Plasma Myoglobin Research Articles

Small heat shock proteins translocate to the cytoskeleton in human skeletal muscle following eccentric exercise independently of phosphorylation

Small heat shock proteins (sHSPs) are a subgroup of the highly conserved family of HSPs that are stress inducible and confer resistance to cellular stress and injury. This study aimed to quantitatively examine whether type of contraction (concentric or eccentric) affects sHSPs, HSP27 and αB-crystallin, localization, and phosphorylation in human muscle. Vastus lateralis muscle biopsies from 11 healthy male volunteers were obtained pre- and 3 h, 24 h, and 7 days following concentric (CONC), eccentric (ECC1), and repeated bout eccentric (ECC2) exercise. No changes were apparent in a control group (n = 5) who performed no exercise. Eccentric exercise induced muscle damage, as evidenced by increased muscle force loss, perceived muscle soreness, and elevated plasma creatine kinase and myoglobin levels. Total HSP27 and αB-crystallin amounts did not change following any type of exercise. Following eccentric exercise (ECC1 and ECC2) phosphorylation of HSP27 at serine 15 (pHSP27-Ser15) was increased approximately 3- to 6-fold at 3 h, and pαB-crystallin-Ser59 increased ~10-fold at 3 h. Prior to exercise most of the sHSP and psHSP pools were present in the cytosolic compartment. Eccentric exercise resulted in partial redistribution of HSP27 (~23%) from the cytosol to the cytoskeletal fraction (~28% for pHSP27-Ser15 and ~7% for pHSP27-Ser82), with subsequent full reversal within 24 h. αB-crystallin also showed partial redistribution from the cytosolic to cytoskeletal fraction (~18% of total) 3 h post-ECC1, but not after ECC2. There was no redistribution or phosphorylation of sHSPs with CONC. Eccentric exercise results in increased sHSP phosphorylation and translocation to the cytoskeletal fraction, but the sHSP translocation is not dependent on their phosphorylation.

The Effects of High Intensity Short Rest Resistance Exercise on Muscle Damage Markers in Men and Women

Within and between sexes, universal load prescription (as assigned in extreme conditioning programs) creates extreme ranges in individual training intensities. Exercise intensity has been proposed to be the main factor determining the degree of muscle damage. Thus, the purpose of this study was to examine markers of muscle damage in resistance-trained men (n = 9) and women (n = 9) from a high intensity (HI) short rest (SR) (HI/SR) resistance exercise protocol. The HI/SR consisted of a descending pyramid scheme starting at 10 repetitions, decreasing 1 repetition per set for the back squat, bench press, and deadlift, as fast as possible. Blood was drawn pre-exercise (pre), immediately postexercise (IP), 15 minutes postexercise (+15), 60 minutes postexercise (+60), and 24 hours postexercise (+24). Women demonstrated significant increases in interleukin 6 (IL-6; IP), creatine kinase (CK; +24), myoglobin (IP, +15, +60), and a greater relative increase when compared with men (+15, +60). Men demonstrated significant increases in myoglobin (IP, +15, +60, +24), IL-6 (IP, +15), CK (IP, +60, +24), and testosterone (IP, +15). There were significant sex interactions observed in CK (IP, +60, +24) and testosterone (IP, +15, +60, +24). Women completed the protocol faster (women: 34:04 ± 9:40 minutes, men: 39:22 ± 14:43 minutes), and at a slightly higher intensity (women: 70.1 ± 3.5%, men 68.8 ± 3.1%); however, men performed significantly more work (men: 14384.6 ± 1854.5 kg, women: 8774.7 ± 1612.7 kg). Overall, women demonstrated a faster inflammatory response with increased acute damage, whereas men demonstrated a greater prolonged damage response. Therefore, strength and conditioning professionals need to be aware of the level of stress imposed on individuals when creating such volitional high intensity metabolic type workouts and allow for adequate progression and recovery from such workouts.

