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Featured researches published by Tyler S. Mangum.


The Journal of Physiology | 2016

Group III/IV muscle afferents limit the intramuscular metabolic perturbation during whole body exercise in humans

Gregory M. Blain; Tyler S. Mangum; Simranjit K. Sidhu; Joshua C. Weavil; Thomas J. Hureau; Jacob E. Jessop; Amber D. Bledsoe; Russell S. Richardson; Markus Amann

The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise‐induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ‐opioid receptor‐sensitive locomotor muscle afferents during a 5 km cycling time trial. The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural ‘drive’ to working locomotor muscle and limits the exercise‐induced intramuscular metabolic perturbation. Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance.


Annals of the American Thoracic Society | 2014

Ventilatory and Sensory Responses in Adult Survivors of Preterm Birth and Bronchopulmonary Dysplasia with Reduced Exercise Capacity

Andrew T. Lovering; J. Elliott; Steven S. Laurie; Kara M. Beasley; Caitlyn E. Gust; Tyler S. Mangum; Igor M. Gladstone; Joseph W. Duke

RATIONALE Adults born very to extremely preterm, with or without bronchopulmonary dysplasia (BPD), have obstructive lung disease, but it is unknown whether this results in respiratory limitations, such as mechanical constraints to Vt expansion during exercise leading to intolerable dyspnea and reduced exercise tolerance, as it does in patients with chronic obstructive pulmonary disease. OBJECTIVES To test the hypothesis that adult survivors of preterm birth (≤32 wk gestational age) with (n = 20) and without BPD (n = 15) with reduced exercise capacity demonstrate clinically important respiratory limitations at near-maximal exercise compared with full-term control subjects (n = 20). METHODS Detailed ventilatory and sensory measurements were made before and during exercise on all patients in the three study groups. MEASUREMENTS AND MAIN RESULTS During exercise at 90% of peak [Formula: see text]o2 ([Formula: see text]o2peak), inspiratory reserve volume decreased to ∼0.5 L in all groups, but this occurred at significantly lower absolute workloads and [Formula: see text]e in ex-preterm subjects with and without BPD compared with full-term control subjects. Severe dyspnea was present and similar at comparable [Formula: see text]e between all groups, but leg discomfort at comparable workloads was greater in ex-preterm subjects with and without BPD compared with control subjects. At 50 to 90% of [Formula: see text]o2peak, exercise-induced expiratory flow limitation was significantly greater in ex-preterm subjects with BPD compared with ex-preterm subjects without BPD and control subjects. The degree of expiratory flow limitation in ex-preterm subjects with and without BPD was significantly related to neonatal O2 therapy duration. CONCLUSIONS Severe dyspnea and leg discomfort associated with critical constraints on Vt expansion may lead to reduced exercise tolerance in adults born very or extremely preterm, whether or not their birth was complicated by BPD and despite differences in expiratory flow limitation. In this regard, adults born very or extremely preterm have respiratory limitations to exercise similar to patients with chronic obstructive pulmonary disease.


Clinical Neurophysiology | 2017

Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise

Simranjit K. Sidhu; Joshua C. Weavil; Tyler S. Mangum; Jacob E. Jessop; Russell S. Richardson; David E. Morgan; Markus Amann

OBJECTIVE To investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise. METHODS Fourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability. RESULTS While fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13±3% higher (P<0.05), resulting in a decrease in MEP/CMEP (P<0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (-53±3% vs. -39±3%; P<0.01), the reduction in voluntary muscle activation was smaller (-2±2% vs. -10±2%; P<0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13±3% and 25±6% in FENT (P<0.05). CONCLUSION During non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue. SIGNIFICANCE Group III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans.


The Journal of Physiology | 2016

Symmorphosis and skeletal muscle V̇O2 max : in vivo and in vitro measures reveal differing constraints in the exercise-trained and untrained human.

