Microcirculatory structure-function relationships in skeletal muscle of diabetic rats

1994 ◽  
Vol 266 (4) ◽  
pp. H1502-H1511 ◽  
Author(s):  
W. L. Sexton ◽  
D. C. Poole ◽  
O. Mathieu-Costello
Keyword(s):  
Skeletal Muscle ◽  
Structure Function ◽  
Surface Area ◽  
Muscle Atrophy ◽  
Muscle Fiber ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Diffusing Capacity ◽  
Capillary Surface ◽  
Cross Sectional

The effects of streptozotocin-induced diabetes on microcirculatory structure-function relationships in skeletal muscle were studied in control (C) and diabetic (D; 65 mg/kg streptozotocin ip) rats 6-8 wk after injection. Capillary exchange capacity was determined from measurements of capillary filtration coefficient (CFC) and permeability-surface area product (PS) for 51Cr-labeled EDTA in maximally vasodilated (papaverine), isolated hindquarters of C (n = 9) and D (n = 12) rats. Capillary numerical density, length, surface area, capillary geometry, and muscle fiber cross-sectional area were determined using morphometric methods in perfusion-fixed plantaris muscles from a second series of C (n = 5) and D (n = 6) rats. Hindquarters of D rats (61 +/- 3 g) weighed less than C rats (90 +/- 3 g) because of marked muscle atrophy. Minimal total vascular resistance was lower in D rats (P < or = 0.05), indicating an increased flow capacity. CFC was not different in C and D rats (0.0282 +/- 0.0020 vs. 0.0330 +/- 0.0025 ml.min-1.mmHg-1 x 100 g-1, respectively). The relationship between PS and flow was depressed in D rats (P < or = 0.05) compared with C rats, which indicated a reduced capillary diffusing capacity. Plantaris muscle weight was 41% less in D rats (174 +/- 9 vs. 293 +/- 11 mg; P < or = 0.001). Morphometric analysis revealed that muscle fiber cross-sectional area was reduced 39% in D rats, which, despite a lower capillary-to-fiber ratio (1.59 +/- 0.04 vs. 2.12 +/- 0.13; P < or = 0.001), resulted in a 27% increase in capillary density in D rats. Capillary diameter was less in D rats (3.58 +/- 0.12 vs. 4.51 +/- 0.23 microns; P < or = 0.005). Total capillary surface area was reduced 42% in D rats; however, capillary surface area per muscle fiber volume was unchanged in D rats (231 +/- 34 vs. 237 +/- 16 cm-1). These data indicate that there is remodeling of the capillary bed in skeletal muscle of D rats, resulting in a reduction in total microvascular surface area. The reduction in capillary surface area is proportional to the degree of muscle atrophy in D rats such that functional microvascular surface area per tissue mass (e.g., CFC) is unchanged. The lower diffusing capacity (PS) in D rats suggests that either small solute permeability is reduced and/or there is greater perfusion heterogeneity in D rat skeletal muscle.

scholarly journals Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle

2012 ◽  
Vol 303 (6) ◽  
pp. L519-L527 ◽  
Author(s):  
Vladimir T. Basic ◽  
Elsa Tadele ◽  
Ali Ateia Elmabsout ◽  
Hongwei Yao ◽  
Irfan Rahman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tumor Suppressor ◽  
Cigarette Smoke ◽  
Muscle Fiber ◽  
Exercise Tolerance ◽  
Skeletal Muscles ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Von Hippel Lindau

Cigarette smoke (CS) is a well-established risk factor in the development of chronic obstructive pulmonary disease (COPD). In contrast, the extent to which CS exposure contributes to the development of the systemic manifestations of COPD, such as skeletal muscle dysfunction and wasting, remains largely unknown. Decreased skeletal muscle capillarization has been previously reported in early stages of COPD and might play an important role in the development of COPD-associated skeletal muscle abnormalities. To investigate the effects of chronic CS exposure on skeletal muscle capillarization and exercise tolerance, a mouse model of CS exposure was used. The 129/SvJ mice were exposed to CS for 6 mo, and the expression of putative elements of the hypoxia-angiogenic signaling cascade as well as muscle capillarization were studied. Additionally, functional tests assessing exercise tolerance/endurance were performed in mice. Compared with controls, skeletal muscles from CS-exposed mice exhibited significantly enhanced expression of von Hippel-Lindau tumor suppressor (VHL), ubiquitin-conjugating enzyme E2D1 (UBE2D1), and prolyl hydroxylase-2 (PHD2). In contrast, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was reduced. Furthermore, reduced muscle fiber cross-sectional area, decreased skeletal muscle capillarization, and reduced exercise tolerance were also observed in CS-exposed animals. Taken together, the current results provide evidence linking chronic CS exposure and induction of VHL expression in skeletal muscles leading toward impaired hypoxia-angiogenesis signal transduction, reduced muscle fiber cross-sectional area, and decreased exercise tolerance.

scholarly journals Automated fiber-type-specific cross-sectional area assessment and myonuclei counting in skeletal muscle

