Lower vascular conductance responses to handgrip exercise are improved following acute antioxidant supplementation in young individuals with post-traumatic stress disorder.

Young individuals with post-traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23 ± 3 years), and 13 age- and sex-matched controls (CTRL) participated in the study. Exercise-induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6 kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P = 0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6 kg: P < 0.01) by blunting elevated exercise-induced MAP responses (3 kg: P = 0.01; 6 kg: P < 0.01). Lower VC responses during handgrip exercise were improved following AO supplementation in young individuals with PTSD. AO supplementation was associated with a blunting of exercise-induced MAP responses in individuals with PTSD displaying elevated MAP responses. This study revealed that young individuals with PTSD exhibit abnormal, peripherally mediated exercise responses that may be linked to a redox imbalance.

Visceral Adiposity, Inflammation, and Testosterone Predict Skeletal Muscle Mitochondrial Mass and Activity in Chronic Spinal Cord Injury.

BACKGROUND: Mitochondrial health is an important predictor of several health-related comorbidities including obesity, type 2 diabetes mellitus, and cardiovascular disease. In persons with spinal cord injury (SCI), mitochondrial health has been linked to several important body composition and metabolic parameters. However, the complex interplay of how mitochondrial health is affected has yet to be determined in this population. OBJECTIVE: In this study, we examined the contribution of visceral adiposity, inflammatory biomarkers, testosterone and circulating serum growth factors as predictors of mitochondrial health in persons with chronic SCI. PARTICIPANTS: Thirty-three individuals with chronic SCI (n = 27 Males, n = 6 Females, age: 40 ± 13.26 years, level of injury: C4-L1, BMI: 23 ± 5.57) participated in this cross-sectional study. METHODS: Visceral adipose tissue (VAT) was measured via magnetic resonance imaging (MRI). After an overnight fast, serum testosterone, inflammatory biomarkers [interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), c-reactive protein (CRP)], and anabolic growth factors [insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3)] were measured. Skeletal muscle biopsies were obtained from the vastus lateralis muscle to measure citrate synthase (CS) and Complex III activity. Regression analyses were used to examine predictors of mitochondrial mass and activity. RESULTS: CS activity was negatively associated with VAT (r 2 = 0.360, p < 0.001), CRP (r 2 = 0.168, p = 0.047), and positively associated with testosterone (r 2 = 0.145, p = 0.042). Complex III activity was negatively associated with VAT relative to total lean mass (VAT:TLM) (r 2 = 0.169, p = 0.033), trended for CRP (r 2 = 0.142, p = 0.069), and positively associated with testosterone (r 2 = 0.224, p = 0.010). Multiple regression showed CS activity was significantly associated with VAT + CRP (r 2 = 0.412, p = 0.008) and VAT + Testosterone (r 2 = 0.433, p = 0.001). Complex III activity was significantly associated with VAT relative to total trunk cross-sectional area (CSA) + CRP (VAT:total trunk CSA + CRP; r 2 = 0.286, p = 0.048) and VAT + Testosterone (r 2 = 0.277, p = 0.024). CONCLUSION: Increased visceral adiposity and associated inflammatory signaling (CRP) along with reduced testosterone levels predict mitochondrial dysfunction following SCI. Specifically, lower VATCSA and higher testosterone levels or lower VATCSA and lower CRP levels positively predict mitochondrial mass and enzyme activity in persons with chronic SCI. Future research should investigate the efficacy of diet, exercise, and potentially testosterone replacement therapy on enhancing mitochondrial health in chronic SCI. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier: [NCT02660073].

Influence of extracellular volume fraction on peak exercise oxygen pulse following thoracic radiotherapy.

BACKGROUND: Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventricle (LV) with an inability to augment exercise stroke volume (SV). The peak exercise oxygen pulse (O2Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O2Pulse following thoracic radiotherapy has not been explored. METHODS: Patients who underwent thoracic radiotherapy for chest malignancies with significant incidental heart dose (≥5 Gray (Gy), ≥10% heart) without a pre-cancer treatment history of HF underwent cardiopulmonary exercise testing to determine O2Pulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with O2Pulse normalized for age/gender/anthropometrics. RESULTS: Thirty patients (median [IQR] age 63 [57-67] years, 18 [60%] female, 2.0 [0.6-3.8] years post-radiotherapy) were included. The peak VO2 was 1376 [1057-1552] mL·min- 1, peak HR = 150 [122-164] bpm, resulting in an O2Pulse of 9.2 [7.5-10.7] mL/beat or 82 (66-96) % of predicted. The ECVF, LV ejection fraction, heart volume receiving ≥10 Gy, and NTproBNP were independently associated with %O2Pulse (P < .001). CONCLUSIONS: In patients with prior radiotherapy heart exposure, %-predicted O2Pulse is inversely associated markers of diffuse fibrosis (ECVF), ventricular wall stress (NTproBNP), radiotherapy heart dose, and positively related to LV function. Increased LV ECVF may reflect a potential etiology of impaired LV SV reserve in patients receiving thoracic radiotherapy for chest malignancies.

