scholarly journals Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction

2014 ◽  
Vol 306 (9) ◽  
pp. H1364-H1370 ◽  
Author(s):  
Dalane W. Kitzman ◽  
Barbara Nicklas ◽  
William E. Kraus ◽  
Mary F. Lyles ◽  
Joel Eggebeen ◽  
...  

Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe exercise intolerance, and its pathophysiology is poorly understood. To determine whether skeletal muscle abnormalities contribute to their severely reduced peak exercise O2 consumption (V̇o2), we examined 22 older HFPEF patients (70 ± 7 yr) compared with 43 age-matched healthy control (HC) subjects using needle biopsy of the vastus lateralis muscle and cardiopulmonary exercise testing to assess muscle fiber type distribution and capillarity and peak V̇o2. In HFPEF versus HC patients, peak V̇o2 (14.7 ± 2.1 vs. 22.9 ± 6.6 ml·kg−1·min−1, P < 0.001) and 6-min walk distance (454 ± 72 vs. 573 ± 71 m, P < 0.001) were reduced. In HFPEF versus HC patients, the percentage of type I fibers (39.0 ± 11.4% vs. 53.7 ± 12.4%, P < 0.001), type I-to-type II fiber ratio (0.72 ± 0.39 vs. 1.36 ± 0.85, P = 0.001), and capillary-to-fiber ratio (1.35 ± 0.32 vs. 2.53 ± 1.37, P = 0.006) were reduced, whereas the percentage of type II fibers was greater (61 ± 11.4% vs. 46.3 ± 12.4%, P < 0.001). In univariate analyses, the percentage of type I fibers ( r = 0.39, P = 0.003), type I-to-type II fiber ratio ( r = 0.33, P = 0.02), and capillary-to-fiber ratio ( r = 0.59, P < 0.0001) were positively related to peak V̇o2. In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak V̇o2. We conclude that older HFPEF patients have significant abnormalities in skeletal muscle, characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio, and these may contribute to their severe exercise intolerance. This suggests potential new therapeutic targets in this difficult to treat disorder.

1998 ◽  
Vol 35 (5) ◽  
pp. 419-424 ◽  
Author(s):  
Jerald B. Moon ◽  
Sue Ann Thompson ◽  
Elise Jaeckel ◽  
John W. Canady

Objective This study examined the muscle fiber type distribution within the normal adult levator veli palatini muscle. Methods Levator veli palatini muscle tissue was harvested from the palates of 12 (seven female, five male) adult noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type II fiber types were differentiated by the intensity of, or by the inhibition of, staining of matched fibers at each pH level. Type I fibers stained light at pH 10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at pH 10.4. Main outcome Measures The number of fibers counted for each specimen ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing in each muscle tissue sample were determined and expressed as a percentage of the total number of fibers identified. A few identified fibers could not be labelled as either Type I or Type II. Results The overall proportion of Type I fibers, averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and 44.4% Type II fibers. Conclusions Observed fiber type distributions were similar to those reported for other articulatory muscles, but differed slightly from previously reported distributions for normal levator veli palatini. The distributions observed in this study provide a baseline against which to relate fiber type data from the levator veli palatini of cleft palates to the functional status of the velopharyngeal mechanism.


1996 ◽  
Vol 270 (1) ◽  
pp. H115-H120 ◽  
Author(s):  
H. N. Sabbah ◽  
H. Shimoyama ◽  
V. G. Sharov ◽  
T. Kono ◽  
R. C. Gupta ◽  
...  

The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). In untreated dogs, the proportion of type I fibers was 27 +/- 1% before randomization and decreased to 23 +/- 1% (P < 0.05) at the end of 3 mo of follow up. In dogs treated with enalapril or metoprolol, the proportion of type I fibers was 30 +/- 4 and 28 +/- 2% before randomization and 33 +/- 4 and 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.


1986 ◽  
Vol 64 (9) ◽  
pp. 1245-1251 ◽  
Author(s):  
C. Bouchard ◽  
J. A. Simoneau ◽  
G. Lortie ◽  
M. R. Boulay ◽  
M. Marcotte ◽  
...  

