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M R Drost

Publications and source records attributed to M R Drost.

At least 19 recordsLinked to original sources
PubMed2005

Skeletal Muscle wasting and contractile performance in septic rats.

We investigated the temporal effects of sepsis on muscle wasting and function in order to study the contribution of wasting to the decline in muscle function; we also studied the fiber-type specificity of this muscle wasting. Sepsis was induced by injecting rats intraperitoneally with a zymosan suspension. At 2 h and at 2, 6, and 11 days after injection, muscle function was measured using in situ electrical stimulation, Zymosan injection induced severe muscle wasting compared to pair-fed and ad libitum fed controls. At 6 days, isometric force-generating capacity was drastically reduced in zymosan-treated rats. We conclude that this was fully accounted fo by the reduction of muscle mas. At day 6, we also observed increased activity of the 20S proteasome in gastrocnemius but not soleus muscle from septic rats. In tibialis anterior but not in soleus, muscle wasting occurred in a fiber-type specific fashion, i.e., the reduction in cross-sectional area was significantly smaller in type 1 than type 2A and 2B/X fibers. These findings suggest that both the inherent function of a muscle and the muscle fiber-type distribution affect the responsiveness to catabolic signals.

Animals↗
PubMed2005

Ubiquitin-proteasome-dependent proteolytic activity remains elevated after zymosan-induced sepsis in rats while muscle mass recovers.

We studied the role of the ubiquitin-proteasome system in rat skeletal muscle during sepsis and subsequent recovery. Sepsis was induced with intraperitoneal zymosan injections. This model allows one to study a sustained and reversible catabolic phase and mimics the events that prevail in septic and subsequently recovering patients. In addition, the role of the ubiquitin-proteasome system during muscle recovery is poorly documented. There was a trend for increased ubiquitin-conjugate formation in the muscle wasting phase, which was abolished during the recovery phase. The trypsin- and chymotrypsin-like peptidase activities of the 20S proteasome peaked at day 6 following zymosan injection (i.e. when both muscle mass and muscle fiber cross-sectional area were reduced the most), but remained elevated when muscle mass and muscle fiber cross-sectional area were recovering (11 days). This clearly suggests a role for the ubiquitin-proteasome pathway in the muscle remodeling and/or recovery process. Protein levels of 19S complex and 20S proteasome subunits did not increase throughout the study, pointing to alternative mechanisms regulating proteasome activities. Overall these data support a role for ubiquitin-proteasome dependent proteolysis in the zymosan septic model, in both the catabolic and muscle recovery phases.

Animals↗
PubMed2003

Finite element modelling of contracting skeletal muscle.

To describe the mechanical behaviour of biological tissues and transport processes in biological tissues, conservation laws such as conservation of mass, momentum and energy play a central role. Mathematically these are cast into the form of partial differential equations. Because of nonlinear material behaviour, inhomogeneous properties and usually a complex geometry, it is impossible to find closed-form analytical solutions for these sets of equations. The objective of the finite element method is to find approximate solutions for these problems. The concepts of the finite element method are explained on a finite element continuum model of skeletal muscle. In this case, the momentum equations have to be solved with an extra constraint, because the material behaves as nearly incompressible. The material behaviour consists of a highly nonlinear passive part and an active part. The latter is described with a two-state Huxley model. This means that an extra nonlinear partial differential equation has to be solved. The problems and solutions involved with this procedure are explained. The model is used to describe the mechanical behaviour of a tibialis anterior of a rat. The results have been compared with experimentally determined strains at the surface of the muscle. Qualitatively there is good agreement between measured and calculated strains, but the measured strains were higher.

Animals↗
PubMed2003

An ionised/non-ionised dual porosity model of intervertebral disc tissue.

