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. Anterior crural muscles (tibialis anterior, extensor digitorum longus [EDL], and extensor hallucis muscles) of wildtype (WT) and mdx mice were injured in vivo with 50 ECC contractions and torque was measured immediately before and after the contraction bout. Following the in vivo assessment, EDL ex vivo isometric and caffeine forces were analyzed. In vivo isometric torque and ex vivo force in WT muscle were reduced 38 and 30% (p < 0.001), while caffeine force was also reduced (p = 0.021), albeit to a lesser degree (9%). In contrast, in vivo isometric torque, ex vivo isometric force and ex vivo caffeine-induced force were all reduced 56-67% (p < 0.001) in mdx muscle and did not differ from one another (p = 0.114). Disproportional reductions in isometric strength and caffeine-induced force confirm that ECC contractions uncoupled the plasmalemma from the ryanodine receptors (RyRs) in WT muscle. In mdx muscle, the proportional reductions in isometric strength and caffeine-induced force following ECC contractions reveal that dysfunction occurs at and/or distal to the RyRs immediately post-injury. Thus, weakness in injured mdx muscle cannot be isolated to one mechanism, rather several steps of muscle contraction are disrupted.

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.

ABSTRACT: 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. However, because of the disparity in injury models, it is unknown whether three or more bouts provide further adaptation. Therefore, we performed a systematic review of the literature to evaluate whether a third bout of skeletal muscle ECC impacts immediate strength loss and rate of strength recovery compared with a second bout. A search of the literature in Web of Science, SCOPUS, Medline, and the American College of Sports Medicine database was conducted between May and September 2019 using the keywords eccentric contraction or lengthening contraction and muscle and repeated or multiple, and bout. Eleven studies with 12 experimental groups, using 72 human subjects, 48 mice, and 11 rabbits, met the inclusion criteria. A meta-analysis using a random effects model and effect sizes (ESs; Hedges' g) calculated from the standardized mean differences was completed. Calculated ESs for immediate strength loss provided no evidence that a third bout of ECC results in greater loss of strength compared with a second bout (ES = -0.12, 95% confidence interval [CI] = -0.41 to 0.17). Furthermore, the rate of strength recovery was not different between a second and third bout (ES = -0.15, 95% CI = -1.01 to 0.70). These results indicate a third bout of skeletal muscle ECC does not improve indices of strength loss or rate of strength recovery compared with a second bout. Therefore, coaches and athletes should expect some level of persistent weakness after each of their initial training sessions involving ECC, and the faster recovery of strength deficits in the second bout documented by previous research is not different from a third bout.

Downhill Running Impairs Activation and Strength of the Elbow Flexors.

ABSTRACT: 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. Subjects completed either downhill running for 1 hour (injured group; n = 6) or sedentary behavior (control group; n = 6). Strength and voluntary activation (%VA) were measured by isometric twitch interpolation of the elbow flexor and knee extensor muscles at the following time points in relation to the injury: before injury (Pre), after injury (Post), 24 hours after injury (24Post), and 48 hours after injury (48Post). Mean (±SE) knee extensor strength was significantly reduced (53.5 ± 9.9%) Post and remained reduced at 24Post and 48Post in the injury group. Knee extensor muscle twitch strength was reduced Post and 24Post after the downhill run (p < 0.022). Elbow flexor muscle strength was significantly reduced Post (13.2 ± 3.9%) and 24Post (17.3 ± 4.0%). Elbow flexor muscle twitch strength was not significantly different at any time point. Elbow flexor muscle %VA was not significantly reduced compared with Pre, at Post (16.2 ± 5.1%), 24Post (20.9 ± 6.7%), or 48Post (12.9 ± 4.5%). A 1-hour downhill run significantly injured the knee extensors. The elbow flexor muscles remained uninjured, but strength of these muscles was impaired by reduced %VA. These data suggest muscle injury can lead to prolonged strength deficits in muscles distant from the injury and should be accounted for when scheduling training that may lead to delayed-onset muscle soreness.

