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Sample records for cardiac muscle tissue

  1. Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture.

    Science.gov (United States)

    Feinberg, Adam W; Alford, Patrick W; Jin, Hongwei; Ripplinger, Crystal M; Werdich, Andreas A; Sheehy, Sean P; Grosberg, Anna; Parker, Kevin Kit

    2012-08-01

    The heart is a muscular organ with a wrapping, laminar structure embedded with neural and vascular networks, collagen fibrils, fibroblasts, and cardiac myocytes that facilitate contraction. We hypothesized that these non-muscle components may have functional benefit, serving as important structural alignment cues in inter- and intra-cellular organization of cardiac myocytes. Previous studies have demonstrated that alignment of engineered myocardium enhances calcium handling, but how this impacts actual force generation remains unclear. Quantitative assays are needed to determine the effect of alignment on contractile function and muscle physiology. To test this, micropatterned surfaces were used to build 2-dimensional myocardium from neonatal rat ventricular myocytes with distinct architectures: confluent isotropic (serving as the unaligned control), confluent anisotropic, and 20 μm spaced, parallel arrays of multicellular myocardial fibers. We combined image analysis of sarcomere orientation with muscular thin film contractile force assays in order to calculate the peak sarcomere-generated stress as a function of tissue architecture. Here we report that increasing peak systolic stress in engineered cardiac tissues corresponds with increasing sarcomere alignment. This change is larger than would be anticipated from enhanced calcium handling and increased uniaxial alignment alone. These results suggest that boundary conditions (heterogeneities) encoded in the extracellular space can regulate muscle tissue function, and that structural organization and cytoskeletal alignment are critically important for maximizing peak force generation.

  2. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

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    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  3. Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen;

    2015-01-01

    fibers. Biopsies of left ventricular cardiac muscle and soleus muscle, a type I-rich oxidative skeletal muscle, were obtained from 15 healthy domestic cats. Enzymatic activity of citrate synthase (CS), a biomarker of mitochondrial content, was measured. Mitochondrial OXPHOS capacity with various kinds...... of non-fatty-acid substrates and fatty-acid substrate in permeabilized muscle fiber was measured by using high-resolution respirometry. CS activity in the heart was 3 times higher than in the soleus muscle. Mitochondrial state 3 respiration, ADP-stimulated respiration, with complex I-linked and complex I...

  4. Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen;

    2015-01-01

    No studies have investigated the mitochondrial function in permeabilized muscle fiber from cats. The aim of this study was to investigate tissue-specific and substrate-specific characteristics of mitochondrial oxidative phosphorylation (OXPHOS) capacity in feline permeabilized oxidative muscle...

  5. Metabolic aspects of cardiac and skeletal muscle tissues in the condition of hypoxia, ischaemia and reperfusion induced by extracorporeal circulation.

    Science.gov (United States)

    Corbucci, G G; Menichetti, A; Cogliati, A; Ruvolo, C

    1995-01-01

    Extracorporeal circulation (ECC) during aortopulmonary bypass surgery allows the investigation of the metabolic and biochemical effects of hypoxia (skeletal muscle), ischaemia (cardiac muscle) and reperfusion (skeletal and cardiac muscle) in homogeneous groups of patients. In this study we examined the mitochondrial enzymic response to oxidative stress in 40 subjects, and analysis was carried out on heart and skeletal-muscle biopsies taken before, during and after aortic clamping and 115 min of ECC. The results obtained constitute a clinical and biochemical picture characterized by some peculiar adaptive changes of enzymic activities which thus antagonize the oxidative damage due to acute hypoxia, ischaemia and reperfusion. Consequently it seems that this cellular protective mechanism plays a crucial role in the reversibility of oxidative damage in hypoxic and ischaemic tissues.

  6. Fetal cardiac muscle contractility decreases with gestational age: a color-coded tissue velocity imaging study

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    Elmstedt Nina

    2012-05-01

    Full Text Available Abstract Background Present data regarding how the fetal heart works and develops throughout gestation is limited. However, the possibility to analyze the myocardial velocity profile provides new possibilities to gain further knowledge in this area. Thus, the objective of this study was to evaluate human fetal myocardial characteristics and deformation properties using color-coded tissue velocity imaging (TVI. Methods TVI recordings from 55 healthy fetuses, at 18 to 42 weeks of gestation, were acquired at a frame rate of 201–273 frames/s for offline analysis using software enabling retrieval of the myocardial velocity curve and 2D anatomical information. The measurements were taken from an apical four-chamber view, and the acquired data was correlated using regression analysis. Results Left ventricular length and width increased uniformly with gestational age. Atrioventricular plane displacement and the E’/A’ ratio also increased with gestational age, while a longitudinal shortening was demonstrated. Conclusions Fetal cardiac muscle contractility decreases with gestational age. As numerous fetal- and pregnancy-associated conditions directly influence the pumping function of the fetal heart, we believe that this new insight into the physiology of the human fetal cardiovascular system could contribute to make diagnosis and risk assessment easier and more accurate.

  7. Chronic hindlimb suspension unloading markedly decreases turnover rates of skeletal and cardiac muscle proteins and adipose tissue triglycerides.

    Science.gov (United States)

    Bederman, Ilya R; Lai, Nicola; Shuster, Jeffrey; Henderson, Leigh; Ewart, Steven; Cabrera, Marco E

    2015-07-01

    We previously showed that a single bolus of "doubly-labeled" water ((2)H2 (18)O) can be used to simultaneously determine energy expenditure and turnover rates (synthesis and degradation) of tissue-specific lipids and proteins by modeling labeling patterns of protein-bound alanine and triglyceride-bound glycerol (Bederman IR, Dufner DA, Alexander JC, Previs SF. Am J Physiol Endocrinol Metab 290: E1048-E1056, 2006). Using this novel method, we quantified changes in the whole body and tissue-specific energy balance in a rat model of simulated "microgravity" induced by hindlimb suspension unloading (HSU). After chronic HSU (3 wk), rats exhibited marked atrophy of skeletal and cardiac muscles and significant decrease in adipose tissue mass. For example, soleus muscle mass progressively decreased 11, 43, and 52%. We found similar energy expenditure between control (90 ± 3 kcal · kg(-1)· day(-1)) and hindlimb suspended (81 ± 6 kcal/kg day) animals. By comparing food intake (∼ 112 kcal · kg(-1) · day(-1)) and expenditure, we found that animals maintained positive calorie balance proportional to their body weight. From multicompartmental fitting of (2)H-labeling patterns, we found significantly (P triglycerides. Specifically, we found that synthesis rates of skeletal and cardiac muscle proteins were affected to a much greater degree compared with the decrease in degradation rates, resulting in large negative balance and significant tissue loss. In contrast, we found a small decrease in adipose tissue triglyceride synthesis paired with a large decrease in degradation, resulting in smaller negative energy balance and loss of fat mass. We conclude that HSU in rats differentially affects turnover of muscle proteins vs. adipose tissue triglycerides.

  8. Nanomaterials for Cardiac Myocyte Tissue Engineering

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    Rodolfo Amezcua

    2016-07-01

    Full Text Available Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

  9. Clofibrate, calcium and cardiac muscle.

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    Fairhurst, A S; Wickie, G; Peabody, T

    1982-03-01

    The anti-hyperlipidemic drug clofibrate produces negative inotropic effects and arrythmias in isolated perfused rabbit heart Langendorff preparations. In electrically stimulated rat left atria, clofibrate produces negative inotropic effects, the speed of onset and extent of which are decreased by raising the Ca concentration of the bathing medium. Sensitivity of isolated rat atria to clofibrate is not increased when the tissues are stimulated under slow Ca channel conditions, in which the tissues are activated by either isoproterenol or dibutyryl cyclic AMP, although sensitivity to clofibrate is decreased when atria are exposed to increasing concentrations of norepinephrine. Increasing the stimulation frequency of isolated guinea-pig atria to produce a positive treppe also decreases the inhibitory effect of clofibrate, while in rat atria the typical negative treppe is altered towards a positive treppe in presence of clofibrate. The effects of paired electrical stimulation are not diminished by the drug, suggesting that Ca release from the sarcoplasmic reticulum is not affected by clofibrate, although the drug inhibits the rate of Ca uptake by isolated cardiac sarcoplasmic reticulum and mitochondria. These results suggest that clofibrate has multiple effects on Ca functions in cardiac muscle.

  10. Cardiac tissue engineering

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    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  11. Cardiac tissue engineering: state of the art.

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    Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas

    2014-01-17

    The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

  12. Distilling complexity to advance cardiac tissue engineering

    OpenAIRE

    Ogle, Brenda M.; Bursac, Nenad; Domian, Ibrahim; Huang, Ngan F.; Menasché, Philippe; Murry, Charles; Pruitt, Beth; Radisic, Milica; Wu, Joseph C; Wu, Sean M.; Zhang, Jianyi; Zimmermann, Wolfram-Hubertus; Vunjak-Novakovic, Gordana

    2016-01-01

    The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or “big questions” were articulated that, if addressed, could substantially advance the current state-of-the-art in modeling heart disease and realizing heart repa...

  13. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

    2011-04-08

    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  14. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I

    2014-01-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac......, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), psmooth muscle (222±13; 115±2; 48±2 umol•g(-1)•min(-1), p

  15. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

      The connective tissue content of skeletal muscle is believed to be the major factor responsible for defining the eating quality of different meat cuts, although attempts to correlate quantifications based on traditional histological methods have not as yet been able to prove this relation....... Collagen, being the major protein in connective tissue, has been extensively investigated with regard to its relation to meat tenderness, but the results have been rather conflicting. Meat from older animals is tougher than that from younger animals, and changes in the properties of the collagen due...... that collagen plays a significant role in determining the tenderness of meat. What are we missing? Therefore, fundamental aspects of connective tissue research have been the centre of attention throughout this thesis. A holistic view has been applied, glancing at this complex tissue which has many facets...

  16. Noninvasive, near infrared spectroscopic-measured muscle pH and PO2 indicate tissue perfusion for cardiac surgical patients undergoing cardiopulmonary bypass

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    Soller, Babs R.; Idwasi, Patrick O.; Balaguer, Jorge; Levin, Steven; Simsir, Sinan A.; Vander Salm, Thomas J.; Collette, Helen; Heard, Stephen O.

    2003-01-01

    OBJECTIVE: To determine whether near infrared spectroscopic measurement of tissue pH and Po2 has sufficient accuracy to assess variation in tissue perfusion resulting from changes in blood pressure and metabolic demand during cardiopulmonary bypass. DESIGN: Prospective clinical study. SETTING: Academic medical center. SUBJECTS: Eighteen elective cardiac surgical patients. INTERVENTION: Cardiac surgery under cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: A near infrared spectroscopic fiber optic probe was placed over the hypothenar eminence. Reference Po2 and pH sensors were inserted in the abductor digiti minimi (V). Data were collected every 30 secs during surgery and for 6 hrs following cardiopulmonary bypass. Calibration equations developed from one third of the data were used with the remaining data to investigate sensitivity of the near infrared spectroscopic measurement to physiologic changes resulting from cardiopulmonary bypass. Near infrared spectroscopic and reference pH and Po2 measurements were compared for each subject using standard error of prediction. Near infrared spectroscopic pH and Po2 at baseline were compared with values during cardiopulmonary bypass just before rewarming commenced (hypotensive, hypothermic), after rewarming (hypotensive, normothermic) just before discontinuation of cardiopulmonary bypass, and at 6 hrs following cardiopulmonary bypass (normotensive, normothermic) using mixed-model analysis of variance. Near infrared spectroscopic pH and Po2 were well correlated with the invasive measurement of pH (R2 =.84) and Po2 (R 2 =.66) with an average standard error of prediction of 0.022 +/- 0.008 pH units and 6 +/- 3 mm Hg, respectively. The average difference between the invasive and near infrared spectroscopic measurement was near zero for both the pH and Po2 measurements. Near infrared spectroscopic Po2 significantly decreased 50% on initiation of cardiopulmonary bypass and remained depressed throughout the bypass and

  17. Avenanthramides are bioavailable and accumulate in hepatic, cardiac, and skeletal muscle tissue following oral gavage in rats

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    Avenanthramides (AVA), polyphenols found exclusively in oats (Avena sativa L.), may play a role in the anti-inflammatory and anti-atherogenic activity of oats. The bioavailability of AVA has been demonstrated previously, but its distribution at the organ and tissue level and the extent of conjugati...

  18. [Muscles and connective tissue: histology].

    Science.gov (United States)

    Delage, J-P

    2012-10-01

    Here, we give some comments about the DVD movies "Muscle Attitudes" from Endovivo productions, the movies up lighting some loss in the attention given to studies on the connective tissue, and especially them into muscles. The main characteristics of the different components in the intra-muscular connective tissue (perimysium, endomysium, epimysium) are shown here with special references to their ordered architecture and special references to their spatial distributions. This connective tissue is abundant into the muscles and is in continuity with the muscles in vicinity, with their tendons and their sheath, sticking the whole on skin. This connective tissue has also very abundant connections on the muscles fibres. It is then assumed that the connective tissue sticks every organs or cells of the locomotion system. Considering the elastic properties of the collagen fibres which are the most abundant component of connective tissue, it is possible to up light a panel of connective tissue associated functions such as the transmission of muscle contractions or the regulation of protein and energetic muscles metabolism.

