Hans Hoppeler

Influences of endurance training on the ultrastructural composition of the different muscle fiber types in humans

AbstractTo investigate changes in the ultrastructure of the different muscle fiber types induced by endurance training ten sedentary subjects (five women and five men) were exercised on bicycle ergometers 5 times a week for 30 min. After 6 weeks of training there were significant changes in

Response of Skeletal Muscle Mitochondria to Hypoxia

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Plasticity of skeletal muscle mitochondria: structure and function.

(+14%), in the percentage of type I (+12%) and type IIB fibers (−24%) as well as in the volume densities of mitochondria. The latter increased 35% in type I, 55% in type IIA and 35% in type IIB fibers. The relative increase in subsarcolemmal mitochondria was larger than in interfibrillar mitochondria in all fiber types. There was also a significant increase in the volume density of intracellular lipid in type II fibres. It is concluded that high intensity endurance training leads to an enhancement of the oxidative capacity in all muscle fiber types.

Measuring error and sampling variation in stereology: comparison of the efficiency of various methods for planar image analysis

BACKGROUND Ruptures of the tendons of the rotator cuff lead to profound and possibly irreversible changes in the structure and physiological properties of the rotator cuff muscles. Muscle atrophy and fatty infiltration are important prognostic factors that affect the natural history and outcome of treatment. The purpose of this study was to examine the amount of muscle atrophy and fatty infiltration in an animal model and to determine whether the repair of a long-standing tendon tear can reverse these changes. METHODS The infraspinatus tendon in six sheep was released and encased in a silicone tube to prevent spontaneous healing. The musculotendinous unit was allowed to retract for forty weeks. Throughout this period, the muscular changes were studied with use of computed tomography, histological analysis, and electron microscopy. At forty weeks, the elasticity, intramuscular pressure, and perfusion were measured intraoperatively and a tendon repair was carried out. The structural changes of the muscle were studied for thirty-five weeks after the repair. The animals were then killed, and the musculotendinous units were examined macroscopically and by computed tomography, histological analysis, and electron microscopy. RESULTS At the time of the tendon release, the infraspinatus showed no fatty changes. The force needed to cause a tendon excursion of 1 cm was a mean (and standard deviation) of 6.8 +/- 1 N. The application of tension on the tendon did not alter the perfusion and decreased the intramuscular pressure. After the tendon release, muscular atrophy developed and there was a significant increase (p < 0.001) in interfascicular and intrafascicular fat, representing fatty infiltration rather than fatty degeneration. Furthermore, there was an increase of interstitial connective tissue. At the time of the tendon repair, between forty and forty-two weeks after the release, there was a sevenfold poorer elasticity of the musculotendinous unit but preserved muscle perfusion. The structural changes increased six weeks after the repair and then recovered partially at twelve and thirty-five weeks thereafter but only to the amount demonstrated before the repair. CONCLUSIONS Musculotendinous retraction induced by tendon release is associated with profound changes in the structure and function of the affected muscle. Vascularization, intramuscular pressure, and individual fiber composition are not markedly affected, and muscle fibers do not appear to degenerate. However, muscle atrophy, infiltration by fat cells, and an increase of interstitial connective tissue lead to impairment of the physiological properties of the muscle. These changes were irreversible under the conditions of this experiment with the repair technique used.

Design of the mammalian respiratory system. VI. Distribution of mitochondria and capillaries in various muscles

This review explores the current concepts relating the structural and functional modifications of skeletal muscle mitochondria to the molecular mechanisms activated when organisms are exposed to a hypoxic environment. In contrast to earlier assumptions it is now established that permanent or long‐term exposure to severe environmental hypoxia decreases the mitochondrial content of muscle fibres. Oxidative muscle metabolism is shifted towards a higher reliance on carbohydrates as a fuel, and intramyocellular lipid substrate stores are reduced. Moreover, in muscle cells of mountaineers returning from the Himalayas, we find accumulations of lipofuscin, believed to be a mitochondrial degradation product. Low mitochondrial contents are also observed in high‐altitude natives such as Sherpas. In these subjects high‐altitude performance seems to be improved by better coupling between ATP demand and supply pathways as well as better metabolite homeostasis. The hypoxia‐inducible factor 1 (HIF‐1) has been identified as a master regulator for the expression of genes involved in the hypoxia response, such as genes coding for glucose transporters, glycolytic enzymes and vascular endothelial growth factor (VEGF). HIF‐1 achieves this by binding to hypoxia response elements in the promoter regions of these genes, whereby the increase of HIF‐1 in hypoxia is the consequence of a reduced degradation of its dominant subunit HIF‐1α. A further mechanism that seems implicated in the hypoxia response of muscle mitochondria is related to the formation of reactive oxygen species (ROS) in mitochondria during oxidative phosphorylation. How exactly ROS interfere with HIF‐1α as well as MAP kinase and other signalling pathways is debated. The current evidence suggests that mitochondria themselves could be important players in oxygen sensing.

