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Biomedical subjects

H J Appell

Publications and source records attributed to H J Appell.

At least 19 recordsLinked to original sources

Administration of tourniquet. I. Are edema and oxidative stress related to each other and to the duration of ischemia in reperfused skeletal muscle?

One hindlimb of mice was subjected to 60, 90 and 120 min ischemia by application of a tourniquet followed by a 60-min reperfusion period. An additional experimental group received a tourniquet for 90 min without subsequent reperfusion. The soleus muscle (from the contralateral side also as control) was removed and evaluated for muscle weight, protein weight, protein content, and glutathione concentrations. Ischemia alone without subsequent reperfusion did not produce significant changes. With postischemic reperfusion, the protein content and muscle weight increased, probably because of an increased capillary permeability, leading to muscle edema. Oxidative stress was also present during reperfusion, correlating well with the changes in protein content. The intensity of these alterations appeared to depend on the period of ischemia.

Animals

Administration of tourniquet. II. Prevention of postischemic oxidative stress can reduce muscle edema.

An experimental group of mice were subjected to a hindlimb tourniquet for 90 min followed by 60 min postischemic reperfusion (ischemia/reperfusion, I/R). Two further groups with the same experimental procedure received allopurinol to inhibit endothelial xanthine oxidase to produce oxygen free radicals (I/R-allo) or vitamin E as a radical scavenger (I/R-vitE). The soleus muscle was examined, and the contralateral muscle served as control. Glutathione (both reduced and oxidized forms, GSH and GSSG) concentrations and the relative protein content were measured. Additionally, the muscles were examined under the electron microscope for pathological alterations. The results showed: (i) the existence of much oxidative stress in the I/R group, but not in the I/R-allo and I/R-vitE groups; (ii) an increased protein content indicative for high capillary permeability in the I/R group, but not in the I/R-allo and I/R-vitE groups; (iii) considerably fewer capillary endothelial disturbances in the I/R-allo and I/R-vitE groups than in the I/R group. We conclude that allopurinol and vitamin E diminished the occurrence of oxidative stress and of edema in postischemic skeletal muscle.

Animals

Consequences of selection on muscle composition. A comparative study on gracilis muscle in wild and domestic pigs.

European domestic pigs are derived from the European wild pig by genetic selection and differ in their muscular-growth ability. Thus, it was the aim of this study to investigate the consequences of genetic selection on muscle composition and fibre size in the gracilis muscle. Fibre typing based on the ATPase reaction revealed that this muscle in wild pigs is composed mainly of type-I and -IIa fibres, whereas, in domestic pigs, type-IIb fibres were predominant. For all fibre types, domestic pigs had about threefold larger fibres than wild pigs. Type-I fibres tended to be the smallest fibres in domestic pigs, but the largest fibres in wild pigs, which may be due to long-term training effects in the free-ranging animals. Giant fibres as an indicator of degeneration were obvious only in the domestic-pig samples. Their occurrence, as well as the larger fibre size and the predominance of type-IIb fibres in domestic pigs, may be ascribed to high concentrations of growth hormone. It is concluded that selection for muscular growth may favour metabolic dysbalances within the muscle and, therefore, degenerative processes.

Adenosine Triphosphatases

Do invading leucocytes contribute to the decrease in glutathione concentrations indicating oxidative stress in exercised muscle, or are they important for its recovery?

Mice were subjected to one session of strenuous running exercise and their soleus muscles were examined in respect of changes in ultrastructure and to their concentration of reduced glutathione [GSH] which are indicators of oxidative stress. It was hypothesized that invading leucocytes contributed to oxidative stress and they were functionally inhibited in one experimental group by the administration of colchicine. Exercise led to an immediate decrease in [GSH] of about 60%, which slowly recovered during 96 h after exercise. With the administration of colchicine after exercise, [GSH] was higher than in the untreated exercise group 48 h after exercise, indicating an inhibition of the ability of leucocytes to produce oxidative stress. However, at 96 h after exercise, [GSH] was lower in the treated exercise group than in the untreated group. The morphological evaluation of the percentage of affected fibres showed that the invasion of leucocytes increased muscle fibre damage. The results suggested that invading leucocytes enhanced production of reactive species of oxygen that may have participated in inducing muscle damage. However, inhibition of leucocyte invasion did not permit their scavenger action of removing cell debris, which appeared to produce even more oxidative stress in the muscle.

Animals

Skeletal muscle damage during tourniquet-induced ischaemia. The initial step towards atrophy after orthopaedic surgery?

Muscle biopsies from the vastus lateralis muscle of patients who had undergone anterior cruciate ligament surgery under conditions of tourniquet-induced ischaemia were examined under the electron microscope at different periods of time up to 90 min of ischaemia. The severity of the alterations in ultrastructure appeared to depend on the period of ischaemia. The pathological changes consisted of accumulation of lysosomes, persistent intrafibre oedema, and some extracellular oedema. Signs of fibre necrosis were found after 90 min of ischaemia. Capillary ultrastructure was only altered with regard to some swelling of the endothelium and marked thickening of the basement membrane. It was concluded that skeletal muscle could be severely affected even during relatively short periods of ischaemia, which might facilitate the development of muscle atrophy during immobilization after orthopaedic surgery.

