Biomedical subjects

H Hoppeler

Publications and source records attributed to H Hoppeler.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of diet on the replenishment of intramyocellular lipids after exercise.

BACKGROUND: Muscle triglycerides are important as a source of energy and in relation to metabolic sensitivity. However, the classic biopsy method does not distinguish intra- from extracellular fat, and their regulation by exercise and diet is largely unknown. Magnetic resonance spectroscopy (MRS) is available to assess the intramyocellular lipid (IMCL) pool non-invasively in humans. AIM OF THE STUDY: The aim of this work was to use sequential MRS measurements of IMCL and glycogen to explore the role of three levels of dietary fat on the replenishment of these energy stores after exercise. METHODS: Following 2 h of exercise, two subjects (S1, S2) were fed one of three diets (15%, 40% or 70% fat energy), each on a separate occasion. IMCL and glycogen were measured by MRS in the tibialis anterior muscle before, after exercise, and at 10 and at 32 h of recovery. RESULTS: Initial IMCL concentration (mmol.kg-1: 3.0 in S1 and 1.8 in S2) was reduced to 70% after exercise. The rate of replenishment was minimal with the low-fat (mmol.kg-1.24 h-1: 0.7 and 0.0) and much higher with both higher fat diets (mmol.kg-1.24 h-1: 3.1 and 3.2 in S1, 0.7 and 0.9 in S2). Glycogen and IMCL replenishments were inversely correlated. CONCLUSIONS: IMCL and glycogen can vary acutely in response to diet after exercise. Studies are needed to determine if such variations occur within the range of ordinary diets and to clarify the functional significance of IMCL in differently active individuals.

Adult↗

PubMed2000

Structural and functional limits for oxygen supply to muscle.

Environmental oxygen is transported by the respiratory cascade to the site of oxidation in active tissues. Under conditions of heavy exercise it is ultimately the working skeletal muscle cells that determine the aerobic demand as over 90% of energy is spent in muscle cells. Oxygen is transported in the circulation bound to haemoglobin of erythrocytes while substrates are transported in the plasma. The supply of oxygen must be continuous because there are only minimal oxygen stores in the body of most mammalian species while substrates are stored in significant quantities both within muscle cells as also in organismic substrate stores. The pathways for oxygen and substrates ultimately converge in muscle mitochondria. In mammals, a structural limitation of carbohydrate and lipid transfer from the microvascular system to muscle cells is reached at a moderate work intensity (i.e. at less than 50% of VO2max). At higher work rates intracellular substrate stores must be used for oxidation. It is therefore not surprising to find larger intramyocellular carbohydrate and lipid stores in 'athletic' species as well as in endurance-trained human athletes. The transfer limitations for carbohydrates and lipids presumably occur on the level of the sarcolemma. These findings imply that the design of the respiratory cascade from lungs to muscle mitochondria has to be analysed with regard to satisfying the demand for oxygen of the working muscle cells. Substrate stores are replenished at low flux rates during periods of rest and are stored intracellularly. They are therefore locally available to mitochondria for aerobic work at high intensities.

Animals↗

PubMed2000

Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. Oral administration of creatine has been shown to improve muscle strength in healthy subjects. The objective of this study was to examine the effect of oral creatine supplementation on muscle weakness, disease activity and activities of daily living in patients with RA. METHODS: During a period of 3 weeks, 12 patients with RA were treated with creatine monohydrate (20 g/day for 5 days followed by 2 g/day for 16 days). They were examined on entry and at the end of the study. The patients were investigated clinically, blood and urine samples were obtained, muscle biopsies were performed before and after treatment, muscle strength was determined, and self-administered patient questionnaires were completed. RESULTS: From all patients we were able to obtain full clinical and questionnaire data, while biopsies were taken from 12 patients at the start and from nine patients at the end of the study. Muscle strength, as determined by the muscle strength index, increased in eight of 12 patients. In contrast, physical functional ability and disease activity did not change significantly. The creatine concentration in serum and skeletal muscle increased significantly, while creatine phosphate and total creatine did not increase in skeletal muscle. The skeletal muscle creatine content was associated with muscle strength at baseline but not after administration of creatine. The changes in muscle strength were not associated with the changes in skeletal muscle creatine or creatine phosphate. CONCLUSION: Although the skeletal muscle creatine content and muscle strength increased with creatine administration in some patients with RA, a clear clinical benefit could not be demonstrated for this treatment when the patients were considered as one group.