  19. Cardiac Muscle Studies with Rat Ventricular Strips

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    Whitten, Bert K.; Faleschini, Richard J.

    1977-01-01

    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  20. Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity.

    Science.gov (United States)

    Hughes, Michael; Lilleker, James B; Herrick, Ariane L; Chinoy, Hector

    2015-05-01

    Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. While cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research.

  1. Biomimetic materials design for cardiac tissue regeneration.

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    Dunn, David A; Hodge, Alexander J; Lipke, Elizabeth A

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. In the absence of sufficient numbers of organs for heart transplant, alternate approaches for healing or replacing diseased heart tissue are under investigation. Designing biomimetic materials to support these approaches will be essential to their overall success. Strategies for cardiac tissue engineering include injection of cells, implantation of three-dimensional tissue constructs or patches, injection of acellular materials, and replacement of valves. To replicate physiological function and facilitate engraftment into native tissue, materials used in these approaches should have properties that mimic those of the natural cardiac environment. Multiple aspects of the cardiac microenvironment have been emulated using biomimetic materials including delivery of bioactive factors, presentation of cell-specific adhesion sites, design of surface topography to guide tissue alignment and dictate cell shape, modulation of mechanical stiffness and electrical conductivity, and fabrication of three-dimensional structures to guide tissue formation and function. Biomaterials can be engineered to assist in stem cell expansion and differentiation, to protect cells during injection and facilitate their retention and survival in vivo, and to provide mechanical support and guidance for engineered tissue formation. Numerous studies have investigated the use of biomimetic materials for cardiac regeneration. Biomimetic material design will continue to exploit advances in nanotechnology to better recreate the cellular environment and advance cardiac regeneration. Overall, biomimetic materials are moving the field of cardiac regenerative medicine forward and promise to deliver new therapies in combating heart disease.

  2. Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization.

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    Carrier, R L; Papadaki, M; Rupnick, M; Schoen, F J; Bursac, N; Langer, R; Freed, L E; Vunjak-Novakovic, G

    1999-09-01

    Cardiac tissue engineering has been motivated by the need to create functional tissue equivalents for scientific studies and cardiac tissue repair. We previously demonstrated that contractile cardiac cell-polymer constructs can be cultivated using isolated cells, 3-dimensional scaffolds, and bioreactors. In the present work, we examined the effects of (1) cell source (neonatal rat or embryonic chick), (2) initial cell seeding density, (3) cell seeding vessel, and (4) tissue culture vessel on the structure and composition of engineered cardiac muscle. Constructs seeded under well-mixed conditions with rat heart cells at a high initial density ((6-8) x 10(6) cells/polymer scaffold) maintained structural integrity and contained macroscopic contractile areas (approximately 20 mm(2)). Seeding in rotating vessels (laminar flow) rather than mixed flasks (turbulent flow) resulted in 23% higher seeding efficiency and 20% less cell damage as assessed by medium lactate dehydrogenase levels (p laminar and dynamic, yielded constructs with a more active, aerobic metabolism as compared to constructs cultured in mixed or static flasks. After 1-2 weeks of cultivation, tissue constructs expressed cardiac specific proteins and ultrastructural features and had approximately 2-6 times lower cellularity (p < 0.05) but similar metabolic activity per unit cell when compared to native cardiac tissue.

  3. In utero undernutrition programs skeletal and cardiac muscle metabolism

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    Brittany eBeauchamp

    2016-01-01

    Full Text Available In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease.

  4. Electrical stimulation systems for cardiac tissue engineering.

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    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

    2009-01-01

    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures.

  5. Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia.

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    Shum, Angie M Y; Fung, David C Y; Corley, Susan M; McGill, Max C; Bentley, Nicholas L; Tan, Timothy C; Wilkins, Marc R; Polly, Patsie

    2015-12-01

    Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response.

  6. Developmental changes in the protein profiles of human cardiac and skeletal muscle.

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    Tipler, T D; Edwards, Y H; Hopkinson, D A

    1978-05-01

    1. The use of SDS electrophoresis as a tool for the analysis of development processes in man has been evaluated. 2. The protein profiles of cardiac and skeletal muscle from foetal (10--24 weeks gestation) infant and adult specimens have been analysed and striking developmental changes were found which involved all the major proteins. 3. Before 20 weeks gestation the soluble protein profile of skeletal muscle appears to consist largely of extracellular proteins. 4. Myoglobin was found in foetal cardiac muscle from 20 weeks gestation but was not demonstrable in foetal (greater than 24 weeks) skeletal muscle. Foetal and adult myoglobin were indistinguishable. 5. A limited survey of the protein patterns of brain, liver and kidney was carried out. In general these tissues show less developmental change than skeletal or cardiac muscle.

  7. Recombinant proteins secreted from tissue-engineered bioartificial muscle improve cardiac dysfunction and suppress cardiomyocyte apoptosis in rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    RONG Shu-ling; WANG Yong-jin; WANG Xiao-lin; LU Yong-xin; WU Yin; LIU Qi-yun; MI Shao-hua; XU Yu-lan

    2010-01-01

    Background Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats.Methods Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n=6) and MI-GFP group (n=6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n=6)and S-GFP group (n=6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting.Results Primary rat myoblasts were retrovirally transduced to

  8. Contractile Properties of Esophageal Striated Muscle: Comparison with Cardiac and Skeletal Muscles in Rats

    Directory of Open Access Journals (Sweden)

    Takahiko Shiina

    2010-01-01

    Full Text Available The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis.

  9. Coiled fiber scaffolds embedded with gold nanoparticles improve the performance of engineered cardiac tissues

    Science.gov (United States)

    Fleischer, Sharon; Shevach, Michal; Feiner, Ron; Dvir, Tal

    2014-07-01

    Coiled perimysial fibers within the heart muscle provide it with the ability to contract and relax efficiently. Here, we report on a new nanocomposite scaffold for cardiac tissue engineering, integrating coiled electrospun fibers with gold nanoparticles. Cultivation of cardiac cells within the hybrid scaffolds promoted cell organization into elongated and aligned tissues generating a strong contraction force, high contraction rate and low excitation threshold.Coiled perimysial fibers within the heart muscle provide it with the ability to contract and relax efficiently. Here, we report on a new nanocomposite scaffold for cardiac tissue engineering, integrating coiled electrospun fibers with gold nanoparticles. Cultivation of cardiac cells within the hybrid scaffolds promoted cell organization into elongated and aligned tissues generating a strong contraction force, high contraction rate and low excitation threshold. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00300d

  10. Metalloproteinase expression is altered in cardiac and skeletal muscle in cancer cachexia.

    Science.gov (United States)

    Devine, Raymond D; Bicer, Sabahattin; Reiser, Peter J; Velten, Markus; Wold, Loren E

    2015-08-15

    Cardiac and skeletal muscle dysfunction is a recognized effect of cancer-induced cachexia, with alterations in heart function leading to heart failure and negatively impacting patient morbidity. Cachexia is a complex and multifaceted disease state with several potential contributors to cardiac and skeletal muscle dysfunction. Matrix metalloproteinases (MMPs) are a family of enzymes capable of degrading components of the extracellular matrix (ECM). Changes to the ECM cause disruption both in the connections between cells at the basement membrane and in cell-to-cell interactions. In the present study, we used a murine model of C26 adenocarcinoma-induced cancer cachexia to determine changes in MMP gene and protein expression in cardiac and skeletal muscle. We analyzed MMP-2, MMP-3, MMP-9, and MMP-14 as they have been shown to contribute to both cardiac and skeletal muscle ECM changes and, thereby, to pathology in models of heart failure and muscular dystrophy. In our model, cardiac and skeletal muscles showed a significant increase in RNA and protein levels of several MMPs and tissue inhibitors of metalloproteinases. Cardiac muscle showed significant protein increases in MMP-2, MMP-3, MMP-9, and MMP-14, whereas skeletal muscles showed increases in MMP-2, MMP-3, and MMP-14. Furthermore, collagen deposition was increased after C26 adenocarcinoma-induced cancer cachexia as indicated by an increased left ventricular picrosirius red-positive-stained area. Increases in serum hydroxyproline suggest increased collagen turnover, implicating skeletal muscle remodeling. Our findings demonstrate that cancer cachexia-associated matrix remodeling results in cardiac fibrosis and possible skeletal muscle remodeling. With these findings, MMPs represent a possible therapeutic target for the treatment of cancer-induced cachexia.

  11. Enantioselective disposition of (R/S)-albuterol in skeletal and cardiac muscle.

    Science.gov (United States)

    Jacobson, Glenn A; Yee, Kwang Choon; Premilovac, Dino; Rattigan, Stephen

    2014-06-01

    Significant enhancement of skeletal muscle function has been observed with racemic albuterol (salbutamol). There is now general acceptance that the R-albuterol enantiomer elicits the pharmacological response, both in the lungs and extrapulmonary, while S-albuterol is pharmacologically inert. The objective of this study was to investigate the distribution of (R/S)-albuterol enantiomers into skeletal and cardiac muscle. Initially oral dosing was undertaken in neonatal mice administered a maximum tolerable dose of racemic albuterol. An in vivo infusion rat model was employed for the investigation of albuterol uptake into skeletal and cardiac muscle over 4 h. Tissue concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). From the oral dosing model, mean (±SD) levels of racemic albuterol after 5 days were 915 (±293) ng/mL in plasma, 2574 (±196) ng/g in muscle, and 53 (±6.6) ng/g in brain with enantioselective partitioning (muscle:plasma ratio of 5.7 and 1.7 for R- and S-albuterol, respectively). In the infusion model, enantioselective disposition was observed in skeletal muscle (muscle:plasma ratio of 1.2-1.7 and 0.6-0.7 for R- and S-albuterol, respectively) and in cardiac muscle (4.1 and 0.5, respectively). In conclusion, there is greater partitioning of active (R)-albuterol than inactive (S)-albuterol into both skeletal and cardiac muscle compared to plasma. These findings have relevance for albuterol sports doping, cardiac effects, and therapeutic use in muscle wasting diseases. Furthermore, the greater muscle partitioning of the active R-albuterol, and the availability of pure R-albuterol formulations highlight shortcomings in doping control measures using non-enantioselective assays.

  12. Breast muscle tissue characteristics in growing broilers

    Science.gov (United States)

    Muscle cell development in broilers influences growth rate, breast meat yield, and meat quality. The objective of this study was to characterize muscle tissue changes in breast muscles from two commercial lines of broilers from 21 to 56 days of age. The experiment was designed as a 2×2×6 factorial...

  13. Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways

    Science.gov (United States)

    Leucine activates mammalian target of rapamycin (mTOR) to upregulate protein synthesis (PS). To examine enteral Leu effects on PS and signaling activation, 5-d-old piglets were fed for 24 h diets containing: (i) LP, (ii) LP+L, or (iii) HP. PS in skeletal muscles, heart, liver, pancreas, and jejunum...

  14. Mechanostimulation Protocols for Cardiac Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Marco Govoni

    2013-01-01

    Full Text Available Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

  15. Engineering skeletal muscle tissue in bioreactor systems

    Institute of Scientific and Technical Information of China (English)

    An Yang; Li Dong

    2014-01-01

    Objective To give a concise review of the current state of the art in tissue engineering (TE) related to skeletal muscle and kinds of bioreactor environment.Data sources The review was based on data obtained from the published articles and guidelines.Study selection A total of 106 articles were selected from several hundred original articles or reviews.The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of engineered muscle tissue in bioreactor.Results Skeletal muscle TE is a promising interdisciplinary field which aims at the reconstruction of skeletal muscle loss.Although numerous studies have indicated that engineering skeletal muscle tissue may be of great importance in medicine in the near future,this technique still represents a limited degree of success.Since tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen,carbon dioxide,nutrients and waste products.Moreover,functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural calls.Third,in order to engineer muscle tissue successfully,it may be beneficial to mimic the in vivo environment of muscle through association with adequate stimuli from bioreactors.Conclusion Vascular system and bioreactors are necessary for development and maintenance of engineered muscle in order to provide circulation within the construct.

  16. Optimization of electrical stimulation parameters for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

    2011-06-01

    In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering.

  17. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    Science.gov (United States)

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

  18. Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

    Energy Technology Data Exchange (ETDEWEB)

    Josephson, Matthew P.; Sikkink, Laura A. [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Penheiter, Alan R. [Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905 (United States); Burghardt, Thomas P., E-mail: burghardt@mayo.edu [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 (United States); Ajtai, Katalin [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. Black-Right-Pointing-Pointer Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. Black-Right-Pointing-Pointer It is a widely believed that MYL2 is a poor substrate for smMLCK. Black-Right-Pointing-Pointer In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. Black-Right-Pointing-Pointer Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca{sup 2+} sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis-Menten V{sub max} and K{sub M} for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant

  19. Zika Attacks Nerves, Muscles, Other Tissues

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164010.html Zika Attacks Nerves, Muscles, Other Tissues Monkey study may ... 2017 (HealthDay News) -- Scientists have learned where the Zika virus attacks the body in monkeys. In their ...

