Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

Changes in cardiorespiratory function and fatigue following 12 weeks of exercise training in women with systemic lupus erythematosus: a pilot study.

OBJECTIVE: In patients with systemic lupus erythematosus (SLE), fatigue is a debilitating symptom with poorly understood pathophysiology. Cardiorespiratory dysfunction has been hypothesised as a contributor to SLE-fatigue. The purpose of this exploratory study was to examine changes in cardiorespiratory function, following an exercise training programme in women with SLE, together with patient reported outcomes and other pathophysiological measures that may underlie SLE-fatigue. METHODS: Sixteen women with SLE and fatigue (Fatigue Severity Scale (FSS) ≥3) were enrolled in a supervised aerobic exercise training programme of vigorous intensity. The primary outcome was time to reach anaerobic threshold (AT-Time) during a cardiopulmonary exercise test (CPET). Secondary outcomes included changes in the 10-minute walk test (10MWT), FSS scores and the Patient Reported Outcomes Measurement Information System (PROMIS-57) survey. Mitochondrial function was assessed by the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) metabolic potential ratio. RESULTS: Following 12 weeks of exercise training, AT-Time increased by 93±82 (mean±SD) s (p<0.001), 10MWT increased by 84±66 m (p<0.001) and peak oxygen uptake (VO2) increased by 1.4±2.0 mL/kg/min (p=0.013). There were improvements in FSS score (-1.4±1.0, p<0.0001) and in most of the PROMIS-57 domains. The decrease in FSS scores correlated with an increase in the OCR/ECAR ratio (Pearson's correlation r=-0.59, p=0.03). A subset of subjects (9/15) had significant reduction in their Interferon Stimulated Genes (ISG) (p=0.007) accompanied by a significant increase in the OCR/ECAR ratio (p=0.013). CONCLUSIONS: Cardiorespiratory function was improved in concomitance with reductions in fatigue following a 12-week aerobic exercise programme. The reduction in fatigue scores correlated with improvements in mitochondrial function.

EMG median frequency shifts without change in muscle oxygenation following novel locomotor training in individuals with incomplete spinal cord injury.

OBJECTIVES: To examine the effect of muscle fiber recruitment patterns on muscle oxygen utilization during treadmill walking in a group of individuals who have incomplete spinal cord injury. METHODS: 5 participants with motor incomplete spinal cord injury (Age; 42.2 ± 18.8 years, Male; n = 4) completed an over ground locomotor training program. Muscle utilization/oxygenation and activation of the medial gastrocnemius were measured by near infrared spectroscopy and surface electromyography pre- and post-over ground locomotor training during two separate treadmill walking bouts at self-selected speeds. Outcomes were changes in deoxygenation hemoglobin/myoglobin concentrations, and the change in median power of the power spectrum of the electromyography after training. RESULTS: A significant increase in median power of the power spectrum of the electromyography signal was observed during both bouts of treadmill walking, 6-minute walking bout and longer fatiguing bout (49% p = 0.047 and 48% p = 0.035, respectively) post-over ground locomotor training. There was no significant change in muscle utilization/oxygenation post-over ground locomotor training. There was no significant effect of median power of the power spectrum on deoxygenation hemoglobin/myoglobin during either of the walking bouts. CONCLUSIONS: The main finding of the current study was that median power of the power spectrum significantly increased following 12 weeks of over ground locomotor training, with no significant change in deoxygenation hemoglobin/myoglobin. The recruitment of more and/or larger motor units was seen in conjunction with no changes in muscle oxygen utilization for the same walking task.Implications for RehabilitationThe reduction of skeletal muscle innervation in Spinal Cord Injury may adversely affect the orderly recruitment of motor units, which could in turn blunt the oxidative metabolic response during physical activity.Over-ground locomotor could be a useful tool in the rehabilitative process following an incomplete spinal cord injury.

Walking endurance, muscle oxygen extraction, and perceived fatigability after overground locomotor training in incomplete spinal cord injury: A pilot study.

