Jakob Lindberg Nielsen

Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction

In the last decade muscle training performed using a combination of low external loads and partial restriction of blood flow to the exercising limb has gained increasing interest, since it leads to significant gains in muscle strength and muscle mass. The cellular mechanisms responsible for the muscular adaptations induced by this training paradigm are not fully understood. This study shows that 3 weeks of high‐frequency, low‐intensity muscle exercise with partial blood flow restriction induces increases in maximal muscle strength accompanied by highly marked gains in muscle fibre size. Furthermore, the results indicate that these muscular adaptations rely on a considerable upregulation in myogenic satellite cells number, resulting in nuclear addition to the exercised myofibres. The results contribute to a better understanding of the physiological mechanisms underlying the gain in muscle strength and muscle mass observed with blood flow restricted low‐intensity resistance exercise.

Progressive resistance training rebuilds lean body mass in head and neck cancer patients after radiotherapy--results from the randomized DAHANCA 25B trial.

PURPOSE The critical weight loss observed in head and neck squamous cell carcinoma (HNSCC) patients following radiotherapy is mainly due to loss of lean body mass. This is associated with decreases in muscle strength, functional performance and Quality of Life (QoL). The present study investigated the effect of progressive resistance training (PRT) on lean body mass, muscle strength and functional performance in HNSCC patients following radiotherapy. PATIENTS AND METHODS Following radiotherapy HNSCC patients were randomized into two groups: Early Exercise (EE, n=20) initiated 12 weeks of PRT followed by 12 weeks of self-chosen physical activity. Delayed Exercise (DE, n=21) initiated 12 weeks of self-chosen physical activity followed by 12 weeks of PRT. Lean body mass, muscle strength, functional performance and QoL were evaluated at baseline and after week 12 and 24. RESULTS In the first 12 weeks lean body mass increased by 4.3% in EE after PRT and in the last 12 weeks by 4.2% in DE after PRT. These increases were significantly larger than the changes after self-chosen physical activity (p ≤ 0.005). Regardless of PRT start-up time, the odds ratio of increasing lean body mass by more than 4% after PRT was 6.26 (p<0.05). PRT significantly increased muscle strength, whereas functional performance increased significantly more than after self-chosen physical activity only after delayed onset of PRT. Overall QoL improved significantly more in EE than DE from baseline to week 12. CONCLUSION PRT effectively increased lean body mass and muscle strength in HNSCC patients following radiotherapy, irrespectively of early or delayed start-up.

Mechanical Muscle Function and Lean Body Mass During Supervised Strength Training and Testosterone Therapy in Aging Men with Low-Normal Testosterone Levels

To examine the effect of strength training and testosterone therapy on mechanical muscle function and lean body mass (LBM) in aging men with low‐normal testosterone levels in a randomized, double‐blind, placebo‐controlled 24‐week study.

Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes

The aim was to determine if the metabolic adaptations, particularly PGC‐1α and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg−1·min−1, n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg−1·dw−1) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF‐1, COX‐IV, GLUT4 and PPAR‐α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC‐1α, TFAM, NRF‐1, COX‐IV, PPAR‐α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained.

Lean body mass and muscle function in head and neck cancer patients and healthy individuals - results from the DAHANCA 25 study

Abstract Introduction. Loss of lean body mass is common following radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) and may reduce maximal muscle strength and functional performance. However, the associations between lean body mass, muscle strength and functional performance are unclear and no studies in HNSCC patients have compared the levels of these variables to the levels seen in healthy individuals. Purpose. The purpose of the present study was to investigate the associations between lean body mass, maximal muscle strength and functional performance in HNSCC patients and to compare the levels of these variables after radiotherapy and after progressive resistance training with the levels in healthy individuals. Material and methods. Lean body mass (dual energy X-ray absorptiometry), maximal muscle strength (isokinetic dynamometry) and functional performance (10 m max gait speed, 30 s chair rise, 30 s arm curl, stair climb) from HNSCC patients from the DAHANCA 25 trials and data from 24 healthy individuals were included. Results. Lean body mass and maximal muscle strength were significantly associated according to the gender and age-adjusted linear regression model (p < 0.0001). In addition, maximal muscle strength were associated with 30 s arm curl performance, 10 m max gait speed and 30 s chair rise (p < 0.0001). Multiple regression analyses showed that HNSCC patients expressed significant lower levels of the investigated variables after radiotherapy than healthy individuals (p < 0.0001), and that all differences were evened out after training. Conclusions. Significant associations were found between lean body mass, maximal muscle strength and functional performance in HNSCC patients. Patients expressed lower levels of these variables compared with healthy individuals, suggesting that lean body mass is a clinically relevant health factor in HNSCC patients.

Blood flow restricted training leads to myocellular macrophage infiltration and upregulation of heat shock proteins, but no apparent muscle damage

Muscular contractions performed using a combination of low external loads and partial restriction of limb blood flow appear to induce substantial gains in muscle strength and muscle mass. This exercise regime may initially induce muscular stress and damage; however, the effects of a period of blood flow restricted training on these parameters remain largely unknown. The present study shows that short‐term, high‐frequency, low‐load muscle training performed with partial blood flow restriction does not induce significant muscular damage. However, signs of myocellular stress and inflammation that were observed in the early phase of training and after the training intervention, respectively, may be facilitating the previously reported gains in myogenic satellite cell content and muscle hypertrophy. The present results improve our current knowledge about the physiological effects of low‐load muscular contractions performed under blood flow restriction and may provide important information of relevance for future therapeutic treatment of muscular atrophy.

