Publications by year
2023
Campbell M (2023). Effects of Short-Term Lower Limb Immobilisation on Neuromuscular Function.
Abstract:
Effects of Short-Term Lower Limb Immobilisation on Neuromuscular Function
Single-limb or whole-body immobilisation or inactivity can occur as a consequence of injury, illness, frailty, and surgery. Such periods of immobilisation result in decreased muscle strength which is in part due to muscle atrophy. However, the loss in muscle. strength during immobilisation is typically greater and occurs faster than the loss of muscle size. As such, muscle atrophy cannot fully explain the immobilisation-induced loss in muscle strength. Muscle strength is strongly influenced by neural processes, so it is likely that changes in neuromuscular function (NMF) also contribute to immobilisation-induced loss of strength. Therefore, the aim of the thesis was to enhance the understanding of the early phases of immobilisation and the contribution that neuromuscular function may play in the observed declines in strength.
A systematic review of the literature on the effects of periods of segmental limb immobilisation, identified that declines in strength (~2% per day immobilised) were 5-fold greater than the reductions in muscle size (~0.4% per day). Muscle contractility was impaired with declines of ~1% per day in the rate of force development and ~1% per day in relaxation rate. Central drive was also impaired at 0.5% per day loss. The key finding of the systematic review was that the magnitude of muscle strength loss is greater than muscle atrophy in the first few days of immobilisation, and loss of contractility is an important contributing factor to functional loss especially in early stages of immobilisation. However, only 10% of the included studies investigated the effects of immobilisation for less than 7 days despite the results indicating that this is the period in which the largest rate of change in all outcome measures, other than muscle size, occurs. Based on the findings of the systematic review we then investigated the effects of periods of 12h and of 48 h single leg immobilisation via fixed angle knee brace on neuromuscular function of the knee extensors via contractions evoked by peripheral nerve electrical stimulation (PNS) and transcranial magnetic stimulation (TMS).
The 12h immobilisation protocol induced a significant 5% decrease in muscle strength but no statistically significant effects on contractility, excitability, or voluntary activation (all p > 0.05) compared to the non-immobilised limb. In a second experimental study, we investigated the effects of 48 h of single leg immobilisation, utilising the same outcome measures as well as muscle size measures with MRI. The experimental paradigm was altered to include a control group and data were interrogated with ANCOVA. Muscle strength declined by ~10%, despite no change in muscle size (-0.5%). Significant reductions in muscle contractility were observed with lengthening of time to peak twitch in resting muscle (PNS - 18%; TMS -16%) and during potentiated twitches (PNS -19%; TMS -19%). Alongside this elevations in central drive (7%) were observed using the twitch interpolation technique. In summary, 48 h of single limb immobilisation can cause significant reductions in muscle strength as a result of reductions in muscle contractility and supraspinal neural drive that cannot be ameliorated by increased spinal contributions to the voluntary activation. Finally, we interrogated the impact of different control paradigms for immobilisation research i.e. within person non-immobilised limb control versus a separate non-immobilised control group. This study explores the potential for cross education between immobilised and non-immobilised limbs and/or compensatory overload and hence fatigue of the non-immobilised leg, to confound the control comparison. Strength significantly declined 6.5% following 48h of immobilisation on the contralateral limb alongside increases in sarcolemma excitability (M-wave amplitude: Vastus lateralis 5%; M-wave area: Vastus lateralis 8%; Vastus medialis 13%), but no changes in contractility or central drive were observed. The data observed in the non-immobilised limb suggests an inability to produce maximal force but did not provide clear evidence as to why this had occurred.
The findings presented in the thesis have demonstrated the impact of short-term immobilisation on muscle strength and size, and neuromuscular function. During the early phase of immobilisation reduced contractility plays a key role in driving the observed declines in strength. The non-immobilised limb exhibits loss of strength and increased peripheral excitability, and thus studies examining the effects of single limb immobilisation should employ a control group as comparator.
Abstract.
2021
O’Leary MF, Jackman SR, Sabou VR, Campbell MI, Tang JCY, Dutton J, Bowtell JL (2021). Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus Lateralis Myosin Regulatory Light Chain Phosphorylation But Does Not Alter Markers of Bone Turnover: a Randomised Controlled Trial.
O’Leary MF, Jackman SR, Sabou VR, Campbell MI, Tang JCY, Dutton J, Bowtell JL (2021). Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus lateralis Myosin Regulatory Light Chain Phosphorylation but Does Not Alter Markers of Bone Turnover.
Nutrients,
13(12), 4282-4282.
