Role of Magnetic Resonance Spectroscopy in Evaluation of Cerebral Metabolic Status Before and After Carotid Endarterectomy/Thromboendarterectomy and Carotid Artery Stenting in Patients with Asymptomatic Critical Internal Carotid Artery Stenosis.

BACKGROUND The relative efficacy of carotid endarterectomy (CEA)/thromboendarterectomy (TEA) and carotid artery stenting (CAS) already has been compared in randomized controlled trials and a meta-analysis, but only limited data exist describing the status of cerebral metabolism before and after these interventions. The aim of the present study was to compare metabolic changes before and after treatment of carotid stenosis and assess their potential clinical implications.   MATERIAL AND METHODS Patients with asymptomatic unilateral critical internal CAS were imaged with proton 3T magnetic resonance spectroscopy (H-MRS) because the technique is more sensitive than regular magnetic resonance imaging for detection of the early signs of ischemic events. Abnormal metabolite ratios detected with H-MRS may precede actual morphological changes associated with hypoperfusion as well as reperfusion changes. Ipsilateral and contralateral middle cerebral artery vascular territories were both evaluated before and after vascular intervention. H-MRS was performed within 24 h before and after surgery. Correlations in the metabolic data from H-MRS for N-acetylaspartic acid (NAA)+N-acetylaspartylglutamate, creatinine (Cr)+phosphocreatinine, and phosphocholine+glycerophosphocholine (Cho) were sought. RESULTS H-MRS voxels from 11 subjects were analyzed. Values for dCho/CrI, dCho/CrC and Cho/Naal (P<0.001) were significantly higher ipsilaterally than contralaterally. Ratios for dNaa/ChoC and Cho/NaaC were significantly higher on the non-operated side (P<0.001). CONCLUSIONS H-MRS may be helpful for assessment of patients with CAS, particularly because unlike other modalities, it reveals postoperative changes in metabolic brain status. Initial results indicate the important role of perioperative neuroprotective treatment.

Nicotinic acid receptor agonists impair myocardial contractility by energy starvation.

Nicotinic acid receptor agonists have previously been shown to cause acute reductions in cardiac contractility. We sought to uncover the changes in cardiac metabolism underlying these alterations in function. In nine humans, we recorded cardiac energetics and function before and after a single oral dose of nicotinic acid using cardiac MRI to demonstrate contractile function and Phosphorus-31 (31 P) magnetic resonance spectroscopy to demonstrate myocardial energetics. Nicotinic Acid 400 mg lowered ejection fraction by 4% (64 ± 8% to 60 ± 7%, P = .03), and was accompanied by a fall in phosphocreatine/ATP ratio by 0.4 (2.2 ± 0.4 to 1.8 ± 0.1, P = .04). In four groups of eight Wistar rats, we used pyruvate dehydrogenase (PDH) flux studies to demonstrate changes in carbohydrate metabolism induced by the nicotinic acid receptor agonist, Acipimox, using hyperpolarized Carbon-13 (13 C) magnetic resonance spectroscopy. In rats which had been starved overnight, Acipimox caused a fall in ejection fraction by 7.8% (67.5 ± 8.9 to 60 ± 3.1, P = .03) and a nearly threefold rise in flux through PDH (from 0.182 ± 0.114 to 0.486 ± 0.139, P = .002), though this rise did not match pyruvate dehydrogenase flux observed in rats fed carbohydrate rich chow (0.726 ± 0.201). In fed rats, Acipimox decreased pyruvate dehydrogenase flux (to 0.512 ± 0.13, P = .04). Concentration of plasma insulin fell by two-thirds in fed rats administered Acipimox (from 1695 ± 891 ng/L to 550 ± 222 ng/L, P = .005) in spite of glucose concentrations remaining the same. In conclusion, we demonstrate that nicotinic acid receptor agonists impair cardiac contractility associated with a decline in cardiac energetics and show that the mechanism is likely a combination of reduced fatty acid availability and a failure to upregulate carbohydrate metabolism, essentially starving the heart of fuel.

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis.

OBJECTIVES: The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases. METHODS: Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort. Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model. RESULTS: Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%. Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified. CONCLUSIONS: PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.