Adult↗

PubMed2000

Eccentric ergometry: increases in locomotor muscle size and strength at low training intensities.

Lengthening (eccentric) muscle contractions are characterized by several unusual properties that may result in unique skeletal muscle adaptations. In particular, high forces are produced with very little energy demand. Eccentrically trained muscles gain strength, but the specific nature of fiber size and composition is poorly known. This study assesses the structural and functional changes that occur to normal locomotor muscle after chronic eccentric ergometry at training intensities, measured as oxygen uptake, that do not influence the muscle when exercised concentrically. Male subjects trained on either eccentric or concentric cycle ergometers for 8 wk at a training intensity starting at 54% and ending at 65% of their peak heart rates. The isometric leg strength increased significantly in the eccentrically trained group by 36%, as did the cross-sectional area of the muscle fiber by 52%, but the muscle ultrastructure remained unchanged. There were no changes in either fiber size, composition, or isometric strength in the concentrically trained group. The responses of muscle to eccentric training appear to be similar to resistance training.

Adult↗

PubMed2000

Structural changes in arm muscles after microgravity.

Disuse muscle atrophy is a well-known consequence of spaceflight. However, most of the available muscle data concern lower limb muscles of rats and primates exposed to microgravity aboard Russian Cosmos biosatellites and American Space Shuttles. The purpose of our study was, therefore, to provide information concerning the effects of a 14-day spaceflight on two upper limb muscles of rhesus monkeys (Macaca mulatta). Our objective was to compare structural adaptations after 14 days of microgravity in a slow-twitch extensor muscle, i.e., the triceps, with a fast-twitch flexor muscle, i.e., the biceps. We hypothesize that muscle responses will be muscle specific, i.e., slow will differ from fast muscles, flexors will differ from extensors, and arms will differ from legs.

Animals↗

PubMed1999

Vascular growth in hypoxic skeletal muscle.

The critical role of skeletal muscle capillaries is the supply of oxygen to skeletal muscle fibers during conditions of maximal aerobic work. The supply of substrates under these conditions is not limited by the vascular bed but rather by the capacity of the sarcolemmal transporter systems. Because of this dominant role of oxygen supply in muscle tissue, hypoxia has generally been considered to be an important stimulus for capillary neo-formation in skeletal muscle. Early morphometric work seemed to indicate that animals exposed to permanent hypoxia had in fact a significantly improved vascular supply in muscle tissue. Later work questioned these early findings and it was concluded that hypoxia per se was not a sufficient stimulus for capillary neo-formation but that additional stimuli such as cold-exposure needed to be present. In humans exposed to severe hypoxia during simulated or real ascents to Mt. Everest an increase in capillary density was in fact found. However, this increase could be shown to result from a reduction of muscle fiber volume and not from capillary growth. Broadly compatible results were obtained in animal experiments in which changes in capillarity were assessed in muscles with limited blood supply which were exposed to chronic electrical stimulation. Recently we have shown that endurance exercise training in humans results in a rise in mRNA of vascular endothelial growth factor (VEGF) only when carried out vigorously and in hypoxia. These results indicate that molecular techniques will allow in the near future to delineate the role played by hypoxia in capillary neo-formation.

Altitude↗

PubMed1999

Carnitine homeostasis in patients with rheumatoid arthritis.

