Perspectives on Exertional Rhabdomyolysis.

Exertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate.

Glucocorticoid Receptor (NR3C1) Variants Associate with the Muscle Strength and Size Response to Resistance Training.

Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European-American adults (n = 602, 23.

Relationships between physical activity and muscular strength among healthy adults across the lifespan.

The purpose of this study was to examine relationships between objective and self-report measures of physical activity and muscle strength among healthy adults ranging in age from 20 to 91 years. Participants (n = 412) were mostly Caucasian men (48 %) and women (52 %) 43.9 ± 16.

Pericyte NF-κB activation enhances endothelial cell proliferation and proangiogenic cytokine secretion in vitro.

Pericytes are skeletal muscle resident, multipotent stem cells that are localized to the microvasculature. In vivo, studies have shown that they respond to damage through activation of nuclear-factor kappa-B (NF-κB), but the downstream effects of NF-κB activation on endothelial cell proliferation and cell-cell signaling during repair remain unknown. The purpose of this study was to examine pericyte NF-κB activation in a model of skeletal muscle damage; and use genetic manipulation to study the effects of changes in pericyte NF-κB activation on endothelial cell proliferation and cytokine secretion.

Extracellular matrix remodeling and its contribution to protective adaptation following lengthening contractions in human muscle.

This study determined the contribution of extracellular matrix (ECM) remodeling to the protective adaptation of human skeletal muscle known as the repeated-bout effect (RBE). Muscle biopsies were obtained 3 hours, 2 days, and 27 days following an initial bout (B1) of lengthening contractions (LCs) and 2 days following a repeated bout (B2) in 2 separate studies. Biopsies from the nonexercised legs served as controls.

Effects of Atorvastatin on Resting and Peak Exercise Blood Pressure among Normotensive Men and Women.

Statins are the most widely prescribed and effective medication for reducing low density lipoprotein cholesterol. Statins may also lower resting blood pressure (BP); however, results are inconsistent. We sought to determine if the maximum dose of atorvastatin reduces resting BP and the peak systolic BP (SBP) achieved on a graded exercise stress test (GEST) among a large sample of 419 healthy men (48%) and women (52%).

SLC30A8 nonsynonymous variant is associated with recovery following exercise and skeletal muscle size and strength.

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise.

Increases in creatine kinase with atorvastatin treatment are not associated with decreases in muscular performance.

Background: The present study examined if increases in creatine kinase (CK) levels during high-dose atorvastatin treatment are associated with changes in skeletal muscle function and symptoms.

Methods: The Effect of Statins on Muscle Performance study (STOMP) investigated the effects of atorvastatin 80 mg daily for 6 months on muscle performance, exercise capacity, and the incidence of statin-associated muscle complaints in healthy adults.

Results: CK levels increased with atorvastatin (n = 202) from 132.

A contralateral repeated bout effect attenuates induction of NF-κB DNA binding following eccentric exercise.

We investigated the existence of contralateral repeated bout effect and tested if the attenuation of nuclear factor-kappa B (NF-κB; an important regulator of muscle inflammation) induction following eccentric exercise is a potential mechanism. Thirty-one healthy men performed two bouts of knee extension eccentric exercise, initially with one leg and then with the opposite leg 4 wk later. Vastus lateralis muscle biopsies of both exercised and control legs were taken 3 h postexercise.

NF-KB activity functions in primary pericytes in a cell- and non-cell-autonomous manner to affect myotube formation.

Introduction: Skeletal muscle regeneration following damage relies on proliferation and differentiation of muscle precursor cells (MPCs). We recently observed increased NF-kB activity in vascular-associated muscle resident pericytes following muscle damage in humans. We determined how altered NF-kB activity in human primary pericytes (HPPs) affects their myogenic differentiation (cell-autonomous effects), as well as proliferation and differentiation of co-cultured MPCs (non-cell-autonomous effects).

Alterations in osteopontin modify muscle size in females in both humans and mice.

Purpose: An osteopontin (OPN; SPP1) gene promoter polymorphism modifies disease severity in Duchenne muscular dystrophy, and we hypothesized that it might also modify muscle phenotypes in healthy volunteers.