Energy System Contributions in Upper and Lower Body Wingate Tests in Highly Trained Athletes.

PURPOSE: This study compared the energy system contributions and relationship between mechanical and energy system variables in upper and lower body Wingate tests (WAnT) in judo athletes. METHOD: Eleven male judo athletes (18 ± 1 years, 174.3 ± 5.3 cm, 72.6 ± 9.9 kg, 11.8 ± 1.7% body fat) attended two laboratory sessions to perform two WAnT (upper and lower body) and two incremental tests (upper and lower body). The energy contributions of the oxidative, glycolytic, and phosphagen (ATP-PCr) systems were estimated based on oxygen consumption ( V˙O2 ) during WAnT, delta of lactate, and the fast phase of excess V˙O2 , respectively. RESULTS: The upper and lower body presented similar results of oxidative (21 ± 4% vs 23 ± 3%) and ATP-PCr system contributions (29 ± 6% vs 32 ± 5%). The glycolytic system contribution (50 ± 5% vs 45 ± 4%) was higher in the upper body. The variance of mechanical variables in upper body was explained by glycolytic (R2 = 0.49-0.62) and oxidative systems (R2 = 0.44-0.49), whereas the variance of mechanical variables in lower body was explained by ATP-PCr (R2 = 0.41-0.55) and glycolytic systems (R2 = 0.62-0.94). CONCLUSIONS: During WAnT, the glycolytic system presented the major energy contribution, being higher in the upper body. Moreover, mechanical and energy system variables presented a distinct relationship when comparing upper and lower body WAnT.

Exercise Response Variations in Skeletal Muscle PCr Recovery Rate and Insulin Sensitivity Relate to Muscle Epigenomic Profiles in Individuals With Type 2 Diabetes.

OBJECTIVE: Some individuals with type 2 diabetes do not reap metabolic benefits from exercise training, yet the underlying mechanisms of training response variation are largely unexplored. We classified individuals with type 2 diabetes (n = 17) as nonresponders (n = 6) or responders (n = 11) based on changes in phosphocreatine (PCr) recovery rate after 10 weeks of aerobic training. We aimed to determine whether the training response variation in PCr recovery rate was marked by distinct epigenomic profiles in muscle prior to training. RESEARCH DESIGN AND METHODS: PCr recovery rate as an indicator of in vivo muscle mitochondrial function in vastus lateralis (31P-magnetic resonance spectroscopy), insulin sensitivity (M-value; hyperinsulinemic-euglycemic clamp), aerobic capacity (Vo2peak), and blood profiles were determined pretraining and post-training. Muscle biopsies were performed pretraining in vastus lateralis for the isolation of primary skeletal muscle cells (HSkMCs) and assessments of global DNA methylation and RNA sequencing in muscle tissue and HSkMCs. RESULTS: By design, nonresponders decreased and responders increased PCr recovery rate with training. In nonresponders, insulin sensitivity did not improve and glycemic control (HbA1c) worsened. In responders, insulin sensitivity improved. Vo2peak improved by ∼12% in both groups. Nonresponders and responders were distinguished by distinct pretraining molecular (DNA methylation, RNA expression) patterns in muscle tissue, as well as in HSkMCs. Enrichment analyses identified elevations in glutathione regulation, insulin signaling, and mitochondrial metabolism in nonresponders pretraining, which was reflected in vivo by higher pretraining PCr recovery rate and insulin sensitivity in these same individuals. CONCLUSIONS: A training response variation for clinical risk factors in individuals with type 2 diabetes is reflected by distinct basal myocellular epigenomic profiles in muscle tissue, some of which are maintained in HSkMCs, suggesting a cell-autonomous underpinning. Our data provide new evidence to potentially shift the diabetes treatment paradigm for individuals who do not benefit from training, such that supplemental treatment can be designed.

Comparison of methods for estimating glomerular filtration rate in head and neck cancer patients treated with cisplatin.

