Biomedical subjects

Hans Degens

Publications and source records attributed to Hans Degens.

13 recordsLinked to original sources

PubMed2006

Acute hypoxia limits endurance but does not affect muscle contractile properties.

Acute hypoxia causes skeletal muscle dysfunction in vitro, but little is known about its effect on muscle function in vivo. In 10 healthy male subjects, isometric contractile properties and fatigue resistance of the quadriceps muscle were determined during normoxia and hypoxia using electrically evoked and voluntary contractions. The oxygen saturation (SaO(2); 96.9 +/- 0.7 vs. 79.9 +/- 3.0%; P < 0.001) was reduced during hypoxia. The maximal voluntary contraction (MVC), force-frequency relation, and contraction and relaxation times were unaffected by hypoxia. The endurance time of a sustained 30% MVC was reduced in hypoxia (248 +/- 104 vs. 217 +/- 76 s; P < 0.05), but not that of a sustained 70% MVC. Fatigue induced by electrically evoked intermittent contractions was unaltered. Thus, acute hypoxia has no significant impact on contractile properties of skeletal muscle in vivo but causes reduced endurance during low-level sustained voluntary contractions. This indicates that skeletal muscle dysfunction during conditions associated with prolonged hypoxemia, except for limited endurance, is not due to acute effects of hypoxemia.

Adenosine Triphosphate↗

PubMed2006

Maintenance of heterogeneity of capillary spacing is essential for adequate oxygenation in the soleus muscle of the growing rat.

OBJECTIVES: Normal muscle growth is accompanied by capillary proliferation, which usually lags behind the increase in muscle size, causing a decline in mean capillary density (CD). It is not known, however, how the capillary distribution is affected and what impact it has on the oxygenation of the muscle. METHODS: The capillarization of soleus muscles of rats (64-425 g) was determined with the method of capillary domains. As well as quantifying CD, capillary to fiber ratio (C:F), and fiber size, this method provides a measure of the heterogeneity of capillary spacing. Capillary locations were used to mathematically model oxygenation levels within the muscle. RESULTS: The increase in muscle mass was largely attributable to 5-fold increase in fiber size, accompanied by a more than 3-fold rise in C:F. The mismatch between rates of angiogenesis and muscle growth resulted in a decrease in CD. However, the heterogeneity of capillary spacing was unaffected (heterogeneity index logRSD: 0.091 +/- 0.013; mean +/- SD) as was muscle PO2, with modal values between 4 and 60 mmHg (0.5 and 8 kPa). CONCLUSIONS: Angiogenesis during normal muscle growth does not maintain CD, but with similar heterogeneity of capillary spacing it preserves the potential for adequate intramuscular oxygenation.

Animals↗

PubMed2006

A dynamic extensor brace reduces electromyographic activity of wrist extensor muscles in patients with lateral epicondylalgia.

STUDY DESIGN: Semiexperimental study. OBJECTIVE: To investigate the effect of an external wrist extension force on extensor muscle activity during hand gripping in patients with lateral epicondylalgia. BACKGROUND: Lateral epicondylalgia or "tennis elbow" is a common, often disabling ailment affecting millions of people. An optimal treatment strategy remains to be identified. The use of an external wrist extension force may reduce the extensor muscle activity during gripping in these patients. METHODS: Muscle activity of the extensor carpi radialis brevis (ECRB), extensor digitorum communis (EDC), and extensor carpi radialis longus (ECRL) was measured using surface EMG. Subjects gripped at an intensity of 10%, 20%, and 30% of the maximum voluntary contraction (MVC) force with and without the dynamic extensor brace and with and without an applied external wrist extension force of 1%, 2%, and 3% of MVC. RESULTS: At all levels of MVC gripping, the EMG signal of the ECRB and EDC were significantly lower for gripping with than without brace. An extension force of 3% of the MVC force significantly reduced the EMG signal of all muscles in almost all measurement conditions. CONCLUSIONS: The results of this study indicate that the dynamic extensor brace as well as the external extension force significantly reduced the EMG signal of the wrist extensor muscles during gripping in patients with lateral epicondylalgia. Based on these results, the dynamic extensor brace could be a promising new intervention for lateral epicondylalgia.

Adult↗

PubMed2005

Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart.