Adaptive variation in the mammalian respiratory system in relation to energetic demand: I. Introduction to problem and strategy

Memory impairments constitute an increasing objective and subjective problem with advancing age. The aim of the present study was to investigate the impact of working memory training on memory performance. The authors trained a sample of 80-year-old adults twice weekly over a time period of 3 months. Participants were tested on 4 different memory measures before, immediately after, and 1 year after training completion. The authors found overall increased memory performance in the experimental group compared to an active control group immediately after training completion. This increase was especially pronounced in visual working memory performance and, to a smaller degree, also in visual episodic memory. No group differences were found 1 year after training completion. The results indicate that even in old?old adults, brain plasticity is strong enough to result in transfer effects, that is, performance increases in tasks that were not trained during the intervention.

Estimating length density and quantifying anisotropy in skeletal muscle capillaries

Mitochondria in skeletal muscle tissue can undergo rapid and characteristic changes as a consequence of manipulations of muscle use and environmental conditions. Endurance exercise training leads to increases of mitochondrial volume of up to 50% in training interventions of a few weeks in previously untrained subjects. Additionally, a shift of substrate metabolism toward a higher reliance on lipids is observed, structurally reflected as a doubling of the intramyocellular lipid content. A similar increase in intramyocellular lipids without an increase in mitochondrial volume is observed as a consequence of a high-fat diet. Strength training has a major impact on muscle myofibrillar volume, however the mitochondrial compartment appears relatively unchanged. Bedrest and microgravity conditions lead to losses of both myofibrillar and mitochondrial volume, likely as a consequence of the decrease in metabolic and mechanical stress on muscle tissue. Permanent severe hypoxia leads to a loss of muscle mass and muscle oxidative capacity; however, hypoxia signaling events are triggered, which lead to distinct reprogramming phenomena of the transcriptome of the muscle cells. The molecular mechanisms that orchestrate the plasticity of skeletal muscle mitochondria are just beginning to unfold. The present data indicate that transcriptional events largely contribute to increases in mitochondrial mass in human skeletal muscle with endurance training. Expression of mitochondrial proteins from the nuclear and mitochondrial genomes is coordinated and involves the nuclear-encoded transcription factors NRF-1 and TFAM. Transcription of genes encoding the mitochondrial proteins involved in beta oxidation can be regulated separately from the genes of the Krebs cycle and the respiratory chain. Transcription factors AP-1 and PPARalpha/gamma and the protein kinase AMPK are signaling molecules that transduce the metabolic and mechanical factors sensed during endurance training into the complex transcriptional adaptations of mitochondrial proteins.

The interplay of central and peripheral factors in limiting maximal O2 consumption in man after prolonged bed rest

An evaluation is made of the relative efficiency (precision of the final estimate per unit time of measurement on a given set of sections) of different methods for planar analysis aimed at estimating aggregate, overall stereological parameters (such as Vv, Sv). The methods tested are point‐counting with different densities of test points (4 ≤ PT ≤ 900 per picture), semiautomatic computer image analysis with MOP and automatic image analysis with Quantimet, for obtaining Vv and Sv estimates. One biological sample as well as three synthetic model structures with known coefficients of variation between sections are used. The standard error of an estimate is mainly determined by the coefficient of variation between sampling units (= sections in the present paper) so that measuring each sample unit with a very high precision is not necessary. Automatic image analysis and point‐counting with a 100‐point grid were the most efficient methods for reducing the relative standard errors of the Vv and Sv estimates to equivalent levels in the synthetic models. Using a 64‐point grid was as precise, and about 11 times faster than using a tracing device for obtaining the estimate of Vv in the biological sample.