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. J Strength Cond Res 32(10): 2872-2877, 2018-Some studies suggest that exogenous melatonin supplementation may improve athletic performance in hot humid environments because of its precooling effect. However, melatonin is also consumed as a sleep aid for its depressive effects on the central nervous system (CNS), which may hinder performance. Therefore, this study was conducted to determine whether consuming a 5-mg supplement of melatonin would affect performance in a laboratory-simulated 32.2-km cycling time trial. The time trial was conducted in a thermoneutral environment to separate CNS depressive effects of the melatonin from the cooling effects. Trained male subjects (n = 10; V[Combining Dot Above]O2max = 62.7 ± 6.3 ml·kg·min; age = 25.1 ± 4.0 years; mass = 69.9 ± 9.1 kg; height = 176.0 ± 7.1 cm) performed three 32.2-km time trials on an electronically braked cycle ergometer. The first trial was a familiarization. During the 2 experimental trials, subjects received in a random order either a placebo or a 5-mg melatonin supplement 15 minutes before exercise in a double-blind, crossover design. Variables were measured before exercise and at 8-km intervals. The mean 32.2-km time trial completion times for the melatonin (64.94 ± 5.95 minutes) and placebo (65.26 ± 6.85 minutes) trials were not different (p = 0.682). The mean time trial power output for the melatonin (190.4 ± 40.4 watts) and placebo (190.0 ± 45.7 watts) trials was not different (p = 0.927). Rectal temperature was not significantly different for melatonin compared with placebo (p = 0.827). These results suggest that a 5-mg melatonin supplement administered 15 minutes before exercise does not measurably impact the performance of a 32.2-km cycling time trial in a thermoneutral environment.

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. These interventions also increase Ca(2+) influx to enhance refilling of sarcoplasmic reticulum Ca(2+) stores, slow muscle fatigue, and increase running endurance without negatively impacting cardiac function. FKBP12 deficiency or longer treatments with low dose rapamycin or SLF increase the percentage of type I fibers, further adding to fatigue resistance. We demonstrate that FKBP12 and its ligands impact multiple aspects of muscle function.

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. Maximal aerobic treadmill tests and blood samples were measured before and after supplementation to determine VO2max, hematocrit (Hct), and hemoglobin (Hb). VO2max, Hct, and Hb did not differ between the ECH and PLA groups before or after supplementation. Furthermore, supplementation of ECH failed to improve VO2max (67.37 ± 4.62 vs. 67.23 ± 5.82 ml·kg(-1)·min(-1)), Hct (43.57 ± 2.38 vs. 42.85 ± 1.46%), or Hb (14.93 ± 1.27 vs. 15.55 ± 0.80 g·dL(-1)) from baseline measurements. Echinacea purpurea supplementation of 8,000 mg·d(-1) for 6 weeks failed to increase VO2max, Hct, or Hb in trained endurance runners and thus does not seem to influence physiological variables that affect distance running performance.

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 ± 5.7 years; 50.05 ± 1.67 VO2peak). Running economy was determined at treadmill speeds eliciting 65 and 75% of the individual's peak rate of oxygen uptake (VO2peak) 1 day before and 2 days after injury induction. Lower extremity muscle injury was induced with a 30-minute downhill treadmill run (6 × 5 minutes runs, 2 minutes rest, -12% grade, and 12.9 km·h(-1)) that elicited 55% VO2peak. Maximal quadriceps isometric torque was reduced immediately and 2 days after the downhill run by 18 and 10%, and a moderate degree of muscle soreness was present. Two days after the injury, steady-state VO2 and metabolic work (VO2 L·km(-1)) were significantly greater (4-6%) during the 65% VO2peak run. Additionally, postinjury VCO2, VE and rating of perceived exertion were greater at 65% but not at 75% VO2peak, whereas whole blood-lactate concentrations did not change pre-injury to postinjury at either intensity. In conclusion, low-intensity downhill running reduces RE at 65% but not 75% VO2peak. The results of this study and other studies indicate the magnitude to which RE is altered after downhill running is dependent on the severity of the injury and intensity of the RE test.

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). NO has been shown to play a role in muscle regeneration after injury. However, less is known about its role during injury. In this study we aimed to determine whether NO synthase (NOS) inhibition exacerbates functional deficits immediately after the performance of eccentric contractions. METHODS: Wild-type mouse extensor digitorum longus (EDL) muscles underwent in vitro functional testing in the presence or absence of a non-specific NOS inhibitor (L-NAME, 10 mM) before and after performance of 10 eccentric contractions. RESULTS: After eccentric contractions, P(o) was reduced by ∽25% for muscle in regular physiological solution but by ∽50% with the addition of L-NAME (P = 0.009). CONCLUSIONS: Non-specific blockade of NOS exacerbates functional deficits immediately after eccentric contractions, suggesting that NO signaling protects skeletal muscle from excessive injury in healthy muscle.