Objective: The purpose of this study was to examine the effects of overground locomotor training (OLT) on walking endurance and gastrocnemius oxygen extraction in people with chronic cervical motor-incomplete spinal cord injury (SCI).Design: Prospective single-arm pre-post pilot study.Setting: Human Performance Research Laboratory.Participants: Adult men with traumatic chronic cervical SCI (n = 6; age = 30.8 ± 12.5).Intervention: Twenty-four sessions of structured OLT.Outcome measures: Walking endurance was determined during a constant work-rate time-to-exhaustion treadmill test. Normalized perceived fatigability was calculated by dividing subjective ratings of tiredness by walking time. Cardiorespiratory outcomes and muscle oxygen extraction were analyzed using breath-by-breath gas-exchange and near-infrared spectroscopy.Results: OLT resulted in large effects on walking endurance (1232 ± 446 s vs 1645 ± 255 s; d = 1.1; P = 0.045) and normalized perceived fatigability (5.3 ± 1.5 a.u. vs 3.6 ± 0.9 a.u.; d = 1.3; P = 0.033). Small-to-medium effects on absolute (2.8 ± 2.5 a.u. vs 4.2 ± 3.5 a.u.; d = 0.42; P = 0.035) and isotime (2.8 ± 2.5 a.u. vs 3.8 ± 3.0 a.u.; d = 0.33; P = 0.023) muscle oxygen extraction were also observed after OLT.Conclusion: These findings provide preliminary data supporting the potential for improved walking endurance, enhanced muscle O2 extraction, and reduced perceived fatigability in people with chronic cervical motor-incomplete SCI following the OLT program described in this study.

Carbon Dioxide Expiration and Performance Fatigability Following Aerobic Exercise Training: A Longitudinal, Observational, Pilot Study.

Purpose: This study examined the influence of aerobic exercise training (AET) on components of carbon dioxide expiration (VCO2), cardiorespiratory function, and fatigability. Methods: Twenty healthy adults completed peak cardiopulmonary exercise (CPX) and submaximal tests before and after a vigorous, 4-week AET regimen. Each test was followed by a 10-min recovery and endurance test at 70% of peak wattage attained during CPX. Fatigability was assessed using testing durations and power output. Respiratory buffering (excess VCO2) and non-buffering (metabolic VCO2) were calculated. Data were analyzed for significance (p<0.05) using regressions and paired t-tests. Results: Significant improvements in all measures of fatigability were observed after AET. A significant increase in excess VCO2 was observed, though not in metabolic VCO2. Excess VCO2 was strongly predictive of fatigability measures. Conclusion: Significant decreases in fatigability are often observed in clinical populations such as obstructive or restrictive lung disease or pulmonary hypertension following AET, even when peak cardiorespiratory function does not appear to adapt. Decreases in fatigability appear to predict longevity with no yet identified mechanism. These results suggest that respiratory buffering and metabolic components of VCO2 may adapt independently to AET, introducing foundational plausibility for an influence of respiratory buffering adaptation to AET on fatigability status.

Effect of differential muscle activation patterns on muscle deoxygenation and microvascular haemoglobin regulation.