  20. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    OpenAIRE

    André Luiz Lisboa Cordeiro; Thiago Araújo de Melo; Daniela Neves; Julianne Luna; Mateus Souza Esquivel; André Raimundo França Guimarães; Daniel Lago Borges; Jefferson Petto

    2016-01-01

    Abstract Introduction: Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective: To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods: This is a clinical randomized controlled tri...

  1. Enabling microscale and nanoscale approaches for bioengineered cardiac tissue.

    Science.gov (United States)

    Chan, Vincent; Raman, Ritu; Cvetkovic, Caroline; Bashir, Rashid

    2013-03-26

    In this issue of ACS Nano, Shin et al. present their finding that the addition of carbon nanotubes (CNT) in gelatin methacrylate (GelMA) results in improved functionality of bioengineered cardiac tissue. These CNT-GelMA hybrid materials demonstrate cardiac tissue with enhanced electrophysiological performance; improved mechanical integrity; better cell adhesion, viability, uniformity, and organization; increased beating rate and lowered excitation threshold; and protective effects against cardio-inhibitory and cardio-toxic drugs. In this Perspective, we outline recent progress in cardiac tissue engineering and prospects for future development. Bioengineered cardiac tissues can be used to build "heart-on-a-chip" devices for drug safety and efficacy testing, fabricate bioactuators for biointegrated robotics and reverse-engineered life forms, treat abnormal cardiac rhythms, and perhaps one day cure heart disease with tissue and organ transplants.

  2. Detection of Trabeculae and Papillary Muscles in Cardiac MR Images

    NARCIS (Netherlands)

    Spreeuwers, L.J.; Bangma, S.J.; Meerwaldt, R.J.H.W.; Vonken, E.J.; Breeuwer, M.

    2005-01-01

    With the improvement of the quality of MR imagery, more and more details become visible. Only 5-10 years ago cardiac images of the heart were still so unsharp that finer details of the heart like the papillary muscles and the trabeculae were hardly visible and it was simply impossible to determine t

  3. Strategies to Study Desmin in Cardiac Muscle and Culture Systems.

    Science.gov (United States)

    Diokmetzidou, Antigoni; Tsikitis, Mary; Nikouli, Sofia; Kloukina, Ismini; Tsoupri, Elsa; Papathanasiou, Stamatis; Psarras, Stelios; Mavroidis, Manolis; Capetanaki, Yassemi

    2016-01-01

    Intermediate filament (IF) cytoskeleton comprises the fine-tuning cellular machinery regulating critical homeostatic mechanisms. In skeletal and cardiac muscle, deficiency or disturbance of the IF network leads to severe pathology, particularly in the latter. The three-dimensional scaffold of the muscle-specific IF protein desmin interconnects key features of the cardiac muscle cells, including the Z-disks, intercalated disks, plasma membrane, nucleus, mitochondria, lysosomes, and potentially sarcoplasmic reticulum. This is crucial for the highly organized striated muscle, in which effective energy production and transmission as well as mechanochemical signaling are tightly coordinated among the organelles and the contractile apparatus. The role of desmin and desmin-associated proteins in the biogenesis, trafficking, and organelle function, as well as the development, differentiation, and survival of the cardiac muscle begins to be enlightened, but the precise mechanisms remain elusive. We propose a set of experimental tools that can be used, in vivo and in vitro, to unravel crucial new pathways by which the IF cytoskeleton facilitates proper organelle function, homeostasis, and cytoprotection and further understand how its disturbance and deficiency lead to disease.

  4. Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats

    Directory of Open Access Journals (Sweden)

    Guidot David M

    2008-04-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 infection and the consequent acquired immunodeficiency syndrome (AIDS has protean manifestations, including muscle wasting and cardiomyopathy, which contribute to its high morbidity. The pathogenesis of these myopathies remains partially understood, and may include nutritional deficiencies, biochemical abnormalities, inflammation, and other mechanisms due to viral infection and replication. Growing evidence has suggested that HIV-1-related proteins expressed by the host in response to viral infection, including Tat and gp120, may also be involved in the pathophysiology of AIDS, particularly in cells or tissues that are not directly infected with HIV-1. To explore the potentially independent effects of HIV-1-related proteins on heart and skeletal muscles, we used a transgenic rat model that expresses several HIV-1-related proteins (e.g., Tat, gp120, and Nef. Outcome measures included basic heart and skeletal muscle morphology, glutathione metabolism and oxidative stress, and gene expressions of atrogin-1, muscle ring finger protein-1 (MuRF-1 and Transforming Growth Factor-β1 (TGFβ1, three factors associated with muscle catabolism. Results Consistent with HIV-1 associated myopathies in humans, HIV-1 transgenic rats had increased relative heart masses, decreased relative masses of soleus, plantaris and gastrocnemius muscles, and decreased total and myosin heavy chain type-specific plantaris muscle fiber areas. In both tissues, the levels of cystine (Cyss, the oxidized form of the anti-oxidant cysteine (Cys, and Cyss:Cys ratios were significantly elevated, and cardiac tissue from HIV-1 transgenic rats had altered glutathione metabolism, all reflective of significant oxidative stress. In HIV-1 transgenic rat hearts, MuRF-1 gene expression was increased. Further, HIV-1-related protein expression also increased atrogin-1 (~14- and ~3-fold and TGFβ1 (~5-fold and ~3-fold in heart and

  5. Cardiac cachexia and muscle wasting: definition, physiopathology, and clinical consequences

    Directory of Open Access Journals (Sweden)

    Okoshi MP

    2014-11-01

    Full Text Available Marina P Okoshi,1 Fernando G Romeiro,1 Paula F Martinez,1,2 Silvio A Oliveira Jr,1,2 Bertha F Polegato,1 Katashi Okoshi11Internal Medicine Department, Botucatu Medical School, Sao Paulo State University, UNESP, Sao Paulo, Brazil; 2School of Physiotherapy, Federal University of Mato Grosso do Sul, Campo Grande, BrazilAbstract: Cachexia and muscle wasting are frequently observed in heart failure patients. Cachexia is a predictor of reduced survival, independent of important parameters such as age, heart failure functional class, and functional capacity. Muscle and fat wasting can also predict adverse outcome during cardiac failure. Only more recently were these conditions defined in International Consensus. Considering that heart failure is an inflammatory disease, cardiac cachexia has been diagnosed by finding a body weight loss >5%, in the absence of other diseases and independent of other criteria. Muscle wasting has been defined as lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean for healthy individuals between 20 years and 30 years old from the same ethnic group. The etiology of heart failure-associated cachexia and muscle wasting is multifactorial, and the underlying physiopathological mechanisms are not completely understood. The most important factors are reduced food intake, gastrointestinal alterations, immunological activation, neurohormonal abnormalities, and an imbalance between anabolic and catabolic processes. Cachexia and muscle wasting have clinical consequences in several organs and systems including the gastrointestinal and erythropoietic systems, and the heart, previously affected by the primary disease. We hope that a better understanding of the mechanisms involved in their physiopathology will allow the development of pharmacological and nonpharmacological therapies to effectively prevent and treat heart failure-induced cachexia and muscle wasting before significant body

  6. [Epicardial adipose tissue and its role in cardiac physiology and disease].

    Science.gov (United States)

    Toczyłowski, Kacper; Gruca, Michał; Baranowski, Marcin

    2013-06-20

    Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  7. The Role of Vitamin D in Skeletal and Cardiac Muscle Function

    Directory of Open Access Journals (Sweden)

    Patsie ePolly

    2014-04-01

    Full Text Available Myopathy is a feature of many inflammatory syndromes. Chronic inflammation has been linked to pathophysiological mechanisms which implicate 1,25 dihydroxyvitamin D3 (1,25-(OH2D3-mediated signaling pathways with emerging evidence supporting a role for the vitamin D receptor (VDR in contractile and metabolic function of both skeletal and cardiac muscle. Altered VDR expression in skeletal and cardiac muscle has been reported to result in significant effects on metabolism, calcium signaling and fibrosis in these tissues. Elevated levels of serum inflammatory cytokines, such as IL-6, TNF- and IFN, have been shown to impact myogenic and nuclear receptor signaling pathways in cancer-induced cachexia. The dysregulation of nuclear receptors, such as VDR and RXR in muscle cells, has also been postulated to result in myopathy via their effects on muscle structural integrity and metabolism. Future research directions include generating transcriptome-wide information incorporating VDR and its gene targets and using systems biology approaches to identify altered molecular networks in human tissues such as muscle. These approaches will aid in the development of novel therapeutic targeting strategies for inflammation-induced myopathies.

  8. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  9. Bioactive polymers for cardiac tissue engineering

    Science.gov (United States)

    Wall, Samuel Thomas

    2007-05-01

    Prevalent in the US and worldwide, acute myocardial infarctions (AMI) can cause ischemic injuries to the heart that persist and lead to progressive degradation of the organ. Tissue engineering techniques exploiting biomaterials present a hopeful means of treating these injuries, either by mechanically stabilizing the injured ventricle, or by fostering cell growth to replace myocytes lost to damage. This thesis describes the development and testing of a synthetic extracellular matrix for cardiac tissue engineering applications. The first stage of this process was using an advanced finite element model of an injured ovine left ventricle to evaluate the potential benefits of injecting synthetic materials into the heart. These simulations indicated that addition of small amounts non-contractile material (on the order of 1--5% total wall volume) to infarct border zone regions reduced pathological systolic fiber stress to levels near those found in normal remote regions. Simulations also determined that direct addition to the infarct itself caused increases in ventricle ejection fraction while the underlying performance of the pump, ascertained by the Starling relation, was not improved. From these theoretical results, biomaterials were developed specifically for injection into the injured myocardium, and were characterized and tested for their mechanical properties and ability to sustain the proliferation of a stem cell population suitable for transplantation. Thermoresponsive synthetic copolymer hydrogels consisting of N-isopropylacrylamide and acrylic acid, p(NIPAAm-co-AAc), crosslinked with protease degradable amino acid sequences and modified with integrin binding ligands were synthesized, characterized in vitro, and used for myocardial implantation. These injectable materials could maintain a population of bone marrow derived mesenchymal stem cells in both two dimensional and three dimensional culture, and when tested in vivo in a murine infarct model they

  10. Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression.

    Directory of Open Access Journals (Sweden)

    Kelly C Clause

    Full Text Available Skeletal muscle derived stem cells (MDSCs transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC and cardiac specific troponin-I (cTn-I positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13 and 20 (ED20, neonatal day 0 (ND0 and 4 (ND4, postnatal day 10 (PND10, and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle.

  11. Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip.

    Science.gov (United States)

    Grosberg, Anna; Alford, Patrick W; McCain, Megan L; Parker, Kevin Kit

    2011-12-21

    Traditionally, muscle physiology experiments require multiple tissue samples to obtain morphometric, electrophysiological, and contractility data. Furthermore, these experiments are commonly completed one at a time on cover slips of single cells, isotropic monolayers, or in isolated muscle strips. In all of these cases, variability of the samples hinders quantitative comparisons among experimental groups. Here, we report the design of a "heart on a chip" that exploits muscular thin film technology--biohybrid constructs of an engineered, anisotropic ventricular myocardium on an elastomeric thin film--to measure contractility, combined with a quantification of action potential propagation, and cytoskeletal architecture in multiple tissues in the same experiment. We report techniques for real-time data collection and analysis during pharmacological intervention. The chip is an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle.

  12. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    Science.gov (United States)

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  13. From syncitium to regulated pump: a cardiac muscle cellular update.

    Science.gov (United States)

    Korzick, Donna H

    2011-03-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca(2+) microdomains and local control theory, with particular emphasis on the role of Ca(2+) sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca(2+) cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca(2+) from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca(2+) homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca(2+)-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle.

  14. Cardiac pathological changes of Atlantic salmon (Salmo salar L.) affected with heart and skeletal muscle inflammation (HSMI)

    DEFF Research Database (Denmark)

    Yousaf, Muhammad Naveed; Koppang, Erling Olaf; Skjødt, Karsten

    2012-01-01

    Heart and skeletal muscle inflammation (HSMI) is a disease of marine farmed Atlantic salmon where the pathological changes associated with the disease involve necrosis and an infiltration of inflammatory cells into different regions of the heart and skeletal muscle. The aim of this work...... was to characterize cardiac changes and inflammatory cell types associated with a clinical HSMI outbreak in Atlantic salmon using immunohistochemistry. Different immune cells and cardiac tissue responses associated with the disease were identified using different markers. The spectrum of inflammatory cells associated...

  15. Short-range mechanical properties of skeletal and cardiac muscles.

    Science.gov (United States)

    Campbell, Kenneth S

    2010-01-01

    Striated muscles are disproportionately stiff for small movements. This facet of their behavior can be demonstrated by measuring the force produced when the muscle is stretched more than about 1% of its initial length. When this is done, it can be seen that force rises rapidly during the initial phases of the movement and much less rapidly during the latter stages of the stretch. Experiments performed using chemically permeabilized skeletal and cardiac muscles show that the initial stiffness of the preparations increases in proportion with isometric force as the free Ca²(+) concentration in the bathing solution is raised from a minimal to a saturating value. This is strong evidence that the short-range mechanical properties of activated muscle result from stretching myosin cross-bridges that are attached between the thick and thin filaments. Relaxed intact muscles also exhibit short-range mechanical properties but the molecular mechanisms underlying this behavior are less clear. This chapter summarizes some of the interesting features of short-range mechanical properties in different types of muscle preparation, describes some of the likely underlying mechanisms and discusses the potential physiological significance of the behavior.