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. Muscles from WT mice exhibited increased fatigue resistance and COX content after training. Muscles from RyR1Y522S/wt mice demonstrated no significant change in fatigability or COX and CS after training. However, muscles from RyR1Y522S/wt mice displayed less intrinsic fatigability and greater COX/CS content and muscle damage than WT mice. CONCLUSIONS: RyR1Y522S/wt mice can run without having rhabdomyolysis, and their inability to adapt to training appears to stem from intrinsic enhancement of mitochondrial enzymes and fatigue resistance.

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. METHODS: Anterior crural muscles of C57BL/6 female mice (3-5 months) were subjected to repeated bouts of in vivo ECCs, with isometric torque being measured immediately before and after injury. A total of six bouts were completed with 7 d between each bout. Protein content of dystrophin, ß-sarcoglycan, and junctophilin were then assessed via immunoblotting in injured and uninjured muscles. RESULTS: When expressed relative to preinjury isometric torque of bout 1, deficits in postinjury isometric torque during bout 2 (38%) did not differ from bout 1 (36%; P = 0.646) and were attenuated during bouts 3 through 6 (range, 24%-15%; P ≤ 0.014). Contents of dystrophin, ß-sarcoglycan, and junctophilin did not change immediately after a single bout of 50 maximal ECCs (P ≥ 0.155); however, as a result of repeated bouts, contents of dystrophin, ß-sarcoglycan, and junctophilin all increased compared with muscles that completed one or no bouts of ECC contractions (P ≤ 0.003). CONCLUSIONS: The RBE represents a physiological measure of skeletal muscle plasticity. Here, we demonstrate that repeated bouts of ECC contractions increase contents of dystrophin, ß-sarcoglycan, and junctophilin and attenuate postinjury torque deficits. Given our results, accumulation of membrane-associated proteins likely contributes to strength adaptations observed after repeated bouts of ECC contractions.

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., wheel running) exercise on the thermal sensitivity of isolated MH-susceptible mouse muscle (RyR1(Y522S/wt)). Eccentric, but not concentric, exercise attenuated the thermal sensitivity of MH-susceptible muscle.

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. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice.

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. Moreover, EDL muscle isometric specific force deficits were fully recovered for RYR1Y522S/wt but not WT mice 14 days postinjury. The percentage of fibers in TA muscle exhibiting signs of muscle damage 7 and 14 days postinjury were at least three times less in RYR1Y522S/wt than in WT mice. Uninjured and injured EDL muscle from RYR1Y522S/wt mice also displayed greater S-glutathionylation of RYR1 than that from WT mice. During the weekly injury bouts, torque production by RYR1Y522S/wt mice was fully recovered before the third and fourth injury bouts, whereas torque was still reduced for WT mice. Three days after multiple injury bouts, there were approximately 50% fewer fibers exhibiting signs of muscle damage in RYR1Y522S/wt than in WT TA muscle. These findings indicate that the RYR1Y522S/wt mutation protects skeletal muscle from exercise-induced muscle injury and do not support a direct association between MH susceptibility and contraction-induced rhabdomyolysis when core temperature is maintained at lower physiological temperatures during 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. Consistent with the decreased voltage-gated Ca2+ release, maximal tetanic force production is decreased and the force frequency curves are shifted to the right in extensor digitorum longus (EDL) muscles of the mutant mice. In contrast, there is no decrease in maximal tetanic force production in the mutant diaphragm or soleus muscle. The force frequency curve is shifted to the left in the FKBP12-deficient diaphragm muscle compared with controls. No changes in myosin heavy chain (MHC) phenotype are observed in EDL or soleus muscle of the FKBP12-deficient mice, but diaphragm muscle displays an increased ratio of slow to fast MHC isoforms. Also, calcineurin levels are increased in the diaphragm of the mutant mice but not in the soleus or EDL. In summary, FKBP12 deficiency alters both orthograde and retrograde coupling between the L-type Ca2+ channel and RyR1 and the consequences of these changes depend on muscle type and activity. In highly used muscles such as the diaphragm, adaptation to the loss of FKBP12 occurs, possibly due to the increased Ca2+ influx.

