title: Skeletal muscle microbiopsy: a validation study of a minimally invasive technique Contractile fatigue, muscle morphometry, and blood lactate in chronic obstructive pulmonary disease. Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Exercise training restores uncoupling protein-3 content in limb muscles of patients with chronic obstructive pulmonary disease. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes. Skeletal muscle adaptations to interval training in patients with advanced COPD.
abstract: The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease ( COPD ) is of growing interest , but often requires biopsies , usually with the Bergström technique . The current study was design ed to test the validity of a minimally invasive technique : the microbiopsy . In 17 patients with COPD and four normal subjects , two specimens of the vastus lateralis were taken percutaneously under local anaesthesia , one with a 16-gauge needle ( microbiopsy ) and the other with the Bergström needle .  The enzymatic activity of citrate synthase ( CS ) and phosphofructokinase ( PFK ) , and the myosin heavy chain ( MyoHC ) composition were measured for both techniques . The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy . The microbiopsy sample weight reached 55±17 mg . The two techniques showed excellent agreement for CS activity and MyoHC composition . The PFK activity did not differ statistically between the techniques , but the agreement was moderate . The agreement between both biopsy techniques was stable over time . The median ( range ) fibre number within the microbiopsy specimens was 144 ( 38–286 ) . In conclusion , the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects , compared with the Bergström technique We hypothesized that patients with chronic obstructive pulmonary disease developing contractile fatigue of the quadriceps during cycle exercise may have characteristic metabolic and muscle features that could increase their susceptibility to fatigue , thus differentiating them from those who do not develop fatigue . We examined , in 32 patients , the fiber-type proportion , enzymatic activities , and capillary density in the vastus lateralis and the arterial blood lactate level during constant work-rate cycling exercise . Contractile fatigue was defined as a postexercise fall in quadriceps twitch force greater than 15 % of resting values . Twenty-two patients developed contractile fatigue after exercise . No significant differences were found between fatiguers and non-fatiguers for the endurance time , fiber-type proportion , and oxidative enzyme activities . The lactate dehydrogenase activity was significantly higher ( p < 0.05 ) and muscle capillarization significantly reduced in fatiguers ( p < 0.05 ) . Compared with non-fatiguers , the arterial lactate level during exercise was significantly higher in fatiguers ( p < 0.001 ) . A significant relationship was found between the fall in quadriceps twitch force and lactate dehydrogenase activity , capillary/fiber ratio , and blood lactate level . We conclude that changes in muscle enzymatic profile and capillarization with a greater reliance on glycolytic metabolism during exercise are associated with contractile fatigue in patients with chronic obstructive pulmonary disease This study aim ed to investigate the relationship between skeletal muscle , fibre type composition , functional respiratory impairment and exercise tolerance in patients with moderate to severe chronic obstructive pulmonary disease ( COPD ) . A group of 22 COPD patients and 10 healthy control subjects were studied . In COPD patients , vital capacity ( VC ) and forced expiratory volume in one second ( FEV1 ) were reduced to 79 % and 51 % , respectively . Diffusion indices ( transfer factor of the lung for carbon monoxide ( TL , CO ) and carbon monoxide transfer coefficient ( KCO ) ) were also reduced . Arterial oxygen tension ( Pa , O2 ) was normal or slightly altered . A maximal exercise test was performed and anaerobic threshold was calculated . Muscle sample s from vastus lateralis were obtained by needle biopsy . Myosin heavy chain ( MHC ) and light chain ( MLC ) isoforms were separated by gel electrophoresis and quantified by densitometry . MHC isoforms were considered as molecular markers of fibre types . The proportion of the fast MHC-2B isoform was increased in COPD patients . TL , CO , KCO , VC and FEV1 were positively correlated with slow MHC isoform content . TL , CO and KCO were also negatively correlated with the content of the fast MHC-2B isoform . No correlation was found between exercise parameters and MHC isoform composition . The co-ordinated expression between MHC and MLC isoforms was altered in COPD patients . We conclude that reduced oxygen availability , probably in combination with muscle disuse , may determine muscle alterations in chronic obstructive pulmonary disease patients . The altered correlations between myosin heavy chain and light chain isoforms suggest that co-ordinated protein expression is lost in chronic obstructive pulmonary disease muscles Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p < 0.001 ) . Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p < 0.001 ) . Interventions were well tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels Oxidative capacity and uncoupling protein-3 ( UCP3 ) content are reduced in limb muscles of patients with chronic obstructive pulmonary disease ( COPD ) . It has been hypothesized that the physiological role of UCP3 is to protect mitochondria against lipotoxicity in cases where fatty acid influx exceeds the capacity to oxidize them . Exercise training improves oxidative capacity and reduces UCP3 protein content in healthy subjects , but the response of UCP3 to training in COPD is unknown . We studied the effect of exercise training on UCP3 content in limb muscles of COPD patients . For this , seven healthy age-matched subjects and thirteen patients with COPD were studied . All patients were admitted to an 8-wk exercise training intervention .  