NEW FINDINGS: What is the central question of this study? Does the presence and extent of heterogeneity in the ratio of O2 delivery to uptake across human muscles relate specifically to different muscle activation patterns? What is the main finding and its importance? During ramp incremental knee-extension and cycling exercise, the profiles of muscle deoxygenation (deoxy[haemoglobin + myoglobin]) and diffusive O2 potential (total[haemoglobin + myoglobin]) in the vastus lateralis corresponded to different muscle activation strategies. However, this was not the case for the rectus femoris, where muscle activation and deoxygenation profiles were dissociated and might therefore be determined by other structural and/or functional attributes (e.g. arteriolar vascular regulation and control of red blood cell flux). ABSTRACT: Near-infrared spectroscopy has revealed considerable heterogeneity in the ratio of O2 delivery to uptake as identified by disparate deoxygenation {deoxy[haemoglobin + myoglobin] (deoxy[Hb + Mb])} values in the exercising quadriceps. However, whether this represents a recruitment phenomenon or contrasting vascular and metabolic control, as seen among fibre types, has not been established. We used knee-extension (KE) and cycling (CE) incremental exercise protocols to examine whether differential muscle activation profiles could account for the heterogeneity of deoxy[Hb + Mb] and microvascular haemoconcentration (i.e. total[Hb + Mb]). Using time-resolved near-infrared spectroscopy for the quadriceps femoris (vastus lateralis and rectus femoris) during exhaustive ramp exercise in eight participants, we tested the following hypotheses: (i) the deoxy[Hb + Mb] (i.e. fractional O2 extraction) would relate to muscle activation levels across exercise protocols; and (ii) KE would induce greater total[Hb + Mb] (i.e. diffusive O2 potential) at task failure (i.e. peak O2 uptake) than CE irrespective of muscle site. At a given level of muscle activation, as assessed by the relative integrated EMG normalized to maximal voluntary contraction (%iEMGmax ), the vastus lateralis deoxy[Hb + Mb] profile was not different between exercise protocols. However, at peak O2 uptake and until 20% iEMGmax for CE, rectus femoris exhibited a lower deoxy[Hb + Mb] (83.2 ± 15.5 versus 98.2 ± 19.4 µm) for KE than for CE (P < 0.05). The total[Hb + Mb] at peak O2 uptake was not different between exercise protocols for either muscle site. These data support the hypothesis that the contrasting patterns of convective and diffusive O2 transport correspond to different muscle activation patterns in vastus lateralis but not rectus femoris. Thus, the differential deoxygenation profiles for rectus femoris across exercise protocols might be dependent upon specific facets of muscle architecture and functional haemodynamic events.

Recovery Off-Kinetics Following Exhaustive Upper Body Exercise in Spinal Cord Injury.

BACKGROUND: People with spinal cord injury (SCI) present with impaired autonomic control when the lesion is above T6. This could lead to delayed cardiorespiratory recovery following vigorous physical activity. OBJECTIVES: To characterize and compare gas exchange off-kinetics following exhaustive exercise in individuals with SCI and an apparently healthy control group. METHODS: Participants were 19 individuals with SCI who presented with the inability to voluntarily lift their legs against gravity (age, 44.6 ± 14.2 years; AIS A, n = 5; AIS B, n = 7; AIS C, n = 7; paraplegia, n = 14; tetraplegia, n = 5) and 10 healthy comparisons (COM; age, 30.5 ± 5.3 years). All participants performed an arm ergometer cardiopulmonary exercise test (aCPET) to volitional exhaustion followed by a 10-minute passive recovery. O2 uptake (V̇o2 ) and CO2 output (V̇co2 ) off-kinetics was examined using a mono-exponential model in which tau off (τoff ) and mean response time (MRT) were determined. The off-kinetics transition constant (Ktoff ) was calculated as ΔV̇o2 /MRT. Student t tests were used to compare SCI versus COM group means. RESULTS: COM had a significantly higher relative peak V̇o2 compared to SCI (1.70 ± 0.55 L/min vs 1.19 ± 0.51 L/min, p = .019). No difference was observed for τoff between the groups, however Ktoff for both V̇o2 and V̇co2 was significantly lower in the SCI compared to the COM group. CONCLUSION: A reduced Ktoff during recovery may suggest inefficiencies in replenishing muscle ATP stores and lactate clearance in these participants with SCI. These findings may contribute to the observed lower cardiorespiratory fitness and greater fatigability typically reported in individuals with SCI.

Modulation of left ventricular diastolic filling during exercise in persons with cervical motor incomplete spinal cord injury.

