Mechanisms of weakness in Mdx muscle following in vivo eccentric contractions.

Skeletal muscle of the dystrophin-deficient mdx mouse is hypersensitive to eccentric (ECC) contraction-induced strength loss due to plasmalemmal electrical dysfunction. Despite plasmalemmal inexcitability being a logical mechanism responsible for weakness, it remains unclear if processes up- and/or down-stream remain functionally intact in injured mdx muscle. The purpose of this study was to analyze additional processes necessary for excitation-contraction coupling that are potentially disrupted by ECC contractions.

Membrane Proteins Increase with the Repeated Bout Effect.

Purpose: The ability of skeletal muscle to adapt to eccentric (ECC) contraction-induced injury is known as the repeated bout effect (RBE). Despite the RBE being a well-established phenomenon observed in skeletal muscle, cellular and molecular events particularly those at the membranes that contribute to the adaptive potential of muscle have yet to be established. Therefore, the purpose of this study was to examine how membrane-associated proteins respond to the RBE.

Muscle Strength Does Not Adapt From a Second to Third Bout of Eccentric Contractions: A Systematic Review and Meta-Analysis of the Repeated Bout Effect.

Lindsay, A, Abbott, G, Ingalls, CP, and Baumann, CW. Muscle strength does not adapt from a second to third bout of eccentric contractions: A systematic review and meta-analysis of the repeated bout effect. J Strength Cond Res 35(2): 576-584, 2021-The greatest muscle strength adaptations to repeated bouts of eccentric contractions (ECC) occur after the initial injury, with little to no change in subsequent bouts.

Downhill Running Impairs Activation and Strength of the Elbow Flexors.

Brandenberger, KJ, Warren, GL, Ingalls, CP, Otis, JS, and Doyle, JA. Downhill running impairs activation and strength of the elbow flexors. J Strength Cond Res 35(8): 2145-2150, 2021-The purpose of this study was to determine if knee extensor injury induced by 1 hour of downhill running attenuated force production in the elbow flexors.

Consumption of a 5-mg Melatonin Supplement Does Not Affect 32.2-km Cycling Time Trial Performance.

Brandenberger, KJ, Ingalls, CP, Rupp, JC, and Doyle, JA. Consumption of a 5-mg melatonin supplement does not affect 32.2-km cycling time trial performance.

Recovery of strength is dependent on mTORC1 signaling after eccentric muscle injury.

Introduction: Eccentric contractions may cause immediate and long-term reductions in muscle strength that can be recovered through increased protein synthesis rates. The purpose of this study was to determine whether the mechanistic target-of-rapamycin complex 1 (mTORC1), a vital controller of protein synthesis rates, is required for return of muscle strength after injury.

Methods: Isometric muscle strength was assessed before, immediately after, and then 3, 7, and 14 days after a single bout of 150 eccentric contractions in mice that received daily injections of saline or rapamycin.

Eccentric contractions disrupt FKBP12 content in mouse skeletal muscle.

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from impaired voltage-gated sarcoplasmic reticulum (SR) Ca(2+) release. FKBP12 is a 12-kD immunophilin known to bind to the SR Ca(2+) release channel (ryanodine receptor, RyR1) and plays an important role in excitation-contraction coupling. To assess the effects of eccentric contractions on FKBP12 content, we measured anterior crural muscle (tibialis anterior [TA], extensor digitorum longus [EDL], extensor hallucis longus muscles) strength and FKBP12 content in pellet and supernatant fractions after centrifugation via immunoblotting from mice before and after a single bout of either 150 eccentric or concentric contractions.

Ligands for FKBP12 increase Ca2+ influx and protein synthesis to improve skeletal muscle function.

Rapamycin at high doses (2-10 mg/kg body weight) inhibits mammalian target of rapamycin complex 1 (mTORC1) and protein synthesis in mice. In contrast, low doses of rapamycin (10 μg/kg) increase mTORC1 activity and protein synthesis in skeletal muscle. Similar changes are found with SLF (synthetic ligand for FKBP12, which does not inhibit mTORC1) and in mice with a skeletal muscle-specific FKBP12 deficiency.

Muscle injury after low-intensity downhill running reduces running economy.

Contraction-induced muscle injury may reduce running economy (RE) by altering motor unit recruitment, lowering contraction economy, and disturbing running mechanics, any of which may have a deleterious effect on endurance performance. The purpose of this study was to determine if RE is reduced 2 days after performing injurious, low-intensity exercise in 11 healthy active men (27.5 ± 5.

Echinacea purpurea supplementation does not enhance VO2max in distance runners.

Oral supplementation of Echinacea purpurea (ECH) has been reported to increase levels of serum erythropoietin and as a result improve endurance performance in untrained subjects. The purpose of this study was to determine if ECH supplementation alters maximal oxygen uptake (VO2max) in trained endurance runners. Using a double-blind design, 16 trained endurance runners (9 ECH and 7 placebo [PLA]) supplemented with either 8,000 mg·d(-1) of ECH or wheat flour (PLA) for 6 weeks.

Immediate force loss after eccentric contractions is increased with L-NAME administration, a nitric oxide synthase inhibitor.

Introduction: Nitric oxide (NO) signaling regulates many biological processes in skeletal muscle, wherein aberrant signaling contributes to myopathic conditions (e.g., Duchenne muscular dystrophy).

Skeletal muscle lipid peroxidation and insulin resistance in humans.