Methods: Gene association studies were carried out for OPN (rs28357094) in the FAMuSS cohort (n = 752; mean ± SD age = 23.7 ± 5.

Effect of statins on skeletal muscle function.

Background: Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied.

Methods And Results: The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.

25(OH) vitamin D is associated with greater muscle strength in healthy men and women.

Purpose: The purpose of the study was to examine the relation between serum 25-hydroxy vitamin D (25(OH)D) levels and muscle strength in 419 healthy men and women over a broad age range (20-76 yr).

Methods: Isometric and isokinetic strength of the arms and legs was measured using computerized dynamometry, and its relation to vitamin D was tested in multivariate models controlling for age, gender, resting HR, systolic blood pressure, diastolic blood pressure, body mass index, maximal oxygen uptake (VO(2max)), physical activity counts, and season of vitamin D measurement.

Results: Vitamin D was significantly associated with arm and leg muscle strength when controlling for age and gender.

Effects of quercetin supplementation on markers of muscle damage and inflammation after eccentric exercise.

The flavonoid quercetin is purported to have potent antioxidant and anti-inflammatory properties. This study examined if quercetin supplementation attenuates indicators of exercise-induced muscle damage in a double-blind laboratory study. Thirty healthy subjects were randomized to quercetin (QU) or placebo (PL) supplementation and performed 2 separate sessions of 24 eccentric contractions of the elbow flexors.

Variants of the ankyrin repeat domain 6 gene (ANKRD6) and muscle and physical activity phenotypes among European-derived American adults.

Ankyrin repeat domain 6 (ANKRD6) is a ubiquitous protein that associates with early development in mammals and is highly expressed in the brain, spinal cord, and heart of humans. We examined the role of 8 ANKRD6 single-nucleotide polymorphisms (SNPs) on muscle performance and habitual physical activity (PA). Single-nucleotide polymorphisms were 545 T>A (rs9362667), 485 M>L (rs61736690), 233 T>M (rs2273238), 128 I>L (rs3748085), 631 P>L (rs61739327), 122 Q>E (rs16881983), 197805 G>A (rs9344950), and 710 L>X (NOVEL).

Transcriptional deficits in oxidative phosphorylation with statin myopathy.

Introduction: Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are widely used drugs for hyperlipidemia and are generally well-tolerated, but the can produce skeletal muscle toxicity. The molecular mechanisms driving statin myopathy are unknown. We investigated the effects of statin treatment and eccentric (damaging) exercise on transcriptional patterns between statin myopathy (Sym; N = 9) and statin-tolerant subjects (Asym; N = 6).

Activation of nuclear factor-κB following muscle eccentric contractions in humans is localized primarily to skeletal muscle-residing pericytes.

Limited data exist on the molecular mechanisms that govern skeletal muscle regeneration in humans. This study characterized the early molecular alterations in humans to eccentric contractions (ECs), a stimulus known to induce a muscle regenerative response. Thirty-five subjects completed 100 ECs of the knee extensors with 1 leg, and muscle biopsies were taken from both legs 3 h post-EC.

The 1p13.3 LDL (C)-associated locus shows large effect sizes in young populations.

Genome-wide association studies (GWASs) have identified polymorphic loci associated with coronary artery disease (CAD) risk factors (i.e. serum lipids) in adult populations (42-69 y).

AKT1 polymorphisms are associated with risk for metabolic syndrome.

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin,insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that makeup metabolic syndrome.

CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training.

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation.

Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans.

Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age ± SD = 22.1 ± 3.

Knockdown of metallothionein 1 and 2 does not affect atrophy or oxidant activity in a novel in vitro model.

Skeletal muscle atrophy is a significant health problem that results in decreased muscle size and function and has been associated with increases in oxidative stress. The molecular mechanisms that regulate muscle atrophy, however, are largely unknown. The metallothioneins (MT), a family of genes with antioxidant properties, have been found to be consistently upregulated during muscle atrophy, although their function during muscle atrophy is unknown.