A Prior High-Intensity Exercise Bout Attenuates the Vascular Dysfunction Resulting From a Prolonged Sedentary Bout.

BACKGROUND: This study sought to determine the impact of an acute prior bout of high-intensity interval aerobic exercise on attenuating the vascular dysfunction associated with a prolonged sedentary bout. METHODS: Ten young (24 ± 1 y) healthy males completed two 3-hour sessions of prolonged sitting with (SIT-EX) and without (SIT) a high-intensity interval aerobic exercise session performed immediately prior. Prior to and 3 hours into the sitting bout, leg vascular function was assessed with the passive leg movement technique, and blood samples were obtained from the lower limb to evaluate changes in oxidative stress (malondialdehyde and superoxide dismutase) and inflammation (interleukin-6). RESULTS: No presitting differences in leg vascular function (assessed via passive leg movement technique-induced hyperemia) were revealed between conditions. After 3 hours of prolonged sitting, leg vascular function was significantly reduced in the SIT condition, but unchanged in the SIT-EX. Lower limb blood samples revealed no alterations in oxidative stress, antioxidant capacity, or inflammation in either condition. CONCLUSIONS: This study revealed that lower limb vascular dysfunction was significantly attenuated by an acute presitting bout of high-intensity interval aerobic exercise. Further analysis of lower limb blood samples revealed no changes in circulating oxidative stress or inflammation in either condition.

Accuracy and precision of quantitative 31P-MRS measurements of human skeletal muscle mitochondrial function.

Although theoretically sound, the accuracy and precision of (31)P-magnetic resonance spectroscopy ((31)P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control [linear, kinetic, and multipoint adenosine diphosphate (ADP) and phosphorylation potential], this study sought to determine the accuracy and precision of (31)P-MRS assessments of peak mitochondrial adenosine-triphosphate (ATP) synthesis rate utilizing directly measured peak respiration (State 3) in permeabilized skeletal muscle fibers. In 23 subjects of different fitness levels, (31)P-MRS during a 24-s maximal isometric knee extension and high-resolution respirometry in muscle fibers from the vastus lateralis was performed. Although significantly correlated with State 3 respiration (r = 0.72), both the linear (45 ± 13 mM/min) and phosphorylation potential (47 ± 16 mM/min) models grossly overestimated the calculated in vitro peak ATP synthesis rate (P < 0.05). Of the ADP models, the kinetic model was well correlated with State 3 respiration (r = 0.72, P < 0.05), but moderately overestimated ATP synthesis rate (P < 0.05), while the multipoint model, although being somewhat less well correlated with State 3 respiration (r = 0.55, P < 0.05), most accurately reflected peak ATP synthesis rate. Of note, the PCr recovery time constant (τ), a qualitative index of mitochondrial capacity, exhibited the strongest correlation with State 3 respiration (r = 0.80, P < 0.05). Therefore, this study reveals that each of the (31)P-MRS data analyses, including PCr τ, exhibit precision in terms of mitochondrial capacity. As only the multipoint ADP model did not overstimate the peak skeletal muscle mitochondrial ATP synthesis, the multipoint ADP model is the only quantitative approach to exhibit both accuracy and precision.

Effects of a fruit/berry/vegetable supplement on muscle function and oxidative stress.

PURPOSE: This study tested the effectiveness of a fruit, berry, and vegetable concentrate (FVC), Juice Plus+® (NSA LLC, Collierville, TN), supplement on muscle function and oxidative stress in response to an acute bout of eccentric exercise (EE). METHODS: Forty-one healthy volunteers (age = 18-35 yr) were randomly assigned to either a placebo (P) or an FVC treatment taking capsules for 28 d (6 d(-1)) before EE and for the next 4 d. All subjects completed four sets of 12 repetitions of eccentric elbow flexion with their nondominant arm. Blood, muscle soreness (MS), range of motion (ROM), and maximal isometric force (MIF) of the elbow flexors were obtained before and immediately after exercise and at 2, 6, 24, 48, and 72 h postexercise. Plasma was analyzed for creatine kinase (CK), lipid hydroperoxides, malondialdehyde (MDA), and protein carbonyls (PC). Glutathione ratio was determined from whole-blood extracts. RESULTS: MS, ROM, MIF, and plasma CK demonstrated significant time effects independent of treatment. MS and plasma CK increased over time, whereas ROM and MIF decreased over time. There was a significant time and time × treatment effect for plasma PC and MDA. PC and MDA increased over time in the P group (P < 0.01) but were not significantly altered in the FVC-treated group at any time. No significant changes were noted in lipid hydroperoxides. The glutathione ratio was elevated immediately postexercise in both groups (P < 0.01) and elevated 6 h postexercise with P compared with the FVC-treated group (P < 0.05). CONCLUSION: This study reports that 4 wk of pretreatment with an FVC can attenuate blood oxidative stress markers induced by EE but had no significant impact on the functional changes related to pain and muscle damage.