Jayson R. Gifford; Ryan S. Garten; Ashley D. Nelson; Joel D. Trinity; Gwenael Layec; Melissa A. H. Witman; Joshua C. Weavil; Tyler S. Mangum; Corey R. Hart; Cory Etheredge; Jake Jessop; Amber D. Bledsoe; David E. Morgan; D. Walter Wray; Matthew J. Rossman; Russell S. Richardson

The concept of symmorphosis predicts that the capacity of each step of the oxygen cascade is attuned to the task demanded of it during aerobic exercise at maximal rates of oxygen consumption ( V̇O2 max ) such that no single process is limiting or in excess at V̇O2 max . The present study challenges the applicability of this concept to humans by revealing clear, albeit very different, limitations and excesses in oxygen supply and consumption among untrained and endurance‐trained humans. Among untrained individuals, V̇O2 max is limited by the capacity of the mitochondria to consume oxygen, despite an excess of oxygen supply, whereas, among trained individuals, V̇O2 max is limited by the supply of oxygen to the mitochondria, despite an excess of mitochondrial respiratory capacity.


Journal of Applied Physiology | 2014

Exercise- and hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses is reduced in older adults

H. Cameron Norris; Tyler S. Mangum; Joseph W. Duke; Taylor B. Straley; Jerold A. Hawn; Randy D. Goodman; Andrew T. Lovering

Mean pulmonary arterial pressure (Ppa) during exercise is significantly higher in individuals aged ≥50 yr compared with their younger counterparts, but the reasons for this are unknown. Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) can be detected during exercise or while breathing hypoxic gas mixtures using saline contrast echocardiography in almost all healthy young individuals. It has been previously hypothesized that a lower degree of exercise-induced blood flow through IPAVA is associated with high Ppa during exercise. This association may suggest that individuals who are known to have high Ppa during exercise, such as those ≥50 yr of age, may have lower blood flow through IPAVA, but the presence and degree of exercise-induced blood flow through IPAVA has not been specifically studied in older populations. Using transthoracic saline contrast echocardiography, we investigated the potential effects of age on exercise-induced blood flow through IPAVA in a cross-section of subjects aged 19-72 yr. To verify our findings, we assessed the effects of age on hypoxia-induced blood flow through IPAVA. Age groups were ≤41 yr (younger, n = 16) and ≥50 yr (older, n = 14). Qualitatively measured exercise- and hypoxia-induced blood flow through IPAVA was significantly lower in older individuals compared with younger controls. Older individuals also had significantly higher pulmonary arterial systolic pressure and total pulmonary resistance (TPR) during exercise. Low blood flow through IPAVA was independently associated with high TPR. The reasons for the age-related decrease in blood flow through IPAVA are unknown.


Journal of Applied Physiology | 2013

Normal pulmonary gas exchange efficiency and absence of exercise-induced arterial hypoxemia in adults with bronchopulmonary dysplasia

Andrew T. Lovering; Steven S. Laurie; Jonathan E. Elliott; Kara M. Beasley; Ximeng Yang; Caitlyn E. Gust; Tyler S. Mangum; Randall D. Goodman; Jerold A. Hawn; Igor M. Gladstone

Cardiopulmonary function is reduced in adults born very preterm, but it is unknown if this results in reduced pulmonary gas exchange efficiency during exercise and, consequently, leads to reduced aerobic capacity in subjects with and without bronchopulmonary dysplasia (BPD). We hypothesized that an excessively large alveolar to arterial oxygen difference (AaDO2) and resulting exercise-induced arterial hypoxemia (EIAH) would contribute to reduced aerobic fitness in adults born very preterm with and without BPD. Measurements of pulmonary function, lung volumes and diffusion capacity for carbon monoxide (DLco) were made at rest. Measurements of maximal oxygen consumption, peak workload, temperature- and tonometry-corrected arterial blood gases, and direct measure of hemoglobin saturation with oxygen (SaO2) were made preexercise and during cycle ergometer exercise in ex-preterm subjects ≤32-wk gestational age, with BPD (n = 12), without BPD (PRE; n = 12), and full term controls (CONT; n = 12) breathing room air. Both BPD and PRE had reduced pulmonary function and reduced DLco compared with CONT. The AaDO2 was not significantly different between groups, and there was no evidence of EIAH (SaO2 < 95% and/or AaDO2 ≥ 40 Torr) in any subject group preexercise or at any workload. Arterial O2 content was not significantly different between the groups preexercise or during exercise. However, peak power output was decreased in BPD and PRE subjects compared with CONT. We conclude that EIAH in adult subjects born very preterm with and without BPD does not likely contribute to the reduction in aerobic exercise capacity observed in these subjects.