Eccentric exercise-induced muscle damage of pre-adolescent and adolescent boys in comparison to young men

This study compared changes in indirect muscle damage markers after maximal eccentric exercise of the elbow flexors (EF) among pre-adolescent (9-10 years), adolescent (14-15 years) and post-adolescent (20-25 years) men to test the hypothesis that the magnitude of muscle damage would increase with increase in age. Thirteen untrained men of each age group performed two bouts (ECC1, ECC2) of 30 maximal EF eccentric contractions. Several indirect muscle damage markers were measured from the exercised arm before, immediately after, and 1-5 days post-exercise. Changes in maximal voluntary concentric contraction torque of the EF (MVC), range of motion of the elbow joint, upper arm circumference (CIR), muscle passive stiffness, muscle soreness, plasma creatine kinase activity and myoglobin concentration after ECC1 and ECC2 were compared amongst groups by a mixed-design two-way ANOVA. MVC before exercise was smaller (P < 0.05) for pre-adolescent (8.9 ± 1.9 Nm) than adolescent (25.1 ± 3.9 Nm) and adult (35.3 ± 4.6 Nm), and for adolescent than adult. Changes in all variables after ECC1 were smaller (P < 0.05) for pre-adolescent and adolescent when compared with adult, and all except CIR changes were smaller (P < 0.05) for pre-adolescent than adolescent. After ECC2, changes in all variables were smaller (P < 0.05) than those after ECC1 for all groups, but the magnitude of the changes was different among groups (P < 0.05) in the same way as that after ECC1. These results indicate that the magnitude of muscle damage is increased from pre-adolescent, adolescent to post-adolescent men.

Effects of Acute Resistance Exercise on Muscle Damage and Perceptual Measures Between Men Who Are Lean and Obese

The purpose of this investigation was to assess indices of muscle damage and psychological stress between young, untrained, lean, and obese men. Using a between-subject design, 19 young men (9 lean men [age, 20.1 ± 2.1 years; body mass, 71.7 ± 5.8 kg; height, 177.8 ± 8.7 cm; body fat (BF), 14.7 ± 3.5%], 5 World Health Organization [WHO] class 1 obese men [age, 21.6 ± 2.5 years; body mass, 97.8 ± 8.6 kg; height, 176.3 ± 3.7 cm; BF, 34.7 ± 3.0%], and 5 WHO class 2 or 3 men [age, 20.0 ± 1.4 years; body mass, 120.8 ± 10.5 kg; height, 177.7 ± 5.2 cm; BF, 40.5 ± 5.8%]) volunteered and completed an acute resistance exercise (RE) protocol (6 exercises performed for 3 sets of 10 repetitions at an intensity of 85-95% of a 10 repetition maximum). Plasma myoglobin and serum creatine kinase were obtained before and immediately after exercise, and in recovery (at +110 minutes and +24 hours). Perceptual measures including rating of perceived exertion, pain and soreness, fatigue, and general soreness were assessed at different time points (during exercise for rating of perceived exertion, and for the fatigue and soreness measures before, immediately after, and at 24 hours of recovery from exercise). The primary findings of this investigation were that lean and obese, sedentary, young men do not significantly differ from each other in terms of indirect, humoral measures of muscle damage, or perceptual scales in response to a moderate-intensity acute RE bout, despite using significantly more exercise volume relative to fat mass (FM). We conclude that excess FM during daily activities of life provides a protective effect for muscle damage. When strength training individuals who are obese, practitioners should be aware of how excess FM affects muscle damage and total volume. But these considerations do not preclude individuals who are obese from using well-designed RE workouts which use free-weight, multijoint movements that stimulate all of the major muscle groups.

Transcriptome analysis of neutrophils after endurance exercise reveals novel signaling mechanisms in the immune response to physiological stress