  16. Characterization of electrical stimulation electrodes for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, Nina; Cannizzaro, Chris; Figallo, Elisa; Voldman, Joel; Vunjak-Novakovic, Gordana

    2006-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. The goal of this study was to assess the conditions of electrical stimulation with respect to the electrode geometry, material properties and charge-transfer characteristics at the electrode-electrolyte interface. We compared various biocompatible materials, including nanoporous carbon, stainless steel, titanium and titanium nitride, for use in cardiac tissue engineering bioreactors. The faradaic and non-faradaic charge transfer mechanisms were assessed by electrochemical impedance spectroscopy (EIS), studying current injection characteristics, and examining surface properties of electrodes with scanning electron microscopy. Carbon electrodes were found to have the best current injection characteristics. However, these electrodes require careful handling because of their limited mechanical strength. The efficacy of various electrodes for use in 2-D and 3-D cardiac tissue engineering systems with neonatal rat cardiomyocytes is being determined by assessing cell viability, amplitude of contractions, excitation thresholds, maximum capture rate, and tissue morphology.

  17. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    Science.gov (United States)

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  18. Hydrogel based injectable scaffolds for cardiac tissue regeneration.

    Science.gov (United States)

    Radhakrishnan, Janani; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2014-01-01

    Tissue engineering promises to be an effective strategy that can overcome the lacuna existing in the current pharmacological and interventional therapies and heart transplantation. Heart failure continues to be a major contributor to the morbidity and mortality across the globe. This may be attributed to the limited regeneration capacity after the adult cardiomyocytes are terminally differentiated or injured. Various strategies involving acellular scaffolds, stem cells, and combinations of stem cells, scaffolds and growth factors have been investigated for effective cardiac tissue regeneration. Recently, injectable hydrogels have emerged as a potential candidate among various categories of biomaterials for cardiac tissue regeneration due to improved patient compliance and facile administration via minimal invasive mode that treats complex infarction. This review discusses in detail on the advances made in the field of injectable materials for cardiac tissue engineering highlighting their merits over their preformed counterparts.

  19. Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

    Science.gov (United States)

    Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

    2012-11-13

    The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

  20. Cardiac elastography: detecting pathological changes in myocardium tissues

    Science.gov (United States)

    Konofagou, Elisa E.; Harrigan, Timothy; Solomon, Scott

    2003-05-01

    Estimation of the mechanical properties of the cardiac muscle has been shown to play a crucial role in the detection of cardiovascular disease. Elastography was recently shown feasible on RF cardiac data in vivo. In this paper, the role of elastography in the detection of ischemia/infarct is explored with simulations and in vivo experiments. In finite-element simulations of a portion of the cardiac muscle containing an infarcted region, the cardiac cycle was simulated with successive compressive and tensile strains ranging between -30% and 20%. The incremental elastic modulus was also mapped uisng adaptive methods. We then demonstrated this technique utilizing envelope-detected sonographic data (Hewlett-Packard Sonos 5500) in a patient with a known myocardial infarction. In cine-loop and M-Mode elastograms from both normal and infarcted regions in simulations and experiments, the infarcted region was identifed by the up to one order of magnitude lower incremental axial displacements and strains, and higher modulus. Information on motion, deformation and mechanical property should constitute a unique tool for noninvasive cardiac diagnosis.

  1. Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle.

    Science.gov (United States)

    Morash, Andrea J; Kotwica, Aleksandra O; Murray, Andrew J

    2013-09-01

    Exposure to hypobaric hypoxia is sufficient to decrease cardiac PCr/ATP and alters skeletal muscle energetics in humans. Cellular mechanisms underlying the different metabolic responses of these tissues and the time-dependent nature of these changes are currently unknown, but altered substrate utilization and mitochondrial function may be a contributory factor. We therefore sought to investigate the effects of acute (1 day) and more sustained (7 days) hypoxia (13% O₂) on the transcription factor peroxisome proliferator-activated receptor α (PPARα) and its targets in mouse cardiac and skeletal muscle. In the heart, PPARα expression was 40% higher than in normoxia after 1 and 7 days of hypoxia. Activities of carnitine palmitoyltransferase (CPT) I and β-hydroxyacyl-CoA dehydrogenase (HOAD) were 75% and 35% lower, respectively, after 1 day of hypoxia, returning to normoxic levels after 7 days. Oxidative phosphorylation respiration rates using palmitoyl-carnitine followed a similar pattern, while respiration using pyruvate decreased. In skeletal muscle, PPARα expression and CPT I activity were 20% and 65% lower, respectively, after 1 day of hypoxia, remaining at this level after 7 days with no change in HOAD activity. Oxidative phosphorylation respiration rates using palmitoyl-carnitine were lower in skeletal muscle throughout hypoxia, while respiration using pyruvate remained unchanged. The rate of CO₂ production from palmitate oxidation was significantly lower in both tissues throughout hypoxia. Thus cardiac muscle may remain reliant on fatty acids during sustained hypoxia, while skeletal muscle decreases fatty acid oxidation and maintains pyruvate oxidation.

  2. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men.

    Science.gov (United States)

    Asmar, Ali; Asmar, Meena; Simonsen, Lene; Madsbad, Sten; Holst, Jens J; Hartmann, Bolette; Sorensen, Charlotte M; Bülow, Jens

    2017-02-01

    In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and/or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose tissue blood flow (ATBF) was measured by the (133)Xenon clearance technique. Leg and splanchnic blood flow were measured by Fick's Principle, using indocyanine green as indicator. In the GLP-1 study, cardiac output increased significantly together with a significant increase in arterial pulse pressure and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac output acutely due to a GLP-1-induced vasodilation in adipose tissue and skeletal muscle together with an increase in cardiac work.

  3. Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels

    Science.gov (United States)

    Tang, Wanjian; Blair, Cheavar A.; Walton, Shane D.; Málnási-Csizmadia, András; Campbell, Kenneth S.; Yengo, Christopher M.

    2017-01-01

    Inherited cardiomyopathies are a common form of heart disease that are caused by mutations in sarcomeric proteins with beta cardiac myosin (MYH7) being one of the most frequently affected genes. Since the discovery of the first cardiomyopathy associated mutation in beta-cardiac myosin, a major goal has been to correlate the in vitro myosin motor properties with the contractile performance of cardiac muscle. There has been substantial progress in developing assays to measure the force and velocity properties of purified cardiac muscle myosin but it is still challenging to correlate results from molecular and tissue-level experiments. Mutations that cause hypertrophic cardiomyopathy are more common than mutations that lead to dilated cardiomyopathy and are also often associated with increased isometric force and hyper-contractility. Therefore, the development of drugs designed to decrease isometric force by reducing the duty ratio (the proportion of time myosin spends bound to actin during its ATPase cycle) has been proposed for the treatment of hypertrophic cardiomyopathy. Para-Nitroblebbistatin is a small molecule drug proposed to decrease the duty ratio of class II myosins. We examined the impact of this drug on human beta cardiac myosin using purified myosin motor assays and studies of permeabilized muscle fiber mechanics. We find that with purified human beta-cardiac myosin para-Nitroblebbistatin slows actin-activated ATPase and in vitro motility without altering the ADP release rate constant. In permeabilized human myocardium, para-Nitroblebbistatin reduces isometric force, power, and calcium sensitivity while not changing shortening velocity or the rate of force development (ktr). Therefore, designing a drug that reduces the myosin duty ratio by inhibiting strong attachment to actin while not changing detachment can cause a reduction in force without changing shortening velocity or relaxation. PMID:28119616

  4. Design of electrical stimulation bioreactors for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, N; Marsano, A; Cannizzaro, C; Voldman, J; Vunjak-Novakovic, G

    2008-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

  5. Epicardial adipose tissue and its role in cardiac physiology and disease 

    Directory of Open Access Journals (Sweden)

    Kacper Toczyłowski

    2013-06-01

    Full Text Available Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  6. Cardiac conductive system excitation maps using intracardiac tissue Doppler imaging

    Institute of Scientific and Technical Information of China (English)

    尹立雪; 郑昌琼; 蔡力; 郑翊; 李春梅; 邓燕; 罗芸; 李德玉; 赵树魁

    2003-01-01

    Objective To precisely visualize cardiac anatomic structures and simultaneously depict ele ctro-mechanical events for the purpose of precise underblood intervention. Methods Intracardiac high-resolution tissue Doppler imaging was used to map realt imemyocardial contractions in response to electrical activation within the anat omic structure of the cardiac conductive system using a canine open-chest model . Results The detailed inner anatomic structure of the cardiac conductive system at differ entsites (i.e., sino-atrial, atrial wall, atrial-ventricular node and ventr icular wall) with the inside onset and propagation of myocardial velocity and ac celeration induced by electrical activation was clearly visualized and quan titatively evaluated.Conclusion The simultaneous single modality visualization of the anatomy, function and electrical events of the cardiac conductive system will foster target pacing and pre cision ablation.

  7. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    Directory of Open Access Journals (Sweden)

    Fabricio Furtado Vieira

    Full Text Available Abstract Background: Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX in the cardiac muscle. Objectives: To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods: We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt and relaxation (-df/dt, contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP, and contraction force induced by caffeine. Results: In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05, increased +df/dt and -df/dt (p < 0.001, low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001, reduction of the maximum force in caffeine-induced contraction (p < 0.003, and decreased total contraction time (p < 0.001. The maximal contraction force did not differ significantly between groups (p = 0.973. Conclusion: We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  8. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    Science.gov (United States)

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; da Silva, Priscyla Oliveira; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-01-01

    Background Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. Objectives To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. Results In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). Conclusion We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  9. Cardiac tissue engineering and regeneration using cell-based therapy

    Directory of Open Access Journals (Sweden)

    Alrefai MT

    2015-05-01

    Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

  10. Cardiac Time Intervals by Tissue Doppler Imaging M-Mode

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Mogelvang, Rasmus; de Knegt, Martina Chantal;

    2016-01-01

    PURPOSE: To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining...... MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function. METHODS: In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic...... the MPITDI and MPIConv measured. RESULTS: IVRT, IVRT/ET and MPI all increased significantly with increasing age in both genders (pcardiac function. MPITDI...

  11. Electroactive 3D materials for cardiac tissue engineering

    Science.gov (United States)

    Gelmi, Amy; Zhang, Jiabin; Cieslar-Pobuda, Artur; Ljunngren, Monika K.; Los, Marek Jan; Rafat, Mehrdad; Jager, Edwin W. H.

    2015-04-01

    By-pass surgery and heart transplantation are traditionally used to restore the heart's functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

  12. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  13. Force Transmission between Synergistic Skeletal Muscles through Connective Tissue Linkages

    Directory of Open Access Journals (Sweden)

    Huub Maas

    2010-01-01

    Full Text Available The classic view of skeletal muscle is that force is generated within its muscle fibers and then directly transmitted in-series, usually via tendon, onto the skeleton. In contrast, recent results suggest that muscles are mechanically connected to surrounding structures and cannot be considered as independent actuators. This article will review experiments on mechanical interactions between muscles mediated by such epimuscular myofascial force transmission in physiological and pathological muscle conditions. In a reduced preparation, involving supraphysiological muscle conditions, it is shown that connective tissues surrounding muscles are capable of transmitting substantial force. In more physiologically relevant conditions of intact muscles, however, it appears that the role of this myofascial pathway is small. In addition, it is hypothesized that connective tissues can serve as a safety net for traumatic events in muscle or tendon. Future studies are needed to investigate the importance of intermuscular force transmission during movement in health and disease.

  14. Regulation of the cardiac muscle ryanodine receptor by glutathione transferases.

    Science.gov (United States)

    Dulhunty, Angela F; Hewawasam, Ruwani; Liu, Dan; Casarotto, Marco G; Board, Philip G

    2011-05-01

    Glutathione transferases (GSTs) are generally recognized for their role in phase II detoxification reactions. However, it is becoming increasingly apparent that members of the GST family also have a diverse range of other functions that are, in general, unrelated to detoxification. One such action is a specific inhibition of the cardiac isoform of the ryanodine receptor (RyR2) intracellular Ca(2+) release channel. In this review, we compare functional and physical interactions between members of the GST family, including GSTO1-1, GSTA1-1, and GSTM2-2, with RyR2 and with the skeletal isoform of the ryanodine receptor (RyR1). The active part of the muscle-specific GSTM2-2 is localized to its nonenzymatic C-terminal α-helical bundle, centered around α-helix 6. The GSTM2-2 binding site is in divergent region 3 (DR3 region) of RyR2. The sequence differences between the DR3 regions of RyR1 and RyR2 explain the specificity of the GSTs for one isoform of the protein. GSTM2-2 is one of the few known endogenous inhibitors of the cardiac RyR and is likely to be important in maintaining low RyR2 activity during diastole. We discuss interactions between a nonenzymatic member of the GST structural family, the CLIC-2 (type 2 chloride intracellular channel) protein, which inhibits both RyR1 and RyR2. The possibility that the GST and CLIC2 proteins bind to different sites on the RyR, and that different structures within the GST and CLIC proteins bind to RyR channels, is discussed. We conclude that the C-terminal part of GSTM2-2 may provide the basis of a therapeutic compound for use in cardiac disorders.