Cardiac hypertrophy and failure are associated with alterations in cardiac substrate metabolism. It remains to be established, however, whether genomically driven changes in cardiac glucose and fatty acid (FA) metabolism represent a key event of the hypertrophic remodeling process. Accordingly, we investigated metabolic gene expression and substrate metabolism during compensatory hypertrophy, in relation to other cardiac remodeling processes. Thereto, cardiac hypertrophy was induced in rats by supra-renal aortic constriction to various degrees, resulting in increased heart/body weight ratios of 22% (Aob-1), 24% (Aob-2) and 32% (Aob-3) (p < 0.005) after 4 weeks. The unaltered ejection fraction in all groups indicated that the hypertrophy was still compensatory in nature. beta-Myosin Heavy Chain protein and ANF mRNA levels were increased in all groups. Only in Aob-3 rats were SERCA2a mRNA levels markedly reduced. In this group, glycolytic capacity was modestly elevated (+ 25%; p < 0.01). Notwithstanding these phenotypical changes, the expression of genes involved in FA metabolism and FA oxidation rate in cardiac homogenates was completely preserved, irrespective of the degree of hypertrophy. These findings indicate that cardiac FA oxidative capacity is preserved during compensatory hypertrophy, and that a decline in metabolic gene expression does not represent a hallmark of the development of hypertrophy.

Animals↗

PubMed2005

Diaphragm dysfunction in chronic obstructive pulmonary disease.

RATIONALE: Hypercapnic respiratory failure because of inspiratory muscle weakness is the most important cause of death in chronic obstructive pulmonary disease (COPD). However, the pathophysiology of failure of the diaphragm to generate force in COPD is in part unclear. OBJECTIVES: The present study investigated contractile function and myosin heavy chain content of diaphragm muscle single fibers from patients with COPD. METHODS: Skinned muscle fibers were isolated from muscle biopsies from the diaphragm of eight patients with mild to moderate COPD and five patients without COPD (mean FEV(1) % predicted, 70 and 100%, respectively). Contractile function of single fibers was assessed, and afterwards, myosin heavy chain content was determined in these fibers. In diaphragm muscle homogenates, the level of ubiquitin-protein conjugation was determined. RESULTS: Diaphragm muscle fibers from patients with COPD showed reduced force generation per cross-sectional area, and reduced myosin heavy chain content per half sarcomere. In addition, these fibers had decreased Ca2+ sensitivity of force generation, and slower cross-bridge cycling kinetics. Our observations were present in fibers expressing slow and 2A isoforms of myosin heavy chain. Ubiquitin-protein conjugation was increased in diaphragm muscle homogenates of patients with mild to moderate COPD. CONCLUSIONS: Early in the development of COPD, diaphragm fiber contractile function is impaired. Our data suggest that enhanced diaphragm protein degradation through the ubiquitin-proteasome pathway plays a role in loss of contractile protein and, consequently, failure of the diaphragm to generate force.

Adult↗

PubMed2004

The application of an external wrist extension force reduces electromyographic activity of wrist extensor muscles during gripping.

STUDY DESIGN: Experimental repeated-measures study. OBJECTIVE: To investigate the effect of different extension forces applied to the palm of the hand on electromyographic (EMG) activity of the wrist extensor muscles during hand gripping. BACKGROUND: Lateral epicondylitis is usually caused by repetitive wrist extension that leads to an overuse injury. The current theory is that the process of lateral epicondylitis begins with an overuse injury that leads to microtearing of the extensor carpi radialis brevis muscle and occasionally the extensor digitorum communis muscle. Use of an external wrist extension force might reduce muscle activity during gripping. METHODS: Muscle activity was measured using surface EMG while subjects gripped at an intensity of 10%, 20%, and 30% of the maximum voluntary contraction force without, and with, an applied external wrist extension force of 1%, 2%, and 3% of maximum voluntary contraction. RESULTS: Applying an extension force to the palm of the hand reduced EMG activity of the extensor muscles at the same strength generation during hand gripping. The muscles with the most significant reduction in EMG level, the extensor carpi radialis brevis and extensor digitorum communis, are those muscles that are most often involved with lateral epicondylitis. CONCLUSIONS: This study shows that an external extension force reduces EMG activity of the wrist extensor muscles during gripping in healthy volunteers. As the extension force increased, a greater reduction in muscle activity was noted.

Adult↗

PubMed2003

Skeletal muscle function and hypertrophy are diminished in old age.