The purpose of the study was to estimate the genetic effect for skeletal muscle characteristics using pairs of nontwin brothers (n = 32), dizygotic (DZ) twins (n = 26), and monozygotic (MZ) twins (n = 35). They were submitted to a needle biopsy of the vastus lateralis for the determination of fiber type distribution (I, IIa, IIb) and the following enzymes were assayed for maximal activity: creatine kinase, hexokinase, phosphofructokinase (PFK), lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase (OGDH). For the percentage of type I fibers, intraclass correlations were 0.33 (p < 0.05), 0.52 (p < 0.01), and 0.55 (p < 0.01) in brothers and DZ and MZ twins, respectively. MZ twins exhibited significant within-pair resemblance for all enzyme activities (0.30 ≤ r ≤ 0.68). In spite of these correlations, genetic analyses performed with the twin data alone indicated that there was no significant genetic effect for muscle fiber type I, IIa, and IIb distribution and fiber areas. Although there were significant correlations in MZ twins for all muscle enzyme activities, the often nonsignificant intraclass coefficients found in brothers and DZ twins suggest that variations in enzyme activities are highly related to common environmental conditions and nongenetic factors. However, genetic factors appear to be involved in the variation of regulatory enzymes of the glycolytic (PFK) and citric acid cycle (OGDH) pathways and in the variation of the oxidative to glycolytic activity ratio (PFK/OGDH ratio). Data show that these genetic effects reach only about 25–50% of the total phenotypic variation when data are adjusted for age and sex differences.


2007 ◽  
Vol 103 (6) ◽  
pp. 2105-2111 ◽  
Author(s):  
A. R. Tupling ◽  
E. Bombardier ◽  
R. D. Stewart ◽  
C. Vigna ◽  
A. E. Aqui

To investigate the time course of fiber type-specific heat shock protein 70 (Hsp70) expression in human skeletal muscle after acute exercise, 10 untrained male volunteers performed single-legged isometric knee extensor exercise at 60% of their maximal voluntary contraction (MVC) with a 50% duty cycle (5-s contraction and 5-s relaxation) for 30 min. Muscle biopsies were collected from the vastus lateralis before (Pre) exercise in the rested control leg (C) and immediately after exercise (Post) in the exercised leg (E) only and on recovery days 1 (R1), 2 (R2), 3 (R3), and 6 (R6) from both legs. As demonstrated by Western blot analysis, whole muscle Hsp70 content was unchanged ( P > 0.05) immediately after exercise (Pre vs. Post), was increased ( P < 0.05) by ∼43% at R1, and remained elevated throughout the entire recovery period in E only. Hsp70 expression was also assessed in individual muscle fiber types I, IIA, and IIAX/IIX by immunohistochemistry. There were no fiber type differences ( P > 0.05) in basal Hsp70 expression. Immediately after exercise, Hsp70 expression was increased ( P < 0.05) in type I fibers by ∼87% but was unchanged ( P > 0.05) in type II fibers (Pre vs. Post). At R1 and throughout recovery, Hsp70 content in E was increased above basal levels ( P < 0.05) in all fiber types, but Hsp70 expression was always highest ( P < 0.05) in type I fibers. Hsp70 content in C was not different from Pre at any time throughout recovery. Glycogen depletion was observed at Post in all type II, but not type I, fibers, suggesting that the fiber type differences in exercise-induced Hsp70 expression were not related to glycogen availability. These results demonstrate that the time course of exercise-induced Hsp70 expression in human skeletal muscle is fiber type specific.


1989 ◽  
Vol 257 (5) ◽  
pp. E736-E742 ◽  
Author(s):  
W. H. Martin ◽  
A. R. Coggan ◽  
R. J. Spina ◽  
J. E. Saffitz

The density and distribution of beta-adrenergic receptors in type I and II fibers of human gastrocnemius and quadriceps muscles were characterized in ten healthy sedentary subjects and in a subgroup of six subjects before and after 12 wk of endurance exercise training. Total tissue content of beta-receptors was measured in frozen sections of skeletal muscle biopsies incubated with 125I-labeled cyanopindolol in the presence and absence of 10(-5) M L-propranolol. The relative beta-receptor densities of type I and II fibers were delineated autoradiographically. Muscle fiber types were identified in adjacent serial sections by histochemical staining of myofibrillar adenosine-triphosphatase (ATPase) activity. Type I fibers had a threefold greater beta-receptor density than type II fibers of the same muscle [P less than 0.001; type I-to-type II fiber ratio of beta-receptor density was 3.06 +/- 0.43 (SD)]. Exercise training elicited a change in muscle fiber subtype composition (+34% type IIa and -42% type IIb; P less than 0.05 and P = 0.066, respectively), a 40% increase in citrate synthase activity of skeletal muscle (P = 0.01), and a 23% rise in peak oxygen uptake (P less than 0.001). However, no change in total tissue content of beta-receptors was observed after exercise training, even when receptor density was adjusted for preconditioning fiber type composition. Thus beta-receptor density of type I fibers of human skeletal muscle is threefold greater than that of type II fibers. Enhanced capacity for aerobic metabolism after endurance exercise training is not associated with upregulation of total beta-receptor density.