Neutrophils serve as an intriguing model for the study of innate immune cellular activity induced by physiological stress. We measured changes in the transcriptome of circulating neutrophils following an experimental exercise trial (EXTRI) consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Blood samples were taken at baseline, 3 h, 48 h, and 96 h post-EXTRI from eight healthy, endurance-trained, male subjects. RNA was extracted from isolated neutrophils. Differential gene expression was evaluated using Illumina microarrays and validated with quantitative PCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Blood concentrations of muscle damage indexes, neutrophils, interleukin (IL)-6 and IL-10 were increased (P < 0.05) 3 h post-EXTRI. Upregulated groups of functionally related genes 3 h post-EXTRI included gene sets associated with the recognition of tissue damage, the IL-1 receptor, and Toll-like receptor (TLR) pathways (familywise error rate, P value < 0.05). The core enrichment for these pathways included TLRs, low-affinity immunoglobulin receptors, S100 calcium binding protein A12, and negative regulators of innate immunity, e.g., IL-1 receptor antagonist, and IL-1 receptor associated kinase-3. Plasma myoglobin changes correlated with neutrophil TLR4 gene expression (r = 0.74; P < 0.05). Neutrophils had returned to their nonactivated state 48 h post-EXTRI, indicating that their initial proinflammatory response was transient and rapidly counterregulated. This study provides novel insight into the signaling mechanisms underlying the neutrophil responses to endurance exercise, suggesting that their transcriptional activity was particularly induced by damage-associated molecule patterns, hypothetically originating from the leakage of muscle components into the circulation.

Eccentric exercise transiently affects mice skeletal muscle mitochondrial function

Eccentric exercise (EE) is known to induce damage and dysfunction in skeletal muscle. However, the possible role of mitochondrial (dys)function, including the vulnerability to mitochondrial permeability transition pore (MPTP) opening, is unclear. Therefore, this study aimed to analyze the impact of a single acute bout of downhill running on skeletal muscle mitochondrial function. Thirty 12-week-old Charles River CD1 male mice were randomly assigned into control (C) or exercised groups. EE consisted of 120 min of downhill treadmill running at a -16° gradient. Exercised animals were sacrificed immediately (Ecc0h) and 48 h (Ecc48h) after the end of the running bout. Plasma and skeletal muscles were then obtained. Muscle mitochondrial function, including oxygen consumption prior to and after anoxia and reoxygenation, membrane potential, and MPTP opening, were evaluated. Respiratory chain complexI, II, and V activities were determined. EE significantly increased plasma creatine kinase activity (119.4 ± 5.6 vs. 1061.3 ± 46.3 vs. 256.8 ± 15.3 U·L(-1), C, Ecc0h and Ecc48h, respectively) and myoglobin and interleukin-6 content. Impaired state 3 and respiratory control ratio (8.4 ± 0.4 vs. 5.6 ± 0.9 vs. 8.4 ± 0.5, C, Ecc0h and Ecc48h, respectively), as well as increased susceptibility to MPTP opening, seen by cyclosporin A-sensitive high swelling amplitude, lower time to maximal swelling velocity (313.8 ± 17.7 vs. 244.5 ± 19.4 vs. 298.5 ± 8.7 s, C, Ecc0h and Ecc48h, respectively), and calcium release immediately after the end of exercise (C vs. Ecc0h) were observed. EE induced a transient impairment in the activity of complex V (C vs. Ecc0h). No significant changes from the C group were observed 48 h after the end of EE (C vs. Ecc48h) in any analyzed parameters. In conclusion, prolonged EE transiently impaired mice skeletal muscle mitochondrial function and increased susceptibility to calcium-induced MPTP opening.

Abstract TMP104: Arm Ischemic Preconditioning Prevents Stroke Recurrence in Octogenarians with Intracranial Arterial Stenosis

Introduction: Symptomatic atherosclerotic intracranial arterial stenosis (SAIS) has a high incidence of stroke and recurrence, especially in octogenarians. Currently available therapies including stenting are unable to prevent strokes recurrence completely and may result in worse clinical outcomes. Emerging experimental investigations have suggested that remote ischemic preconditioning may be clinically effective in stroke intervention. Hypothesis: Brief repetitive bilateral arm ischemic preconditioning (BAIPC) may be safe and prevent stroke occurrence and recurrence in octogenarians with SAIS. Methods: A total of 58 consecutive octogenarians with SIAS (diagnosed by imaging) enrolled in this prospective, single blind and randomized study. All patients enrolled underwent standard medical care. In addition, patients in BAIPC group (n=30) underwent five cycles consisting of bilateral arms 5min ischemia followed by 5min reperfusion twice daily for the total of 180 consecutive days. Blood pressure, heart rate, local skins integrity and plasma myoglobin levels before and during the first 30-days of treatment were documented. Finally, Plasma levels of thrombosis and inflammation markers, clinical outcomes (modified Rankin Scale 0-1) and the incidence of stroke recurrence during the180-days of treatment in the two groups were compared. Clinical Trial Registration-URL: www.clinicaltrials.gov , unique identifier: NCT01570231 . Results: Compared to the controls (n=28), BAIPC had no adverse effects on blood pressure, heart rate, local skins integrity and plasma myoglobin, and BAIPC did not contribute to cerebral hemorrhage. BAIPC decreased plasma levels of hsCRP, IL-6, PAI-1, leukocyte count, platelet aggregation rate as well as increased TPA, improved the 180-days of modified Rankin Scale and decreased the incidences of ischemic stroke recurrence and TIA onset (6.7% and 23.3% in BAIPC group versus 28.6% and 39.3% in control group, P &lt; 0.01). Conclusions: Our study provides a proof-of-concept that BAIPC is a safe and feasible method to protect the ischemic brain in octogenarians with SIAS. Further investigation in an enlarged trial is ongoing.