Muscle loss occurs during aging. To investigate whether the hypertrophic response is attenuated at old age, we used male Fischer 344 (26 months old; n = 5) and Fischer 344 x Brown Norway rats (6, 9, and 33 months old; n = 8, 10, and 6, respectively). Hypertrophy of the left plantaris muscle was induced by surgical denervation of its agonists. The right leg served as control. The mass and maximal tetanic force (P(0)) of control muscles declined by approximately 30% between 9 and 26 months (P < 0.05). Fatigue resistance during intermittent isometric contractions was reduced by approximately 60% at 33 months. At 33 months, the attenuated hypertrophy was accompanied by a decrease rather than an increase in P(0). Yet, hypertrophy was accompanied by a 25% rise in fatigue resistance at all ages (P = 0.001). Thus, aging is associated with a decline in muscle mass and function. In addition, at advanced age, the hypertrophic response is reduced and a hypertrophic stimulus even aggravates the age-associated muscle weakening.

Aging↗

PubMed2003

Capillarization and vascular endothelial growth factor expression in hypertrophying anterior latissimus dorsi muscle of the Japanese quail.

Hypertrophy may increase the diffusion distances from capillaries to the interior of the muscle fibers. We hypothesized that capillary proliferation occurs during hypertrophy, which is accompanied by an up-regulation of vascular endothelial growth factor (VEGF). Hypertrophy of the left anterior latissimus dorsi muscle of Japanese quail (2-3 months old) was induced by 1-4 week stretch-overload. Capillarization was analyzed in cross-sections stained for ATPase. VEGF expression was determined with RT-PCR. Initially, hypertrophy was not accompanied by increases in fiber cross-sectional area (FCSA), but after 1 week the average FCSA did increase. The capillary to fiber ratio was decreased after 1 week, but returned to control values in subsequent weeks. This indicates that capillary proliferation occurred, because this model is characterized by extensive fiber proliferation. The absence of any significant change in VEGF mRNA levels indicates that increased levels of VEGF mRNA are not crucial for capillary proliferation during muscle hypertrophy.

Animals↗

PubMed2003

Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats.

Inhibitors of differentiation (Id) proteins are repressors of myogenic regulatory factors and have been implicated in apoptosis and muscle atrophy during aging. Indeed, we have previously found that Id levels are elevated in muscles from old rodents, possibly as a consequence of loss of alpha-motoneurons during senescence. To determine if Id2 proteins increase after denervation and if this is accompanied by increased apoptosis in aged as compared with adult animals, the gastrocnemius and soleus muscles were denervated in 1 limb of Fischer 344 x Brown Norway rats aged 9 months (adult, n = 12) and 33 months (aged, n = 9), while the contralateral limb served as the intra-animal control. After 14 days, the muscles in each limb were removed. The levels of Id1, Id2, and Id3 mRNA and protein were significantly greater in muscles of old as compared with young adult rats. Denervation, however, did not significantly increase Id1, Id2, and Id3 mRNA in soleus or gastrocnemius muscles from either young or old rats. Also Id2 protein levels were similar in denervated and control muscles from young adult and old rats. In young adult rats only, denervation induced an increase in Id1 and Id3 protein levels in both the soleus (Id1 113%; Id3 900%) and gastrocnemius (Id1 86%; Id3 80%). Denervation induced a significant increase in caspase 8 in both soleus and gastrocnemius muscles from young (101% and 147%, respectively) and old rats (167% and 190%, respectively). Bax protein levels, as estimated by western blots, increased by 726% and 1087% after denervation in the soleus and by 368% and 49% in the gastrocnemius muscles of young and old rats, respectively. The data suggest that the denervation-induced muscle loss was at least partly due to apoptosis as indicated by elevated caspase 8 and Bax levels in denervated muscles. While Id2 may have a role in aging-induced sarcopenia, Id2 does not appear to directly regulate apoptosis during denervation. The elevated Id expression in muscles from aged animals is therefore not a direct consequence of loss of alpha-motoneurons during senescence.

Aging↗

PubMed2003

Vascular endothelial growth factor, capillarization, and function of the rat plantaris muscle at the onset of hypertrophy.