PURPOSE: To characterize left ventricular diastolic function during an exertional challenge in adults with incomplete cervical spinal cord Injury (icSCI). METHODS: In this cross-sectional study, a two-group convenience sample was used to compare left ventricular LV diastolic performance during a 5-10 W·min-1 incremental arm ergometer exercise protocol, using bioimpedance cardiography. Subjects were eight males with cervical incomplete spinal cord injury (icSCI; C5-C7: age 39 ± 14 years) versus eight able-bodied males (CON: age 38 ± 13 years). Left ventricular (LV) diastolic indices included end-diastolic volume (EDV) and early diastolic filling ratio (EDFR). LV ejection time (LVET), inotropic index (dZ/dT2) and stroke volume (SV) were compared between the groups at peak exercise, and maximum workload for the icSCI group (isomax). RESULTS: EDV (at peak exercise:131.4 ± 7.3 vs 188.78 ± 9.4, p < 0.001; at isomax: 131.4 ± 7.3 vs 169 ± 23, p = 0.0009) and EDFR (at peak exercise 73 ± 14% vs 119 ± 11%, p = 0.006; at isomax 94 ± 10; p = 0.009) were significantly reduced in icSCI compared to CON, respectively. Significant differences in LVET (icSCI: 273 ± 48 vs CON: 305 ± 68; p = 0.1) and dZ/dT2 (icSCI: 0.64 ± 0.11 vs CON: 0.85 ± 0.31; p = 0.1) were not observed at isomax, despite a significant decrease in SV in the subjects with icSCI (77.1 ± 6.05 mL vs 105.8 ± 9.2 mL, p < 0.00) CONCLUSION: Left ventricular filling was impaired in the subjects with icSCI as evidenced at both peak exercise and isomax. It is likely that restrictions on the skeletal muscle pump mechanized the impairment but increased left ventricular wall stiffness could not be excluded as a mediator.

Oxygen uptake on-kinetics before and after aerobic exercise training in individuals with traumatic brain injury.

Objective: The high prevalence of fatigue among persons with traumatic brain injury (TBI) may be related to poor cardiorespiratory fitness observed in this population. Oxygen uptake on-kinetics is a method of assessing cardiorespiratory fitness and may be used to examine performance fatigability (decline in performance during a given activity) in persons with TBI.Purpose: To examine the effect of aerobic exercise training on oxygen uptake on-kinetics during treadmill walking in individuals with TBI.Methods: Seven ambulatory adults with chronic non-penetrating TBI performed short moderate-intensity (3-6 metabolic equivalents) walking bouts on a treadmill, prior to and following an aerobic exercise training program (clinicaltrials.gov: NCT01294332). The 12-week training program consisted of vigorous-intensity exercise on a treadmill for 30 min, 3 times a week. Breath-by-breath pulmonary gas exchange was measured throughout the bouts, and oxygen uptake on-kinetics described the time taken to achieve a steady-state response.Results: Faster oxygen uptake on-kinetics was observed after exercise training, for both the absolute and relative intensity as pre-training.Conclusions: Faster oxygen uptake on-kinetics following aerobic exercise training suggests an attenuated decline in physical performance during a standardized walking bout and improved performance fatigability in these individuals with TBI.Implications for rehabilitationSevere fatigue is a common complaint among persons with traumatic brain injury (TBI).Oxygen uptake on-kinetics may be used as an objective physiological measure of performance fatigability in persons with TBI.Faster oxygen uptake on-kinetics following aerobic exercise training suggests improved performance fatigability in these individuals with TBI.Aerobic exercise training appeared beneficial for reducing performance fatigability and may be considered as part of the rehabilitative strategy for those living with TBI.

Fatigability, oxygen uptake kinetics and muscle deoxygenation in incomplete spinal cord injury during treadmill walking.