High Cut-Off Renal Replacement Therapy for Removal of Myoglobin in Severe Rhabdomyolysis and Acute Kidney Injury: A Case Series

Background/Aim: Rhabdomyolysis is associated with the release of myoglobin into the circulation, promoting acute kidney injury (AKI). In severe rhabdomyolysis, dialysis-dependent AKI doubles mortality. Standard blood purification techniques have limited efficacy in removing myoglobin. We describe high cut-off (HCO) renal replacement therapy (RRT) as a novel approach for extracorporeal elimination of myoglobin in rhabdomyolysis-associated AKI. Methods: With an in vivo molecular cut-off at 45 kDa, HCO filters are effective in removing myoglobin (17.8 kDa). Clearances across standard and HCO filters using continuous or intermittent RRT are reviewed in a case series of 11 patients with severe rhabdomyolysis and dialysis-dependent AKI. Results: Median myoglobin clearance across standard high-flux filters was 3.3 (interquartile range 2.3–3.9) ml/min for sustained low-efficiency daily dialysis (SLEDD) batch hemodialysis (HD) and 3.7 (2.9–6.7) ml/min for conventional HD. Respective clearances using HCO filters (membrane surface area: 1.1 m²) were 21.7 (20.3–26.1) ml/min (SLEDD) and 44.2 (41.3–47.0) ml/min (HD). Corrected for filter size, up to 20-fold higher clearances were obtained using HCO filters, resulting in profound and sustained reduction of plasma myoglobin concentration. Conclusions: As a novel approach, HCO RRT allows for rapid and effective removal of myoglobin from the circulation. In light of the pathogenic role in AKI, reducing exposure of the kidney to myoglobin may improve renal recovery and patient outcome. Our data pave the way for prospective trials, addressing this issue.

Effect of two maximal isometric contractions on eccentric exercise-induced muscle damage of the elbow flexors

This study investigated the time wise protective effect conferred by two maximal voluntary isometric contractions (2MVCs) at 20° elbow flexion on muscle damage induced by 30 maximal isokinetic (60° s(-1)) eccentric contractions of the elbow flexors (MaxECC). Sixty-five young untrained men were randomly assigned to a control group that did not perform 2MVCs, or one of four experimental groups (n = 13 per group) who performed 2MVCs either immediately (0d), 2 (2d), 4 (4d) or 7 days (7d) before MaxECC. Changes in maximal isokinetic (60° s(-1)) concentric torque (MVC-CON), optimum angle (OA), range of motion, upper arm circumference, muscle soreness, plasma creatine kinase activity and myoglobin concentration, and ultrasound echo-intensity following MaxECC were compared among the groups by a two-way repeated measures ANOVA. No significant changes in any variables were evident following 2MVCs. The 2d and 4d groups showed 16-62 % smaller (P < 0.05) changes in all variables following MaxECC than the control, 0d and 7d groups. The 2d group showed 14-34 % smaller (P < 0.05) changes in all variables except for OA compared with the 4d group. The changes in the variables were similar among the control, 0d and 7d groups. These results show that 2MVCs that were performed between 2 and 4 days before MaxECC attenuated the magnitude of muscle damage, but no such effect was evident if the 2MVCs were performed immediately or 7 days before MaxECC. It is concluded that the protective effect conferred by 2MVCs is relatively short-lived, and there is a window for the effect to be conferred.