Cisplatin is a chemotherapeutic agent widely used in the treatment of various solid tumors. Cisplatin induces nephrotoxicity and may lead to long-term reduction of kidney function. Consequently, determination of glomerular filtration rate (GFR) is used to monitor potential kidney damage. This study aimed to compare two commonly used algorithms for estimating GFR (eGFR) from plasma creatinine (PCr) with 51Cr-EDTA clearance (CrCl) as a reference method. This was a retrospective single center study of 94 head and neck cancer patients treated with cisplatin. CrCl was performed once before, during, and after treatment, and PCr was measured concurrently. eGFR was assessed from PCr applying the Cockcroft-Gault (CG) and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. Agreement was assessed applying the statistical methods of Bland and Altman. A predefined limit of clinically acceptable variation between CrCl and eGFR of 14% was applied. Comparison of CrCl and eGFRCKD revealed a positive slope of the linear regression line, suggesting proportional bias (p < 0.001). No systematic bias was found for eGFRCG. Pre-treatment, 42 (46%), 53 (56%) and 48 (53%) observations were within the clinically acceptable limit of variation for standardized eGFRCKD, BSA corrected eGFRCKD, and eGFRCG, respectively. The observed body weight changes were significant. In conclusion, estimated GFRCKD cannot sufficiently replace CrCl in the assessment of GFR during treatment with cisplatin due to systematic bias. Consequently, if CrCl is unavailable, then the CG equation is the better choice provided proper attention is paid to the large variation between methods.

Adiabatic excitation for 31 P MR spectroscopy in the human heart at 7 T: A feasibility study.

PURPOSE: Phosphorus magnetic resonance spectroscopy (31 P-MRS) provides a unique tool for assessing cardiac energy metabolism, often quantified using the phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio. Surface coils are typically used for excitation for 31 P-MRS, but they create an inhomogeneous excitation field across the myocardium, producing undesirable, spatially varying partial saturation. Therefore, we implemented adiabatic excitation in a 3D chemical shift imaging (CSI) sequence for cardiac 31 P-MRS at 7 Tesla (T). METHODS: We optimized an adiabatic half passage pulse with bandwidth sufficient to excite PCr and γ-ATP together. In addition, the CSI sequence was modified to allow interleaved excitation of PCr and γ-ATP, then 2,3-DPG, to enable PCr/ATP determination with blood correction. Nine volunteers were scanned at 2 transmit voltages to confirm that measured PCr/ATP was independent of B1+ (i.e. over the adiabatic threshold). Six septal voxels were evaluated for each volunteer. RESULTS: Phantom experiments showed that adiabatic excitation can be reached at the depth of the heart using our pulse. The mean evaluated cardiac PCr/ATP ratio from all 9 volunteers corrected for blood signal was 2.14 ± 0.16. Comparing the two acquisitions with different voltages resulted in a minimal mean difference of -0.005. CONCLUSION: Adiabatic excitation is possible in the human heart at 7 T, and gives consistent PCr/ATP ratios. Magn Reson Med 78:1667-1673, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Short-term remote ischemic preconditioning is not associated with improved blood pressure and exercise capacity in young adults.

We sought to determine whether a 9-day remote ischemic preconditioning (IPC) causes improvements in exercise performance, energetics, and blood pressure. Ten participants (mean age 24 ± 4 years) had no changes in aerobic capacity (preintervention: 38 ± 10 mL/(kg·min)(-1) vs. postintervention: 38 ± 10 mL/(kg·min)(-1)), blood pressure (preintervention: 112 ± 7/66 ± 6 mm Hg vs. postintervention: 112 ± 10/62 ± 5 mm Hg), cardiac phosphocreatinine-to-adenosine-triphosphate ratio (preintervention: 2.1 ± 0.5 vs. postintervention: 2.3 ± 0.4), and postexercise skeletal muscle phosphocreatine recovery (preintervention: 34 ± 11 s vs. postintervention: 31 ± 11 s). Short-term remote IPC may be ineffective in improving these outcomes.

Creatine kinase adenosine triphosphate and phosphocreatine energy supply in a single kindred of patients with hypertrophic cardiomyopathy.

