The effect of a single 2 h bout of aerobic exercise on ectopic lipids in skeletal muscle, liver and the myocardium.

AIMS/HYPOTHESIS Ectopic lipids are fuel stores in non-adipose tissues (skeletal muscle [intramyocellular lipids; IMCL], liver [intrahepatocellular lipids; IHCL] and heart [intracardiomyocellular lipids; ICCL]). IMCL can be depleted by physical activity. Preliminary data suggest that aerobic exercise increases IHCL. Data on exercise-induced changes on ICCL is scarce. Increased IMCL and IHCL have been related to insulin resistance in skeletal muscles and liver, whereas this has not been documented in the heart. The aim of this study was to assess the acute effect of aerobic exercise on the flexibility of IMCL, IHCL and ICCL in insulin-sensitive participants in relation to fat availability, insulin sensitivity and exercise capacity. METHODS Healthy physically active men were included. [Formula: see text] was assessed by spiroergometry and insulin sensitivity was calculated using the HOMA index. Visceral and subcutaneous fat were separately quantified by MRI. Following a standardised dietary fat load over 3 days, IMCL, IHCL and ICCL were measured using MR spectroscopy before and after a 2 h exercise session at 50-60% of [Formula: see text]. Metabolites were measured during exercise. RESULTS Ten men (age 28.9 ± 6.4 years, mean ± SD; [Formula: see text] 56.3 ± 6.4 ml kg(-1) min(-1); BMI 22.75 ± 1.4 kg/m(2)) were recruited. A 2 h exercise session resulted in a significant decrease in IMCL (-17 ± 22%, p = 0.008) and ICCL (-17 ± 14%, p = 0.002) and increase in IHCL (42 ± 29%, p = 0.004). No significant correlations were found between the relative changes in ectopic lipids, fat availability, insulin sensitivity, exercise capacity or changes of metabolites during exercise. CONCLUSIONS/INTERPRETATION In this group, physical exercise decreased ICCL and IMCL but increased IHCL. Fat availability, insulin sensitivity, exercise capacity and metabolites during exercise are not the only factors affecting ectopic lipids during exercise.

Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial.

AIMS Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. METHODS AND RESULTS In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode (P = 0.057) and the PIDS optimized mode (P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode (P = 0.092) and 109.5 W in the PIDS optimized mode (P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode (P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. CONCLUSION PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. TRIAL REGISTRATION NCT00769678.

Myogenin modulates exercise endurance by altering skeletal muscle metabolism

The function of myogenic regulatory factors (MRFs) during adult life is not well understood. The requirement of one of these MRFs, myogenin (Myog), during embryonic muscle development suggests an equally important role in adult muscle. In this study, we have determined the function of myogenin during adult life using a conditional allele of Myog. In contrast to embryonic development, myogenin is not required for adult viability, and Myog-deleted mice exhibited no remarkable phenotypic changes during sedentary life. Remarkably, sedentary Myog-deleted mice demonstrated enhanced exercise endurance during involuntary treadmill running. Altered blood glucose and lactate levels in sedentary Myog-deleted mice after exhaustion suggest an enhanced glycolytic metabolism and an ability to excessively deplete muscle and liver glycogen stores. Traditional changes associated with enhanced exercise endurance, such as fiber type switching, and increased oxidative potential, were not detected in sedentary Myog-deleted mice. After long-term voluntary exercise, trained Myog-deleted mice demonstrated an enhanced adaptive response to exercise. Trained Myog-deleted mice exhibited superior exercise endurance associated with an increased proportion of slow-twitch fibers and increased oxidative capacity. In a parallel experiment, dystrophin-deficient young adult mice showed attenuated muscle fatigue following the deletion of Myog. These results demonstrate a novel and unexpected role for myogenin in modulating skeletal muscle metabolism.

The course of radiographic loosening, pain and functional outcome around the first revision of a total hip arthroplasty