PURPOSE: The purpose of the present study was to characterize hypothesized relationships among fatigability and cardiorespiratory fitness in individuals with chronic motor-incomplete SCI (iSCI) during treadmill walking. The theoretical framework was that exacerbated fatigability would occur concomitantly with diminished cardiorespiratory fitness in people with iSCI. METHODS: Subjects with iSCI (n = 8) and an able-bodied reference group (REF) (n = 8) completed a 6-min walking bout followed by a walking bout of 30-min or until volitional exhaustion, both at a self-selected walking speed. Fatigability was assessed using both perceived fatigability and performance fatigability measures. Pulmonary oxygen uptake kinetics (VO2 on-kinetics) was measured breath-by-breath and changes in deoxygenated hemoglobin/myoglobin concentration (∆[HHb]) of the lateral gastrocnemius was measured by near-infrared spectroscopy. Adjustment of VO2 and ∆[HHb] on-kinetics were modeled using a mono-exponential equation. RESULTS: Perceived fatigability and performance fatigability were 52% and 44% greater in the iSCI group compared to the REF group (p = 0.003 and p = 0.004). Phase II time constant (τp) of VO2 on-kinetics and ∆[HHb] ½ time during resting arterial occlusion were 55.4% and 16.3% slower in iSCI vs REF (p < 0.01 and p = 0.047, respectively). CONCLUSIONS: The results of the present study may suggest that compromised O2 delivery and/or utilization may have contributed to the severity of fatigability in these individuals with iSCI. The understanding of the extent to which fatigability and VO2 and Δ[HHb] on-kinetics impacts locomotion after iSCI will assist in the future development of targeted interventions to enhance function.

Effect of Aerobic Exercise Training on Mood in People With Traumatic Brain Injury: A Pilot Study.

BACKGROUND: Exercise training is associated with elevations in mood in patients with various chronic illnesses and disabilities. However, little is known regarding the effect of exercise training on short and long-term mood changes in those with traumatic brain injury (TBI). OBJECTIVE: The purpose of this study was to examine the time course of mood alterations in response to a vigorous, 12-week aerobic exercise training regimen in ambulatory individuals with chronic TBI (>6 months postinjury). METHODS: Short and long-term mood changes were measured using the Profile of Mood States-Short Form, before and after specific aerobic exercise bouts performed during the 12-week training regimen. RESULTS: Ten subjects with nonpenetrating TBI (6.6 ± 6.8 years after injury) completed the training regimen. A significant improvement in overall mood was observed following 12 weeks of aerobic exercise training (P = .04), with moderate to large effect sizes observed for short-term mood improvements following individual bouts of exercise. CONCLUSIONS: Specific improvements in long-term mood state and short-term mood responses following individual exercise sessions were observed in these individuals with TBI. The largest improvement in overall mood was observed at 12 weeks of exercise training, with improvements emerging as early as 4 weeks into the training regimen.

Changes in fatigability following intense aerobic exercise training in patients with interstitial lung disease.

OBJECTIVE: To determine if, in patients with interstitial lung disease (ILD), fatigue might be lessened after vigorous aerobic exercise. METHODS: 13 physically inactive patients (5 men and 8 women; age 57.2 ± 9.1 years, BMI 28.2 ± 4.6 kgm(-2)) with ILD of heterogeneous etiology and able to walk on a motor driven treadmill without physical limitation were enrolled. Subjects underwent cardiopulmonary exercise (CPET) and 6-min walk (6MWT) tests and completed Fatigue Severity Scale and Human Activity Profile questionnaires before and after an aerobic exercise-training regimen. The training regimen required participation in at least 24 of 30 prescribed aerobic exercise training sessions at a target heart rate of 70-80% of the heart rate reserve, 30 min per session, 3 times per week for 10 weeks. RESULTS: After training, a 55% (p < 0.001) increase in time to anaerobic threshold on the CPET, and an 11% (p = 0.045) reduction in performance fatigability index (PFI), calculated from the performance on the 6MWT were observed. Distance walked on the 6MWT (6MWD) increased by 49.7 ± 46.9 m (p = 0.002). Significant improvements in scores on the Fatigue Severity Scale (p = 0.046) and Human Activity Profile (AAS p = 0.024; MAS p = 0.029) were also observed. No adverse events related to the training regimen were noted. CONCLUSION: After training, the decrease in fatigability appeared to result in increased 6MWD and was associated with physical activity. Since significant declines in 6MWD may be a marker for impending mortality in ILD, a better understanding of the etiological state of fatigue in patients with ILD and its reversal might provide fundamental insight into disease progression and even survival. [ClinicalTrials.gov identifier NCT00678821].

Cardiorespiratory function before and after aerobic exercise training in patients with interstitial lung disease.