2019 ◽  
Vol 126 (6) ◽  
pp. 1607-1618 ◽  
Author(s):  
Daniel Jacko ◽  
Käthe Bersiner ◽  
Jonas Hebchen ◽  
Markus de Marées ◽  
Wilhelm Bloch ◽  
...  

αB-crystallin (CRYAB) is an important actor in the immediate cell stabilizing response following mechanical stress in skeletal muscle. Yet, only little is known regarding myofiber type-specific stress responses of CRYAB. We investigated whether the phosphorylation of CRYAB at serine 59 (pCRYABSer59) and its cytoskeleton association are influenced by varying load-intensity and -volume in a fiber type-specific manner. Male subjects were assigned to 1, 5, and 10 sets of different acute resistance exercise protocols: hypertrophy (HYP), maximum strength (MAX), strength endurance (SE), low intensity (LI), and three sets of maximum eccentric resistance exercise (ECC). Skeletal muscle biopsies were taken at baseline and 30 min after exercise. Western blot revealed an increase inpCRYABSer59only following 5 and 10 sets in groups HYP, MAX, SE, and LI as well as following 3 sets in the ECC group. In type I fibers, immunohistochemistry determined increasedpCRYABSer59in all groups. In type II fibers,pCRYABSer59only increased in MAX and ECC groups, with the increase in type II fibers exceeding that of type I fibers in ECC. Association of CRYAB andpCRYABSer59with the cytoskeleton reflected the fiber type-specific phosphorylation pattern. Phosphorylation of CRYAB and its association with the cytoskeleton in type I and II myofibers is highly specific in terms of loading intensity and volume. Most likely, this is based on specific recruitment patterns of the different myofiber entities due to the different resistance exercise loadings. We conclude thatpCRYABSer59indicates contraction-induced mechanical stress exposure of single myofibers in consequence of resistance exercise.NEW & NOTEWORTHY We determined that the phosphorylation of αB-crystallin at serine 59 (pCRYABSer59) after resistance exercise differs between myofiber types in a load- and intensity-dependent manner. The determination ofpCRYABSer59could serve as a marker indirectly indicating contractile involvement and applied mechanical stress on individual fibers. By that, it is possible to retrospectively assess the impact of resistance exercise loading on skeletal muscle fiber entities.


2016 ◽  
Vol 121 (5) ◽  
pp. 1074-1086 ◽  
Author(s):  
Ben D. Perry ◽  
Victoria L. Wyckelsma ◽  
Robyn M. Murphy ◽  
Collene H. Steward ◽  
Mitchell Anderson ◽  
...  

Physical training increases skeletal muscle Na+,K+-ATPase content (NKA) and improves exercise performance, but the effects of inactivity per se on NKA content and isoform abundance in human muscle are unknown. We investigated the effects of 23-day unilateral lower limb suspension (ULLS) and subsequent 4-wk resistance training (RT) on muscle function and NKA in 6 healthy adults, measuring quadriceps muscle peak torque; fatigue and venous [K+] during intense one-legged cycling exercise; and skeletal muscle NKA content ([3H]ouabain binding) and NKA isoform abundances (immunoblotting) in muscle homogenates (α1-3, β1–2) and in single fibers (α1–3, β1). In the unloaded leg after ULLS, quadriceps peak torque and cycling time to fatigue declined by 22 and 23%, respectively, which were restored with RT. Whole muscle NKA content and homogenate NKA α1–3 and β1–2 isoform abundances were unchanged with ULLS or RT. However, in single muscle fibers, NKA α3 in type I (−66%, P = 0.006) and β1 in type II fibers (−40%, P = 0.016) decreased after ULLS, with other NKA isoforms unchanged. After RT, NKA α1 (79%, P = 0.004) and β1 (35%, P = 0.01) increased in type II fibers, while α2 (76%, P = 0.028) and α3 (142%, P = 0.004) increased in type I fibers compared with post-ULLS. Despite considerably impaired muscle function and earlier fatigue onset, muscle NKA content and homogenate α1 and α2 abundances were unchanged, thus being resilient to inactivity induced by ULLS. Nonetheless, fiber type-specific downregulation with inactivity and upregulation with RT of several NKA isoforms indicate complex regulation of muscle NKA expression in humans.


1990 ◽  
Vol 68 (5) ◽  
pp. 1896-1901 ◽  
Author(s):  
A. R. Coggan ◽  
R. J. Spina ◽  
M. A. Rogers ◽  
D. S. King ◽  
M. Brown ◽  
...  