Objective: The relationships among skeletal muscle lipid peroxidation, intramyocellular lipid content (IMCL), and insulin sensitivity were evaluated in nine insulin-sensitive (IS), 13 insulin-resistant (IR), and 10 adults with type 2 diabetes (T2DM).

Design: Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp [glucose disposal rate (GDR)]. Lipid peroxidation was assessed by 4-hydroxynonenal (HNE)-protein adducts and general oxidative stress by protein carbonyl content.

Oxidative capacity and fatigability in run-trained malignant hyperthermia-susceptible mice.

Introduction: The purpose of this study was to test the hypothesis that malignant hyperthermia model mice (RyR1Y522S/wt) are more vulnerable to exercise-induced muscle injury and fatigability and adapt less to run training.

Methods: After 6 weeks of voluntary wheel running, we measured anterior crural muscle fatigability, muscle injury, and cytochrome oxidase (COX) and citrate synthase (CS).

Results: Although RyR1Y522S/wt mice ran without undergoing MH episodes, they ran 42% less distance than wild-type (WT) mice.

Anaerobic work capacity's contribution to 5-km-race performance in female runners.

Purpose: The purpose of this study was to examine the relationship between anaerobic characteristics and 5-km-race performance in trained female cross-country runners (N = 13).

Methods: The runners performed 50-m sprints and a 5-km time trial on an outdoor 400-m track and maximal anaerobic (MART) and aerobic running tests on a motorized treadmill. Anaerobic characteristics were determined by the mean velocity of the 50-m sprint (v50m) and the peak velocity in the MART (vMART).

Adaptation of insulin-resistance indicators to a repeated bout of eccentric exercise in human skeletal muscle.

This study determined whether disrupted glucose and insulin responses to an oral glucose-tolerance test (OGTT) induced by eccentric exercise were attenuated after a repeated bout. Female participants (n = 10, age 24.7 +/- 3.

Effect of prior exercise on thermal sensitivity of malignant hyperthermia-susceptible muscle.

Malignant hyperthermia (MH) episodes may occur upon exposure to halogenated anesthetics, during resistance and endurance exercise, and in response to thermal stress. The purpose of this study was to investigate the effects of prior eccentric and concentric (i.e.

Eccentric contractions do not induce rhabdomyolysis in malignant hyperthermia susceptible mice.

Recent studies suggest a link between exercise-induced rhabdomyolysis and mutations of the ryanodine receptor (RYR1) associated with malignant hyperthermia (MH). We hypothesized that MH-susceptible mice (RYR1Y522S/wt) would exhibit greater anterior crural muscle [tibialis anterior (TA) and extensor digitorum longus (EDL) muscles] damage and strength deficits following the performance of a single or repeated bouts of eccentric contractions compared with wild-type (WT) mice. After a single injury bout, RYR1Y522S/wt mice produced more isometric torque than WT mice immediately and 3 and 7 days postinjury.

FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury.

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts.

Carbohydrate-protein drinks do not enhance recovery from exercise-induced muscle injury.

This study examined the effects of carbohydrate (CHO), carbohydrate-protein (CHO+PRO), or placebo (PLA) beverages on recovery from novel eccentric exercise. Female participants performed 30 min of downhill treadmill running (-12% grade, 8.0 mph), followed by consumption of a CHO, CHO+PRO, or PLA beverage immediately, 30, and 60 min after exercise.

Altered excitation-contraction coupling with skeletal muscle specific FKBP12 deficiency.

The immunophilin FKBP12 binds the skeletal muscle Ca2+ release channel or ryanodine receptor (RyR1), but the functional consequences of this interaction are not known. In this study, we have generated skeletal muscle specific FKBP12-deficient mice to investigate the role of FKBP12 in skeletal muscle. Primary myotubes from these mice show no obvious change in either Ca2+ stores or resting Ca2+ levels but display decreased voltage-gated intracellular Ca2+ release and increased L-type Ca2+ currents.

Adaptation to lengthening contraction-induced injury in mouse muscle.

Adaptations to repeated bouts of injury-inducing lengthening contractions were studied in mouse anterior crural muscles. Five bouts of 150 lengthening contractions were performed in vivo, with each bout separated by 2 wk of rest. Three primary observations were made.

Dihydropyridine and ryanodine receptor binding after eccentric contractions in mouse skeletal muscle.

The purpose of this study was to determine whether there are alterations in the dihydropyridine and/or ryanodine receptors that might explain the excitation-contraction uncoupling associated with eccentric contraction-induced skeletal muscle injury. The left anterior crural muscles (i.e.

Temperature dependency of force loss and Ca(2+) homeostasis in mouse EDL muscle after eccentric contractions.

The goals of this study were first to determine the effect of temperature on the force loss that results from eccentric contractions in mouse extensor digitorum longus (EDL) muscles and then to evaluate a potential role for altered Ca(2+) homeostasis explaining the greater isometric force loss observed at the higher temperatures. Isolated muscles performed five eccentric or five isometric contractions at either 15, 20, 25, 30, 33.5, or 37 degrees C.

What mechanisms contribute to the strength loss that occurs during and in the recovery from skeletal muscle injury?

In the workplace or on the athletic field, muscle strength can be decreased by 50% or more following performance of a relatively few high-force, eccentric contractions. The strength loss can be prolonged, taking a month or more for complete recovery. It is important to understand the cause(s) of the strength loss so we can develop means of preventing or attenuating this loss.