The volume of the intrafibrillar water space--i.e. the water contained inside the collagen fibres--is a key parameter that is relevant to concepts of connective tissue structure and function. Confined compression and swelling experiments on annulus fibrosus samples are interpreted in terms of a dual porosity model that distinguishes between a non-ionised intrafibrillar porosity and an ionised extrafibrillar porosity. Both porosities intercommunicate and are saturated with a monovalent ionic solution, i.c. NaCl. The extrafibrillar fixed charge density of the samples is assessed using radiotracer techniques and the collagen content is evaluated by measurement of hydroxyproline concentration. The interpretation of the experimental data yields values for the intrafibrillar water content, the average activity coefficient of the ions, the Donnan osmotic coefficient, the fraction of intrafibrillar water, the stress-free deformation state, and an effective stress-strain relationship as a function of the radial position in the disc. A linear fit between the second Piola-Kirchhoff effective stress and Green-Lagrange strain yielded an effective stiffness: H(e)=1.087 +/- 0.657 MPa. The average fraction of intrafibrillar water was 1.16 g/g collagen. The results were sensitive to changes in the activity and osmotic coefficients and the fraction of intrafibrillar water. The fixed charge density increased with distance from the outer edge of the annulus, whereas the hydroxyproline decreased.

Animals↗
PubMed2003

Spatial and temporal heterogeneity of superficial muscle strain during in situ fixed-end contractions.

Numerical models of contracting muscle offer a powerful tool to study local mechanical load. For validation of these models, the spatial and temporal distribution of strain was quantified in fixed-end contracting rat tibialis anterior muscle in situ at optimal muscle length (L(o)) and at 120 degrees plantar flexion as well as at 125 and 33Hz stimulation frequency. We studied the hypothesis that after termination of stimulation in situ muscle segments near the motor endplates elongate while segments away from the endplates shorten. We show that both spatial and temporal inhomogeneities in muscle deformation occurred during contraction. Muscle plateau shortening strain equalled 4.1%. Maximal plateau shortening of a muscle segment was much larger (9.6%) and occurred distally (at 0.26 of the scaled length of the muscle). Manipulating torque levels by decreasing the stimulation frequency at the same muscle length induced a decrease in torque ( approximately 20%) with a smaller effect on the level and no effect on the pattern of muscle deformation. During relaxation, distal segments actively shortened at the expense of proximal muscle segments, which elongated. The segments undergoing lengthening were nearer to motor endplates than segments undergoing shortening. In conclusion, the present study provides experimental data on magnitude of contraction-induced deformation needed for validation of numerical models. Local muscle deformation is heterogeneous both temporally and spatially and may be related to proximity to the motor endplates.

Animals↗
PubMed2002

Ankle-foot orthosis has limited effect on walking test parameters among patients with peripheral ankle dorsiflexor paresis.

The aim of this study was to determine the relationship between ankle dorsiflexor strength and performances on several walking tests and to determine the effect of ankle-foot orthosis (AFO) use on walking tests. The following tests were used: 10-metre walking test (with and without three stairs), a complex walking task (6-minute walk with cognitive loading) and a subjective evaluation (SIP68 mobility scale and questionnaire). Isometric strength of the ankle dorsiflexors was measured. All walking tests were performed with and without AFO in random order. When relating torque values to walking performances, the highest correlation was found with the "10 metre" and "10 metre with stairs" test (r = -0.51, i.e. an inverse relationship). No threshold in the degree of paresis was found below which walking disability suddenly increased. No significant improvement could be demonstrated from AFO use on the 10-metre tests. Improvement on the 6-minute test was nearly significant (p = 0.06), the questionnaire revealed a positive opinion on AFO use related to overall walking function and effort. Thus, we have to conclude that these walking tests do not aid the clinician in estimating the severity of (progression of) the paresis nor to detect differences in degree of paresis between subjects.

Adult↗
PubMed2002

Increased muscle fatigability in GLUT-4-deficient mice.

GLUT-4 plays a predominant role in glucose uptake during muscle contraction. In the present study, we have investigated in mice whether disruption of the GLUT-4 gene affects isometric and shortening contractile performance of the dorsal flexor muscle complex in situ. Moreover, we have explored the hypothesis that lack of GLUT-4 enhances muscle fatigability. Isometric performance normalized to muscle mass during a single tetanic contraction did not differ between wild-type (WT) and GLUT-4-deficient [GLUT-4(-/-)] mice. Shortening contractions, however, revealed a significant 1.4-fold decrease in peak power per unit mass, most likely caused by the fiber-type transition from fast-glycolytic fibers (IIB) to fast-oxidative fibers (IIA) in GLUT-4(-/-) dorsal flexors. In addition, the resting glycogen content was significantly lower (34%) in the dorsal flexor complex of GLUT-4(-/-) mice than in WT mice. Moreover, the muscle complex of GLUT-4(-/-) mice showed enhanced susceptibility to fatigue, which may be related to the decline in the muscle carbohydrate store. The significant decrease in relative work output during the steady-state phase of the fatigue protocol suggests that energy supply via alternative routes is not capable to compensate fully for the lack of GLUT-4.