Electrochemical sensor systems based on one dimensional (1D) nanostructures for analysis of bioaffinity interactions

It was shown that modification of screen printed graphite electrodes with gold nanoparticles (AuNPs) decorated Pb nanowires (PbNWs) demonstrates the enhancement of sensor's analytical characteristics such as effective surface area, electro catalytic properties and heterogeneous electron transfer kinetics. The reason for such improvement may be the synergistic effect ofAuNPs and PbNWs. Nanowires ensembles on electrode surface were employed for the detection of hemeproteins cytochrome P450 2B4, cytochrome c, and cardiac myoglobin in human plasma. Composite materials based on nanoparticles with different dimentions (3D three dimensional gold nanoparticles and 1D one dimensional Pb nanowires make it possible to construct biosensors with low detection limit of proteins.

Prognostic Implications of Plasma Myoglobin Levels in Patients with Chronic Kidney Disease

Purpose Poor cardiovascular outcomes in chronic kidney disease (CKD) patients have prompted nephrologists to look for biomarkers that may improve risk stratification in this population. The objective of this study was to evaluate plasma myoglobin (Mb) levels according to the CKD stage and to determine whether they are associated with overall, cardiovascular (CV) mortality, CV events, and renal outcomes. Methods Plasma Mb levels were determined in 140 CKD patients at different stage (mean ± SD age: 67 ± 12; males: 61%) who were prospectively monitored for overall and CV mortality, CV events and CKD progression. Twenty-seven healthy subjects served as controls. Results Plasma Mb levels were higher in CKD patients than in controls and progressively increased as the glomerular filtration rate fell. Hemoglobin levels, CKD stage, the aortic calcification score and brain natriuretic peptide levels were associated with plasma Mb concentrations. In a multivariate analysis, only CKD stage was associated with Mb levels. During follow up (mean duration: 968 ± 374 days), 44 patients died and 63 had a cardiovascular event. In a crude analysis, plasma Mb &gt;73.8 μg/l predicted overall and cardiovascular mortality and the occurrence of cardiovascular events (p = 0.01, 0.05 and 0.01, respectively). However, this association was lost after adjustment for other prognostic factors for mortality. Plasma Mb was not a significant predictor of the progression of CKD either. Conclusions Plasma Mb levels were significantly higher in predialysis or dialyzed CKD patients than in healthy controls. However, we could not identify a relevant clinical outcome associated with this elevation. Larger studies are needed to confirm the present results.

Attenuation of Eccentric Exercise–Induced Muscle Damage by Preconditioning Exercises

This study compared the effect of an initial exercise consisting of either low-intensity eccentric or maximal isometric contractions (ISOs) on protective effect against maximal eccentric contraction (MaxECC)-induced muscle damage. Untrained young men were placed into one of five groups (n = 13 per group): MaxECC, 10% ECC, 20% ECC, 90° ISO, and 20° ISO. The MaxECC, 10% ECC, and 20% ECC groups performed 30 ECCs of the elbow flexors using a dumbbell equivalent to 100%, 10%, and 20% of maximal voluntary isometric contraction strength, respectively. The 90° ISO and 20° ISO groups performed 30 ISOs at 90° and 20° of elbow flexion, respectively. Three weeks later, all subjects performed 30 MaxECCs with the arm used for the first bout. Changes in maximal voluntary isometric and concentric contraction strength, range of motion, upper arm circumference, plasma creatine kinase and myoglobin concentration, and muscle soreness before and for 5 d after the first and second exercise bouts were compared among groups by a two-way repeated-measure ANOVA. Changes in all measures after the first bout were smaller (P < 0.05) for 10% ECC, 20% ECC, 90° ISO, and 20° ISO groups compared with MaxECC group, and the changes were smaller (P < 0.05) for 10% ECC and 90° ISO than 20° ISO and 20% ECC groups. When compared with the first bout of MaxECC group, changes in the measures after the second bout were smaller for 20% ECC and 20° ISO groups with greater protective effect evident for 20° ISO group, but the protective effect conferred by these was smaller (P < 0.05) compared with MaxECCs. These results suggest that there is threshold intensity for ECCs to confer protective effect, and ISOs at a long muscle length provide preconditioning effect.