A lethal and extensively characterized familial form of hypertrophic cardiomyopathy (HC) is due to a point mutation (Arg403Gln) in the cardiac ß-myosin heavy chain gene. Although this is associated with abnormal energy metabolism and progression to heart failure in an animal model, in vivo cardiac energetics have not been characterized in patients with this mutation. Noninvasive phosphorus saturation transfer magnetic resonance spectroscopy was used to measure the adenosine triphosphate supplied by the creatine kinase (CK) reaction and phosphocreatine, the heart's primary energy reserve, in 9 of 10 patients from a single kindred with HC caused by the Arg403GIn mutation and 17 age-matched healthy controls. Systolic and diastolic function was assessed by echocardiography in all 10 patients with HC. The patients with HC had impairment of diastolic function and mild systolic dysfunction, when assessed using global systolic longitudinal strain. Myocardial phosphocreatine was significantly decreased by 24% in patients (7.1 ± 2.3 µmol/g) compared with the controls (9.4 ± 1.2 µmol/g; p = 0.003). The pseudo-first-order CK rate-constant was 26% lower (0.28 ± 0.15 vs 0.38 ± 0.07 s⁻¹, p = 0.035) and the forward CK flux was 44% lower (2.0 ± 1.4 vs 3.6 ± 0.9 µmol/g/s, p = 0.001) than in the controls. The contractile abnormalities did not correlate with the metabolic indexes. In conclusion, myocardial phosphocreatine and CK-ATP delivery are significantly reduced in patients with HC caused by the Arg403Gln mutation, akin to previous results from mice with the same mutation. A lack of a relation between energetic and contractile abnormalities suggests the former result from the sarcomeric mutation and not a late consequence of mechanical dysfunction.

Metabolomic signatures in guinea pigs infected with epidemic-associated W-Beijing strains of Mycobacterium tuberculosis.

With the understanding that the laboratory propagated strain of Mycobacterium tuberculosis H37Rv is of modest virulence and is drug susceptible, in the present study, we performed a nuclear magnetic resonance-based metabolomic analysis of lung tissues and serum obtained from guinea pigs infected by low dose aerosol exposure to clinical isolates of Mycobacterium tuberculosis. High Resolution Magic Angle Spinning NMR coupled with multivariate statistical analysis of 159 lung tissues obtained from multiple locations of age-matched naïve and 30 and 60 days of infected guinea pig lungs revealed a wide dispersal of metabolic patterns, but within these, distinct clusters of signatures could be seen that differentiated between naive control and infected animals. Several metabolites were identified that changed in concert with the progression of each infection. Major metabolites that could be interpreted as indicating host glutaminolysis were consistent with activated host immune cells encountering increasingly hypoxic conditions in the necrotic lung lesions. Moreover, glutathione levels were constantly elevated, probably in response to oxygen radical production in these lesions. Additional distinct signatures were also seen in infected serum, with altered levels of several metabolites. Multivariate statistical analysis clearly differentiated the infected from the uninfected sera; in addition, Receiver Operator Characteristic curve generated with principal component 1 scores showed an area under the curve of 0.908. These data raise optimism that discrete metabolomic signatures can be defined that can predict the progression of the tuberculosis disease process, and form the basis of an innovative and rapid diagnostic process.

Protective effect of α-mangostin on cardiac reperfusion damage by attenuation of oxidative stress.

This study was designed to investigate if α-mangostin (α-M), a xanthone present in the pericarp of Garcinia mangostana L., was able to protect against reperfusion injury in Langendorff-reperfused hearts. It was observed that α-M maintains the cardiac mechanical work, diminishes the area of infarct, and prevents the decrease in cardiac ATP and phosphocreatine levels in the reperfused myocardium. The protective effect of this xanthone was associated with reduction of oxidative stress. α-M treatment prevented reperfusion injury-induced protein oxidation (protein carbonyl content), lipid peroxidation (malondialdehyde and 4-hydroxynonenal content), and diminution of glutathione content. In fact, after α-M treatment, the values in these parameters were comparable to those obtained in nonreperfused hearts. In summary, α-M induces a protective effect in postischemic heart associated to the prevention of oxidative stress secondary to reperfusion injury.

Skeletal muscle mitochondrial function is associated with longitudinal growth velocity in children and adolescents.