PURPOSE: To characterize the cardiorespiratory response to exercise before and after aerobic exercise training in patients with interstitial lung disease. METHODS: We performed a clinical study, examining 13 patients (New York Heart Association/World Health Organization Functional class II or III) before and after 10 weeks of supervised treadmill exercise walking, at 70% to 80% of heart rate reserve, 30 to 45 minutes per session, 3 times a week. Outcome variables included measures of cardiorespiratory function during a treadmill cardiopulmonary exercise test, with additional near infrared spectroscopy measurements of peripheral oxygen extraction and bioimpedance cardiography measurements of cardiac output. Six-minute walk test distance was also measured. RESULTS: All subjects participated in at least 24 of their 30 scheduled exercise sessions with no significant adverse events. After training, the mean 6-minute walk test distance increased by 52 ± 48 m (P = .001), peak treadmill cardiopulmonary exercise test time increased by 163 ± 130 s (P = .001), and time to achieve gas exchange threshold increased by 145 ± 37 s (P < .001). Despite a negligible increase in peak (Equation is included in full-text article.)o2 with no changes to cardiac output, the overall work rate/(Equation is included in full-text article.)o2 relationship was enhanced after training. Muscle O2 extraction increased by 16% (P = .049) after training. CONCLUSIONS: Clinically significant improvements in cardiorespiratory function were observed after aerobic exercise training in this group of subjects with interstitial lung disease. These improvements appear to have been mediated by increases in the peripheral extraction of O2 rather than changes in O2 delivery.

Improved Cardiorespiratory Fitness With Aerobic Exercise Training in Individuals With Traumatic Brain Injury.

OBJECTIVE: To examine cardiorespiratory fitness in individuals with traumatic brain injury (TBI), before and following participation in a supervised 12-week aerobic exercise training program. METHODS: Ten subjects with nonpenetrating TBI (TBI severity: mild, 50%; moderate, 40%; severe, 10%; time since injury [mean ± SD]: 6.6 ± 6.8 years) performed exercise training on a treadmill 3 times a week for 30 minutes at vigorous intensity (70%-80% of heart rate reserve). All subjects completed a cardiopulmonary exercise test, with pulmonary gas exchange measured and a questionnaire related to fatigue (Fatigue Severity Scale) at baseline and following exercise training. RESULTS: After training, increases (P < .01) in peak oxygen consumption ((Equation is included in full-text article.); +3.1 ± 2.4 mL/min/kg), time to volitional fatigue (+1.4 ± 0.8 minutes), and peak work rate (+59 ± 43 W) were observed. At the anaerobic threshold, (Equation is included in full-text article.)(+3.6 ± 2.1 mL/kg/min), treadmill time (+1.8 ± 1.1 minutes), and work rate (+37 ± 39 W) were higher (P < .01) following exercise training. Subjects also reported significantly lower (P < .05) Fatigue Severity Scale composite scores (-0.9 ± 1.3) following exercise training. CONCLUSION: These findings suggest that individuals with TBI may benefit from participation in vigorous aerobic exercise training with improved cardiorespiratory fitness and diminished fatigue.

Effect of voluntary hyperventilation with supplemental CO2 on pulmonary O2 uptake and leg blood flow kinetics during moderate-intensity exercise.

