Joshua C. Weavil

Spinal μ-opioid receptor-sensitive lower limb muscle afferents determine corticospinal responsiveness and promote central fatigue in upper limb muscle

We aimed to elucidate the role of group III/IV locomotor muscle afferents in the development of central fatigue and the responsiveness of the corticospinal tract in relation to an unexercised arm muscle. Intrathecal fentanyl, a μ‐opioid receptor agonist, was employed to attenuate afferent feedback from the leg muscles during intense cycling exercise characterized by either no or severe peripheral locomotor muscle fatigue. In the absence of locomotor muscle fatigue, group III/IV‐mediated leg afferent feedback facilitates the responsiveness of the motor pathway to upper limb flexor muscles. By contrast, in the presence of leg fatigue, group III/IV locomotor muscle afferents facilitate supraspinal fatigue in a remote muscle not involved in the exercise and disfacilitate the responsiveness of associated corticospinal projections.

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

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.

Comments on Point: Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia.

112:1788-1794, 2012. ; J Appl Physiol Joshua C. Weavil, Peter Bartsch and Charles F. Nelatury Samuel Verges, Patrick Levy, Eric M. Snyder, Bruce D. Johnson, Jonathon L. Stickford, Y. Millet, Benjamin D. Levine, James H. Wessel III, Bernard Wuyam, Renaud Tamisier, MacInnis, Michael S. Koehle, Thomas Rupp, Marc Jubeau, Stephane Perrey, Guillaume Laymon, Jack A. Loeppky, Matiram Pun, Kai Schommer, Mary C. Vagula, Martin J. S. Chapman, Johnny Conkin, Hugo Nespoulet, Darren P. Casey, Bryan J. Taylor, Abigail Olivier Girard, Michael S. Koehle, Jordan A. Guenette, Samuel Verges, Robert F. normobaric hypoxia induces/does not induce different responses from Comments on Point:Counterpoint: Hypobaric hypoxia

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

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.

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

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.

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

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.

Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans

We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined. With no hemodynamic effect at rest, fentanyl blockade during exercise attenuated both cardiac output and QL ∼17% in YNG, while the decrease in cardiac output in OLD (∼5%) was significantly smaller with no impact on QL (P = 0.8). Therefore, in the face of similar significant ∼7% reduction in MAP during exercise with fentanyl blockade in both groups, LVC significantly increased ∼11% in OLD, but decreased ∼8% in YNG. The opposing direction of change was reflected in SVC with a significant ∼5% increase in OLD and a ∼12% decrease in YNG. Thus while cardiac output seems to account for the majority of group III/IV-mediated MAP responses in YNG, the impact of neural feedback on the heart may decrease with age and alterations in SVC become more prominent in mediating the similar exercise pressor reflex in OLD. Interestingly, in terms of peripheral hemodynamics, while group III/IV-mediated feedback plays a clear role in increasing LVC during exercise in the YNG, these afferents seem to actually reduce LVC in OLD. These peripheral findings may help explain the limited exercise-induced peripheral vasodilation often associated with aging.

Fatigue diminishes motoneuronal excitability during cycling exercise

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.

Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise

We investigated the contribution of group III/IV muscle afferents to carotid baroreflex resetting during electrically evoked (no central command) and voluntary (requiring central command) isometric knee extension exercise. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ‐opioid receptor‐sensitive group III/IV leg muscle afferent feedback. Spontaneous carotid baroreflex control was assessed by loading and unloading the carotid baroreceptors with a variable pressure neck chamber. Group III/IV muscle afferents did not influence spontaneous carotid baroreflex responsiveness at rest or during exercise. Afferent feedback accounted for at least 50% of the exercise‐induced increase in the carotid baroreflex blood pressure and heart rate operating points, adjustments that are critical for an appropriate cardiovascular response to exercise. These findings suggest that group III/IV muscle afferent feedback is, independent of central command, critical for the resetting of the carotid baroreflex blood pressure and heart rate operating points, but not for spontaneous baroreflex responsiveness.

Low Intensity Resistance Exercise Training with Blood Flow Restriction: Insight into Cardiovascular Function, and Skeletal Muscle Hypertrophy in Humans

Attenuated functional exercise capacity in elderly and diseased populations is a common problem, and stems primarily from physical inactivity. Decreased function and exercise capacity can be restored by maintaining muscular strength and mass, which are key factors in an independent and healthy life. Resistance exercise has been used to prevent muscle loss and improve muscular strength and mass. However, the intensities necessary for traditional resistance training to increase muscular strength and mass may be contraindicated for some at risk populations, such as diseased populations and the elderly. Therefore, an alternative exercise modality is required. Recently, blood flow restriction (BFR) with low intensity resistance exercise (LIRE) has been used for such special populations to improve their function and exercise capacity. Although BFR+LIRE has been intensively studied for a decade, a comprehensive review detailing the effects of BFR+LIRE on both skeletal muscle and vascular function is not available. Therefore, the purpose of this review is to discuss previous studies documenting the effects of BFR+LIRE on hormonal and transcriptional factors in muscle hypertrophy and vascular function, including changes in hemodynamics, and endothelial function.