Many older athletes are capable of endurance performances equal to those of young runners who have higher maximal O2 uptakes (VO2max). To determine whether this is a result of differences in skeletal muscle characteristics, gastrocnemius muscle biopsy samples were obtained from eight master athletes [aged 63 +/- 6 (SD) yr] and eight young (aged 26 +/- 3 yr) runners. The young runners were matched with the master athletes for 10-km running performance and for their volume, pace, and type of training. Despite similar 10-km run times, VO2max was 11% lower (P less than 0.05) in the master athletes. Fiber type distribution did not differ between groups, with both groups having 60% type I and very few type IIb fibers. Succinate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase activities, however, were 31 and 24% higher in the master athletes compared with the matched young runners, whereas lactate dehydrogenase activity was 46% lower (all P less than 0.05). The capillary-to-fiber ratio was also greater in the master athletes; however, capillary density was similar in the two groups, because of the master athletes' 34% larger (P less than 0.05) type I fibers. These differences in skeletal muscle characteristics may explain the master athletes' ability to perform as well as some young runners despite having a lower VO2max.


2020 ◽  
Vol 128 (4) ◽  
pp. 795-804 ◽  
Author(s):  
Tatiana Moro ◽  
Camille R. Brightwell ◽  
Elena Volpi ◽  
Blake B. Rasmussen ◽  
Christopher S. Fry

Aging induces physiological decline in human skeletal muscle function and morphology, including type II fiber atrophy and an increase in type I fiber frequency. Resistance exercise training (RET) is an effective strategy to overcome muscle mass loss and improve strength, with a stronger effect on type II fibers. In the present study, we sought to determine the effect of a 12-wk progressive RET program on the fiber type-specific skeletal muscle hypertrophic response in older adults. Nineteen subjects [10 men and 9 women (71.1 ± 4.3 yr)] were studied before and after the 12-wk program. Immunohistochemical analysis was used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area (CSA), satellite cell abundance, myonuclear content, and lipid droplet density. RET induced an increase in MyHC type II fiber frequency and a concomitant decrease in MyHC type I fiber frequency. Mean CSA increased significantly only in MyHC type II fibers (+23.3%, P < 0.05), but myonuclear content increased only in MyHC type I fibers ( P < 0.05), with no change in MyHC type II fibers. Satellite cell content increased ~40% in both fiber types ( P > 0.05). RET induced adaptations to the capillary supply to satellite cells, with the distance between satellite cells and the nearest capillary increasing in type I fibers and decreasing in type II fibers. Both fiber types showed similar decrements in intramuscular lipid density with training ( P < 0.05). Our data provide intriguing evidence for a fiber type-specific response to RET in older adults and suggest flexibility in the myonuclear domain of type II fibers during a hypertrophic stimulus. NEW & NOTEWORTHY In older adults, progressive resistance exercise training (RET) increased skeletal muscle fiber volume and cross-sectional area independently of myonuclear accretion, leading to an expansion of the myonuclear domain. Fiber type-specific analyses illuminated differential adaptation; type II fibers underwent hypertrophy and exhibited myonuclear domain plasticity, whereas myonuclear accretion occurred in type I fibers in the absence of a robust hypertrophic response. RET also augmented satellite cell-capillary interaction and reduced intramyocellular lipid density to improve muscle quality.


1993 ◽  
Vol 74 (2) ◽  
pp. 911-915 ◽  
Author(s):  
G. R. Adams ◽  
B. M. Hather ◽  
K. M. Baldwin ◽  
G. A. Dudley

We recently reported that 19 wk of heavy resistance training caused a decrease in the percentage of type IIb and an increase in the percentage of type IIa fibers as determined by qualitative histochemical analyses of myofibrillar adenosinetriphosphatase activity of biopsies of musculus vastus lateralis (Hather et al. Acta Physiol. Scand. 143: 177–185, 1991). These data were interpreted to suggest that resistance training had caused transformation among the fast-twitch fiber subtypes. To more clearly establish the influence of resistance training on muscle fiber composition, biopsies from the original study were analyzed biochemically for myosin heavy chain (MHC) composition by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and histochemically for fiber types by use of myofibrillar adenosinetriphosphatase activity. The results show that after training (n = 13), IIb MHC composition decreased (P < 0.05) from 19 +/- 4 to 7 +/- 1%. IIa MHC, in contrast, increased (P < 0.05) from 48 +/- 3 to 60 +/- 2%. These responses were essentially mirrored by alterations in fiber type distribution. The percentage of type IIb fibers decreased (P < 0.05) from 18 +/- 3 to 1 +/- 1%, whereas the percentage of type IIa fibers increased from 46 +/- 4 to 60 +/- 3% (P < 0.05). Neither I MHC composition nor type I fiber percentage changed with training. The control group (n = 4) showed no changes in MHC composition or fiber type distribution. These results suggest that heavy resistance training alters MHC composition in human skeletal muscle, presumably reflecting a change in genetic expression.


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