  15. Tissue-specific effects of hypothyroidism on postnatal muscle development in the barnacle goose.

    Science.gov (United States)

    Deaton, K E; Bishop, C M; Butler, P J

    1998-03-01

    The hypothesis that tissue-specific levels of thyroid hormones may be required for normal locomotor muscle development was investigated in the barnacle goose Branta leucopsis. Hypothyroidism was induced in goslings by treatment with methimazole from either 3 days or 2 weeks of age, and birds were killed at 7 weeks of age. The masses of the pectoralis, iliofibularis, semimembranosus and cardiac ventricle muscles were measured, and samples from these tissues were analysed for the mass-specific activity of the mitochondrial enzyme citrate synthase (CS). An ultrastructural electron micrograph analysis of the pectoralis was also carried out. No significant differences were found between the two hypothyroid groups except for the effect on the relative mass of the iliofibularis muscle. Developmental responses to hypothyroidism were found to be tissue-specific. Hypothyroidism resulted in a significantly lower relative cardiac ventricle mass (by 17 %) and CS activity of the leg muscles (by 34 %), while absolute leg muscle mass was not affected. The relative mass of the pectoralis was significantly lower (by 57 %) in hypothyroid birds and showed a significant, uniformly lower CS activity (by 60-83 %) as a result of a lower mitochondrial fractional volume. Haematocrit and capillary-to-fibre ratio in the pectoralis were also significantly lower in hypothyroid birds, and skeletal growth and plumage development were affected.

  16. Transgenic overexpression of LARGE induces α-dystroglycan hyperglycosylation in skeletal and cardiac muscle.

    Directory of Open Access Journals (Sweden)

    Martin Brockington

    Full Text Available BACKGROUND: LARGE is one of seven putative or demonstrated glycosyltransferase enzymes defective in a common group of muscular dystrophies with reduced glycosylation of α-dystroglycan. Overexpression of LARGE induces hyperglycosylation of α-dystroglycan in both wild type and in cells from dystroglycanopathy patients, irrespective of their primary gene defect, restoring functional glycosylation. Viral delivery of LARGE to skeletal muscle in animal models of dystroglycanopathy has identical effects in vivo, suggesting that the restoration of functional glycosylation could have therapeutic applications in these disorders. Pharmacological strategies to upregulate Large expression are also being explored. METHODOLOGY/PRINCIPAL FINDINGS: In order to asses the safety and efficacy of long term LARGE over-expression in vivo, we have generated four mouse lines expressing a human LARGE transgene. On observation, LARGE transgenic mice were indistinguishable from the wild type littermates. Tissue analysis from young mice of all four lines showed a variable pattern of transgene expression: highest in skeletal and cardiac muscles, and lower in brain, kidney and liver. Transgene expression in striated muscles correlated with α-dystroglycan hyperglycosylation, as determined by immunoreactivity to antibody IIH6 and increased laminin binding on an overlay assay. Other components of the dystroglycan complex and extracellular matrix ligands were normally expressed, and general muscle histology was indistinguishable from wild type controls. Further detailed muscle physiological analysis demonstrated a loss of force in response to eccentric exercise in the older, but not in the younger mice, suggesting this deficit developed over time. However this remained a subclinical feature as no pathology was observed in older mice in any muscles including the diaphragm, which is sensitive to mechanical load-induced damage. CONCLUSIONS/SIGNIFICANCE: This work shows that

  17. Dynamics of wave fronts and filaments in anisotropic cardiac tissue

    CERN Document Server

    Dierckx, Hans J F M

    2015-01-01

    The heartbeat is mediated between cardiac cells by waves of electrical depolarisation. During cardiac arrhythmias, electrical activity was found to be organised in scroll waves which rotate around a dynamical filament curve. In this thesis, a curved-space approach is used to mathematically capture anisotropy of wave propagation. We derive for the first time the covariant laws of motion for traveling wave fronts and scroll wave filaments in anisotropic excitable media such as cardiac tissue. We show that locally varying anisotropy yields non-zero Riemann tensor components, which may alter the stability of scroll wave filaments. The instability of scroll wave filaments has been linked to transition from ventricular tachycardia to fibrillation.

  18. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

    DEFF Research Database (Denmark)

    Asmar, Ali; Asmar, Meena; Simonsen, Lene

    2017-01-01

    In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and....../or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose...... and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac...

  19. Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle

    OpenAIRE

    Morash, Andrea J.; Kotwica, Aleksandra O; Murray, Andrew J.

    2013-01-01

    Exposure to hypobaric hypoxia is sufficient to decrease cardiac PCr/ATP and alters skeletal muscle energetics in humans. Cellular mechanisms underlying the different metabolic responses of these tissues and the time-dependent nature of these changes are currently unknown, but altered substrate utilization and mitochondrial function may be a contributory factor. We therefore sought to investigate the effects of acute (1 day) and more sustained (7 days) hypoxia (13% O2) on the transcription fac...

  20. Electrospun biocomposite nanofibrous patch for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P; Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School of Integrative Sciences and Engineering, National University of Singapore (Singapore); Ghasemi-Mobarakeh, Laleh, E-mail: nnimpp@nus.edu.s [Islamic Azad University, Najafabad Branch, Isfahan (Iran, Islamic Republic of)

    2011-10-15

    A bioengineered construct that matches the chemical, mechanical, biological properties and extracellular matrix morphology of native tissue could be suitable as a cardiac patch for supporting the heart after myocardial infarction. The potential of utilizing a composite nanofibrous scaffold of poly(dl-lactide-co-glycolide)/gelatin (PLGA/Gel) as a biomimetic cardiac patch is studied by culturing a population of cardiomyocyte containing cells on the electrospun scaffolds. The chemical characterization and mechanical properties of the electrospun PLGA and PLGA/Gel nanofibers were studied by Fourier transform infrared spectroscopy, scanning electron microscopy and tensile measurements. The biocompatibility of the scaffolds was also studied and the cardiomyocytes seeded on PLGA/Gel nanofibers were found to express the typical functional cardiac proteins such as alpha-actinin and troponin I, showing the easy integration of cardiomyocytes on PLGA/Gel scaffolds. Our studies strengthen the application of electrospun PLGA/Gel nanofibers as a bio-mechanical support for injured myocardium and as a potential substrate for induction of endogenous cardiomyocyte proliferation, ultimately reducing the cardiac dysfunction and improving cardiac remodeling.

  1. Fabrication and characterization of bio-engineered cardiac pseudo tissues

    Energy Technology Data Exchange (ETDEWEB)

    Xu Tao; Boland, Thomas [Department of Bioengineering, 420 Rhodes Hall, Clemson University, Clemson, SC 29634 (United States); Baicu, Catalin; Aho, Michael; Zile, Michael, E-mail: tboland@clemson.ed [Department of Medicine, Medical University of South Carolina, Charleston, SC 29425 (United States)

    2009-09-15

    We report on fabricating functional three-dimensional (3D) tissue constructs using an inkjet based bio-prototyping method. With the use of modified inkjet printers, contractile cardiac hybrids that exhibit the forms of the 3D rectangular sheet and even the 'half heart' (with two connected ventricles) have been fabricated by arranging alternate layers of biocompatible alginate hydrogels and mammalian cardiac cells according to pre-designed 3D patterns. In this study, primary feline adult and H1 cardiomyocytes were used as model cardiac cells. Alginate hydrogels with controlled micro-shell structures were built by spraying cross-linkers in micro-drops onto un-gelled alginic acid. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Microscopic and macroscopic contractile functions of these cardiomyocyte constructs were observed in vitro. These results suggest that the inkjet bio-prototyping method could be used for hierarchical design of functional cardiac pseudo tissues, balanced with porosity for mass transport and structural support.

  2. Nuclear morphology and deformation in engineered cardiac myocytes and tissues.

    Science.gov (United States)

    Bray, Mark-Anthony P; Adams, William J; Geisse, Nicholas A; Feinberg, Adam W; Sheehy, Sean P; Parker, Kevin K

    2010-07-01

    Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease.

  3. Optical control of excitation waves in cardiac tissue

    Science.gov (United States)

    Burton, Rebecca A. B.; Klimas, Aleksandra; Ambrosi, Christina M.; Tomek, Jakub; Corbett, Alex; Entcheva, Emilia; Bub, Gil

    2015-12-01

    In nature, macroscopic excitation waves are found in a diverse range of settings including chemical reactions, metal rust, yeast, amoeba and the heart and brain. In the case of living biological tissue, the spatiotemporal patterns formed by these excitation waves are different in healthy and diseased states. Current electrical and pharmacological methods for wave modulation lack the spatiotemporal precision needed to control these patterns. Optical methods have the potential to overcome these limitations, but to date have only been demonstrated in simple systems, such as the Belousov-Zhabotinsky chemical reaction. Here, we combine dye-free optical imaging with optogenetic actuation to achieve dynamic control of cardiac excitation waves. Illumination with patterned light is demonstrated to optically control the direction, speed and spiral chirality of such waves in cardiac tissue. This all-optical approach offers a new experimental platform for the study and control of pattern formation in complex biological excitable systems.

  4. Approximate analytical solutions for excitation and propagation in cardiac tissue

    Science.gov (United States)

    Greene, D'Artagnan; Shiferaw, Yohannes

    2015-04-01

    It is well known that a variety of cardiac arrhythmias are initiated by a focal excitation in heart tissue. At the single cell level these currents are typically induced by intracellular processes such as spontaneous calcium release (SCR). However, it is not understood how the size and morphology of these focal excitations are related to the electrophysiological properties of cardiac cells. In this paper a detailed physiologically based ionic model is analyzed by projecting the excitation dynamics to a reduced one-dimensional parameter space. Based on this analysis we show that the inward current required for an excitation to occur is largely dictated by the voltage dependence of the inward rectifier potassium current (IK 1) , and is insensitive to the detailed properties of the sodium current. We derive an analytical expression relating the size of a stimulus and the critical current required to induce a propagating action potential (AP), and argue that this relationship determines the necessary number of cells that must undergo SCR in order to induce ectopic activity in cardiac tissue. Finally, we show that, once a focal excitation begins to propagate, its propagation characteristics, such as the conduction velocity and the critical radius for propagation, are largely determined by the sodium and gap junction currents with a substantially lesser effect due to repolarizing potassium currents. These results reveal the relationship between ion channel properties and important tissue scale processes such as excitation and propagation.

  5. The Strength-Interval Curve in Cardiac Tissue

    Directory of Open Access Journals (Sweden)

    Sunil M. Kandel

    2013-01-01

    Full Text Available The bidomain model describes the electrical properties of cardiac tissue and is often used to simulate the response of the heart to an electric shock. The strength-interval curve summarizes how refractory tissue is excited. This paper analyzes calculations of the strength-interval curve when a stimulus is applied through a unipolar electrode. In particular, the bidomain model is used to clarify why the cathodal and anodal strength-interval curves are different, and what the mechanism of the “dip” in the anodal strength-interval curve is.

  6. Cardiac tissue ablation with catheter-based microwave heating.

    Science.gov (United States)

    Rappaport, C

    2004-11-01

    The common condition of atrial fibrillation is often treated by cutting diseased cardiac tissue to disrupt abnormal electrical conduction pathways. Heating abnormal tissue with electromagnetic power provides a minimally invasive surgical alternative to treat these cardiac arrhythmias. Radio frequency ablation has become the method of choice of many physicians. Recently, microwave power has also been shown to have great therapeutic benefit in medical treatment requiring precise heating of biological tissue. Since microwave power tends to be deposited throughout the volume of biological media, microwave heating offers advantages over other heating modalities that tend to heat primarily the contacting surface. It is also possible to heat a deeper volume of tissue with more precise control using microwaves than with purely thermal conduction or RF electrode heating. Microwave Cardiac Ablation (MCA) is used to treat heart tissue that allows abnormal electrical conduction by heating it to the point of inactivation. Microwave antennas that fit within catheter systems can be positioned close to diseased tissue. Specialized antenna designs that unfurl from the catheter within the heart can then radiate specifically shaped fields, which overcome problems such as excessive surface heating at the contact point. The state of the art in MCA is reviewed in this paper and a novel catheter-based unfurling wide aperture antenna is described. This antenna consists of the centre conductor of a coaxial line, shaped into a spiral and insulated from blood and tissue by a non-conductive fluid filled balloon. Initially stretched straight inside a catheter for transluminal guiding, once in place at the cardiac target, the coiled spiral antenna is advanced into the inflated balloon. Power is applied in the range of 50-150 W at the reserved industrial, scientific and medical (ISM) frequency of 915 MHz for 30-90 s to create an irreversible lesion. The antenna is then retracted back into the

  7. Practical aspects of cardiac tissue engineering with electrical stimulation.

    Science.gov (United States)

    Cannizzaro, Christopher; Tandon, Nina; Figallo, Elisa; Park, Hyoungshin; Gerecht, Sharon; Radisic, Milica; Elvassore, Nicola; Vunjak-Novakovic, Gordana

    2007-01-01

    Heart disease is a leading cause of death in western society. Despite the success of heart transplantation, a chronic shortage of donor organs, along with the associated immunological complications of this approach, demands that alternative treatments be found. One such option is to repair, rather than replace, the heart with engineered cardiac tissue. Multiple studies have shown that to attain functional tissue, assembly signaling cues must be recapitulated in vitro. In their native environment, cardiomyocytes are directed to beat in synchrony by propagation of pacing current through the tissue. Recently, we have shown that electrical stimulation directs neonatal cardiomyocytes to assemble into native-like tissue in vitro. This chapter provides detailed methods we have employed in taking this "biomimetic" approach. After an initial discussion on how electric field stimulation can influence cell behavior, we examine the practical aspects of cardiac tissue engineering with electrical stimulation, such as electrode selection and cell seeding protocols, and conclude with what we feel are the remaining challenges to be overcome.