CONTEXT: Periods of rapid growth require an increase in energy use and substrate formation. Mitochondrial function contributes to each of these and therefore may play a role in longitudinal growth. METHODS: Twenty-nine children and adolescents of ages 8-15 yr were enrolled in a comprehensive longitudinal assessment of glucose homeostasis and mitochondrial function. Fasting laboratory studies and an estimate of mitochondrial function (as assessed by the time to recovery of phosphocreatine (PCr) concentration after submaximal quadriceps extension/flexion exercise using (31)P magnetic resonance spectroscopy) were obtained at baseline and annually for 2 yr. RESULTS: Data were complete for 23 subjects. Subjects were 11.3 ± 1.9 (sd) yr old at the beginning of the study; 61% were male. Average annualized growth velocity at 1 yr for boys was 7.1 ± 1.5 cm/yr and for girls 6.5 ± 1.7 cm/yr. More rapid recovery of PCr concentration, suggestive of greater skeletal muscle oxidative phosphorylation capacity at baseline, was associated with faster growth velocity in the subsequent year (r(2) = 0.29; P = 0.008). In multivariate modeling, baseline mitochondrial function remained significantly and independently associated with growth (R(2) for model = 0.51; P = 0.05 for effect of phosphocreatine recovery time constant), controlling for age, gender, Tanner stage, body mass index Z-score, and height Z-score. CONCLUSIONS: We report a novel association between time to recovery of PCr concentration after submaximal exercise and faster annual linear growth in healthy children. Future studies are needed to determine the physiological mechanisms and clinical consequences of this observation.

[Pharmacokinetics and metabolic disposition of exogenous phosphocreatine in rats].

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.

Pilot study on the effect of grounding on delayed-onset muscle soreness.

OBJECTIVES: The purpose of this pilot study was to determine whether there are markers that can be used to study the effects of grounding on delayed-onset muscle soreness (DOMS). DESIGN AND SUBJECTS: Eight (8) healthy subjects were exposed to an eccentric exercise that caused DOMS in gastrocnemius muscles of both legs. Four (4) subjects were grounded with electrode patches and patented conductive sheets connected to the earth. Four (4) control subjects were treated identically, except that the grounding systems were not connected to the earth. OUTCOME MEASURES: Complete blood counts, blood chemistry, enzyme chemistry, serum and saliva cortisols, magnetic resonance imaging and spectroscopy and pain levels were taken at the same time of day before the eccentric exercise and 24, 48, and 72 hours afterwards. Parameters consistently differing by 10% or more, normalized to baseline, were considered worthy of further study. RESULTS: Parameters that differed by these criteria included white blood cell counts, bilirubin, creatine kinase, phosphocreatine/inorganic phosphate ratios, glycerolphosphorylcholine, phosphorylcholine, the visual analogue pain scale, and pressure measurements on the right gastrocnemius. CONCLUSIONS: In a pilot study, grounding the body to the earth alters measures of immune system activity and pain. Since this is the first intervention that appears to speed recovery from DOMS, the pilot provides a basis for a larger study.

Metabolic profiling of heat or anoxic stress in mouse C2C12 myotubes using multinuclear magnetic resonance spectroscopy.

In the present study, the metabolic effects of heat and anoxic stress in myotubes from the mouse cell line C2C12 were investigated by using a combination of (13)C, (1)H, and (31)P nuclear magnetic resonance (NMR) spectroscopy and enrichment with [(13)C]-glucose. Both the (13)C and the (1)H NMR spectra showed reduced levels of the amino acids alanine, glutamate, and aspartate after heat or anoxic stress. The decreases were smallest at 42 degrees C, larger at 45 degrees C, and most pronounced after anoxic conditions. In addition, in both the (1)H and the (31)P NMR spectra, decreases in the high-energy phosphate compounds adenosine triphosphate and phosphocreatine with increasing severity of stress were identified. At anoxic conditions, an increase in (13)C-labeled lactate and appearance of glycerol-3-phosphate were observed. Accumulation of lactate and glycerol-3-phosphate is in agreement with a shift to anaerobic metabolism due to inhibition of the aerobic pathway in the mitochondria. Conversely, lower levels of unlabeled ((12)C) lactate were apparent at increasing severity of stress, which indicate that lactate is released from the myotubes to the medium. In conclusion, the metabolites identified in the present study may be useful markers for identifying severity of stress in muscles.