Background: The published data on pain and physical function before and after revision of total hip arthroplasty (THA) is scarce. The study reports the course and interrelationships of radiographic loosening, pain and physical function 5 year before and after a first revision THA. Methods: The study was based on the IDES-THA database. All patients with their first THA revision for aseptic loosening and a documented index surgery on the same side and at least one pre-revision and one post-revision follow-up were selected. Only patients with an intact contralateral hip joint (Charnley class-A) were included. Follow-ups within ±5.5 years around the revision time point were analyzed. Annual prevalences of radiographic component loosening and the non-desired outcomes (moderate/severe/intolerable pain, walking <30 minutes, hip flexion range <90°) were calculated. Results: Signs of radiographic component loosening started to increase about 4 years before revision surgery. Two years later, a sharp increase of painful hips from 15% to 80% in the revision year was observed. In the year after revision surgery, this rate dropped back to below 10%. Walking capacity started to noticeably deteriorate 3 years before revision and in the revision year about 65% of patients could not walk longer than 30 minutes. As opposed to pain, walking capacity did not recover to pre-revision levels and the best outcome was only reached two years post-revision. Hip flexion range had the slowest and least extent of deterioration (≈45% flexed <70° in the revision year) but with the best outcomes at only three years after revision surgery it took the longest to recover. Conclusion: Prevalence of radiological loosening signs and/or pain intensity follow an almost parallel course around the first revision of a THA for aseptic component loosening. This process begins about 4 years (radiographic loosening) before the actual revision surgery and intensifies about 2 years later (pain). It also involves walking capacity and hip range of motion. While pain levels go back to levels similar to those after primary surgery, range of motion and even more walking capacity remain moderately compromised.

Inhibition of meningitis-associated neutrophil apoptosis by TNF-α depends on functional PI3-kinase in monocytes

In bacterial meningitis, neutrophils cope with bacterial infection but also lead to tissue damage. The balance of beneficial and harmful effects may depend on the lifespan of the neutrophils in the CNS. Here, we show that CSF of patients with meningococcal meningitis contains a neutrophil apoptosis-inhibiting capacity that correlates with TNF-α content. In vitro experiments show that Neisseria meningitidis as well as LPS derived from these bacteria regulated neutrophil apoptosis mainly by stimulating TNF-α production in monocytes. Whereas LPS-induced PI3K-dependent survival signals in monocytes are critical for neutrophil survival, PI3K signaling in granulocytes did not contribute to the increased lifespan of neutrophils. We conclude that LPS-driven PI3K signaling in monocytes regulates neutrophil apoptosis and thereby, may be crucial in the initiation of secondary brain damage in bacterial meningitis.

Chronometric features of processing unpleasant stimuli: a functional MRI-based transcranial magnetic stimulation study.

The quick identification of potentially threatening events is a crucial cognitive capacity to survive in a changing environment. Previous functional MRI data revealed the right dorsolateral prefrontal cortex and the region of the left intraparietal sulcus (IPS) to be involved in the perception of emotionally negative stimuli. For assessing chronometric aspects of emotion processing, we applied transcranial magnetic stimulation above these areas at different times after negative and neutral picture presentation. An interference with emotion processing was found with transcranial magnetic stimulation above the dorsolateral prefrontal cortex 200-300 ms and above the left intraparietal sulcus 240/260 ms after negative stimuli. The data suggest a parallel and conjoint involvement of prefrontal and parietal areas for the identification of emotionally negative stimuli.

Seasonal Variation in the Capacity for Plant Trait Measures to Predict Grassland Carbon and Water Fluxes

There is a need for accurate predictions of ecosystem carbon (C) and water fluxes in field conditions. Previous research has shown that ecosystem properties can be predicted from community abundance-weighted means (CWM) of plant functional traits and measures of trait variability within a community (FDvar). The capacity for traits to predict carbon (C) and water fluxes, and the seasonal dependency of these trait-function relationships has not been fully explored. Here we measured daytime C and water fluxes over four seasons in grasslands of a range of successional ages in southern England. In a model selection procedure, we related these fluxes to environmental covariates and plant biomass measures before adding CWM and FDvar plant trait measures that were scaled up from measures of individual plants grown in greenhouse conditions. Models describing fluxes in periods of low biological activity contained few predictors, which were usually abiotic factors. In more biologically active periods, models contained more predictors, including plant trait measures. Field-based plant biomass measures were generally better predictors of fluxes than CWM and FDvar traits. However, when these measures were used in combination traits accounted for additional variation. Where traits were significant predictors their identity often reflected seasonal vegetation dynamics. These results suggest that database derived trait measures can improve the prediction of ecosystem C and water fluxes. Controlled studies and those involving more detailed flux measurements are required to validate and explore these findings, a worthwhile effort given the potential for using simple vegetation measures to help predict landscape-scale fluxes.

Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure: The Vent-HeFT trial: a European prospective multicentre randomized trial

AIMS Vent-HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training (IMT) on aerobic training (AT) in patients with chronic heart failure (CHF). METHODS AND RESULTS Forty-three CHF patients with a mean age of 58 ± 12 years, peak oxygen consumption (peak VO2 ) 17.9 ± 5 mL/kg/min, and LVEF 29.5 ± 5% were randomized to an AT/IMT group (n = 21) or to an AT/SHAM group (n = 22) in a 12-week exercise programme. AT involved 45 min of ergometer training at 70-80% of maximum heart rate, three times a week for both groups. In the AT/IMT group, IMT was performed at 60% of sustained maximal inspiratory pressure (SPImax ) while in the AT/SHAM group it was performed at 10% of SPImax , using a computer biofeedback trainer for 30 min, three times a week. At baseline and at 3 months, patients were evaluated for exercise capacity, lung function, inspiratory muscle strength (PImax ) and work capacity (SPImax ), quality of life (QoL), LVEF and LV diameter, dyspnoea, C-reactive protein (CRP), and NT-proBNP. IMT resulted in a significantly higher benefit in SPImax (P = 0.02), QoL (P = 0.002), dyspnoea (P = 0.004), CRP (P = 0.03), and NT-proBNP (P = 0.004). In both AT/IMT and AT/SHAM groups PImax (P < 0.001, P = 0.02), peak VO2 (P = 0.008, P = 0.04), and LVEF (P = 0.005, P = 0.002) improved significantly; however, without an additional benefit for either of the groups. CONCLUSION This randomized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF. These findings advocate for application of IMT in cardiac rehabilitation programmes.

DAPK loss in colon cancer tumor buds: implications for migration capacity of disseminating tumor cells.

Defining new therapeutic strategies to overcome therapy resistance due to tumor heterogeneity in colon cancer is challenging. One option is to explore the molecular profile of aggressive disseminating tumor cells. The cytoskeleton-associated Death-associated protein kinase (DAPK) is involved in the cross talk between tumor and immune cells at the invasion front of colorectal cancer. Here dedifferentiated tumor cells histologically defined as tumor budding are associated with a high risk of metastasis and poor prognosis. Analyzing samples from 144 colorectal cancer patients we investigated immunhistochemical DAPK expression in different tumor regions such as center, invasion front, and buds. Functional consequences for tumor aggressiveness were studied in a panel of colon tumor cell lines using different migration, wound healing, and invasion assays. DAPK levels were experimentally modified by siRNA transfection and overexpression as well as inhibitor treatments. We found that DAPK expression was reduced towards the invasion front and was nearly absent in tumor buds. Applying the ECIS system with HCT116 and HCT116 stable lentiviral DAPK knock down cells (HCTshDAPK) we identified an important role for DAPK in decreasing the migratory capacity whereas proliferation was not affected. Furthermore, the migration pattern differed with HCTshDAPK cells showing a cluster-like migration of tumor cell groups. DAPK inhibitor treatment revealed that the migration rate was independent of DAPK's catalytic activity. Modulation of DAPK expression level in SW480 and DLD1 colorectal cancer cells significantly influenced wound closure rate. DAPK seems to be a major player that influences the migratory capability of disseminating tumor cells and possibly affects the dynamic interface between pro- and anti-survival factors at the invasion front of colorectal cancer. This interesting and new finding requires further evaluation.

Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

OBJECTIVE Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. DESIGN Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. RESULTS Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). CONCLUSION A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD.

A path analysis of an after-school health and exercise program for elementary school children in El Paso, Texas

As schools are pressured to perform on academics and standardized examinations, schools are reluctant to dedicate increased time to physical activity. After-school exercise and health programs may provide an opportunity to engage in more physical activity without taking time away from coursework during the day. The current study is a secondary data analysis of data from a randomized trial of a 10-week after-school program (six schools, n = 903) that implemented an exercise component based on the CATCH physical activity component and health modules based on the culturally-tailored Bienestar health education program. Outcome variables included BMI and aerobic capacity, health knowledge and healthy food intentions as assessed through path analysis techniques. Both the baseline model (χ2 (df = 8) = 16.90, p = .031; RMSEA = .035 (90% CI of .010–.058), NNFI = 0.983 and the CFI = 0.995) and the model incorporating intervention participation proved to be a good fit to the data (χ2 (df = 10) = 11.59, p = .314. RMSEA = .013 (90% CI of .010–.039); NNFI = 0.996 and CFI = 0.999). Experimental group participation was not predictive of changes in health knowledge, intentions to eat healthy foods or changes in Body Mass Index, but it was associated with increased aerobic capacity, β = .067, p < .05. School characteristics including SES and Language proficiency proved to be significantly associated with changes in knowledge and physical indicators. Further effects of school level variables on intervention outcomes are recommended so that tailored interventions can be developed aimed at the specific characteristics of each participating school. ^