Exercise capacity was assessed by means of an incremental cycle ergometry test . Biopsies were taken from the vastus lateralis in which UCP3 and lipid peroxidation levels were determined by Western blotting . Citrate synthase and 3-hydroxyacyl-CoA dehydrogenase ( HAD ; an enzyme involved in fatty acid oxidation ) were measured as indexes of muscle oxidative capacity . UCP3 in COPD was approximately 50 % lower compared with healthy age-matched controls . In COPD , training induced upregulation of UCP3 [ from 67.7 ( SD 41.8 ) to 113.8 ( SD 104.2 ) arbitrary units ( AU ) , P = 0.062 ] , especially in the patients who showed no increase in HAD activity [ from 80.9 ( SD 52.6 ) to 167.9 ( SD 109.1 ) AU , P = 0.028 ] , whereas lipid peroxidation levels remained unaltered . We conclude that exercise-training can restore muscle UCP3 protein level in COPD , and the nature of this response complies with the hypothesis that UCP3 may protect against lipotoxicity The present study was aim ed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease . Fourteen patients ( males , FEV1 , 24 + /- 7 % predicted ) were r and omized to either inspiratory muscle or sham training groups . Supervised breathing using a threshold inspiratory device was performed 30 minutes per day , five times a week , for 5 consecutive weeks . The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50 % of their maximal inspiratory pressure . Biopsies from external intercostal muscles and vastus lateralis ( control muscle ) were taken before and after the training period . Muscle sample s were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II . Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group . This improvement was associated with increases in the proportion of type I fibers ( by approximately 38 % , p < 0.05 ) and in the size of type II fibers ( by approximately 21 % , p < 0.05 ) in the external intercostal muscles . No changes were observed in the control muscle . The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles STUDY OBJECTIVES To investigate the response to interval exercise ( IE ) training by looking at changes in morphologic and biochemical characteristics of the vastus lateralis muscle , and to compare these changes to those incurred after constant-load exercise ( CLE ) training . DESIGN R and omized , controlled , parallel , two-group study ( IE vs CLE training ) . SETTING Multidisciplinary , outpatient , hospital-based , pulmonary rehabilitation program . PATIENTS Nineteen patients with stable advanced COPD ( mean + /- SEM FEV1 , 40 + /- 4 % predicted ) . INTERVENTIONS Patients ( n = 10 ) assigned to IE training exercised at a mean intensity of 124 + /- 15 % of baseline peak exercise capacity ( peak work rate [ Wpeak ] ) with 30-s work periods interspersed with 30-s rest periods for 45 min/d . Patients ( n = 9 ) allocated to CLE training exercised at a mean intensity of 75 + /- 5 % Wpeak for 30 min/d . Patients exercised 3 d/wk for 10 weeks . MEASUREMENTS AND RESULTS Needle biopsies of the right vastus lateralis muscle were performed before and after rehabilitation . After IE training , the cross-sectional areas of type I and IIa fibers were significantly increased ( type I before , 3,972 + /- 455 microm2 ; after , 4,934 + /- 467 microm2 [ p = 0.004 ] ; type IIa before , 3,695 + /- 372 microm2 ; after , 4,486 + /- 346 microm2 [ p = 0.008 ] ) , whereas the capillary-to-fiber ratio was significantly enlarged ( from 1.13 + /- 0.08 to 1.24 + /- 0.07 [ p = 0.013 ] ) . Citrate synthase activity increased ( from 14.3 + /- 1.4 to 20.5 + /- 4.2 micromol/min/g ) , albeit not significantly ( p = 0.097 ) . There was also a significant improvement in Wpeak ( by 19 + /- 5 % ; p = 0.04 ) and in lactate threshold ( by 17 + /- 5 % ; p = 0.02 ) . The magnitude of changes in all the above variables was not significantly different compared to that incurred after CLE training . During training sessions , however , ratings of dyspnea and leg discomfort , expressed as fraction of values achieved at baseline Wpeak , were significantly lower ( p < 0.05 ) for IE training ( 73 + /- 9 % and 60 + /- 8 % , respectively ) compared to CLE training ( 83 + /- 10 % and 87 + /- 13 % , respectively ) . CONCLUSIONS High-intensity IE training is equally effective to moderately intense CLE training in inducing peripheral muscle adaptations ; however , IE is associated with fewer training symptoms
target: RESULTS The forced expiratory volume in 1 s ( FEV(1 ) ) , the ratio of FEV(1 ) to forced vital capacity ( FVC ) and body mass index were positively associated with the proportion of type I fibres in COPD .
  This review sheds new light on the relationship between skeletal muscle abnormalities and important hallmarks of the disease in severe COPD , and identifies absence of data in GOLD stages 1 - 2 .
  This review also provides reference values on fibre type composition for diagnostic purpose s in COPD
background: BACKGROUND Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease ( COPD ) which is associated with intrinsic muscular abnormalities .
  One of the most consistently reported alterations is a shift from fibre type I to II in the vastus lateralis of these patients .
  Surprisingly , the relationship between this shift and the severity and phenotype of COPD remains unclear .
  A study was conducted to determine whether vastus lateralis muscle fibre type proportions are associated with COPD disease severity and to provide reference values for the proportions of fibre types in the vastus lateralis in COPD .