Performance and metabolism in repeated sprint exercise: effect of recovery intensity.

This study investigated the effects of a moderate (MI) and a low intensity (LI) active recovery (both compared to a passive recovery) on repeated-sprint performance and muscle metabolism. Nine, male, subjects performed three repeated-sprint cycle tests (6 x 4 s sprints, every 25 s) in a semi-randomized, counter-balanced order. Recovery after each sprint for the MI and LI trials, respectively, was 60 W (approximately 35% VO(2max)) and 20 W (approximately 20% VO(2max). Biopsies were taken from the vastus lateralis pre- and immediately post-test during the MI and LI trials to determine adenosine triphosphate (ATP), phosphocreatine (PCr) and lactate (MLa(-)) content. Compared to passive, significant reductions in peak power of 3.4-6.0% were recorded in the MI trial (4 of 6 sprints; P < 0.05) and reductions of 3.5-3.7% in the LI trial (2 of 6 sprints; P < 0.05), with no differences between the two active trials. No significant differences were evident in ATP, PCr and MLa(-) between the two active recovery trials. In summary, peak power indices during the repeated-sprint test were inferior in the MI and LI active recovery trials, compared to passive. The minimal differences in performance and muscle metabolites between the MI and LI trials suggest that any low-to-moderate level of muscle activation will attenuate the resynthesis of PCr and the recovery of power output during repeated short-sprint exercise.

A test to evaluate the physical impact on technical performance in soccer.

The aim of the study was to develop and examine a test for evaluation of the physical and technical capacity of soccer players. Fourteen youth elite (YE) and seven sub-elite (SE) players performed a physical and technical test (PT-test) consisting of 10 long kicks interspersed with intense intermittent exercise. In addition, a control test (CON-test) without intense exercise was performed. In both cases, the test result was evaluated by the precision of the 10 kicks. The players also performed the Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2). For the SE-players, blood samples were obtained and heart rate was measured before, during, and after the PT-test. A muscle biopsy was collected before and after the PT-test. Coefficient of variation for the PT- and CON-test was 11.7% and 16.0%, respectively. The YE-players performed better (P < 0.05) than the SE-players in both the PT-test (16.3 +/- 0.8 (+/-SE) vs. 13.2 +/- 1.3 points) and CON-test (24.4 +/- 0.7 vs. 20.5 +/- 1.6 points) with no difference in the relative PT-test result (PT-test/CON-test: 0.63 +/- 0.03 vs. 0.64 +/- 0.03). Summed performance of the first 5 repetitions was higher (P < 0.05) than for the last 5 repetitions (8.4 +/- 0.6 vs. 6.9 +/- 0.5; n = 20). The YE-players performed better (P < 0.05) than the SE-players during Yo-Yo IR2 (1023 +/- SE vs. 893 +/- SE m). The mean heart rate during the PT-test was 173 +/- 4 b.p.m. (90 +/- 2% of HRmax). Blood lactate, glucose, and ammonia reached 5.6 +/- 0.7, 6.2 +/- 0.6 mmol L(-1), and 76 +/- 11 umol L(-1) at the end of the test, respectively. After the test muscle CP, glycogen and lactate was 52.9 +/- 6.6, 354 +/- 39, and 25.3 +/- 5.9 mmol kg(-1) d.w., respectively. In summary, the PT-test can be used to evaluate a soccer player's technical skills under conditions similar to intense periods of a soccer game.

Failure of Rhodiola rosea to alter skeletal muscle phosphate kinetics in trained men.