La resistencia especial en el fútbol

La finalidad de esta tesis es establecer un análisis de la metodología de entrenamiento de la resistencia especial en el futbolista. Su objetivo no está vinculado a realizar propuestas prácticas de entrenamiento, sino más bien, se tratará de abordar una posible justificación fisiológico - metabólica, a partir de la relevancia bioenergética de la creatina, en función de la creciente especialización que debe ir adquiriendo el proceso del entrenamiento deportivo a largo plazo, enfocado al logro de altos rendimientos deportivos. A partir del análisis de conceptos terminológicos de referencia, se asienta la idea general de este trabajo, es decir, la estructuración y desarrollo de la resistencia en los deportes de conjunto, como el fútbol. Los pilares de una adecuada planificación son el conocimiento y la aplicación de distintas leyes y principios del entrenamiento deportivo y su relación con los distintos medios y métodos de entrenamiento, como así también, los efectos de adaptación que provocan. Por lo tanto, a partir del análisis de los requerimientos morfológicos - funcionales de las competiciones de elite en fútbol, se pueden elaborar modelos que servirán de base y como objetivo final al cual debe ser orientado el proceso de entrenamiento. Es decir, que un entrenamiento multianual con miras a la formación de futbolistas de elite, debe respetar la especialización creciente de las cargas de entrenamiento, estableciendo una sucesión metodológica adecuada en función de los objetivos de cada etapa. En función de lo expuesto, se realiza un análisis que va desde la resistencia como capacidad física y su metodología de entrenamiento, recorriendo distintos conceptos y manifestaciones, pasando por el análisis de distintas zonas de intensidad o áreas funcionales, y desembocando en la metodología de entrenamiento intermitente de la resistencia o resistencia especial -en los deportes de conjunto-. Y es a partir de todo el análisis precedente que estamos en condiciones de abordar el entrenamiento específico en el fútbol, y más detalladamente la resistencia específica o intermitente que requiere este deporte. El entrenamiento intermitente puede ser considerado como una metodología cuyo énfasis es puesto en modificaciones que se producen a nivel muscular, por sobre factores centrales de rendimiento, presentándose como una variante óptima para el entrenamiento de la resistencia muscular local y específica del futbolista. Básicamente, el entrenamiento intermitente actuaría sobre dos puntos centrales: la mejora del sistema shuttle de la CrP, y sobre la rapidez de entrega de oxígeno al inicio del ejercicio. Aquí aparece la importancia de la suplementación con Cr: que al aumentar las concentraciones del sustrato, y junto con el entrenamiento, que mejora las reacciones enzimáticas implicadas, potenciaría las mejoras buscadas con este tipo de metodología. Queda por determinar cual es el preciso mecanismo de acción por el cual la recuperación de los fosfatos altamente energéticos se produce: si por biogénesis mitocondrial en las fibras reclutadas - generalmente FT -; o mediante el sistema de proteínas transportadoras de Cr - destacando la importancia de las ST - o por algún otro mecanismo no conocido. Su descubrimiento permitiría direccionar más precisamente el entrenamiento deportivo.

La resistencia especial en el fútbol

La finalidad de esta tesis es establecer un análisis de la metodología de entrenamiento de la resistencia especial en el futbolista. Su objetivo no está vinculado a realizar propuestas prácticas de entrenamiento, sino más bien, se tratará de abordar una posible justificación fisiológico - metabólica, a partir de la relevancia bioenergética de la creatina, en función de la creciente especialización que debe ir adquiriendo el proceso del entrenamiento deportivo a largo plazo, enfocado al logro de altos rendimientos deportivos. A partir del análisis de conceptos terminológicos de referencia, se asienta la idea general de este trabajo, es decir, la estructuración y desarrollo de la resistencia en los deportes de conjunto, como el fútbol. Los pilares de una adecuada planificación son el conocimiento y la aplicación de distintas leyes y principios del entrenamiento deportivo y su relación con los distintos medios y métodos de entrenamiento, como así también, los efectos de adaptación que provocan. Por lo tanto, a partir del análisis de los requerimientos morfológicos - funcionales de las competiciones de elite en fútbol, se pueden elaborar modelos que servirán de base y como objetivo final al cual debe ser orientado el proceso de entrenamiento. Es decir, que un entrenamiento multianual con miras a la formación de futbolistas de elite, debe respetar la especialización creciente de las cargas de entrenamiento, estableciendo una sucesión metodológica adecuada en función de los objetivos de cada etapa. En función de lo expuesto, se realiza un análisis que va desde la resistencia como capacidad física y su metodología de entrenamiento, recorriendo distintos conceptos y manifestaciones, pasando por el análisis de distintas zonas de intensidad o áreas funcionales, y desembocando en la metodología de entrenamiento intermitente de la resistencia o resistencia especial -en los deportes de conjunto-. Y es a partir de todo el análisis precedente que estamos en condiciones de abordar el entrenamiento específico en el fútbol, y más detalladamente la resistencia específica o intermitente que requiere este deporte. El entrenamiento intermitente puede ser considerado como una metodología cuyo énfasis es puesto en modificaciones que se producen a nivel muscular, por sobre factores centrales de rendimiento, presentándose como una variante óptima para el entrenamiento de la resistencia muscular local y específica del futbolista. Básicamente, el entrenamiento intermitente actuaría sobre dos puntos centrales: la mejora del sistema shuttle de la CrP, y sobre la rapidez de entrega de oxígeno al inicio del ejercicio. Aquí aparece la importancia de la suplementación con Cr: que al aumentar las concentraciones del sustrato, y junto con el entrenamiento, que mejora las reacciones enzimáticas implicadas, potenciaría las mejoras buscadas con este tipo de metodología. Queda por determinar cual es el preciso mecanismo de acción por el cual la recuperación de los fosfatos altamente energéticos se produce: si por biogénesis mitocondrial en las fibras reclutadas - generalmente FT -; o mediante el sistema de proteínas transportadoras de Cr - destacando la importancia de las ST - o por algún otro mecanismo no conocido. Su descubrimiento permitiría direccionar más precisamente el entrenamiento deportivo.