Myopathy is a frequent finding in patients with rheumatoid arthritis (RA). Since carnitine is important for skeletal muscle energy metabolism, carnitine metabolism was investigated in patients with RA and myopathy. Muscle strength was estimated by determination of a muscle strength index (MSI) which is derived from isometric measurements of muscle strength at knees and elbows. Carnitine was determined by a radioenzymatic method and 3-methylhistidine by high-performance liquid chromatography. In comparison to control subjects, patients had a reduced MSI. Both the 24-h creatinine and 3-methylhistidine excretions were reduced in patients. The plasma carnitine pool was not different between patients and control subjects, except for a higher long-chain acylcarnitine concentration in patients. Urinary excretion of carnitine was decreased in patients, also after normalization for body weight. Accordingly, renal carnitine clearance and excretion fraction were both decreased in patients. Skeletal muscle free- and total carnitine levels were increased in patients, whereas the long-chain acylcarnitine content was markedly decreased. The total skeletal muscle carnitine content showed a negative correlation with the MSI and no association with disease activity. Carnitine deficiency does not explain reduced skeletal muscle strength in patients with RA. Decreased renal carnitine excretion in patients is most likely due to reduced carnitine biosynthesis, leading to more efficient tubular carnitine reabsorption for maintaining the carnitine body stores.

Adult↗

PubMed1999

Skeletal muscle substrate metabolism.

Endurance power of muscles is determined largely by the capacities to oxidize substrates in mitochondria in the process of making ATP by oxidative phosphorylation. This review explores physiological and morphological factors that may cause limitation of carbohydrate and fat utilization by muscle cells. The pathways for oxygen and substrates converge in muscle mitochondria. In mammals, a structural limitation of carbohydrate and lipid transfer from the microvascular system to muscle cells is reached at a moderate work intensity (that is, at 40-50% of VO2max). At higher work rates intracellular substrate stores must be used for oxidation. Because of the importance of these intracellular stores for aerobic work we find larger intramyocellular substrate stores in endurance trained athletes. The transfer limitations for carbohydrates and lipids on the level of the sarcolemma implies that the design of the respiratory cascade from lungs to muscle mitochondria reflects primarily oxygen demand.

Animals↗

PubMed1999

Muscle structure with low- and high-fat diets in well-trained male runners.

Endurance capacity, maximal oxygen uptake capacity (VO2max) and quantitative muscle ultrastructural composition was analyzed in 7 well-trained male runners (mean age 37.1 years, mean VO2max 60 ml/min/kg) after a one month period of a low-fat diet (dietary fat intake 18.4% and a similar period of a high-fat diet (dietary fat intake 40.6%). Between these two interventional periods a washout period of one month was interspersed in which the nutritional fat content was approx. 32%; close to the average American Diet. During all three periods protein content of the nutrition was kept nearly constant at 15%. After the high-fat diet time to exhaustion in the endurance test increased significantly by 21% while VO2max remained unchanged. Muscle mitochondrial volume density remained unchanged while the intramyocellular fat content increased by 60%. Due to large interindividual differences in this variable this difference did not become statistically significant. While some 20% of the mitochondria are located in a subsarcolemmal location, only 10% of the lipid stores are associated with these mitochondria. Less than 2% of the mitochondrial outer surface are in contact with lipid droplets whereas 25-35% of the lipid surface is in contact with mitochondria. None of these variables is significantly altered after a high-fat diet. It is concluded that the change in endurance capacity of the subjects cannot be explained based on the structural changes observed in skeletal muscle tissue. This may be related to methodological problems associated with the determination of intramyocellular fat content.

Adult↗

PubMed1999

Creatine supplementation--part I: performance, clinical chemistry, and muscle volume.