Pulmonary O2 uptake (V(O2p)) and leg blood flow (LBF) kinetics were examined at the onset of moderate-intensity exercise, during hyperventilation with and without associated hypocapnic alkalosis. Seven male subjects (25 ± 6 years old; mean ± SD) performed alternate-leg knee-extension exercise from baseline to moderate-intensity exercise (80% of estimated lactate threshold) and completed four to six repetitions for each of the following three conditions: (i) control [CON; end-tidal partial pressure of CO2 (P(ET, CO2)) ~40 mmHg], i.e. normal breathing with normal inspired CO2 (0.03%); (ii) hypocapnia (HYPO; P(ET, CO2) ~20 mmHg), i.e. sustained hyperventilation with normal inspired CO2 (0.03%); and (iii) normocapnia (NORMO; P(ET, CO2) ~40 mmHg), i.e. sustained hyperventilation with elevated inspired CO2 (~5%). The V(O2p) was measured breath by breath using mass spectrometry and a volume turbine. Femoral artery mean blood velocity was measured by Doppler ultrasound, and LBF was calculated from femoral artery diameter and mean blood velocity. Phase 2 V(O2p) kinetics (τV(O2p)) was different (P < 0.05) amongst all three conditions (CON, 19 ± 7 s; HYPO, 43 ± 17 s; and NORMO, 30 ± 8 s), while LBF kinetics (τLBF) was slower (P < 0.05) in HYPO (31 ± 9 s) compared with both CON (19 ± 3 s) and NORMO (20 ± 6 s). Similar to previous findings, HYPO was associated with slower V(O2p) and LBF kinetics compared with CON. In the present study, preventing the fall in end-tidal P(CO2) (NORMO) restored LBF kinetics, but not V(O2p) kinetics, which remained 'slowed' relative to CON. These data suggest that the hyperventilation manoeuvre itself (i.e. independent of induced hypocapnic alkalosis) may contribute to the slower V(O2p) kinetics observed during HYPO.

Effect of aerobic exercise training on fatigue and physical activity in patients with pulmonary arterial hypertension.

OBJECTIVE: To investigate the effectiveness of an exercise intervention for decreasing fatigue severity and increasing physical activity in individuals with pulmonary arterial hypertension (PAH). A small, phase 2 randomized clinical trial of the effect of aerobic exercise training on fatigue severity and physical activity in patients with idiopathic or PAH associated with other conditions was conducted. METHODS: Twenty-four patients with PAH (24 female; age: 54.4 ± 10.4 years; BMI: 30.8 ± 7.2 kg/m(2)) participated in the study. A convenience sample was recruited in which 9% (28 of 303) of screened patients were enrolled. The project was carried out in a clinical pulmonary rehabilitation clinic during existing pulmonary rehabilitation program sessions. Patients with PH were randomized into a 10-week program that consisted of patient education only or patient education plus an aerobic exercise-training regimen. Both groups received 20 lectures, two per week over the 10-weeks, on topics related to PAH and its management. The aerobic exercise training consisted of 24-30 sessions of treadmill walking for 30-45 min per session at an intensity of 70-80% of heart rate reserve, three days per week over the 10 weeks. RESULTS: After 10-weeks of intervention, patients receiving aerobic exercise training plus education reported routinely engaging in higher levels of physical activity (p < 0.05) and a decrease in fatigue severity (p = 0.03). Patients in the education only group did not report changes in fatigue severity or participation in physical activity. CONCLUSIONS: The 10-week aerobic exercise training intervention resulted in increased physical activity and decreased fatigue in individuals with PAH. ClinicalTrials.gov Identifier: NCT00678821.

Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) restricts the ability to engage in physical activity and decreases longevity. We examined the impact of aerobic exercise training on function and quality of life in patients with World Health Organization group 1 PH. METHODS: Patients were randomized to a 10-week education only (EDU) or education/exercise combined (EXE) group. The exercise program consisted of 24-30 sessions of treadmill walking for 30-45 min per session at 70% to 80% of heart rate reserve. Outcome variables included changes in 6-min walk test (6MWT) distance, time to exercise intolerance, peak work rate (WR) from a cardiopulmonary treadmill test, and quality-of-life measures, including the Short Form Health Survey, version 2 (SF-36v2) and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). RESULTS: Data are presented as mean SD. Twenty-three women (age, 54 11 years; BMI, 31 7 kg/m 2 ) were randomized to the EDU (n 5 13) or EXE (n 5 10) groups. Following 10 weeks of intervention, patients in the EXE group demonstrated an improvement in 6MWT distance (56 45 m; P 5 .002), increased time to exercise intolerance (1.9 1.3 min; P 5 .001), and peak WR (26 23 W; P 5 .004). Additionally, the EXE group scored significantly ( P , .050) better on six of the eight scales on SF-36v2, and fi ve of the six scales on CAMPHOR. In contrast, no significant improvement was observed for any of the outcome measures following EDU. No adverse events were noted in either group. CONCLUSION: Ten weeks of brisk treadmill walking improved 6MWT distance, cardiorespiratory function, and patient-reported quality of life in female patients with group 1 PH.