Low-intensity eccentric contractions attenuate muscle damage induced by subsequent maximal eccentric exercise of the knee extensors in the elderly

This study investigated whether low-intensity eccentric contractions of the knee extensors would attenuate the magnitude of muscle damage induced by maximal eccentric exercise of the same muscle performed 7 days later using elderly individuals. Healthy older men (66.4 ± 4.6 years) were assigned to control or experimental (Exp) group (n = 13 per group). The control group performed six sets of ten maximal eccentric contractions (MaxECC) of the knee extensors of non-dominant leg. The Exp group performed six sets of ten low-intensity eccentric contractions of the knee extensors on a leg extension machine by lowering a weight of 10 % maximal voluntary isometric knee extension strength (10 %ECC) 7 days prior to MaxECC. Changes in maximal voluntary isokinetic concentric torque (MVC-CON), angle at peak torque, range of motion (ROM), upper thigh circumference, muscle soreness, plasma creatine kinase activity and myoglobin (Mb) concentration and B-mode ultrasound echo-intensity before and for 5 days after MaxECC were compared between groups by a mixed factor ANOVA. No significant changes in any variables were observed following 10 %ECC. Following MaxECC, all variables changed significantly, and changes in all variables except for angle at peak torque were significantly different between groups. MVC-CON and ROM decreased smaller and recovered faster (P < 0.05) for Exp than control group, and changes in other variables were smaller (P < 0.05) for Exp group compared with control group. These results suggest that preconditioning knee extensor muscles with low-intensity eccentric contractions was effective for attenuating muscle damage induced by subsequent MaxECC of the knee extensors for elderly individuals.

1504P - Isolated Limb Perfusion in Locally-Advanced Limb Soft Tissue Sarcomas: Retrospective Study of A 23-Year Experience

ABSTRACT Background Hyperthermic isolated limb perfusion (HILP) is a cytoreductive treatment to avoid amputation in limb soft tissue sarcomas (LSTS). HILP drug schedule has been modified to balance treatment activity and toxicity. Methods From 1988 to 2011, 117 patients with unresectable primary or recurrent LSTS underwent HILP. Tumor characteristics, HILP parameters and drugs (doxorubicin; doxorubicin plus TNFa; TNFa plus L-PAM), postoperative plasma myoglobin, tumor response, systemic chemotherapy (CT), site of recurrence and outcome were analyzed. Results The 3 treatment groups were homogeneous for clinical pathological features. The tumor response (necrosis in resected specimen) was comparable (P = .473) (Table) and was correlated with myoglobin (P Conclusions Doxorubicin, doxorubicin + TNFa and TNFa + L-PAM schedules are equally active, with comparable toxicity profiles. Upper LSTS and poor post-HILP necrosis were related with higher amputation rates. Despite preserving limb function, 40% of HILP patients develop a systemic recurrence, particularly when achieving lower responses. Lung relapses lung have a relatively better prognosis. Drug schedule Tumor necrosis, median % (range) Locoregional toxicity according to Wieberdink n° of pts (%) 1- 2 3 4 5 DOXO n = 47 54 (7-91) 38 (80.9) 8 (17.0) 1 (2.1) 0 TNFa + DOXO n = 30 64 (10-100) 24 (80.0) 4 (13.4) 1 (3.3) 1 (3.3) TNFa + L-PAM n = 40 57 (4-91) 37 (92.5) 1 (2.5) 2 (5.0) 0 Disclosure All authors have declared no conflicts of interest.