PURPOSE: Our purpose was to study the effects and side effects of creatine (Cr) supplementation on high-intensity, short-term muscle work, on biochemical parameters related to Cr metabolism in blood and urine, and on muscle volume of the lower limb muscles. METHODS: A cycling ergometer was used in a double-blind, cross-over study on 10 well-trained male physical education students to measure physical performance with 10 repetitive ergometer sprints (6-s duration, 30-s rest) before and after supplementation (5 d, 20 g x d(-1), washout period 61 +/- 8 d, mean +/- SEM, minimum 28 d) with Cr or placebo. Before and after supplementation, blood and urine were taken and the muscle volume of the lower limb was determined by magnetic resonance imaging (MRI). RESULTS: A significant (P << 0.05) increase in performance (+7%) at the end [4-6 s] of the later sprints (4-7 and 8-10) was observed combined with a lower production of blood lactate (-1 mmol x L(-1)) with Cr supplementation. The concentration of Cr was increased significantly in urine (P < 0.001) and serum (P = 0.005), whereas creatinine (Crn) was increased in serum (P < 0.001). Crn in urine and Crn clearance did not change significantly with Cr intake. There were no significant changes in the analyzed blood enzyme activities. A significant gain of body weight (pre-Cr 76.5 +/- 1.7 kg to 77.9 +/- 1.7 kg post-Cr) with Cr supplementation was measured, but no accompanying increase of muscle mass in a limited volume of the lower limb was observed by MRI. CONCLUSION: Cr supplementation is effective in improving short-term performance, and the methods used show no detrimental side effects with this supplementation protocol.

Adult↗

PubMed1999

Creatine supplementation--part II: in vivo magnetic resonance spectroscopy.

PURPOSE: Our purpose was to study effects of creatine (Cr) supplementation on muscle metabolites noninvasively by means of magnetic resonance spectroscopy (MRS) before and after supplementation with Cr or placebo. METHODS: 1H-MRS was used in a comprehensive, double-blind, cross-over study in 10 volunteers to measure Cr in m. tibialis anterior and m. rectus femoris at rest. PCr/ATP was observed in m. quadriceps femoris by 31P-MRS at rest and after exercise. RESULTS: A significant increase in total Cr was observed with Cr intake in m. tibialis anterior (+9.6 +/- 1.7%, P = 0.001) and in m. rectus femoris (+18.0 +/- 1.8%, P < 0.001). PCr/ATP showed a significant increase (+23.9 +/- 2.3%, P < 0.001) in m. quadriceps femoris at rest with Cr supplementation. Post-Cr supplementation recovery rates from exercise were significantly lower (k = 0.029 s(-1), P < 0.01) compared with postplacebo consumption (k = 0.034 s(-1)) and presupplementation (k = 0.037 s(-1)). However, higher levels of PCr/ATP at rest compensate for this reduction of the recovery rate after Cr supplementation. The increase of PCr/ATP determined by 31P-MRS correlates with the increase of Cr observed by 1H-MRS (r = 0.824, P < 0.001). CONCLUSION: Noninvasive observation of Cr and PCr after Cr supplementation shows an increase in a muscle specific manner. Higher preexercise levels of PCr/ATP at rest compensate for significantly slower recovery rates of PCr/ATP after Cr supplementation.

Adenosine Triphosphate↗

PubMed1999

Chronic eccentric exercise: improvements in muscle strength can occur with little demand for oxygen.

Eccentric contractions, the lengthening of muscle while producing force, are a common part of our everyday movements. This study presents a challenge to the accepted notion that eccentric work causes obligatory muscle injury while demonstrating that an increase in muscle strength, via eccentric work, can occur with little demand for oxygen. Nine healthy subjects, ages 18-34, were randomly placed in either an eccentric or a concentric training group. Both groups trained for 6 wk while progressively increasing training frequency and duration. Significant gains in isometric leg strength were seen in the eccentrically trained subjects only. While training, the oxygen consumption required to do the eccentric work was equal to or less than that required to do the concentric work. The results demonstrate that by progressively increasing the eccentric work rate, significant isometric strength gains can be made without muscle injury and with minimal increase in metabolic demand for oxygen. The potential clinical implications of an eccentric training program that uncouples skeletal muscle strength improvements from the demand for oxygen are alluring.

Adolescent↗

PubMed1998

Exercise training in chronic hypoxia has no effect on ventilatory muscle function in humans.