  8. Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Boushel, R; Langberg, Henning; Green, Stefan Mathias;

    2000-01-01

    1. Circulation around tendons may act as a shunt for muscle during exercise. The perfusion and oxygenation of Achilles' peritendinous tissue was measured in parallel with that of calf muscle during exercise to determine (1) whether blood flow is restricted in peritendinous tissue during exercise......, and (2) whether blood flow is coupled to oxidative metabolism. 2. Seven individuals performed dynamic plantar flexion from 1 to 9 W. Radial artery and popliteal venous blood were sampled for O2, peritendinous blood flow was determined by 133Xe-washout, calf blood flow by plethysmography, cardiac output...... by dye dilution, arterial pressure by an arterial catheter-transducer, and muscle and peritendinous O2 saturation by spatially resolved spectroscopy (SRS). 3. Calf blood flow rose 20-fold with exercise, reaching 44 +/- 7 ml (100 g)-1 min-1 (mean +/- s.e.m. ) at 9 W, while Achilles' peritendinous flow...

  9. Rate-dependent activation failure in isolated cardiac cells and tissue due to Na+ channel block.

    Science.gov (United States)

    Varghese, Anthony; Spindler, Anthony J; Paterson, David; Noble, Denis

    2015-11-15

    While it is well established that class-I antiarrhythmics block cardiac sodium channels, the mechanism of action of therapeutic levels of these drugs is not well understood. Using a combination of mathematical modeling and in vitro experiments, we studied the failure of activation of action potentials in single ventricular cells and in tissue caused by Na(+) channel block. Our computations of block and unblock of sodium channels by a theoretical class-Ib antiarrhythmic agent predict differences in the concentrations required to cause activation failure in single cells as opposed to multicellular preparations. We tested and confirmed these in silico predictions with in vitro experiments on isolated guinea-pig ventricular cells and papillary muscles stimulated at various rates (2-6.67 Hz) and exposed to various concentrations (5 × 10(-6) to 500 × 10(-6) mol/l) of lidocaine. The most salient result was that whereas large doses (5 × 10(-4) mol/l or higher) of lidocaine were required to inhibit action potentials temporarily in single cells, much lower doses (5 × 10(-6) mol/l), i.e., therapeutic levels, were sufficient to have the same effect in papillary muscles: a hundredfold difference. Our experimental results and mathematical analysis indicate that the syncytial nature of cardiac tissue explains the effects of clinically relevant doses of Na(+) channel blockers.

  10. Endothermic force generation in skinned cardiac muscle from rat.

    Science.gov (United States)

    Ranatunga, K W

    1999-08-01

    Isometric tension responses to rapid temperature jumps (T-jumps) of 2-6 degrees C were examined in skinned muscle fibre bundles isolated from papillary muscles of the rat heart. T-jumps were induced by an infra-red laser pulse (wave length 1.32 microm, pulse duration 0.2 ms) obtained from a Nd-YAG laser, which heated the fibres and bathing buffer solution in a 50 microl trough; the increased temperature by laser pulse was clamped at the high temperature by a Peltier system (see Ranatunga, 1996). In maximally Ca2+ -activated (pCa ca. 4.5) fibres, the relationship between tension and temperature was non-linear, the increase of active tension with temperature being more pronounced at lower temperatures (below ca. 20 degrees C). A T-jump at any temperature (range 3-35 degrees C) induced an initial step decrease of tension of variable amplitude (Phase 1), probably due to thermal expansion, and it was followed by a tension transient which resulted in a net rise of tension above the pre-T-jump level. The rate of net rise of tension (Phase 2b or endothermic force generation) was 7-10/s at ca. 12 degrees C and its Q10 was 6.3 (below 25 degrees C). In cases where the step decrease of tension in Phase 1 was prominent, an initial quick tension recovery phase (Phase 2a, 70-100/s at 12 degrees C) that did not contribute to a rise of tension above the pre-T-jump level, was also seen. This phase (Phase 2a) appeared to be similar to the quick tension recovery induced by a small length release and its rate increased with temperature with a Q10 of 1.8. In some cases where Phase 2a was present, a slower tension rise (Phase 3) was seen; its rate (ca. 5/s) was temperature-insensitive. The results show that the rate of endothermic force generation in cardiac fibres is clearly different from that of either fast-twitch or slow-twitch mammalian skeletal muscle fibres; implication of such fibre type-specific differences is discussed in relation to the difficulty in identifying the

  11. Endurance training prevents negative effects of the hypoxia mimetic dimethyloxalylglycine on cardiac and skeletal muscle function.

    Science.gov (United States)

    Favier, Francois B; Britto, Florian A; Ponçon, Benjamin; Begue, Gwenaelle; Chabi, Beatrice; Reboul, Cyril; Meyer, Gregory; Py, Guillaume

    2016-02-15

    Hypoxic preconditioning is a promising strategy to prevent hypoxia-induced damages to several tissues. This effect is related to prior stabilization of the hypoxia-inducible factor-1α via inhibition of the prolyl-hydroxylases (PHDs), which are responsible for its degradation under normoxia. Although PHD inhibition has been shown to increase endurance performance in rodents, potential side effects of such a therapy have not been explored. Here, we investigated the effects of 1 wk of dimethyloxalylglycine (DMOG) treatment (150 mg/kg) on exercise capacity, as well as on cardiac and skeletal muscle function in sedentary and endurance-trained rats. DMOG improved maximal aerobic velocity and endurance in both sedentary and trained rats. This effect was associated with an increase in red blood cells without significant alteration of skeletal muscle contractile properties. In sedentary rats, DMOG treatment resulted in enhanced left ventricle (LV) weight together with impairment in diastolic function, LV relaxation, and pulse pressure. Moreover, DMOG decreased maximal oxygen uptake (state 3) of isolated mitochondria from skeletal muscle. Importantly, endurance training reversed the negative effects of DMOG treatment on cardiac function and restored maximal mitochondrial oxygen uptake to the level of sedentary placebo-treated rats. In conclusion, we provide here evidence that the PHD inhibitor DMOG has detrimental influence on myocardial and mitochondrial function in healthy rats. However, one may suppose that the deleterious influence of PHD inhibition would be potentiated in patients with already poor physical condition. Therefore, the present results prompt us to take into consideration the potential side effects of PHD inhibitors when administrated to patients.

  12. Biologically improved nanofibrous scaffolds for cardiac tissue engineering.

    Science.gov (United States)

    Bhaarathy, V; Venugopal, J; Gandhimathi, C; Ponpandian, N; Mangalaraj, D; Ramakrishna, S

    2014-11-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(l-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering.

  13. Biologically improved nanofibrous scaffolds for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Bhaarathy, V. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Lee Kong Chian School of Medicine, Nanyang Technological University, 138673 (Singapore); Venugopal, J., E-mail: nnijrv@nus.edu.sg [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Gandhimathi, C. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Ponpandian, N.; Mangalaraj, D. [Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Ramakrishna, S. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore)

    2014-11-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

  14. Cardiac adipose tissue and atrial fibrillation: the perils of adiposity.

    Science.gov (United States)

    Hatem, Stéphane N; Redheuil, Alban; Gandjbakhch, Estelle

    2016-04-01

    The amount of adipose tissue that accumulates around the atria is associated with the risk, persistence, and severity of atrial fibrillation (AF). A strong body of clinical and experimental evidence indicates that this relationship is not an epiphenomenon but is the result of complex crosstalk between the adipose tissue and the neighbouring atrial myocardium. For instance, epicardial adipose tissue is a major source of adipokines, inflammatory cytokines, or reactive oxidative species, which can contribute to the fibrotic remodelling of the atrial myocardium. Fibro-fatty infiltrations of the subepicardium could also contribute to the functional disorganization of the atrial myocardium. The observation that obesity is associated with distinct structural and functional remodelling of the atria has opened new perspectives of treating AF substrate with aggressive risk factor management. Advances in cardiac imaging should lead to an improved ability to visualize myocardial fat depositions and to localize AF substrates.

  15. Analysis of cardiac tissue by gold cluster ion bombardment

    Science.gov (United States)

    Aranyosiova, M.; Chorvatova, A.; Chorvat, D.; Biro, Cs.; Velic, D.

    2006-07-01

    Specific molecules in cardiac tissue of spontaneously hypertensive rats are studied by using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The investigation determines phospholipids, cholesterol, fatty acids and their fragments in the cardiac tissue, with special focus on cardiolipin. Cardiolipin is a unique phospholipid typical for cardiomyocyte mitochondrial membrane and its decrease is involved in pathologic conditions. In the positive polarity, the fragments of phosphatydilcholine are observed in the mass region of 700-850 u. Peaks over mass 1400 u correspond to intact and cationized molecules of cardiolipin. In animal tissue, cardiolipin contains of almost exclusively 18 carbon fatty acids, mostly linoleic acid. Linoleic acid at 279 u, other fatty acids, and phosphatidylglycerol fragments, as precursors of cardiolipin synthesis, are identified in the negative polarity. These data demonstrate that SIMS technique along with Au 3+ cluster primary ion beam is a good tool for detection of higher mass biomolecules providing approximately 10 times higher yield in comparison with Au +.

  16. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    André Luiz Lisboa Cordeiro

    Full Text Available Abstract Introduction: Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective: To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods: This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results: 50 patients, 27 (54% males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073 and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031. Conclusion: We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery.

  17. Scaling functional patterns of skeletal and cardiac muscles: New non-linear elasticity approach

    CERN Document Server

    Kokshenev, Valery B

    2009-01-01

    Responding mechanically to environmental requests, muscles show a surprisingly large variety of functions. The studies of in vivo cycling muscles qualified skeletal muscles into four principal locomotor patterns: motor, brake, strut, and spring. While much effort of has been done in searching for muscle design patterns, no fundamental concepts underlying empirically established patterns were revealed. In this interdisciplinary study, continuum mechanics is applied to the problem of muscle structure in relation to function. The ability of a powering muscle, treated as a homogenous solid organ, tuned to efficient locomotion via the natural frequency is illuminated through the non-linear elastic muscle moduli controlled by contraction velocity. The exploration of the elastic force patterns known in solid state physics incorporated in activated skeletal and cardiac muscles via the mechanical similarity principle yields analytical rationalization for locomotor muscle patterns. Besides the explanation of the origin...

  18. Three-dimensional cardiac tissue fabrication based on cell sheet technology.

    Science.gov (United States)

    Masuda, Shinako; Shimizu, Tatsuya

    2016-01-15

    Cardiac tissue engineering is a promising therapeutic strategy for severe heart failure. However, conventional tissue engineering methods by seeding cells into biodegradable scaffolds have intrinsic limitations such as inflammatory responses and fibrosis arising from the degradation of scaffolds. On the other hand, we have developed cell sheet engineering as a scaffold-free approach for cardiac tissue engineering. Confluent cultured cells are harvested as an intact cell sheet using a temperature-responsive culture surface. By layering cardiac cell sheets, it is possible to form electrically communicative three-dimensional cardiac constructs. Cell sheet transplantation onto damaged hearts in several animal models has revealed improvements in heart functions. Because of the lack of vasculature, the thickness of viable cardiac cell sheet-layered tissues is limited to three layers. Pre-vascularized structure formation within cardiac tissue and multi-step transplantation methods has enabled the formation of thick vascularized tissues in vivo. Furthermore, development of original bioreactor systems with vascular beds has allowed reconstruction of three-dimensional cardiac tissues with a functional vascular structure in vitro. Large-scale culture systems to generate pluripotent stem cell-derived cardiac cells can create large numbers of cardiac cell sheets. Three-dimensional cardiac tissues fabricated by cell sheet engineering may be applied to treat heart disease and tissue model construction.