Capillary proliferation occurs during compensatory hypertrophy. We investigated whether the expression of vascular endothelial growth factor (VEGF) is elevated at the onset of hypertrophy when capillary proliferation is minimal, and whether muscle damage as assessed by muscle force deficits, may occur at the onset of hypertrophy. To investigate this, we induced in 9-month-old rats, under isoflurane anesthesia, hypertrophy of the left plantaris muscle by denervation of the gastrocnemius and soleus muscles. Capillarization was investigated in both the deep (oxidative) and the superficial (glycolytic) regions of the plantaris muscle. After 2 weeks, muscle mass had increased by 16% (p< 0.01), which was not accompanied by increases in fiber size. The maximal tetanic force (P(0)) and specific tension (P(0).g(-1) or P(0).cm(2)) and twitch characteristics were unaltered, and fatigue resistance of the overloaded muscle was improved (p< 0.05). However, the myosin heavy chain composition was unaltered. Capillary proliferation was not yet evident, but VEGF mRNA and protein levels were elevated 1.5- and 8-fold, respectively (p< 0.05). We concluded that the normal specific tension and the elevated VEGF expression after 2 weeks of overload indicate (1) an absence of or minimal muscle damage at this early time point, and (2) that elevated VEGF expression precedes and is involved in capillary proliferation that occurs during the later stages of compensatory hypertrophy.

Animals↗

PubMed2002

Capillarization in skeletal muscle of rats with cardiac hypertrophy.

PURPOSE: Exercise intolerance during chronic heart failure (CHF) is localized mainly in skeletal muscle. A decreased capillarization may impair exchange of oxygen between capillaries and muscle tissue and in this way contribute to exercise intolerance. We assessed changes in capillary supply in plantaris and diaphragm muscles of a rat aorta-caval fistula (ACF) preparation, a volume overload model for CHF. METHODS: An ACF was created under equithesin anesthesia. Plantaris and diaphragm muscles were removed 6 wk postsurgery and examined for myosin heavy chain (MyHC) content and capillary supply. RESULTS: Cardiac hypertrophy was 96% (P < 0.002) after ACF. The Type IIb MyHC content of the plantaris muscles increased (33.9 +/- 3.3 vs 49.8 +/- 3.8%; mean +/- SEM) at the expense of Type IIa MyHC (17.6 +/- 1.8 vs 11.2 +/- 1.7%) in ACF rats (P < 0.05). In the diaphragm, the number of Type I (32.1 +/- 2.3 vs 40.6 +/- 2.7%) and IIb fibers (40.6 +/- 1.9 vs 49.6 +/- 3.6%) increased at the expense of Type IIa fibers (26.8 +/- 2.5 vs 9.4 +/- 0.9%) (P < 0.05). The capillary number per fiber did not change, and this indicated that no capillary loss occurred with ACF. Also, the capillary density was maintained in the diaphragm and plantaris muscles of ACF rats. Furthermore, the coupling between fiber type, size, and metabolic type of surrounding fibers, with the capillary supply to a fiber, was maintained in rats with an ACF. CONCLUSION: The cardiac hypertrophy induced by volume overload seems adequate to prevent atrophy and changes in the microcirculation of limb and diaphragm muscles.

Animals↗

PubMed2002

Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats.

Aging attenuates the overload-induced increase in myogenic regulatory transcription factor (MRF) expression and the extent of muscle enlargement. To identify whether mRNA levels of repressors of the MRFs are greater in overloaded muscles from aged animals, overload was achieved in plantaris muscle of aged (33 mo; n = 14) and adult (9 mo; n = 17) rats. After 14 days, plantaris muscles in the overloaded limb were ~25% and 6% larger in adult and aged rats, respectively, compared with the contralateral limb. Hypertrophied muscles of adult rats had significantly greater levels of mRNA and protein levels for myogenin and MyoD compared with control muscles, but neither MRF increased with overload in muscles of aged rats. Muscles of aged rats had greater Id mRNA (150-700%) and protein repressor (200-6,000%) levels compared with adult rats. BAX and caspase 9 protein levels were 9,500% and 300% greater, respectively, in both control and hypertrophied muscles of aged rats compared with young adult rats. These data are consistent with the hypothesis that aging increases Id transcripts that activate apoptotic pathways involving BAX. This may contribute to sarcopenia by attenuating MRF protein levels in muscles of old animals.

Aging↗

PubMed2002

Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats.

The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 x Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were approximately 275-650% (P < 0.001) and approximately 500-1,100% (P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were approximately 300-900% greater in fast and slow muscles of aged animals (P < or = 0.02), and Mist 1 mRNA was approximately 50% greater in the plantaris and gastrocnemius muscles (P < 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were approximately 17-740% greater (P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

Aging↗