Animals↗
PubMed2001

In situ assessment of shortening and lengthening contractile properties of hind limb ankle flexors in intact mice.

The availability of animal models with disrupted genes has increased the need for small-scale measurement devices. Recently, we developed an experimental device to assess in situ mechanical properties of isometric contractions of intact muscle complexes of the mouse. Although this apparatus provides valuable information on muscle mechanical performance, it is not appropriate for determining contractile properties during shortening and lengthening contractions. In the present study we therefore developed and evaluated an experimental apparatus for assessment of shortening and lengthening contractile properties of intact plantar and dorsal flexors of the mouse. The current through a custom-built, low-inertia servomotor was measured to assess contractile muscular torque ranging from -50 to mN.m. Evaluation of the fixation procedure of the animal to the apparatus via 3-D monitoring of the muscle-tendon complex length showed that the additional shortening in length due to a contraction with maximal torque output has only minor effects on the measured torque. Furthermore, misalignment of the axis of rotation of the apparatus relative to the axis of rotation in the ankle joint, i.e. eccentricity, during a routine experiment was estimated to be less than 1.0 mm and hence did not influence the measured torque output under our experimental conditions. Peak power per unit muscle mass (mean +/- SD) of intact dorsal and plantar flexors was 0.27 +/- 0.02 and 0.19 +/- 0.03 W.g-1, respectively. The angular velocity at maximal peak power generated by the dorsal flexor complex and the plantar flexor complex was 1100 +/- 190 and 700 +/- 90 degrees.s-1, respectively.

Animals↗
PubMed2001

Murine muscles deficient in creatine kinase tolerate repeated series of high-intensity contractions.

Murine muscles lacking both mitochondrial (Mi-CK) and cytoplasmic (MM-CK) creatine kinase (CK-/-) show depressed mechanical performance in association with low muscle ATP and enhanced IMP content. The aims of the present study were to elucidate the possible role of low ATP and high IMP content in impairment of mechanical performance in CK-/- mice and to establish whether CK-/- muscles are able to sustain repeated series of high-intensity contractions. The dorsal flexors of CK-/- and control mice were subjected in situ to two series of 12 tetanic contractions using a custom-made mouse isometric dynamometer. The muscle content of high-energy phosphates was analysed by HPLC. ATP content declined from 20.6+/-1.9 to 15.5+/-2.4 micromol x g(-1) dry weight (d.w.); IMP content increased from 1.2+/-0.4 to 2.4+/-1.1 micromol x g(-1) d.w. during the first contraction series in CK-/- muscle. Despite these unfavourable changes, maximal torque developed during the first contraction of either series did not differ, indicating that the altered content of ATP and IMP does not play a decisive role in impaired mechanical performance in CK-/- mice. The relative decline in torque during the two series did not differ in CK-/- (-20.4+/-6.6 vs. -23.8+/-9.9%). In contrast, wild-type (WT) muscles showed a significantly more pronounced decline during the second series (-12.3+/-7.4 vs. -20.1+/-6.8%). Muscle ATP and IMP content did not change in CK-/-, whereas in WT IMP content increased significantly during the second contraction series. These findings indicate that CK-/- tolerate repeated series of high-intensity contractions better than WT, while in CK-/- muscle an additional source of energy is mobilised to regenerate ATP during the second series.

Adaptation, Physiological↗
PubMed2001

Spatial interaction between tissue pressure and skeletal muscle perfusion during contraction.

The vascular waterfall theory attributes decreased muscle perfusion during contraction to increased intramuscular pressure (P(IM)) and concomitant increase in venous resistance. Although P(IM) is distributed during contractions, this theory does not account for heterogeneity. This study hypothesises that pressure heterogeneity could affect the interaction between P(IM) rise and perfusion. Regional tissue perfusion during submaximum (100kPa) tetanic contraction is studied, using a finite element model of perfused contracting skeletal muscle. Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar between simulations, but capillary flow and venous pressure differ. In SIM(2), venous pressure and capillary flow correspond to P(IM) distribution, whereas capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half without draining vein. This difference is caused by a high central P(IM), followed by central venous pressure rise, in agreement with the waterfall theory. The high central pressure (SIM(1)), obstructs outflow from the distal veins. Distal venous pressure rises until central blood pressure is reached, although local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is concluded that regional effects contribute to the interaction between P(IM) and perfusion during contraction. Unlike stated by the vascular waterfall theory, venous pressure may locally exceed P(IM). Although this can be explained by the principles of this theory, the theory does not include this phenomenon as such.