Extremely high myoglobin plasma concentrations producing hook effect in a critically ill patient

BackgroundA 21-year old female suffered a cardiac arrest after a one week history of viral illness later shown to be caused by influenza B. The patient required extended cardiopulmonary resuscitation and had further complications including compartment syndrome. MethodsPlasma myoglobin concentration was measured using the Roche Diagnostics electrochemiluminescent myoglobin assay. ResultsThe myoglobin concentration was 205,590μg/l in an undiluted specimen, consistent with severe rhabdomyolysis. Subsequent myoglobin concentrations measured two days later showed dramatic decreases to approximately 1000μg/l, raising suspicion of a hook effect. Dilution and re-analysis of the specimens revealed that the actual myoglobin concentrations were >395,000μg/l, with one specimen possessing an estimated myoglobin concentration of >600,000μg/l. Interestingly, three specimens from this patient did not show evidence of hook effect, with undiluted specimens producing myoglobin concentrations as high as 284,000μg/l. Retrospective analysis of myoglobin results over an 8-year period did not reveal other cases with suspicion of hook effect. The case patient had the highest myoglobin concentrations out of 7301 specimens. ConclusionsThis case illustrates that while the Roche myoglobin assay has a very wide dynamic range, hook effect can occur with extremely high concentrations of plasma myoglobin.

Two maximal isometric contractions attenuate the magnitude of eccentric exercise-induced muscle damage

This study investigated whether maximal voluntary isometric contractions (MVC-ISO) would attenuate the magnitude of eccentric exercise-induced muscle damage. Young untrained men were placed into one of the two experimental groups or one control group (n = 13 per group). Subjects in the experimental groups performed either two or 10 MVC-ISO of the elbow flexors at a long muscle length (20° flexion) 2 days prior to 30 maximal isokinetic eccentric contractions of the elbow flexors. Subjects in the control group performed the eccentric contractions without MVC-ISO. No significant changes in maximal voluntary concentric contraction peak torque, peak torque angle, range of motion, upper arm circumference, plasma creatine kinase (CK) activity and myoglobin concentration, muscle soreness, and ultrasound echo intensity were evident after MVC-ISO. Changes in the variables following eccentric contractions were smaller (P < 0.05) for the 2 MVC-ISO group (e.g., peak torque loss at 5 days after exercise, 23% ± 3%; peak CK activity, 1964 ± 452 IU·L(-1); peak muscle soreness, 46 ± 4 mm) or the 10 MVC-ISO group (13% ± 3%, 877 ± 198 IU·L(-1), 30 ± 4 mm) compared with the control (34% ± 4%, 6192 ± 1747 IU·L(-1), 66 ± 5 mm). The 10 MVC-ISO group showed smaller (P < 0.05) changes in all variables following eccentric contractions compared with the 2 MVC-ISO group. Therefore, two MVC-ISO conferred potent protective effects against muscle damage, whereas greater protective effect was induced by 10 MVC-ISO, which can be used as a strategy to minimize muscle damage.

Prognostic implications of plasma myoglobin levels in patients with chronic kidney disease

Poor cardiovascular outcomes in chronic kidney disease (CKD) patients have prompted nephrologists to look for biomarkers that may improve risk stratification in this population. The objective of this study was to evaluate plasma myoglobin (Mb) levels according to the CKD stage and to determine whether they are associated with overall, cardiovascular (CV) mortality, CV events, and renal outcomes. Plasma Mb levels were determined in 140 CKD patients at different stage (mean ± SD age: 67 ± 12; males: 61%) who were prospectively monitored for overall and CV mortality, CV events and CKD progression. Twenty-seven healthy subjects served as controls. Plasma Mb levels were higher in CKD patients than in controls and progressively increased as the glomerular filtration rate fell. Hemoglobin levels, CKD stage, the aortic calcification score and brain natriuretic peptide levels were associated with plasma Mb concentrations. In a multivariate analysis, only CKD stage was associated with Mb levels. During follow up (mean duration: 968 ± 374 days), 44 patients died and 63 had a cardiovascular event. In a crude analysis, plasma Mb >73.8 µg/l predicted overall and cardiovascular mortality and the occurrence of cardiovascular events (p = 0.01, 0.05 and 0.01, respectively). However, this association was lost after adjustment for other prognostic factors for mortality. Plasma Mb was not a significant predictor of the progression of CKD either. Plasma Mb levels were significantly higher in predialysis or dialyzed CKD patients than in healthy controls. However, we could not identify a relevant clinical outcome associated with this elevation. Larger studies are needed to confirm the present results.

