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.

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.

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.

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.

Improved cognitive performance following aerobic exercise training in people with traumatic brain injury.

OBJECTIVE: To examine cognitive function in individuals with traumatic brain injury (TBI) prior to and after participation in an aerobic exercise training program. DESIGN: Pre-post intervention study. SETTING: Medical research center. PARTICIPANTS: Volunteer sample of individuals (N=7) (age, 33.3±7.9y) with chronic nonpenetrating TBI (injury severity: 3=mild, 4=moderate; time since most current injury: 4.0±5.5y) who were ambulatory. INTERVENTION: Twelve weeks of supervised vigorous aerobic exercise training performed 3 times a week for 30 minutes on a treadmill. MAIN OUTCOME MEASURES: Cognitive function was assessed using the Trail Making Test Part A (TMT-A), Trail Making Test Part B (TMT-B), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Sleep quality and depression were measured with the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory, version 2 (BDI-II). Indices of cardiorespiratory fitness were used to examine the relation between improvements in cognitive function and cardiorespiratory fitness. RESULTS: After training, improvements in cognitive function were observed with greater scores on the TMT-A (10.3±6.8; P=.007), TMT-B (9.6±7.0; P=.011), and RBANS total scale (13.3±9.3; P=.009). No changes were observed in measures of the PSQI and BDI-II. The magnitude of cognitive improvements was also strongly related to the gains in cardiorespiratory fitness. CONCLUSIONS: These findings suggest that vigorous aerobic exercise training may improve specific aspects of cognitive function in individuals with TBI and cardiorespiratory fitness gains may be a determinant of these improvements.

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.

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.

Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination.

Investigations of humans with disorders of sex development (DSDs) resulted in the discovery of many of the now-known mammalian sex-determining genes, including SRY, RSPO1, SOX9, NR5A1, WT1, NR0B1, and WNT4. Here, the locus for an autosomal sex-determining gene was mapped via linkage analysis in two families with 46,XY DSD to the long arm of chromosome 5 with a combined, multipoint parametric LOD score of 6.21. A splice-acceptor mutation (c.634-8T>A) in MAP3K1 segregated with the phenotype in the first family and disrupted RNA splicing. Mutations were demonstrated in the second family (p.Gly616Arg) and in two of 11 sporadic cases (p.Leu189Pro, p.Leu189Arg)-18% prevalence in this cohort of sporadic cases. In cultured primary lymphoblastoid cells from family 1 and the two sporadic cases, these mutations altered the phosphorylation of the downstream targets, p38 and ERK1/2, and enhanced binding of RHOA to the MAP3K1 complex. Map3k1 within the syntenic region was expressed in the embryonic mouse gonad prior to, and after, sex determination. Thus, mutations in MAP3K1 that result in 46,XY DSD with partial or complete gonadal dysgenesis implicate this pathway in normal human sex determination.

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.

Views of internists towards uses of PGD.