Animals↗
PubMed2001

Passive transverse mechanical properties of skeletal muscle under in vivo compression.

The objective of the present study is to determine the passive transverse mechanical properties of skeletal muscle. Compression experiments were performed on four rat tibialis anterior muscles. To assess the stress- and strain-distributions in the muscle during the experiment, a plane stress model of the cross section was developed for each muscle. The incompressible viscoelastic Ogden model was used to describe the passive muscle behaviour. The four material parameters were determined by fitting calculated indentation forces on measured indentation forces. The elastic parameters, mu and alpha, were 15.6+/-5.4 kPa and 21.4+/-5.7, respectively. The viscoelastic parameters, delta and tau, were 0.549+/-0.056 and 6.01+/-0.42 s. When applying the estimated material parameters in a three-dimensional finite element model, the measured behaviour can be accurately simulated.

Animals↗
PubMed2001

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Evaluation of effect of ankle-foot orthosis use on strength restoration of paretic dorsiflexors.

OBJECTIVE: To assess whether a difference exists in restoration of strength between patients with a recent paresis of the dorsiflexors of the ankle using an ankle-foot orthosis (AFO) and patients without an AFO. DESIGN: Prospective case-control study. SETTING: Patients from regional hospitals, tested in a rehabilitation research center. PARTICIPANTS: Twenty-nine patients with a recent (6wk-1yr) peripheral paresis, alternately assigned to a group using an AFO or a control group. There was no significant difference in duration of the paresis and in torque at entering the study (T0) between the 2 groups. INTERVENTIONS: The use of an ankle-foot orthosis. MAIN OUTCOME MEASURES: Isometric torque production of ankle dorsiflexors, expressed as ratio of paretic and healthy side, in 2 measurement sessions, over a period of 6 weeks (T0-T6) with the ankle in 0 degrees and 30 degrees plantarflexion. RESULTS: Both groups had significant restoration of strength +/- standard deviation between T0 and T6 in 30 degrees flexion: non-AFO group 17% +/- 15%, AFO group 9% +/- 12%. No significant difference existed between the 2 groups (30 degrees p = .56). No significant shift in strength ratio 0 degrees :30 degrees occurred (AFO group p = .82). CONCLUSION: The use of an orthosis does not influence restoration of strength in patients with a recent peripheral paresis of the ankle dorsiflexors.

Adult↗
PubMed2001

The effect of seat tilting on pelvic position, balance control, and compensatory postural muscle use in paraplegic subjects.

OBJECTIVE: To study the effect of seat tilting on pelvic tilt, balance control, and postural muscle use in persons with a thoracic spinal cord injury (SCI). DESIGN: Cross-sectional group study. SETTING: Rehabilitation centers and rehabilitation hospital departments. PATIENTS: Ten complete high thoracic SCI (level T2-8) patients, 10 complete low thoracic SCI (level T9-12) patients, and 10 matched able-bodied controls. INTERVENTION: A 10 degrees forward inclination of the seat. MAIN OUTCOME MEASURES: Pelvic tilt, center of pressure displacement, and muscle activity. RESULTS: Anterior tilting of the pelvis as a result of forward inclination of the seat could not be shown, either in persons with or without SCI. Balance control was not influenced by forward inclination of the seat. Participants' overall muscle activity decreased while they were seated in the chair with the forwardly inclined seat. CONCLUSIONS: Evidence provided by the kinematic and electromyographic data is not sufficient to develop a protocol for wheelchair prescription on the basis of pelvic positioning.

Adult↗
PubMed2001

Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice.