Consequences of Succinylcholine Administration to Patients Using Statins

Background Statins cause structural changes in myocytes and provoke myotoxicity, myopathy, and myalgias. Thus, patients taking statins may be especially susceptible to succinylcholine-induced muscle injury. The authors tested the hypothesis that succinylcholine increases plasma concentrations of myoglobin, potassium, and creatine kinase more in patients who take statins than in those who do not and that succinylcholine-induced postoperative muscle pain is aggravated in statin users. Methods Patients who took statins for at least 3 months and those who had never used statins were enrolled. General anesthesia was induced and included 1.5 mg/kg succinylcholine for intubation. The incidence and degree of fasciculation after succinylcholine administration were recorded. Blood samples were obtained before induction and 5 and 20 min and 24 h after succinylcholine administration. Patients were interviewed 2 and 24 h after surgery to determine the degree of myalgia. Results The authors enrolled 38 patients who used statins and 32 who did not. At 20 min, myoglobin was higher in statin users versus nonusers (ratio of medians 1.34 [95% CI: 1.1, 1.7], P = 0.018). Fasciculations in statin users were more intense than in nonusers (P = 0.047). However, plasma potassium and creatine kinase concentrations were similar in statin users and nonusers, as was muscle pain. Conclusions The plasma myoglobin concentration at 20 min was significantly greater in statin users than nonusers, although the difference seems unlikely to be clinically important. The study results suggest that the effect of succinylcholine given to patients taking statins is likely to be small and probably of limited clinical consequence.

Comparison between multiple sets and half-pyramid resistance exercise bouts for muscle damage profile

The present study compared the changes in markers of muscle damage after bouts of resistance exercise employing the Multiple-sets (MS) and Half-pyramid (HP) training systems. Ten healthy men (26.1±6.3 years), who had been involved in regular resistance training, performed MS and HP bouts, 14 days apart, in a randomised, counter-balanced manner. For the MS bout, participants performed three sets of maximum repetitions at 75%-1RM (i.e. 75% of a One Repetition Maximum) for the three exercises, starting with the bench press, followed by pec deck and decline bench press. For the HP bout, the participants performed three sets of maximum repetitions with 67%-1RM, 74%-1RM and 80%-1RM for the first, second and third sets, respectively, for the same three exercise sequences as the MS bout. The total volume of load lifted was equated between both bouts. Muscle soreness, plasma creatine kinase (CK) activity, myoglobin (Mb) and C-reactive protein (CRP) concentrations were assessed before and for three days after each exercise bout, and the changes over time were compared between MS and HP using two-way repeated measures ANOVA. Muscle soreness developed significantly (P<0.01) after both bouts, but no significant difference was observed between MS and HP. Plasma CK activity and Mb concentration increased significantly (P<0.01) without significant differences between bouts, and CRP concentration did not change significantly after either bout. These results suggest that the muscle damage profile is similar for MS and HP, probably due to the similar total volume of load lifted.

Consequences of Succinylcholine Administration to Patients Using Statins

Statins cause structural changes in myocytes and provoke myotoxicity, myopathy, and myalgias. Thus, patients taking statins may be especially susceptible to succinylcholine-induced muscle injury. The authors tested the hypothesis that succinylcholine increases plasma concentrations of myoglobin, potassium, and creatine kinase more in patients who take statins than in those who do not and that succinylcholine-induced postoperative muscle pain is aggravated in statin users. Patients who took statins for at least 3 months and those who had never used statins were enrolled. General anesthesia was induced and included 1.5 mg/kg succinylcholine for intubation. The incidence and degree of fasciculation after succinylcholine administration were recorded. Blood samples were obtained before induction and 5 and 20 min and 24 h after succinylcholine administration. Patients were interviewed 2 and 24 h after surgery to determine the degree of myalgia. The authors enrolled 38 patients who used statins and 32 who did not. At 20 min, myoglobin was higher in statin users versus nonusers (ratio of medians 1.34 [95% CI: 1.1, 1.7], P = 0.018). Fasciculations in statin users were more intense than in nonusers (P = 0.047). However, plasma potassium and creatine kinase concentrations were similar in statin users and nonusers, as was muscle pain. The plasma myoglobin concentration at 20 min was significantly greater in statin users than nonusers, although the difference seems unlikely to be clinically important. The study results suggest that the effect of succinylcholine given to patients taking statins is likely to be small and probably of limited clinical consequence.