Effect of slow release-Fampridine on muscle strength, rate of force development, functional capacity and cognitive function in an enriched population of MS patients. A randomized, double blind, placebo controlled study

DESIGN This study was conducted as a randomized, double blind, placebo-controlled parallel group trial preceded by open label enrichment phase. OBJECTIVES The objectives of this study were 1) to examine the effect of SR-Fampridine treatment on muscle strength in terms of maximal voluntary contraction (MVC) and rate of force development (RFD) of the lower extremities and 2) to replicate previously published data on the effect of slow release-Fampridine (SR-Fampridine) on the functional capacity of the lower limbs, the upper limb and cognitive function, in persons with multiple sclerosis (pwMS). METHODS Previously identified responders to SR-Fampridine were randomized to SR- Fampridine or placebo treatment for four weeks. On days 0 and 26-28 participants underwent testing by isokinetic dynamometry, Nine Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Six Spot Step Test (SSST), Timed 25 Foot Walk Test (T25FW) and 5-Times Sit-to-Stand (5-STS). RESULTS A statistical significant effect of SR-Fampridine on MVC was demonstrated during knee extension, knee flexion and hip flexion of the weakest leg, as well as on RFD during knee extension and knee flexion of the weakest leg. Furthermore, a significant effect of SR-Fampridine on T25FW, SSST and 5-STS was demonstrated. CONCLUSION Gold standard dynamometry assessment of muscle strength showed improved MVC and RFD in persons with MS treated with SR-Fampridine compared to placebo. Furthermore, previous findings on the effects of SR-Fampridine on functional capacity of the lower limbs were replicated. ClinicalTrials.gov identifier: NCT01656148.

Effects of blood-flow-restricted resistance training on muscle function in a 74-year-old male with sporadic inclusion body myositis: a case report

Sporadic inclusion body myositis (sIBM) is a systemic disease that is characterized by substantial skeletal muscle weakness and muscle inflammation, leading to impaired physical function. The objective was to investigate the effect of low‐load resistance exercise with concurrent partial blood flow restriction to the working muscles (blood‐flow‐restricted (BFR) training) in a patient with sIBM. The training consisted of 12 weeks of lower extremity BFR training with low training loads (~25‐RM). The patient was tested for mechanical muscle function and functional capacity before and after 6 and 12 weeks of training. Maximal horizontal gait speed increased by 19%, which was accompanied by 38–92% improvements in mechanical muscle function (maximal isometric strength, rate of force development and muscle power). In conclusion, BFR training was well tolerated by the patient with sIBM and led to substantial improvements in mechanical muscle function and gait speed.

Delayed Effect of Blood-Flow-Restricted Resistance Training on Rapid Force Capacity

Purpose The aim of the present study was to investigate the effect and time course of high-frequent low-load blood flow–restricted (BFR) resistance training on rapid force capacity (i.e., rate of torque development [RTD]). Materials and Methods Ten male subjects (22.8 ± 2.3 yr) performed four sets of knee extensor exercise (20% one-repetition maximum) to concentric failure during concurrent BFR of the thigh (100 mm Hg), and eight work-matched controls (21.9 ± 3.0 yr) trained without BFR (CON). Twenty-three training sessions were performed within 19 d. Maximal slow and fast knee joint velocity muscle strength and rapid force capacity (e.g., RTD) and evoked twitch contractile parameters were assessed before (Pre) and 5 and 12 d after (Post5 and Post12) training. Muscle biopsies were obtained Pre, after 8 d (Mid8), and 3 and 10 d after (Post3 and Post10) training to examine changes in myofiber area and expression of myocellular proteins known to be modified by cellular stress (CaMKII, annexin A6, SNO-CYS). Results RTD remained unchanged after BFR training at Post5, while increasing 15%–20% Post12 (P < 0.01). Evoked muscle twitch parameters showed a general decline Post5 (P < 0.01) while returning to baseline levels at Post12. All contractile parameters essentially remained unchanged in CON. Elevated CaMKII was observed with BFR training at Post3 (57%) and Post10 (71%) (P < 0.05), whereas SNO-CYS increased in CON at Mid8 (P < 0.05). Conclusion This study is the first to show that low-load resistance exercise performed with BFR leads to marked increases in rapid force capacity (RTD). However, a general delayed adaptive response was observed for voluntary contractile parameters (including RTD) in parallel with a decline and subsequent recovery in evoked contractile properties, suggesting the delayed gain in rapid force capacity mainly have a peripheral origin.

Physical function and muscle strength in sporadic inclusion body myositis

Introduction: In this study, self‐reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. Methods: The 36‐item Short Form (SF‐36) Health Survey and 2‐min walk test (2MWT), timed up & go test (TUG), and 30‐s chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). Results: TUG performance was the strongest predictor of self‐reported physical function (r2 = 0.56, P < 0.05). Knee extension strength and between‐limb strength asymmetry were the strongest multi‐regression indicators of TUG performance (r2 = 0.51, P < 0.05). Strength asymmetry showed the strongest single‐factor (negative) association with 2MWT performance (r2 = 0.49, P < 0.05). Discussion: TUG assessment appears to sensitively predict self‐perceived physical function in sIBM patients. Notably, between‐limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve 56: E50–E58, 2017