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. First, there was little, if any, attenuation in the immediate isometric torque losses after lengthening contractions at "physiological" stimulation frequencies (i.e., <125 Hz), although there was a pronounced decrease in torque loss at higher frequencies between the first and second bouts. Second, the immediate losses in strength that occurred after all five lengthening contraction bouts could be explained in part by excitation-contraction uncoupling. Third, the most important adaptation was a significant enhancement in the rate of recovery of strength after the lengthening contractions. It is probable that the accelerated rate of strength recovery resulted from the more rapid loss and subsequent recovery of myofibrillar protein observed after the fifth bout.

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., tibialis anterior, extensor digitorum longus, and extensor hallucis longus) of mice were injured in vivo by 150 eccentric contractions. Peak isometric tetanic torque of the anterior crural muscles was reduced approximately 45% immediately and 3 days after the eccentric contractions. Partial restoration of peak isometric tetanic and subtetanic forces of injured extensor digitorum longus muscles by 10 mM caffeine indicated the presence of excitation-contraction uncoupling. Scatchard analysis of [3H]ryanodine binding indicated that the number of ryanodine receptor binding sites was not altered immediately postinjury but decreased 16% 3 days later. Dihydropyridine receptor binding sites increased approximately 20% immediately after and were elevated to the same extent 3 days after the injury protocol. Muscle injury did not alter the sensitivity of either receptor. These data suggest that a loss or altered sensitivity of the dihydropyridine and ryanodine receptors does not contribute to the excitation-contraction uncoupling immediately after contraction-induced muscle injury. We also concluded that the loss in ryanodine receptors 3 days after injury is not the primary cause of excitation-contraction uncoupling at that time.

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. The cellular-level mechanisms explaining the loss of strength following contraction-induced muscle injury remain controversial. The traditional thought is that initial strength loss is due solely to damage to force-bearing structures within the muscle, as evidenced by histopathology. In addition, inflammation in the days following injury is commonly thought to exacerbate the strength loss. We present data to the contrary. Recent data show that most of the early strength loss results from a failure of excitation-contraction coupling processes and that a slow loss of contractile protein in the days following injury prolongs the time for recovery.

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. There were no changes in peak isometric torque or FKBP12 content in TA muscles after concentric contractions. However, FKBP12 content was reduced in the pelleted fraction immediately after eccentric contractions, and increased in the soluble protein fraction 3 day after injury induction. FKBP12 content was correlated (P = 0.025; R(2) = 0.38) to strength deficits immediately after injury induction. In summary, eccentric contraction-induced muscle injury is associated with significant alterations in FKBP12 content after injury, and is correlated with changes in peak isometric torque.

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). The aerobic characteristics were obtained during the aerobic treadmill test and included maximal oxygen uptake (VO2max), running economy, and ventilatory threshold (VT). RESULTS: Both the vMART (r = .69, P < .01) and VO2max (r = .80, P < .01) correlated with the mean velocity of the 5-km (v5km). A multiple-linear-regression analysis revealed that the combination of VO2max, vMART, and VT explained 81% (R2 = .81, P < .001) of the variation seen in the v5km. The vMART accounted for 31% of the total shared variance, while the combination of VO2max and VT explained the remaining 50%. CONCLUSIONS: These results suggest that among trained female runners who are relatively matched, anaerobic energy production can effectively discriminate the v5km and explain a significant amount of the variation seen in 5-km-race performance.

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. All patients were sedentary. RESULTS: Protein-HNE adducts were elevated 1.6-fold in T2DM compared with IS adults, whereas IR showed intermediate levels of HNE-modified proteins. Protein-HNE adducts correlated with GDR, waist circumference, and body mass index. IMCL was increased by 4.0- and 1.9-fold in T2DM and IR patients, respectively, compared with IS, and was correlated with GDR and waist circumference but not BMI. Protein carbonyls were not different among groups and did not correlate with any of the measured variables. Correlations were detected between IMCL and protein-HNE. CONCLUSION: Our data show for the first time that skeletal muscle protein-HNE adducts are related to the severity of insulin resistance in sedentary adults. These results suggest that muscle lipid peroxidation could be involved in the development of insulin resistance.