Creatine kinase (CK) forms a small family of isoenzymes playing an important role in maintaining the concentration of ATP and ADP in muscle cells. To delineate the impact of a lack of CK activity, we studied contractile performance during a single maximal tetanic contraction and during 12 repeated tetanic contractions of intact dorsal flexors of CK knockout (CK(-/-)) mice. To investigate the effect on ATP regeneration, muscular high-energy phosphate content was determined at rest, immediately after the contraction series, and after a 60-s recovery period. Maximal torque of the dorsal flexors was significantly lower in CK(-/-) mice than in wild-type animals, i.e., 23.7 +/- 5.1 and 33.3 +/- 6.8 mN. m. g(-1) wet wt, respectively. Lower muscle ATP (20.1 +/- 1.4 in CK(-/-) vs. 28.0 +/- 2.1 micromol/g dry wt in controls) and higher IMP (1.2 +/- 0.5 in CK(-/-) vs. 0.3 +/- 0.1 micromol/g dry wt in controls) levels at the onset of contraction may contribute to the declined contractility in CK(-/-) mice. In contrast to wild-type muscles, ATP levels could not be maintained during the series of 12 tetanic contractions of dorsal flexors of CK(-/-) mice and dropped to 15.5 +/- 2.4 micromol/g dry wt. The significant increase in tissue IMP (2.4 +/- 1.1 micromol/g dry wt) content after the contraction series indicates that ATP regeneration through adenylate kinase was not capable of fully compensating for the lack of CK. ATP regeneration via the adenylate kinase pathway is a likely cause of reduced basal adenine nucleotide levels in CK(-/-) mice.

Adenine Nucleotides↗
PubMed2000

Accurate assessment of in situ isometric contractile properties of hindlimb plantar and dorsal flexor muscle complex of intact mice.

An isometric torque sensor for measuring in situ contractions of plantar or dorsal flexors of intact mouse hindlimb has been developed and evaluated. With this device, muscle torque can be accurately measured within the range of -14 mN.m to +14 mN.m. Special attention was paid to fixation of the mouse hindlimb to the measurement device. Halothane-anaesthetized Swiss wild-type mice were positioned on the thermostatic measurement platform, and fixated with a hip and foot fixation system. The novel fixation unit was evaluated by measuring knee and ankle displacements during a contraction. A mathematical muscle model was used to quantify the effects of these displacements on the contractile parameters. Measured ankle and knee displacement, due to non-absolute fixation. resulted in a calculated muscle fibre shortening of 2.5%. Simulations of a contraction with this degree of fibre shortening, using the mathematical muscle model, showed only minor effects on maximal torque generation and the temporal parameters (half-relaxation time and 10-50% rise time). Furthermore, we showed that muscle torque in our set-up is hardly affected by eccentricity between ankle and measurement axis. Measured tetanic muscle torques of intact dorsal and plantar flexors were 3.2+/-0.4 mN.m and 11.8+/-1.6 mN.m, respectively. The half-relaxation time of plantar flexors was significantly higher than that of dorsal flexors (12.9+/-2.7 ms versus 8.8+/-1.2 ms), whereas the 10-50% rise time was longer in plantar (14.9+/-0.6 ms) than in dorsal (11.8+/-2.0 ms) flexors.

Animals↗
PubMed2000

Controlled lengthening or shortening contraction-induced damage is followed by fiber hypertrophy in rat skeletal muscle.

To study the hypothesis that more severe damage, caused by controlled lengthening (L) contractions, results in greater myofiber hypertrophy compared to increase in fiber size followed shortening (S) contractions, tibialis anterior muscles of anesthesized male Wistar rats were subjected to 240 either L or S contractions. The highest increase in muscle beta-glucuronidase activity, an indicator of muscle damage, was observed in L (7.1-fold) 4 days and in S (2.6-fold) 8 days postexercise. Dystrophin- and desmin-negative as well as fibronectin-positive fibers (signs of the early phase of damage) were observed immediately after exercise in the L group. At 4 days, massive myofiber injury was visible, and internally localized nuclei were present at 15-80 days after exercise in the L group. The shift towards more glycolytic fiber types (p<0.05 in L and S) and an increased mean cross-sectional area of type IIX/B fibers (p < 0.001 in L and S) at 80 days were observed in both groups. The observed minor damage with unchanged myofiber structures following S induced, however, an increase in myofiber cross-sectional area of nearly the same magnitude as that following L, which was more damaging. The results do not support the hypothesis that fiber hypertrophy depends on the extent of the myofiber damage upon the exercised muscles.

Animals↗