2013 ◽  
Vol 115 (11) ◽  
pp. 1714-1724 ◽  
Author(s):  
Fujun Liu ◽  
Christopher S. Fry ◽  
Jyothi Mula ◽  
Janna R. Jackson ◽  
Jonah D. Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Cross Sectional Area ◽  
Automated Image Analysis ◽  
Muscle Fiber Type ◽  
Sectional Area ◽  
Cross Sectional ◽  
Exercise Interventions ◽  
Structural And Functional Properties

Skeletal muscle is an exceptionally adaptive tissue that compromises 40% of mammalian body mass. Skeletal muscle functions in locomotion, but also plays important roles in thermogenesis and metabolic homeostasis. Thus characterizing the structural and functional properties of skeletal muscle is important in many facets of biomedical research, ranging from myopathies to rehabilitation sciences to exercise interventions aimed at improving quality of life in the face of chronic disease and aging. In this paper, we focus on automated quantification of three important morphological features of muscle: 1) muscle fiber-type composition; 2) muscle fiber-type-specific cross-sectional area, and 3) myonuclear content and location. We experimentally prove that the proposed automated image analysis approaches for fiber-type-specific assessments and automated myonuclei counting are fast, accurate, and reliable.

scholarly journals A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle

2009 ◽  
Vol 107 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Luciano Dalla Libera ◽  
Barbara Ravara ◽  
Valerio Gobbo ◽  
Elena Tarricone ◽  
Maurizio Vitadello ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Stress Response ◽  
Muscle Atrophy ◽  
Cross Sectional Area ◽  
Heme Oxygenase 1 ◽  
Sectional Area ◽  
Cross Sectional ◽  
Protein Levels ◽  
Antioxidant Stress

It is presently unknown whether oxidative stress increases in disused skeletal muscle in humans. Markers of oxidative stress were investigated in biopsies from the vastus lateralis muscle, collected from healthy subjects before [ time 0 (T0)], after 1 wk (T8), and after 5 wk (T35) of bed rest. An 18% decrease in fiber cross-sectional area was detected in T35 biopsies ( P < 0.05). Carbonylation of muscle proteins significantly increased about twofold at T35 ( P < 0.02) and correlated positively with the decrease in fiber cross-sectional area ( P = 0.04). Conversely, T8 biopsies showed a significant increase in protein levels of heme oxygenase-1 and glucose-regulated protein-75 (Grp75)/mitochondrial heat shock protein-70, two stress proteins involved in the antioxidant defense ( P < 0.05). Heme oxygenase-1 increase, which involved a larger proportion of slow fibers compared with T0, appeared blunted in T35 biopsies. Grp75 protein level increased threefold in T8 biopsies and localized especially in slow fibers ( P < 0.025), to decrease significantly in T35 biopsies ( P < 0.05). Percent change in Grp75 levels positively correlated with fiber cross-sectional area ( P = 0.01). Parallel investigations on rat soleus muscles, performed after 1–15 days of hindlimb suspension, showed that Grp75 protein levels significantly increased after 24 h of unloading ( P = 0.02), i.e., before statistically significant evidence of muscle atrophy, to decrease thereafter in relation to the degree of muscle atrophy ( P = 0.03). Therefore, in humans as in rodents, disuse muscle atrophy is characterized by increased protein carbonylation and by the blunting of the antioxidant stress response evoked by disuse.

scholarly journals Skeletal muscle adaptations to microgravity exposure in the mouse

2003 ◽  
Vol 95 (6) ◽  
pp. 2462-2470 ◽  
Author(s):  
B. C. Harrison ◽  
D. L. Allen ◽  
B. Girten ◽  
L. S. Stodieck ◽  
P. J. Kostenuik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Space Shuttle ◽  
Immunohistochemical Analysis ◽  
Cross Sectional Area ◽  
Fiber Types ◽  
Sectional Area ◽  
Cross Sectional ◽  
Isoform Expression

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to ∼11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced ( P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb ( P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.

scholarly journals Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle cross-sectional area

2010 ◽  
Vol 299 (1) ◽  
pp. R268-R276 ◽  
Author(s):  
Anna C. Kayani ◽  
Graeme L. Close ◽  
Wolfgang H. Dillmann ◽  
Ruben Mestril ◽  
Malcolm J. Jackson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cross Sectional Area ◽  
Force Generation ◽  
Sectional Area ◽  
Wild Type ◽  
Cross Sectional ◽  
Tetanic Force ◽  
Age Related ◽  
Muscle Cross Sectional Area