Preimplantation genetic diagnosis (PGD) is increasingly available, but how physicians view it is unclear. Internists are gatekeepers and sources of information, often treating disorders for which PGD is possible. This quantitative study surveyed 220 US internists, who were found to be divided. Many would recommend PGD for cystic fibrosis (CF; 33.7%), breast cancer (BRCA; 23.4%), familial adenomatous polyposis (FAP; 20.6%) and familial hypertrophic cardiomyopathy (19.9%), but few for social sex selection (5.2%); however, in each case, >50% were unsure. Of those surveyed, 4.9% have suggested PGD to patients. Only 7.1% felt qualified to answer patient questions about it. Internists who would refer for PGD had completed medical training less recently and, for CF, were more likely to have privately insured patients (P<0.033) and patients who reported genetic discrimination (P<0.013). Physicians more likely to refer for BRCA and FAP were less likely to have patients ask about genetic testing. This study suggests that internists often feel they have insufficient knowledge about it and may refer for PGD based on limited understanding. They view possible uses of PGD differently, partly reflecting varying ages of onset and disease treatability. These data have critical implications for training, research and practice. Preimplantation genetic diagnosis (PGD) allows embryos to be screened prior to transfer to a woman's womb for various genetic markers. This procedure raises complex medical, social, psychological and ethical issues, but how physicians view it is unclear. Internists are gatekeepers and sources of information, often treating disorders for which PGD use is possible. We surveyed 220 US internists, who were found to be divided: many would recommend PGD for cystic fibrosis (CF; 33.7%), breast cancer (BRCA; 23.4%), familial adenomatous polyposis (FAP; 20.6%), and familial hypertrophic cardiomyopathy (FHC; 19.9%) and a few for sex selection (5.2%); but in each case, >50% were unsure. Of those surveyed, 4.9% have suggested PGD to patients. Only 7.1% felt qualified to answer patient questions. Internists who would refer for PGD completed medical training less recently and, for CF, were more likely to have privately insured patients and patients who reported genetic discrimination. Physicians more likely to refer for BRCA and FAP were less likely to have patients ask about genetic testing. This quantitative study suggests that internists often feel they have insufficient knowledge and may refer for PGD based on limited understanding. They view possible uses of PGD differently, partly reflecting varying ages of onset and disease treatability. Internists should be made aware of the potential benefit of PGD, but also be taught to refer patients, when appropriate, to clinical geneticists who could then refer the patient to an IVF/PGD team. These data thus have critical implications for training, research and practice.

Attitudes and practices among internists concerning genetic testing.

Many questions remain concerning whether, when, and how physicians order genetic tests, and what factors are involved in their decisions. We surveyed 220 internists from two academic medical centers about their utilization of genetic testing. Rates of genetic utilizations varied widely by disease. Respondents were most likely to have ordered tests for Factor V Leiden (16.8 %), followed by Breast/Ovarian Cancer (15.0 %). In the past 6 months, 65 % had counseled patients on genetic issues, 44 % had ordered genetic tests, 38.5 % had referred patients to a genetic counselor or geneticist, and 27.5 % had received ads from commercial labs for genetic testing. Only 4.5 % had tried to hide or disguise genetic information, and <2 % have had patients report genetic discrimination. Only 53.4 % knew of a geneticist/genetic counselor to whom to refer patients. Most rated their knowledge as very/somewhat poor concerning genetics (73.7 %) and guidelines for genetic testing (87.1 %). Most felt needs for more training on when to order tests (79 %), and how to counsel patients (82 %), interpret results (77.3 %), and maintain privacy (80.6 %). Physicians were more likely to have ordered a genetic test if patients inquired about genetic testing (p < .001), and if physicians had a geneticist/genetic counselor to whom to refer patients (p < .002), had referred patients to a geneticist/genetic counselor in the past 6 months, had more comfort counseling patients about testing (p < .019), counseled patients about genetics, larger practices (p < .032), fewer African-American patients (p < .027), and patients who had reported genetic discrimination (p < .044). In a multiple logistic regression, ordering a genetic test was associated with patients inquiring about testing, having referred patients to a geneticist/genetic counselor and knowing how to order tests. These data suggest that physicians recognize their knowledge deficits, and are interested in training. These findings have important implications for future medical practice, research, and education.

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.

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.

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.

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.

Disclosures of funding sources and conflicts of interest in published HIV/AIDS research conducted in developing countries.