  19. Gap-junction channels inhibit transverse propagation in cardiac muscle

    Directory of Open Access Journals (Sweden)

    Ramasamy Lakshminarayanan

    2005-01-01

    Full Text Available Abstract The effect of adding many gap-junctions (g-j channels between contiguous cells in a linear chain on transverse propagation between parallel chains was examined in a 5 × 5 model (5 parallel chains of 5 cells each for cardiac muscle. The action potential upstrokes were simulated using the PSpice program for circuit analysis. Either a single cell was stimulated (cell A1 or the entire chain was stimulated simultaneously (A-chain. Transverse velocity was calculated from the total propagation time (TPT from when the first AP crossed a Vm of -20 mV and the last AP crossed -20 mV. The number of g-j channels per junction was varied from zero to 100, 1,000 and 10,000 (Rgj of ∞, 100 MΩ, 10 MΩ, 1.0 MΩ, respectively. The longitudinal resistance of the interstitial fluid (ISF space between the parallel chains (Rol2 was varied between 200 KΩ (standard value and 1.0, 5.0, and 10 MΩ. The higher the Rol2 value, the tighter the packing of the chains. It was found that adding many g-j channels inhibited transverse propagation by blocking activation of all 5 chains, unless Rol2 was greatly increased above the standard value of 200 KΩ. This was true for either method of stimulation. This was explained by, when there is strong longitudinal coupling between all 5 cells of a chain awaiting excitation, there must be more transfer energy (i.e., more current to simultaneously excite all 5 cells of a chain.

  20. Effect of Cerium on Cardiac Muscle of Rat and Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The effect of Ce3+ on cardiac muscle of rat and guinea pig was studied. In vitro, 0.05 mmol.L-1 solution of Ce3+ inhibited the contraction of guinea pig atria. The change of action potential duration(APD) of guinea pig papillary muscle exposed to 0.4 mmol·L-1 Ce3+ was significant, and those exposed to 0.1 and 0.2 mmol·L-1 Ce3+ were not significant. In vivo, compared with the control group, the APD for rat cardiac muscle after long-term feed on Ce3+ was significantly delayed in high dose, and that was not significantly delayed in low dose. The results suggest that Ce3+ with long-term high dose intake might affect the influx of Ca2+, Na+ and outflow of K+ for rat cardiac muscle.

  1. Cocaine residue in plasma, cardiac and tracheal tissues of chronic cocaine-treated guinea-pigs

    Directory of Open Access Journals (Sweden)

    Malinee Wongnawa

    2010-03-01

    Full Text Available Supersensitivity of adrenoceptors to catecholamines is one of the mechanisms of cocaine-related cardiac complication. The precise mechanism of cocaine enhancing supersensitivity of adrenoceptors is unconcluded. The aim of this study was todetermine the levels of cocaine in plasma, cardiac and tracheal tissues in order to correlate with the supersensitivity ofadrenoceptors to catecholamines. In this study, two groups of ten guinea-pigs each were injected with 2.5 mg/kg cocaine or normal saline solution intraperitoneally twice daily for 14 days. After 24 hours of cocaine cessation, the cocaine levels in plasma, cardiac and tracheal tissues were determined using high performance liquid chromatography. The results showed that the cocaine levels in plasma and tracheal smooth muscle were 5.08±0.63 ng/ml and 2.8±0.41 ng/mg, respectively, while those in atria and ventricle were lower than 17.5 ng/g and 3.8 ng/g, respectively. These levels were less than the level that had been reported to block norepinephrine uptake (more than 30.34 ng/ml. Moreover, it had been demonstrated that cocainetreatment in the same condition as the present study produced supersensitivity to norepinephrine and epinephrine in isolatedguinea-pig atria as well as in trachea which is almost entirely not innervated by the adrenergic nerves. In addition, supersensitivityto oxymetazoline, isoproterenol and salbutamol which are not the substrates of neuronal reuptake were also demonstrated. All these data support the postsynaptic mechanism of cocaine enhancing supersensitivity which might be correlated with cardiac complication in chronic cocaine use.

  2. Electrical Pacing of Cardiac Tissue Including Potassium Inward Rectification.

    Science.gov (United States)

    Galappaththige, Suran; Roth, Bradley J

    2015-01-01

    In this study cardiac tissue is stimulated electrically through a small unipolar electrode. Numerical simulations predict that around an electrode are adjacent regions of depolarization and hyperpolarization. Experiments have shown that during pacing of resting cardiac tissue the hyperpolarization is often inhibited. Our goal is to determine if the inward rectifying potassium current (IK1) causes the inhibition of hyperpolarization. Numerical simulations were carried out using the bidomain model with potassium dynamics specified to be inward rectifying. In the simulations, adjacent regions of depolarization and hyperpolarization were observed surrounding the electrode. For cathodal currents the virtual anode produces a hyperpolarization that decreases over time. For long duration pulses the current-voltage curve is non-linear, with very small hyperpolarization compared to depolarization. For short pulses, the hyperpolarization is more prominent. Without the inward potassium rectification, the current voltage curve is linear and the hyperpolarization is evident for both long and short pulses. In conclusion, the inward rectification of the potassium current explains the inhibition of hyperpolarization for long duration stimulus pulses, but not for short duration pulses.

  3. Electrical Pacing of Cardiac Tissue Including Potassium Inward Rectification.

    Directory of Open Access Journals (Sweden)

    Suran Galappaththige

    Full Text Available In this study cardiac tissue is stimulated electrically through a small unipolar electrode. Numerical simulations predict that around an electrode are adjacent regions of depolarization and hyperpolarization. Experiments have shown that during pacing of resting cardiac tissue the hyperpolarization is often inhibited. Our goal is to determine if the inward rectifying potassium current (IK1 causes the inhibition of hyperpolarization. Numerical simulations were carried out using the bidomain model with potassium dynamics specified to be inward rectifying. In the simulations, adjacent regions of depolarization and hyperpolarization were observed surrounding the electrode. For cathodal currents the virtual anode produces a hyperpolarization that decreases over time. For long duration pulses the current-voltage curve is non-linear, with very small hyperpolarization compared to depolarization. For short pulses, the hyperpolarization is more prominent. Without the inward potassium rectification, the current voltage curve is linear and the hyperpolarization is evident for both long and short pulses. In conclusion, the inward rectification of the potassium current explains the inhibition of hyperpolarization for long duration stimulus pulses, but not for short duration pulses.

  4. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Götz Pilarczyk

    2016-01-01

    Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

  5. Changes and Significance of Matrix Metalloproteinase and Its Tissue Inhibitor in Plasma and Cardiac Muscle of Rats with Chronic Cardiac Failure Induced by Volume Overload%基质金属蛋白酶及其抑制物在容量过负荷致慢性心力衰竭大鼠血浆及心肌组织中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    张超英; 李晓惠; 伏瑾; 崔小岱

    2011-01-01

    目的 观察容量过负荷致慢性心力衰竭大鼠血浆及心肌组织基质金属蛋白酶-8(MMP-8)及其抑制物-1(TIMP-1)的表达变化,探讨其在慢性心力衰竭发病中的病理生理作用.方法 雄性SD大鼠17只,随机分为分流组(n=9)和对照组(n=8).分流组通过腹主动脉下腔静脉穿刺术建立容量过负荷致慢性充血性心力衰竭动物模型,对照组大鼠除不做穿刺外,余操作过程同分流组.分别测定2组大鼠心功能及血流动力学指标,检测血浆MMP-8及TIMP-1水平,实时荧光定量PCR测定大鼠左心室、右心室MMP-8 mRNA、TIMP-1 mRNA的表达.结果 术后8周,分流组大鼠左心室收缩压、左心室舒张压、左心室内压差、左心室内压最大上升速率及最大下降速率较对照组明显降低(Pa<0.05,0.01);左心室舒张末压较对照组明显升高(P<0.05).分流组大鼠血浆MMP-8、TIMP-1水平均较对照组明显升高(Pa<0.05).与对照组相比,分流组大鼠左心室心肌组织MMP-8 mRNA及左、右心室心肌组织TIMP-1 mRNA水平均有升高趋势,右心室MMP-8 mRNA水平有下降趋势,但2组比较差异均无统计学意义(Pa>0.05);左心室和右心室心肌组织中MMP-8/TIMP-1明显降低,右心室较左心室下降更明显.结论 MMP-8与TIMP-1通过影响胶原代谢,参与容量过负荷致慢性充血性心力衰竭的病理生理过程.%Objective To observe the changes of matrix metalloproteinase - 8 ( MMP - 8 ) and its tissue inhibitors of metallopreteinase -1 ( TIMP - 1 ) in plasma and cardiac muscle of rats with chronic cardiac failure induced by volume overload, and to explore those roles in physiology of chronic cardiac failure. Methods Seventeen male SD rats were randomly divided into 2 groups as follows:9 shunt rat models were established by abdominal aorta and inferior vena cava shunt operation and 8 rats after sham operation served as controls. Hemodynamic and echocardiographic measurements were obtained 8 weeks

  6. From Syncitium to Regulated Pump: A Cardiac Muscle Cellular Update

    Science.gov (United States)

    Korzick, Donna H.

    2011-01-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information…

  7. Finite element analysis of an accordion-like honeycomb scaffold for cardiac tissue engineering.

    Science.gov (United States)

    Jean, Aurélie; Engelmayr, George C

    2010-11-16

    Optimizing the function of tissue engineered cardiac muscle is becoming more feasible with the development of microfabricated scaffolds amenable to mathematical modeling. In the current study, the elastic behavior of a recently developed poly(glycerol sebacate) (PGS) accordion-like honeycomb (ALH) scaffold [Engelmayr et al., 2008. Nature Materials 7 (12), 1003-1010] was analyzed. Specifically, 2D finite element (FE) models of the ALH unit cell (periodic boundary conditions) and tessellations (kinematic uniform boundary conditions) were utilized to determine a representative volume element (RVE) and to retrospectively predict the elastic effective stiffnesses. An RVE of 90 ALH unit cells (≃3.18×4.03mm) was found, indicating that previous experimental uni-axial test samples were mechanically representative. For ALH scaffolds microfabricated from PGS cured 7.5h at 160°C, FE predicted effective stiffnesses in the two orthogonal material directions (0.081±0.012 and 0.033±0.005MPa) matched published experimental data (0.083±0.004 and 0.031±0.002MPa) within 2.4% and 6.4%. Of potential use as a design criterion, model predicted global strain amplifications were lower in ALH (0.54 and 0.34) versus rectangular honeycomb (1.19 and 0.74) scaffolds, appearing to be inversely correlated with previously measured strains-to-failure. Important in matching the anisotropic mechanical properties of native cardiac muscle, FE predicted ALH scaffolds with 50μm wide PGS struts to be maximally anisotropic. The FE model will thus be useful in designing future variants of the ALH pore geometry that simultaneously provide proper cardiac anisotropy and reduced stiffness to enhance heart cell-mediated contractility.

  8. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  9. Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension.

    Science.gov (United States)

    Sala-Mercado, Javier A; Spranger, Marty D; Abu-Hamdah, Rania; Kaur, Jasdeep; Coutsos, Matthew; Stayer, Douglas; Augustyniak, Robert A; O'Leary, Donal S

    2013-11-15

    Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance.

  10. Cardiac tissue structure. Electric field interactions in polarizing the heart: 3D computer models and applications

    Science.gov (United States)

    Entcheva, Emilia

    1998-11-01

    The goal of this research is to investigate the interactions between the cardiac tissue structure and applied electric fields in producing complex polarization patterns. It is hypothesized that the response of the heart in the conditions of strong electric shocks, as those applied in defibrillation, is dominated by mechanisms involving the cardiac muscle structure perceived as a continuum. Analysis is carried out in three-dimensional models of the heart with detailed fiber architecture. Shock-induced transmembrane potentials are calculated using the bidomain model in its finite element implementation. The major new findings of this study can be summarized as follows: (1) The mechanisms of polarization due to cardiac fiber curvature and fiber rotation are elucidated in three-dimensional ellipsoidal hearts of variable geometry; (2) Results are presented showing that the axis of stimulation and the polarization axis on a whole heart level might differ significantly due to geometric and anisotropic factors; (3) Virtual electrode patterns are demonstrated numerically inside the ventricular wall in internal defibrillation conditions. The role of the tissue-bath interface in shaping the shock-induced polarization is revealed; (4) The generation of 3D phase singularity scrolls by shock-induced intramural virtual electrode patterns is proposed as evidence for a possible new mechanism for the failure to defibrillate. The results of this study emphasize the role of unequal anisotropy in the intra- and extracellular domains, as well as the salient fiber architecture characteristics, such as curvature and transmural rotation, in polarizing the myocardium. Experimental support of the above findings was actively sought and found in recent optical mapping studies using voltage-sensitive dyes. If validated in vivo, these findings would significantly enrich the prevailing concepts about the mechanisms of stimulation and defibrillation of the heart.

  11. Decreased hydrogen peroxide production and mitochondrial respiration in skeletal muscle but not cardiac muscle of the green-striped burrowing frog, a natural model of muscle disuse.