Adult

The possible role of intracellular Ca2+ accumulation for the development of immobilization atrophy.

Little is known about the cellular mechanisms which induce the development of skeletal muscle immobilization atrophy. Initial disturbances in cellular homeostasis seem to occur very early during immobilization. The aim of the study was to investigate whether loss of calcium homeostasis might be of etiological importance for atrophy. Therefore a calcium channel blocker (nifedipine) was administered to mice immobilized for four days, and their soleus muscle was investigated comparatively to immobilized animals without nifedipine. The immobilized muscles showed an atrophy of about 15% which was not the case in nifedipine-treated immobilized muscles. Ultrastructural alterations (lysosomes, mitochondrial damage) were found predominantly in the immobilized muscles, but rarely with nifedipine. It was concluded that nifedipine protected the muscle fibers probably against calcium overload, thereby avoiding an autophagic response and an impairment of mitochondrial respiratory function.

Animals

Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage.

In exercise-induced muscle damage, oxidative stress derived from the liberation of reactive oxygen species (ROS) is assumed to be of etiological importance. Xanthine oxidase (XO) located in capillary endothelium is one of the possible sources for ROS, mainly investigated so far under conditions of ischemia/reperfusion. XO can be inhibited by allopurinol. To investigate the contribution of XO for the oxidative stress-induced development of muscle damage, mice were subjected to a single bout of exhaustive running exercise. Another exercised group received allopurinol. The reduced form of glutathione (GSH) was measured to estimate the amount of oxidative stress in soleus muscle, and the same muscle was examined in the light and electron microscope at different periods of time (0, 48, 96 h) after exercise. While exercise alone resulted in a marked reduction of GSH indicative for oxidative stress, which only recovered at 96 h, the administration of allopurinal to exercised animals induced a complete recovery already at 48 h after exercise. Muscle damage was more pronounced in the exercised animals which had not been treated with allopurinol. It is concluded that endothelium-derived ROS contribute reasonably to oxidative stress to exercised muscle and to fiber and capillary damage.

Allopurinol

Nifedipine diminishes exercise-induced muscle damage in mouse.

The purpose of this study was to evaluate the effects of a calcium channel blocker (nifedipine) on the severity of muscle damage induced by intensive exercise. Male Charles River mice were assigned to four groups (8 mice/group): normal control (C), nifedipine (N), nifedipine and exercise (N + E) and exercise (E). The animals of the C group were not submitted to any exercise nor to drug administration. The animals of the N group received 1 mg.kg-1 per day of nifedipine (Adalat 10 mg, Bayer AG), per os, during 3 days. The mice of the N + E group were submitted to a treadmill run (0 degree slope) at 1000 m.h-1 (80% of their maximal speed) for 1 hour. In this group, the administration of the drug was under the same conditions as for the N group. The administration started 24 h before the run. The E group was submitted to the same exercise protocol as the animals of N + E group. The soleus muscle was excised for light and electron microscopic evaluation using routine histological techniques. In the C and N groups no morphological alterations were detected. In the E group the number of alterations of striated pattern was twice that in the N + E group. The number of fibres with central nuclei was 35% in the E group but only 8% in the N + E group. The total number of damaged fibres was significantly higher in the E group. The results suggest that nifedipine may give protection to exercise-induced skeletal muscle damage in mouse, probably because the blocking of channels impaired Ca2+ influx; and the results of this study therefore confirm earlier contentions about the possible role of calcium ions in producing muscle damage after work.

Animals

Exercise, muscle damage and fatigue.

Fatigue as a functional sign and muscle damage as a structural sign can be observed after prolonged exercise like marathon running or after strenuous exercise, especially with the involvement of eccentric contractions. For fatigue due to prolonged exercise, hypoxic conditions and the formation of free oxygen radicals seem to be of aetiological importance, resulting in an elevated lysosomal activity. Eccentric exercise of high intensity rather results in a mechanical stress to the fibres. Although these different mechanisms can be discerned experimentally, both result in similar impairments of muscle function. A good training status may attenuate the clinical signs of fatigue and muscle damage. The symptoms and events occurring during delayed onset of muscle soreness (DOMS) can be explained by a cascade of events following structural damage to muscle proteins.

Animals

[Lack of fatigue of the musculature in patients after immobilization--a paradox?].

The isometric strength of knee extensors was measured in patients six weeks after cruciate ligament surgery over a contraction period of 30 sec. The characteristics of the graph obtained form the measurement system were compared to the graphs of uninjured knee extensor muscles. Apart from strength reductions, as expected for atrophic muscle, the pattern of the strength graph led to the impression that these muscles did not fatigue during prolonged contraction. This paradoxical phenomenon can be explained by the existence of central inhibitory mechanisms.

Anterior Cruciate Ligament

Potentiation of cytostatic but not cytolytic activity of murine macrophages after running stress.

