supervised, hospital-based programs limit patient accessibility to this important intervention. Our proof-of-concept study aimed to provide insight into the usefulness of a prescribed walking regimen along with arginine supplementation to improve outcomes for patients with PAH. Twelve PAH patients (all women) in New York Heart Association (NYHA) functional class (FC) II (n = 7) or III (n = 5) and in stable condition for ≥ 3 months were enrolled. Patients performed home- and fitness-center- based walking at 65–75% heart rate (HR) reserve for 45 min, six sessions/week for 12 weeks. Concomitant L-arginine supplementation (6000 mg/day) was provided to maximize beneficial endothelial training adaptations. Cardiopulmonary exercise testing, 6-min walk testing (6MWT), echocardiography, laboratory studies, and quality of life (QoL) survey (SF-36) were performed at baseline and 12 weeks. Eleven patients completed the study (72 session adherence rate = 96 ± 3%). Objective improvement was demonstrated by the 6MWT distance (increased by 40 ± 13 m, P = 0.01), VO2max (increased by 2 ± 0.7 mL/kg/min, P = 0.02), time-to-VO2max (increased by 2.5 ± 0.6 min, P = 0.001), VO2 at anaerobic threshold (increased by 1.3 ± 0.5 mL/kg/min, P = 0.04), HR recovery (reduced by 68 ± 23% in slope, P = 0.01), and SF-36 subscales of Physical Functioning and Energy/Fatigue (increased by 70 ± 34% and 74 ± 34%, respectively, P < 0.05). No adverse events occurred, and right ventricular function and brain natriuretic peptide levels remained stable, suggesting safety of the intervention. This proof-of-concept study indicates that a simple walking regimen with arginine supplementation is a safe and efficacious intervention for clinically stable PAH patients, with gains in objective function and QoL measures. Further investigation in a randomized controlled trial is warranted.