Rhodiola rosea is an herbal supplement purported to improve resistance to stressors and to enhance physical performance, potentially by improving adenosine triphosphate (ATP) turnover. Phosphocreatine (PCr) kinetics serves as a reflection of ATP turnover. The purpose of this investigation was to examine the effect of R rosea ingestion on human skeletal muscle PCr recovery after exhaustive exercise. Twelve resistance-trained men, aged 19 to 39 years, completed incremental forearm wrist flexion exercise to volitional fatigue, once after ingesting 1500 mg R rosea per day for 4 days, and once after ingesting an equivalent placebo dose. During exercise and recovery from exercise, muscle phosphates were examined using phosphorus 31 nuclear magnetic resonance spectroscopy. [PCr] during recovery was fit with a monoexponential function, and the resulting rate constants (k) were compared between groups. Rating of perceived exertion per stage and time to exhaustion were also compared between groups. For R rosea, k=0.3744+/-0.1532, whereas for placebo, k=0.3956+/-0.2238. Although rating of perceived exertion significantly increased within groups as workload increased, it did not differ between conditions, nor did time to exhaustion (R rosea, 10.71+/-0.54 minutes; placebo, 10.48+/-0.68 minutes). Estimates of [PCr] at time 0, 5, 10, 15, and 20 minutes of recovery were nearly identical between groups. In summary, there were no significant differences between groups for any of theparameters measured. Based on these results, we conclude that R rosea ingestion does not improve ATP turnover during or immediately after exercise.

Conditions of wound healing and cutaneous growth affect metabolic performance of skin following plastic surgery.

The mechanical and structural properties of skin subjected to expansion have been widely investigated in the context of plastic surgery. To determine the actual metabolic state of skin following skin expander placement, we determined the basic biochemical parameters for various conditions of postsurgical wound healing and cutaneous growth. Studying, for the first time, comprehensive metabolic profiles ("metabolomics") of the skin in a minipig model, we found that the lactate/alanine ratios were significantly increased (p<0.05) in skin attached to noninflated expanders vs. control skin, indicating increased anaerobic glycolysis. Furthermore, creatine/phosphocreatine ratios were decreased in skin from inflated vs. noninflated expanders, implying an improved energetic state for stretched skin. In contrast, no significant differences were detected for these parameters on comparing skin from four inflated expanders with different surface structures, even where the histologically determined capsule thickness was significantly different. Overall, the metabolic performance of skin recovering and growing under stretch was found to be superior to that of skin from noninflated expanders, and comparable to that of control skin. Our results are consistent with the assumptions of (i) major hypoxia/ischemia due to reduced perfusion in skin recovering from surgery without an appropriate supportive structure and (ii) minimal metabolic effects of expander surface structures.

Mitochondrial coupling in humans: assessment of the P/O2 ratio at the onset of calf exercise.

Coupling of oxidation to ATP synthesis (P/O2 ratio) is a critical step in the conversion of carbon substrates to fuel (ATP) for cellular activity. The ability to quantitatively assess mitochondrial coupling in vivo can be a valuable tool for basic research and clinical purposes. At the onset of a square wave moderate exercise, the ratio between absolute amount of phosphocreatine split and O2 deficit (corrected for the amount of O2 released from the body O2 stores and in the absence of lactate production), is the mirror image of the P/O2 ratio. To calculate this value, cardiac output (Q), whole body O2 uptake (VO2), O2 deficit (O2(def)) and high-energy phosphates concentration (by 31P-NMR spectroscopy) in the calf muscles were measured on nine healthy volunteers at rest and during moderate intensity plantar flexion exercise (3.44 +/- 0.73 W per unit active muscle mass). Q and VO2 increased (from 4.68 +/- 1.56 to 5.83 +/- 1.59 l min(-1) and from 0.28 +/- 0.05 to 0.48 +/- 0.09 l min(-1), respectively), while phosphocreatine (PCr) concentration decreased significantly (22 +/- 6%) from rest to steady-state exercise. For each volunteer, "gross" O2(def) was corrected for the individual changes in the venous blood O2 stores (representing 49.9 +/- 9.5% of the gross O2(def)) yielding the "net" O2(def). Resting PCr concentration was estimated from the appropriate spectroscopy data. The so calculated P/O2 ratio amounted on average to 4.24 +/- 0.13 and was, in all nine subjects, very close to the literature values obtained directly on intact skeletal muscle. This unfolds the prospect of a non-invasive tool to quantitatively study mitochondrial coupling in vivo.