La resistencia especial en el fútbol

La finalidad de esta tesis es establecer un análisis de la metodología de entrenamiento de la resistencia especial en el futbolista. Su objetivo no está vinculado a realizar propuestas prácticas de entrenamiento, sino más bien, se tratará de abordar una posible justificación fisiológico - metabólica, a partir de la relevancia bioenergética de la creatina, en función de la creciente especialización que debe ir adquiriendo el proceso del entrenamiento deportivo a largo plazo, enfocado al logro de altos rendimientos deportivos. A partir del análisis de conceptos terminológicos de referencia, se asienta la idea general de este trabajo, es decir, la estructuración y desarrollo de la resistencia en los deportes de conjunto, como el fútbol. Los pilares de una adecuada planificación son el conocimiento y la aplicación de distintas leyes y principios del entrenamiento deportivo y su relación con los distintos medios y métodos de entrenamiento, como así también, los efectos de adaptación que provocan. Por lo tanto, a partir del análisis de los requerimientos morfológicos - funcionales de las competiciones de elite en fútbol, se pueden elaborar modelos que servirán de base y como objetivo final al cual debe ser orientado el proceso de entrenamiento. Es decir, que un entrenamiento multianual con miras a la formación de futbolistas de elite, debe respetar la especialización creciente de las cargas de entrenamiento, estableciendo una sucesión metodológica adecuada en función de los objetivos de cada etapa. En función de lo expuesto, se realiza un análisis que va desde la resistencia como capacidad física y su metodología de entrenamiento, recorriendo distintos conceptos y manifestaciones, pasando por el análisis de distintas zonas de intensidad o áreas funcionales, y desembocando en la metodología de entrenamiento intermitente de la resistencia o resistencia especial -en los deportes de conjunto-. Y es a partir de todo el análisis precedente que estamos en condiciones de abordar el entrenamiento específico en el fútbol, y más detalladamente la resistencia específica o intermitente que requiere este deporte. El entrenamiento intermitente puede ser considerado como una metodología cuyo énfasis es puesto en modificaciones que se producen a nivel muscular, por sobre factores centrales de rendimiento, presentándose como una variante óptima para el entrenamiento de la resistencia muscular local y específica del futbolista. Básicamente, el entrenamiento intermitente actuaría sobre dos puntos centrales: la mejora del sistema shuttle de la CrP, y sobre la rapidez de entrega de oxígeno al inicio del ejercicio. Aquí aparece la importancia de la suplementación con Cr: que al aumentar las concentraciones del sustrato, y junto con el entrenamiento, que mejora las reacciones enzimáticas implicadas, potenciaría las mejoras buscadas con este tipo de metodología. Queda por determinar cual es el preciso mecanismo de acción por el cual la recuperación de los fosfatos altamente energéticos se produce: si por biogénesis mitocondrial en las fibras reclutadas - generalmente FT -; o mediante el sistema de proteínas transportadoras de Cr - destacando la importancia de las ST - o por algún otro mecanismo no conocido. Su descubrimiento permitiría direccionar más precisamente el entrenamiento deportivo.