Abstract:
Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus lateralis Myosin Regulatory Light Chain Phosphorylation but Does Not Alter Markers of Bone Turnover
Shatavari has long been used as an Ayurvedic herb for women’s health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor. Postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis. In a randomised double-blind trial, 20 postmenopausal women (68.5 ± 6 years) ingested either placebo (N = 10) or shatavari (N = 10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented as difference scores (Week 6—baseline, median ± interquartile range). Handgrip (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo −0.4 ± 1.3 kg; p = 0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo −0.08 ± 0.5 a.u. shatavari +0.3 ± 1 arbitrary units (a.u.); p = 0.03). Shatavari increased the phosphorylation of Aktser473 (Aktser473 (placebo −0.6 ± 0.6 a.u. shatavari +0.2 ± 1.3 a.u.; p = 0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, β-CTX) and stimulation of human osteoblasts with pooled sera (N = 8 per condition) from placebo and shatavari supplementation conditions did not alter cytokine or metabolic markers of osteoblast activity. Shatavari may improve muscle function and contractility via myosin conformational change and further investigation of its utility in conserving and enhancing musculoskeletal function, in larger and more diverse cohorts, is warranted.
Abstract.
2019
Campbell M, Varley-Campbell J, Fulford J, Taylor B, Mileva KN, Bowtell JL (2019). Correction to: Effect of Immobilisation on Neuromuscular Function in Vivo in Humans: a Systematic Review.
Sports Med,
49(6), 981-986.
Abstract:
Correction to: Effect of Immobilisation on Neuromuscular Function in Vivo in Humans: a Systematic Review.
The following sections 3.5.1 to 3.5.3.2, which previously read.
Abstract.
Author URL.
Campbell M, Varley-Campbell J, Fulford J, Taylor B, Mileva KN, Bowtell JL (2019). Effect of Immobilisation on Neuromuscular Function in Vivo in Humans: a Systematic Review.
Sports Med,
49(6), 931-950.
Abstract:
Effect of Immobilisation on Neuromuscular Function in Vivo in Humans: a Systematic Review.
BACKGROUND: Muscle strength loss following immobilisation has been predominantly attributed to rapid muscle atrophy. However, this cannot fully explain the magnitude of muscle strength loss, so changes in neuromuscular function (NMF) may be involved. OBJECTIVES: We systematically reviewed literature that quantified changes in muscle strength, size and NMF following periods of limb immobilisation in vivo in humans. METHODS: Studies were identified following systematic searches, assessed for inclusion, data extracted and quality appraised by two reviewers. Data were tabulated and reported narratively. RESULTS: Forty eligible studies were included, 22 immobilised lower and 18 immobilised upper limbs. Limb immobilisation ranged from 12 h to 56 days. Isometric muscle strength and muscle size declined following immobilisation; however, change magnitude was greater for strength than size. Evoked resting twitch force decreased for lower but increased for upper limbs. Rate of force development either remained unchanged or slowed for lower and typically slowed for upper limbs. Twitch relaxation rate slowed for both lower and upper limbs. Central motor drive typically decreased for both locations, while electromyography amplitude during maximum voluntary contractions decreased for the lower and presented mixed findings for the upper limbs. Trends imply faster rates of NMF loss relative to size earlier in immobilisation periods for all outcomes. CONCLUSIONS: Limb immobilisation results in non-uniform loss of isometric muscle strength, size and NMF over time. Different outcomes between upper and lower limbs could be attributed to higher degrees of central neural control of upper limb musculature. Future research should focus on muscle function losses and mechanisms following acute immobilisation. REGISTRATION: PROSPERO reference: CRD42016033692.
Abstract.
Author URL.
2018
Jackman SR, Brook MS, Pulsford RM, Cockcroft EJ, Campbell MI, Rankin D, Atherton P, Smith K, Bowtell JL (2018). Tart cherry concentrate does not enhance muscle protein synthesis response to exercise and protein in healthy older men.
Exp Gerontol,
110, 202-208.
Abstract:
Tart cherry concentrate does not enhance muscle protein synthesis response to exercise and protein in healthy older men.
BACKGROUND: Oxidative stress and inflammation may contribute to anabolic resistance in response to protein and exercise in older adults. We investigated whether consumption of montmorency cherry concentrate (MCC) increased anabolic sensitivity to protein ingestion and resistance exercise in healthy older men. METHODS: Sixteen healthy older men were randomized to receive MCC (60 mL·d-1) or placebo (PLA) for two weeks, after baseline measures in week 1. During week 3, participants consumed 10 g whey protein·d-1 and completed three bouts of unilateral leg resistance exercise (4 × 8-10 repetitions at 80% 1RM). Participants consumed a bolus (150 mL) and weekly (50 mL) doses of deuterated water. Body water 2H enrichment was measured in saliva and vastus lateralis biopsies were taken from the non-exercised leg after weeks 1, 2 and 3, and the exercised leg after week 3, to measure tracer incorporation at rest, in response to protein and protein + exercise. RESULTS: Myofibrillar protein synthesis increased in response to exercise + protein compared to rest (p
Abstract.
Author URL.