Journal of Applied Physiology | 2014

Pulmonary gas exchange efficiency during exercise breathing normoxic and hypoxic gas in adults born very preterm with low diffusion capacity.

Joseph W. Duke; Jonathan E. Elliott; Steven S. Laurie; Kara M. Beasley; Tyler S. Mangum; Jerold A. Hawn; Igor M. Gladstone; Andrew T. Lovering

Adults with a history of very preterm birth (<32 wk gestational age; PRET) have reduced lung function and significantly lower lung diffusion capacity for carbon monoxide (DLCO) relative to individuals born at term (CONT). Low DLCO may predispose PRET to diffusion limitation during exercise, particularly while breathing hypoxic gas because of a reduced O2 driving gradient and pulmonary capillary transit time. We hypothesized that PRET would have significantly worse pulmonary gas exchange efficiency [i.e., increased alveolar-to-arterial Po2 difference (AaDO2)] during exercise breathing room air or hypoxic gas (FiO2 = 0.12) compared with CONT. To test this hypothesis, we compared the AaDO2 in PRET (n = 13) with a clinically mild reduction in DLCO (72 ± 7% of predicted) and CONT (n = 14) with normal DLCO (105 ± 10% of predicted) pre- and during exercise breathing room air and hypoxic gas. Measurements of temperature-corrected arterial blood gases, and direct measure of O2 saturation (SaO2), were made prior to and during exercise at 25, 50, and 75% of peak oxygen consumption (V̇o2peak) while breathing room air and hypoxic gas. In addition to DLCO, pulmonary function and exercise capacity were significantly less in PRET. Despite PRET having low DLCO, no differences were observed in the AaDO2 or SaO2 pre- or during exercise breathing room air or hypoxic gas compared with CONT. Although our findings were unexpected, we conclude that reduced pulmonary function and low DLCO resulting from very preterm birth does not cause a measureable reduction in pulmonary gas exchange efficiency.


American Journal of Physiology-regulatory Integrative and Comparative Physiology | 2015

Intensity-dependent alterations in the excitability of cortical and spinal projections to the knee extensors during isometric and locomotor exercise

Joshua C. Weavil; Simranjit K. Sidhu; Tyler S. Mangum; Russell S. Richardson; Markus Amann

We investigated the role of exercise intensity and associated central motor drive in determining corticomotoneuronal excitability. Ten participants performed a series of nonfatiguing (3 s) isometric single-leg knee extensions (ISO; 10-100% of maximal voluntary contractions, MVC) and cycling bouts (30-160% peak aerobic capacity, W peak). At various exercise intensities, electrical potentials were evoked in the vastus lateralis (VL) and rectus femoris (RF) via transcranial magnetic stimulation (motor-evoked potentials, MEP), and electrical stimulation of both the cervicomedullary junction (cervicomedullary evoked potentials, CMEP) and the femoral nerve (maximal M-waves, M max). Whereas M max remained unchanged in both muscles (P > 0.40), voluntary electromyographic activity (EMG) increased in an exercise intensity-dependent manner for ISO and cycling exercise in VL and RF (both P < 0.001). During ISO exercise, MEPs and CMEPs progressively increased in VL and RF until a plateau was reached at ∼ 75% MVC; further increases in contraction intensity did not cause additional changes (P > 0.35). During cycling exercise, VL-MEPs and CMEPs progressively increased by ∼ 65% until a plateau was reached at W peak. In contrast, RF MEPs and CMEPs progressively increased by ∼ 110% throughout the tested cycling intensities without the occurrence of a plateau. Furthermore, alterations in EMG below the plateau influenced corticomotoneuronal excitability similarly between exercise modalities. In both exercise modalities, the MEP-to-CMEP ratio did not change with exercise intensity (P > 0.22). In conclusion, increases in exercise intensity and EMG facilitates the corticomotoneuronal pathway similarly in isometric knee extension and locomotor exercise until a plateau occurs at a submaximal exercise intensity. This facilitation appears to be primarily mediated by increases in excitability of the motoneuron pool.