At the highest altitude, aerobic work is limited by environmental oxygen availability. We therefore reasoned that the hyperpnea associated with endurance training at altitude should provide a strong stimulus for adaptation of the ventilatory muscles. We measured peak inspiratory muscle pressure-flow characteristics (inspiring through graded resistors) and maximum sustainable ventilation capacity in ten permanent residents of La Paz, Bolivia (3600 m) prior to and immediately following 6 weeks of incremental endurance training. Additionally, eight local residents did no training and functioned as controls for the capacity test. While V(O2)max measured in hypoxia increased by 19% (Favier et al., 1995b. J. Appl Physiol. 78, 2286-2293.), none of the tested ventilatory variables showed significant changes. The values for the group mean slopes of maximum inspiratory pressure-flow pairs (- 10.5 vs. - 9.8 cm H2O x sec x L(-1), P=0.301; before versus after training, respectively), maximum inspiratory pressure (112.1+/-8.9 vs. 106.9+/-8.6 cmH2O, P=0.163), peak inspiratory flow (9.8+/-0.41 vs. 10.2+/-0.55 L x sec(-1) P=0.172) and the maximum volitional volume in 12 sec (43.9+/-2.4 vs. 45.6+/-2.4 L in 12 sec, P=0.133) were unchanged with exercise training. Likewise, maximal sustainable minute volume was not different between post-training and control subjects (177.4+/-7.9 vs. 165.4+/-8.4 L x min(-1), P=0.141). These data support the concept that endurance training fails to elicit functional adaptations in ventilatory muscles in humans, even when exercise is done in hypoxia.

Acclimatization↗

PubMed1998

Skeletal muscle response to short endurance training in heart transplant recipients.

OBJECTIVES: We sought to examine the effects of endurance training on the ultrastructural characteristics of skeletal muscle in heart transplant recipients (HTRs) and age-matched control subjects (C). BACKGROUND: Deconditioning is one of the factors involved in the peripheral limitation of exercise capacity of HTRs, and training has proven to be beneficial. METHODS: Biopsies of the vastus lateralis muscle, analyzed by ultrastructural morphometry, and quadriceps muscle cross-sectional area, assessed by computed tomography (CT), were performed in 12 HTRs and 7 age-matched C before and 6 weeks after an endurance training program. Maximal oxygen uptake (peak VO2) was determined by an incremental exercise test. Additionally muscle biopsies were performed before and after a 6-week control period in four HTRs to check for spontaneous improvement. RESULTS: Training resulted in similar increases in peak VO2 (11% in HTRs, 8.5% in C), ventilatory threshold (23% in HTRs, 32% in C) and total endurance work (54% in HTRs, 31% in C). Volume density of total mitochondria increased significantly (26% in HTRs, 33% in C) with a predominant increase of subsarcolemmal mitochondrial volume density (74% in HTRs, 70% in C). The capillary/fiber ratio increased by 19% in C only. In the nontrained group, none of the structural markers was spontaneously modified. CONCLUSIONS: Six weeks of endurance training in HTRs and C led to similar improvements of aerobic work capacity. However, the decreased muscular capillary network in HTRs remained unchanged with training. Immunosuppressive therapy might be responsible for the discrepancy between the normal mitochondrial content and the reduced capillary supply of these patients.

Adult↗

PubMed1998

Fibre-type specific expression of fast and slow essential myosin light chain mRNAs in trained human skeletal muscles.

The fibre-type specific expression patterns of fast and slow isoforms of essential (alkali) myosin light chains (ELC) was analysed in trained, untrained and pathological human muscles. Biopsies from m. vastus lateralis of moderately trained and untrained persons, as well as highly trained endurance and strength athletes were analysed, by in situ hybridization, for the expression of the 'fast' ELC 1f/3f and the 'slow' ELC 1 sb. We wanted to investigate if changes in the fibre-type specific ELC mRNA pattern could be used as markers for training adaptation, especially, if the mRNA of the slow ELC 1sb isoform would appear in type IIA fibres as a result of endurance training (Baumann et al. 1987). We found the fast/slow ELC expression patterns in the fibre types to be remarkably stable. Physiological stress, even high training loads, did not affect it. No IIA fibres expressing ELC 1sb mRNA were found. They could be detected, however, in pathological muscle samples, where fast/slow ELC patterns not found in normal muscles were frequent. Our data suggest that in healthy muscles, only a subset of the theoretically possible combinations of myosin heavy and light chain isoforms are expressed at the level of their mRNAs.