The influence of physical exercise on the tumortoxicity of peritoneal murine macrophages (PMM) was investigated. The tumortoxic activity was discriminated into cytostatic and cytolytic effects. Cytostatic activity of PMM on tumor cells in vitro was studied using the proliferation assay of S-180 sarcoma cells. Cytolytic activity was monitored using the method of the slow form of antibody-dependent cellular cytotoxicity (ADCC) on SW 707 tumor cells. After a single exhaustive running session an increased cytostatic activity of PMM was observed as compared to PMM of sedentary animals. In PMM mediated ADCC no difference was detected between trained and untrained animals. It is concluded that physical exercise is a complex stimulus for macrophages that, at least in parts, triggers their cytotoxic activity against tumor cells.

Animals

Muscular atrophy following immobilisation. A review.

Muscular atrophy regularly occurs as a consequence of immobilisation or disuse after sports injuries. Several experimental models deal with muscle atrophy and are suitable for investigations of the underlying mechanisms of muscle atrophy. Strength loss is the most evident response to atrophy. Muscle strength decreases most dramatically during the first week of immobilisation; little further weakening occurs later on. This is reflected in changes in the EMG of disused muscles and can also be observed in muscle weight and size of muscle fibres. Slow muscles with predominantly oxidative metabolism are most susceptible to atrophy as indicated by various findings: slow muscle fibers show greater atrophy than fast fibres; their relative and probably absolute number is decreased in atrophic muscles; in addition, the oxidative enzyme content is most severely affected by disuse. Atrophic muscle is characterised by a catabolic metabolism. The rate of protein synthesis is reduced and that of protein breakdown increased. Autophagic activities probably play an important role in early stages of muscular atrophy. The oxygen supply to disused muscle may be impaired, although myoglobin content is increased in atrophic muscle. The complete loss of mitochondrial function during the first days of disuse may be of aetiological importance. The amount of connective tissue is increased in atrophic muscle and surrounding periarticular tissue which may lead into a vicious circle of musculoskeletal degeneration. An almost complete recovery from atrophy is possible, yet often the recovery phase is much longer than the total immobilisation period.

Animals

Fine structural changes in electrostimulated human skeletal muscle. Evidence for predominant effects on fast muscle fibres.

Physical education students were subjected to electrical stimulation of relatively high frequency and current amplitude for 19 days. A quantitative study of several morphological parameters was performed on biopsy samples from gastrocnemius, using stereological methods at both light and electron microscopic levels. The main results were: muscle fibre size was increased; nuclear volume was also increased, suggesting that a proliferation of nuclei had occurred; this was paralleled by an increased content of nuclear DNA. The size of single myonuclei was increased, and their heterochromatin fraction was decreased, these changes being most pronounced in type II fibres. The increase in the mitochondrial fraction was also greatest in type II fibres. It is concluded that this type of electrical stimulation has predominant effects on type II fibres.

Cell Nucleus

Satellite cell activation in human skeletal muscle after training: evidence for muscle fiber neoformation.

In subjects who had undergone monopedal bicycle ergometer work for 30 min 4 days a week for 6 weeks under aerobic conditions, biopsies from the M. vastus lateralis were studied in the light and electron microscope. In some cases very small myofibers with central nuclei were found. At the ultrastructural level, these fibers turned out to be myotubes. The satellite cells occasionally appeared to be activated and to fuse with muscle fibers. It was concluded that these observations represented evidence for the development of new muscle fibers.

Adaptation, Physiological

[Possibility of the transformation of muscle fibers by training and the significance of muscle biopsies for recognizing talent in sports].

Different methods for skeletal muscle fibre typing are reported. The demonstration of the ATPase, which is mostly used in the recent past, allows for the differentiation of four types, called I, IIC, IIA, and IIB. Using biochemical methods, a further division based on different myosin types is possible. The transformation of distinct fibre types by means of special training programmes may have been overestimated in the past and is assumed to be of minor importance in sports. Taking muscle biopsies for search of talents in sports does not seem to be meaningful and is unethical.

Aptitude

[Rhabdomyolysis in a bodybuilder using anabolic steroids].

The clinical course and the laboratory findings of a massive rhabdomyolysis in a male bodybuilder is presented. Particularly spectacular are the light- and electron-microscopical pictures of the histological findings. The acute renal failure as the most important and major life-threatening complication of the rhabdomyolysis is considered and the successful therapeutic procedure is described. The probability of a causal relation between anabolic steroids and rhabdomyolysis is discussed as well as the resulting consequences for the care of athletes in sports medicine.

Adult

Muscle biopsy--still a matter of methodological considerations.

A method of open muscle biopsy is described which is not so invasive for the patient and not traumatic for the muscle tissue. The biopsy is performed with the patient under local cutaneous anesthesia. The sample can be obtained from a defined part of the muscle. It allows morphological-quantitative evaluation of a sufficient amount of fibers to arrive at reliable results. The advantages of the described method compared with other open and needle biopsy procedures, especially with regard to the method of anesthesia, are discussed.

Anesthesia, Local