Journal of Neurophysiology | 2016

Fatigue diminishes motoneuronal excitability during cycling exercise

Joshua C. Weavil; Simranjit K. Sidhu; Tyler S. Mangum; Russell S. Richardson; Markus Amann

Exercise-induced fatigue influences the excitability of the motor pathway during single-joint isometric contractions. This study sought to investigate the influence of fatigue on corticospinal excitability during cycling exercise. Eight men performed fatiguing constant-load (80% Wpeak; 241 ± 13 W) cycling to exhaustion during which the percent increase in quadriceps electromyography (ΔEMG; vastus lateralis and rectus femoris) was quantified. During a separate trial, subjects performed two brief (∼45 s) nonfatiguing cycling bouts (244 ± 15 and 331 ± 23W) individually chosen to match the ΔEMG across bouts to that observed during fatiguing cycling. Corticospinal excitability during exercise was quantified by transcranial magnetic, electric transmastoid, and femoral nerve stimulation to elicit motor-evoked potentials (MEP), cervicomedullary evoked potentials (CMEP), and M waves in the quadriceps. Peripheral and central fatigue were expressed as pre- to postexercise reductions in quadriceps twitch force (ΔQtw) and voluntary quadriceps activation (ΔVA). Whereas nonfatiguing cycling caused no measureable fatigue, fatiguing cycling resulted in significant peripheral (ΔQtw: 42 ± 6%) and central (ΔVA: 4 ± 1%) fatigue. During nonfatiguing cycling, the area of MEPs and CMEPs, normalized to M waves, similarly increased in the quadriceps (∼40%; P < 0.05). In contrast, there was no change in normalized MEPs or CMEPs during fatiguing cycling. As a consequence, the ratio of MEP to CMEP was unchanged during both trials (P > 0.5). Therefore, although increases in muscle activation promote corticospinal excitability via motoneuronal facilitation during nonfatiguing cycling, this effect is abolished during fatigue. We conclude that the unaltered excitability of the corticospinal pathway from start of intense cycling exercise to exhaustion is, in part, determined by inhibitory influences on spinal motoneurons obscuring the facilitating effects of muscle activation.


American Journal of Respiratory and Critical Care Medicine | 2017

Exaggerated Increase in Pulmonary Artery Pressure during Exercise in Adults Born Preterm

Steven S. Laurie; J. Elliott; Kara M. Beasley; Tyler S. Mangum; Randall D. Goodman; Joseph W. Duke; Igor M. Gladstone; Andrew T. Lovering

Park S, Shigyo K, Gold B, Roberts J, et al. Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations. Proc Natl Acad Sci USA 2017;114:E4832–E4840. 11. Loraine J, Pu F, Turapov O, Mukamolova GV. Development of an in vitro assay for detection of drug-induced resuscitation-promotingfactor-dependent mycobacteria. Antimicrob Agents Chemother 2016;60:6227–6233. 12. Hu Y, Liu A, Ortega-Muro F, Alameda-Martin L, Mitchison D, Coates A. High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo. Front Microbiol 2015;6:641. 13. Huang W, Qi Y, Diao Y, Yang F, Zha X, Ren C, Huang D, Franken KL, Ottenhoff TH, Wu Q, et al. Use of resuscitation-promoting factor proteins improves the sensitivity of culture-based tuberculosis testing in special samples. Am J Respir Crit Care Med 2014;189:612–614. 14. Chakravorty S, Sen MK, Tyagi JS. Diagnosis of extrapulmonary tuberculosis by smear, culture, and PCR using universal sample processing technology. J Clin Microbiol 2005;43:4357–4362. 15. Weniger T, Krawczyk J, Supply P, Niemann S, Harmsen D. MIRUVNTRplus: a web tool for polyphasic genotyping of Mycobacterium tuberculosis complex bacteria. Nucleic Acids Res 2010;38: W326–W331. 16. World Health Organisation. Definitions and reporting framework for tuberculosis 2013 revision (updated December 2014). 2014 [accessed 2017 Aug 11]. Available from: http://apps.who.int/iris/ bitstream/10665/79199/1/9789241505345_eng.pdf. 17. Turapov O, Glenn S, Kana B, Makarov V, Andrew PW, Mukamolova GV. The in vivo environment accelerates generation of resuscitationpromoting factor-dependent mycobacteria. Am J Respir Crit Care Med 2014;190:1455–1457. 18. Nathan C. Fresh approaches to anti-infective therapies. Sci Transl Med 2012;4:140sr2.

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Markus Amann

University of Wisconsin-Madison

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