The relationship between muscle deoxygenation and activation in different muscles of the quadriceps during cycle ramp exercise.

The relationship between muscle deoxygenation and activation was examined in three different muscles of the quadriceps during cycling ramp exercise. Seven young male adults (24 ± 3 yr; mean ± SD) pedaled at 60 rpm to exhaustion, with a work rate (WR) increase of 20 W/min. Pulmonary oxygen uptake was measured breath-by-breath, while muscle deoxygenation (HHb) and activity were measured by time-resolved near-infrared spectroscopy (NIRS) and surface electromyography (EMG), respectively, at the vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM). Muscle deoxygenation was corrected for adipose tissue thickness and normalized to the amplitude of the HHb response, while EMG signals were integrated (iEMG) and normalized to the maximum iEMG determined from maximal voluntary contractions. Muscle deoxygenation and activation were then plotted as a percentage of maximal work rate (%WR(max)). The HHb response for all three muscle groups was fitted by a sigmoid function, which was determined as the best fitting model. The c/d parameter for the sigmoid fit (representing the %WR(max) at 50% of the total amplitude of the HHb response) was similar between VL (47 ± 12% WR(max)) and VM (43 ± 11% WR(max)), yet greater (P < 0.05) for RF (65 ± 13% WR(max)), demonstrating a "right shift" of the HHb response compared with VL and VM. The iEMG also showed that muscle activation of the RF muscle was lower (P < 0.05) compared with VL and VM throughout the majority of the ramp exercise, which may explain the different HHb response in RF. Therefore, these data suggest that the sigmoid function can be used to model the HHb response in different muscles of the quadriceps; however, simultaneous measures of muscle activation are also needed for the HHb response to be properly interpreted during cycle ramp exercise.

Pulmonary O2 uptake and leg blood flow kinetics during moderate exercise are slowed by hyperventilation-induced hypocapnic alkalosis.

The effect of hyperventilation-induced hypocapnic alkalosis (Hypo) on the adjustment of pulmonary O2 uptake (VO2p) and leg femoral conduit artery ("bulk") blood flow (LBF) during moderate-intensity exercise (Mod) was examined in eight young male adults. Subjects completed four to six repetitions of alternate-leg knee-extension exercise during normal breathing [Con; end-tidal partial pressure of CO2 (PetCO2) approximately 40 mmHg] and sustained hyperventilation (Hypo; PetCO2 approximately 20 mmHg). Increases in work rate were made instantaneously from baseline (3 W) to Mod (80% estimated lactate threshold). VO2p was measured breath by breath by mass spectrometry and volume turbine, and LBF (calculated from mean femoral artery blood velocity and femoral artery diameter) was measured simultaneously by Doppler ultrasound. Concentration changes of deoxy (Delta[HHb])-, oxy (Delta[O2Hb])-, and total hemoglobin-myoglobin (Delta[HbTot]) of the vastus lateralis muscle were measured continuously by near-infrared spectroscopy (NIRS). The kinetics of VO2p, LBF, and Delta[HHb] were modeled using a monoexponential equation by nonlinear regression. The time constants for the phase 2 VO2p (Hypo, 49+/-26 s; Con, 28+/-8 s) and LBF (Hypo, 46+/-16 s; Con, 23+/-6 s) were greater (P<0.05) in Hypo compared with Con. However, the mean response time for the overall Delta[HHb] response was not different between conditions (Hypo, 23+/-5 s; Con, 24+/-3 s), whereas the Delta[HHb] amplitude was greater (P<0.05) in Hypo (8.05+/-7.47 a.u.) compared with Con (6.69+/-6.31 a.u.). Combined, these results suggest that hyperventilation-induced hypocapnic alkalosis is associated with slower convective (i.e., slowed femoral artery and microvascular blood flow) and diffusive (i.e., greater fractional O2 extraction for a given DeltaVO2p) O2 delivery, which may contribute to the hyperventilation-induced slowing of VO2p (and muscle O2 utilization) kinetics.