OBJECTIVES: Disclosures of funding sources and conflicts of interests (COI) in published peer-reviewed journal articles have recently begun to receive some attention, but many critical questions remain, for example, how often such reporting occurs concerning research conducted in the developing world and what factors may be involved. DESIGN: Of all articles indexed in Medline reporting on human subject HIV research in 2007 conducted in four countries (India, Thailand, Nigeria and Uganda), this study explored how many disclosed a funding source and COI, and what factors are involved. RESULTS: Of 221 articles that met the criteria, 67.9% (150) disclosed the presence or absence of a funding source, but only 20% (44) disclosed COI. Studies from Uganda were more likely, and those from Nigeria were less likely to mention a funding source (p<0.001). Of articles in journals that had adopted International Committee of Medical Journal Editors (ICMJE) guidelines, 56% did not disclose COI. Disclosure of funding was more likely when: > or = 50% of the authors and the corresponding author were from the sponsoring country, the sponsor country was the USA, and the articles were published in journals in which more of the editors were from the sponsoring countries. CONCLUSIONS: Of the published studies examined, over a third did not disclose funding source (ie, whether or not there was a funding source) and 80% did not disclose whether COI existed. Most articles in ICMJE-affiliated journals did not disclose COI. These data suggest the need to consider alteration of policies to require that published articles include funding and COI information, to allow readers to assess articles as fully as possible.

Effect of hyperventilation and prior heavy exercise on O2 uptake and muscle deoxygenation kinetics during transitions to moderate exercise.

The effect of hyperventilation-induced hypocapnic alkalosis (HYPO) and prior heavy-intensity exercise (HVY) on pulmonary O(2) uptake (VO(2p)) kinetics were examined in young adults (n = 7) during moderate-intensity exercise (MOD). Subjects completed leg cycling exercise during (1) normal breathing (CON, P(ET)CO(2) approximately 40 mmHg) and (2) controlled hyperventilation (HYPO, P(ET)CO(2) approximately 20 mmHg) throughout the protocol, with each condition repeated on four occasions. The protocol consisted of two MOD transitions (MOD1, MOD2) to 80% estimated lactate threshold with MOD2 preceded by HVY (Delta50%); each transition lasted 6 min and was preceded by 20 W cycling. VO(2p) was measured breath-by-breath and concentration changes in oxy- and deoxy-hemoglobin/myoglobin (Delta[HHb]) of the vastus lateralis muscle were measured by near-infrared spectroscopy. Adjustment of VO(2p) and Delta[HHb] were modeled using a mono-exponential equation by non-linear regression. During MOD1, the phase 2 time constant (tau) for VO(2p)(tauVO(2p)) was greater (P < 0.05) in HYPO (45 +/- 24 s) than CON (28 +/- 17 s). During MOD2, tauVO(2p) was reduced (P < 0.05) in both conditions (HYPO: 24 +/- 7 s, CON: 20 +/- 8 s). The Delta[Hb(TOT)] and Delta[O(2)Hb] were greater (P < 0.05) prior to and throughout MOD2. The Delta[HHb] mean response time was similar in MOD1 and MOD2, and between conditions, however, the MOD1 Delta[HHb] amplitude was greater (P < 0.05) in HYPO compared to CON, with no differences between conditions in MOD2. These findings suggest that the speeding of VO(2p) kinetics after prior HVY in HYPO was related, in part, to an increase in microvascular perfusion.

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.

The effect of suction method, catheter size, and suction pressure on lung volume changes during endotracheal suction in piglets.

We aimed to identify the effect of suction pressure and catheter size on change in lung volume during open and closed endotracheal suction. Anesthetized piglets (n = 12) were intubated with a 4.0-mm endotracheal tube. Lung injury was induced with saline lavage. Three suction methods (open, closed in-line, and closed with a side-port adaptor) were performed in random order using 6, 7, and 8 French gauge (FG) catheters, at vacuum pressures of 80, 140, and 200 mm Hg. Lung volume change was measured with respiratory inductive plethysmography. Overall, open suction resulted in greater lung volume loss during and at 60-s postsuction than either closed method (p < 0.001). When open and closed methods were analyzed separately, volume change was independent of catheter size and suction pressure with open suction. With closed suction, volume loss increased with larger catheter sizes and higher suction pressures (p < 0.001). With an 8-FG catheter and suction pressure of 140 or 200 mm Hg, volume loss was equivalent with open and closed suction. Lung volume changes are influenced by catheter size and suction pressure, as well as suction method. With commonly used suction pressures and catheter sizes, closed suction has no advantage in preventing loss of volume in this animal model.

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.