Adenosine Triphosphatases↗

PubMed1998

Effects of bedrest on deltoideus muscle morphology and enzymes.

To examine the effects of unweighting on the structural and metabolic adaptations of a non-postural muscle, deltoideus muscle biopsies were taken in seven male healthy subjects, before and after a 37 day bedrest. Myofibrillar ATPase histochemistry demonstrated no change in fibre type distributions (I, IIA, IIB), in fibre cross-sectional areas nor in capillary supply. No difference was noted in enzyme activities of oxidative metabolism (citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase), and glycolysis (hexokinase, lactate dehydrogenase). Electron microscopy showed a decrease in the volume density of lipids but no change in mitochondrial volume density and distribution. The results indicate that bedrest induces no major morphological and biochemical changes in deltoideus muscle, contrary to what was previously reported in vastus lateralis muscle. This lack of changes is probably related to an unaltered deltoideus muscle use.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1998

Expression of fos and jun genes in human skeletal muscle after exercise.

It is believed that the induction of the fos and jun gene family of transcription factors might be at the origin of genetic events leading to the differential regulation of muscle-specific genes. We have investigated the effect of a 30-min running bout in untrained subjects on the expression of the mRNAs of all members of the fos and jun gene families, including c-fos, fosB, fosBdel, fra-1, and fra-2 as well as c-jun, junB, and junD. While the fos family members were transiently upregulated 10- to 20-fold (an exception being fra-2) the induction of the jun family members was up to 3-fold only. The induction of c-fos could also be demonstrated at the protein level. Both c-fos and c-jun mRNAs were coinduced in muscle fiber nuclei. The induction was not restricted to a particular fiber type, as expected from established muscle fiber recruitment schemes, but followed a "patchy" pattern confined to certain regions of the muscle. The signals leading to the expression of these immediate early genes are therefore unclear.

Adult↗

PubMed1998

Limits for oxygen and substrate transport in mammals.

Environmental oxygen is transported by the respiratory cascade to the site of oxidation in active tissues. Under conditions of heavy exercise, it is ultimately the working skeletal muscle cells that set the aerobic demand because over 90 % of energy is spent in muscle cells. The pathways for oxygen and substrates converge in muscle mitochondria. In mammals, a structural limitation of carbohydrate and lipid transfer from the microvascular system to the muscle cells is reached at a moderate work intensity (i.e. at 40-50 % of VO2max). At higher work rates, intracellular substrate stores must be used for oxidation. Because of the importance of these intracellular stores for aerobic work, we find larger intramyocellular substrate stores in 'athletic' species as well as in endurance-trained human athletes. The transfer limitations for carbohydrates and lipids at the level of the sarcolemma imply that the design of the respiratory cascade from lungs to muscle mitochondria reflects primarily oxygen demand. Comparative studies indicate that the oxidative capacity of skeletal muscle tissue, and hence maximal oxygen demand, is adjusted by varying mitochondrial content. At the level of microcirculatory oxygen supply, it is found that muscle tissue capillarity is adjusted to muscle oxygen demand but that the capillary erythrocyte volume also plays a role. Oxygen delivery by the heart has long been recognized to be a key link in the oxygen transport chain. In allometric variation it is heart rate and in adaptive variation it is essentially stroke volume, and hence heart size, that determines maximal cardiac output. Again, haematocrit is an important variable that allows the heart of athletic species to generate higher flux rates for oxygen. The pulmonary gas exchanger offers only a negligible resistance to oxygen flux to the periphery. However, in contrast to all other steps in the respiratory cascade, the lungs have only a minimal phenotypical plasticity and appear, therefore, to be built with considerable structural redundancy in all but the most athletic species. Because of the lack of malleability, the lungs may ultimately become limiting for VO2max when adaptive processes have maximized O2 flux through the malleable downstream elements of the respiratory system: the heart, microcirculation and muscle mitochondria.

Animals↗