Skeletal muscle atrophy and weakness are major contributors to frailty and impact significantly on quality of life of older people. Muscle aging is characterized by a loss of maximum tetanic force (Po) generation, primarily due to muscle atrophy, to which mitochondrial dysfunction is hypothesized to contribute. We hypothesized that lifelong overexpression of the mitochondrial heat shock protein (HSP) HSP10 in muscle of mice would protect against development of these deficits. Po generation by extensor digitorum longus muscles of adult and old wild-type and HSP10-overexpressing mice was determined in situ. Muscles were subjected to damaging lengthening contractions, and force generation was remeasured at 3 h or 28 days to examine susceptibility to, and recovery from, damage, respectively. Muscles of old wild-type mice had a 23% deficit in Po generation and a 10% deficit in muscle cross-sectional area compared with muscles of adult wild-type mice. Overexpression of HSP10 prevented this age-related fall in Po generation and reduction in cross-sectional area observed in muscles of old wild-type mice. Additionally, overexpression of HSP10 protected against contraction-induced damage independent of age but did not improve recovery if damage occurred. Preservation of muscle force generation and CSA by HSP10 overexpression was associated with protection against the age-related accumulation of protein carbonyls. Data demonstrate that development of age-related muscle weakness may not be inevitable and show, for the first time, that lifelong overexpression of an HSP prevents the age-related loss of Po generation. These findings support the hypothesis that mitochondrial dysfunction is involved in the development of age-related muscle deficits.

scholarly journals An evaluation of the reliability of muscle fiber cross-sectional area and fiber number measurements in rat skeletal muscle

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Lisa Ceglia ◽  
Sathit Niramitmahapanya ◽  
Lori L Price ◽  
Susan S Harris ◽  
Roger A Fielding ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Rat Skeletal Muscle ◽  
Cross Sectional ◽  
Fiber Number

scholarly journals Skeletal muscle atrophy and dysfunction in breast cancer patients: role for chemotherapy-derived oxidant stress

2018 ◽  
Vol 315 (5) ◽  
pp. C744-C756 ◽  
Author(s):  
Blas A. Guigni ◽  
Damien M. Callahan ◽  
Timothy W. Tourville ◽  
Mark S. Miller ◽  
Brad Fiske ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Skeletal Muscle ◽  
Cancer Patients ◽  
Muscle Fiber ◽  
Cross Sectional Area ◽  
Ros Production ◽  
Sectional Area ◽  
Breast Cancer Patients ◽  
Mitochondrial Content ◽  
Cross Sectional

How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women who were diagnosed with breast cancer and receiving adjuvant chemotherapy following tumor resection and 12 nondiseased controls. Breast cancer patients showed reduced single-muscle fiber cross-sectional area and fractional content of subsarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss, and increased reactive oxygen species (ROS) production in C2C12 murine myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally, concurrent treatment of myotubes with the mitochondrial-targeted antioxidant MitoQ prevented chemotherapy-induced myosin depletion, mitochondrial loss, and ROS production. In patients, reduced mitochondrial content and size and increased expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were associated with reduced muscle fiber cross-sectional area. Our results suggest that chemotherapeutics may adversely affect skeletal muscle in patients and that these effects may be driven through effects of these drugs on mitochondrial content and/or ROS production.

scholarly journals Automated analysis of skeletal muscle fiber cross‐sectional area using CyteSeer image analysis program

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Tatiana Y Kostrominova ◽  
Randall Ingermanson ◽  
Casey A Laris ◽  
Patricia Loy ◽  
Patrick M McDonough
Keyword(s):  
Skeletal Muscle ◽  
Image Analysis ◽  
Muscle Fiber ◽  
Automated Analysis ◽  
Skeletal Muscle Fiber ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Analysis Program ◽  
Cross Sectional

scholarly journals Atrophy patterns in isolated subscapularis lesions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gernot Seppel ◽  
Andreas Voss ◽  
Daniel J. H. Henderson ◽  
Simone Waldt ◽  
Bernhard Haller ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Area Ratio ◽  
Cross Sectional Area ◽  
Control Group ◽  
Sectional Area ◽  
Cross Sectional ◽  
Subscapularis Muscle ◽  
Mri Scans ◽  
The Mean ◽  
The Cross

Abstract Background While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon. Methods Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane. Calculation of the ratio between the upper half of the cross sectional area (CSA) and the total CSA was performed. Eleven MRI scans of patients with subscapularis atrophy following isolated subscapularis tendon tears were analysed and cross sectional area ratio (upper half /total) determined. To guarantee reliable measurement of the CSA and its ratio, bony landmarks were also defined. All parameters were statistically compared for inter-rater reliability, reproducibility and capacity to quantify subscapularis atrophy. Results The mean age in the control group was 49.7 years (± 15.0). The mean cross sectional area (CSA) was 2367.0 mm2 (± 741.4) for the complete subscapularis muscle and 1048.2 mm2 (± 313.3) for the upper half, giving a mean ratio of 0.446 (± 0.046). In the subscapularis repair group the mean age was 56.7 years (± 9.3). With a mean cross sectional area of 1554.7 mm2 (± 419.9) for the complete and of 422.9 mm2 (± 173.6) for the upper half of the subscapularis muscle, giving a mean CSA ratio of 0.269 (± 0.065) which was seen to be significantly lower than that of the control group (p < 0.05). Conclusion Analysis of typical atrophy patterns of the subscapularis muscle demonstrates that the CSA ratio represents a reliable and reproducible assessment tool in quantifying subscapularis atrophy. We propose the classification of subscapularis atrophy as Stage I (mild atrophy) in case of reduction of the cross sectional area ratio < 0.4, Stage II (moderate atrophy) in case of < 0.35 and Stage III (severe atrophy) if < 0.3.

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