    Science.gov (United States)

    Reilly, Beau D; Hickey, Anthony J R; Cramp, Rebecca L; Franklin, Craig E

    2014-04-01

    Suppression of disuse-induced muscle atrophy has been associated with altered mitochondrial reactive oxygen species (ROS) production in mammals. However, despite extended hindlimb immobility, aestivating animals exhibit little skeletal muscle atrophy compared with artificially immobilised mammalian models. Therefore, we studied mitochondrial respiration and ROS (H2O2) production in permeabilised muscle fibres of the green-striped burrowing frog, Cyclorana alboguttata. Mitochondrial respiration within saponin-permeabilised skeletal and cardiac muscle fibres was measured concurrently with ROS production using high-resolution respirometry coupled to custom-made fluorometers. After 4 months of aestivation, C. alboguttata had significantly depressed whole-body metabolism by ~70% relative to control (active) frogs, and mitochondrial respiration in saponin-permeabilised skeletal muscle fibres decreased by almost 50% both in the absence of ADP and during oxidative phosphorylation. Mitochondrial ROS production showed up to an 88% depression in aestivating skeletal muscle when malate, succinate and pyruvate were present at concentrations likely to reflect those in vivo. The percentage ROS released per O2 molecule consumed was also ~94% less at these concentrations, indicating an intrinsic difference in ROS production capacities during aestivation. We also examined mitochondrial respiration and ROS production in permeabilised cardiac muscle fibres and found that aestivating frogs maintained respiratory flux and ROS production at control levels. These results show that aestivating C. alboguttata has the capacity to independently regulate mitochondrial function in skeletal and cardiac muscles. Furthermore, this work indicates that ROS production can be suppressed in the disused skeletal muscle of aestivating frogs, which may in turn protect against potential oxidative damage and preserve skeletal muscle structure during aestivation and following arousal.

  12. A pilot study using Tissue Velocity Ultrasound Imaging (TVI to assess muscle activity pattern in patients with chronic trapezius myalgia

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    Brodin Lars-Åke

    2008-09-01

    Full Text Available Abstract Background Different research techniques indicate alterations in muscle tissue and in neuromuscular control of aching muscles in patients with chronic localized pain. Ultrasound can be used for analysis of muscle tissue dynamics in clinical practice. Aim This study introduces a new muscle tissue sensitive ultrasound technique in order to provide a new methodology for providing a description of local muscle changes. This method is applied to investigate trapezius muscle tissue response – especially with respect to specific regional deformation and deformation rates – during concentric shoulder elevation in patients with chronic trapezius myalgia and healthy controls before and after pain provocation. Methods Patients with trapezius myalgia and healthy controls were analyzed using an ultrasound system equipped with tissue velocity imaging (TVI. The patients performed a standardized 3-cm concentric shoulder elevation before and after pain provocation/exercise at a standardized elevation tempo (30 bpm. A standardized region of interest (ROI, an ellipsis with a size that captures the upper and lower fascia of the trapezius muscle (4 cm width at rest, was placed in the first frame of the loop registration of the elevation. The ROI was re-anchored frame by frame following the same anatomical landmark in the basal fascia during all frames of the concentric phase. In cardiac measurement, tissue velocities are measured in the axial projection towards and against the probe where red colour represents shortening and red lengthening. In the case of measuring the trapezius muscle, tissue deformation measurements are made orthogonally, thus, indirectly. Based on the assumption of muscle volume incompressibility, blue represents tissue contraction and red relaxation. Within the ROI, two variables were calculated as a function of time: deformation and deformation rate. Hereafter, max, mean, and quadratic mean values (RMS of each variable were

  13. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    Science.gov (United States)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  14. Contribution of IL-6 to the Hsp72, Hsp25, and alphaB-crystallin [corrected] responses to inflammation and exercise training in mouse skeletal and cardiac muscle.

    Science.gov (United States)

    Huey, Kimberly A; Meador, Benjamin M

    2008-12-01

    The heat shock proteins (Hsps) Hsp72, Hsp25, and alphaB-crystallin (alphaB C) [corrected]may protect tissues during exercise and/or inflammatory insults; however, no studies have investigated whether exercise training increases both basal and inflammation-induced expression of these Hsps in skeletal or cardiac muscle. IL-6 is produced by muscle during both exercise and inflammation and has been shown to modulate Hsp expression. These studies tested the hypothesis that voluntary wheel running (RW) increases basal and inflammation-induced Hsp72, Hsp25, and alphaB C [corrected] protein through an IL-6-dependent mechanism. We compared Hsp72, Hsp25, alphaB C, [corrected] and IL-6 protein levels 4 h after systemic inflammation induced by lipopolysaccharide (LPS) in skeletal and cardiac muscles of wild-type (IL-6(+/+)) and IL-6 deficient (IL-6(-/-)) mice after 2 wk of RW or normal cage activity (Sed). LPS significantly increased skeletal Hsp72 and Hsp25 relative to saline in Sed IL-6(+/+), but not IL-6(-/-) mice. LPS increased Hsp72 relative to saline in Sed IL-6(+/+) cardiac muscle. RW increased basal Hsp72, Hsp25, and alphaB C [corrected] in skeletal muscle in IL-6(+/+) and IL-6(-/-) mice. However, LPS was not associated with increases in any Hsp in RW IL-6(+/+) or IL-6(-/-) mice. LPS increased IL-6 protein in skeletal muscle and plasma in Sed and RW groups, with a significantly greater response in RW. The major results provide the first in vivo evidence that the absence of IL-6 is associated with reduced skeletal muscle Hsp72 and Hsp25 responses to LPS, but that IL-6 is not required for exercise-induced Hsp upregulation in skeletal or cardiac muscle.

  15. Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development.

    Science.gov (United States)

    Guex, A G; Kocher, F M; Fortunato, G; Körner, E; Hegemann, D; Carrel, T P; Tevaearai, H T; Giraud, M N

    2012-04-01

    Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

  16. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  17. The morphological development of the locomotor and cardiac muscles of the migratory barnacle goose (Branta leucopsis)

    NARCIS (Netherlands)

    Bishop, CM; Butler, PJ; ElHaj, AJ; Egginton, S; Loonen, MJJE

    1996-01-01

    The masses of the locomotor and cardiac muscles of wild barnacle goose goslings, from a migratory population, were examined systematically during development and their values compared to those of pre-migratory geese. Pre-flight development was typified by approximately linear increases of body, leg,

  18. Cellular models and viral vectors for skeletal and cardiac muscle research

    NARCIS (Netherlands)

    Neshati, Zeinab

    2014-01-01

    Skeletal and cardiac muscle disorders are associated with substantial morbidity and mortality. Despite many improvements in the medical and surgical management of these disorders, development of effective treatments has proven to be challenging. This is because of the limited suitability of existing

  19. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    Science.gov (United States)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  20. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

    Science.gov (United States)

    Rogozhnikov, Dmitry; O’Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

    2016-12-01

    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

  1. Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Cicogna

    1999-04-01

    Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

  2. Optimizing PANi doped electroactive substrates as patches for the regeneration of cardiac muscle.

    Science.gov (United States)

    Borriello, A; Guarino, V; Schiavo, L; Alvarez-Perez, M A; Ambrosio, L

    2011-04-01

    In scaffold aided regeneration of muscular tissue, composite materials are currently utilized as a temporary substrate to stimulate tissue formation by controlled electrochemical signals as well as continuous mechanical stimulation until the regeneration processes are completed. Among them, composites from the blending of conductive (CPs) and biocompatible polymers are powerfully emerging as a successful strategy for the regeneration of myocardium due to their unique conductive and biological recognition properties able to assure a more efficient electroactive stimulation of cells. Here, different composite substrates made of synthesized polyaniline (sPANi) and polycaprolactone (PCL) were investigated as platforms for cardiac tissue regeneration. Preliminary, a comparative analysis of substrates conductivity performed on casted films endowed with synthesized polyaniline (sPANi) short fibres or blended with emeraldine base polyaniline (EBPANi) allows to study the attitude of charge transport, depending on the conducting filler amount, shape and spatial distribution. In particular, conducibility tests indicated that sPANi short fibres provide a more efficient transfer of electric signal due to the spatial organization of electroactive needle-like phases up to form a percolative network. On the basis of this characterization, sPANi/PCL electrospun membranes have been also optimized to mimic either the morphological and functional features of the cardiac muscle ECM. The presence of sPANi does not relevantly affect the fibre architecture as confirmed by SEM/image analysis investigation which shows a broader distribution of fibres with only a slight reduction of the average fibre diameter from 7.1 to 6.4 μm. Meanwhile, biological assays--evaluation of cell survival rate by MTT assay and immunostaining of sarcomeric α-actinin of cardiomyocites-like cells--clearly indicate that conductive signals offered by PANi needles, promote the cardiogenic differentiation of h

  3. Negative inotropic actions of nitric oxide require high doses in rat cardiac muscle.

    Science.gov (United States)

    Wyeth, R P; Temma, K; Seifen, E; Kennedy, R H

    1996-08-01

    Initial experiments were designed to determine if vasoactive concentrations of nitric oxide (NO) alter contractility in rat heart. Contractile function was monitored in left atrial and papillary muscles (30 degrees C; paced at 0.5 Hz) during cumulative addition of 3-morpholino-sydnonimine-HCl(SIN-1), an agent that releases NO. At concentrations between 10(-7) and 10(-4) M (NO concentrations of approximately 10(-8)- 3 x 10(-7) M), SIN-1 did not affect contractility in either tissue. Similarly, 10(-4) M SIN-1 did not alter the positive inotropic responses to isoproterenol or increasing extracellular [Ca+2] ([Ca+2]o). To obtain higher concentrations of NO, additional studies were conducted using authentic NO. NO-saturated stock solutions and a corresponding control solvent were adjusted to pH 1.6 with HCl. Dose-dependent effects of NO were examined by adding aliquots of the stock solutions (or control solvent) to the bathing solution. At final concentrations of 1 x 10(-5)- 5 x 10(-4) M, NO produced transient, concentration-dependent decreases in contractility that were paralleled by reductions in buffer pH. Control solvent elicited similar reductions in pHo and transient decreases in contractility; however, the negative inotropic action elicited by the NO-containing solution was approximately 20% greater than that observed in control conditions. These data demonstrate that only high concentrations of NO depress contractility in isolated rat cardiac muscle, and suggest that this effect is mediated by both acidosis and a pHo-independent mechanism.

  4. Precocious appearance of cardiac troponin T pre-mRNAs during early avian embryonic skeletal muscle development in ovo.

    Science.gov (United States)

    Swiderski, R E; Solursh, M

    1990-07-01

    Cardiac troponin T (cTNT), a component of the muscle contractile apparatus, is transiently expressed in skeletal muscle during avian limb development. While cTNT was first detected immunohistochemically in limb buds undergoing overt myogenic differentiation (Hamburger and Hamilton stage 26, about 5 days in ovo), RNA blot analyses of early, predifferentiated wing buds have revealed the presence of cTNT transcripts in limb buds as early as stage 23 (4 days in ovo). Steady-state cTNT poly(A) RNAs of stage 22 through stage 37 fore- and hindlimbs were compared using both cTNT cDNA and cTNT intron-specific probes. In the predifferentiated state, two incompletely processed RNAs (3.8 and 2.4 kb) were expressed in the absence of the mature cTNT transcript, while a third pre-mRNA (3.5 kb) appeared concomitantly with the mature mRNA as differentiation and development proceeded. In addition, a population of unique cTNT transcripts were expressed in a proximal to distal manner in wing buds which had undergone initial overt myogenic differentiation (stage 26). Some of the cTNT pre-mRNAs observed in premyogenic limbs appeared to accumulate stably in a tissue-specific manner, based on their absence from the cardiac poly(A) RNA population. These results suggest that the appearance of cardiac troponin T mRNA, as well as the polypeptide, may be regulated at multiple levels including RNA processing, stability, and/or translation during early skeletal muscle myogenesis.

  5. Reentry Near the Percolation Threshold in a Heterogeneous Discrete Model for Cardiac Tissue

    Science.gov (United States)

    Alonso, Sergio; Bär, Markus

    2013-04-01

    Arrhythmias in cardiac tissue are related to irregular electrical wave propagation in the heart. Cardiac tissue is formed by a discrete cell network, which is often heterogeneous. A localized region with a fraction of nonconducting links surrounded by homogeneous conducting tissue can become a source of reentry and ectopic beats. Extensive simulations in a discrete model of cardiac tissue show that a wave crossing a heterogeneous region of cardiac tissue can disintegrate into irregular patterns, provided the fraction of nonconducting links is close to the percolation threshold of the cell network. The dependence of the reentry probability on this fraction, the system size, and the degree of excitability can be inferred from the size distribution of nonconducting clusters near the percolation threshold.

  6. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard;

    2013-01-01

    of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...

  7. Optical reflectance in fibrous tissues and skeletal muscles

    Science.gov (United States)

    Ranasinghesagara, Janaka C.

    We studied two biological tissues with optically anisotropic structures: high moisture soy protein extrudates and skeletal muscles. High moisture extrusion has been used to produce vegetable meat analogs that resemble real animal meat and have significant health benefits. Since visual and textural properties are key factors for consumer acceptance, assessing fiber formation in the extruded soy protein product is important for quality control purpose. A non-destructive method based on photon migration was developed to measure fiber formation in extruded soy proteins. The measured fiber formation index in intact samples showed good agreement with that obtained from image analysis on peeled samples. By implementing this new method in a fast laser scanning system, we have acquired two dimensional mappings of fiber formation and orientation in the entire sample in real time. In addition to fibrous structures, skeletal muscles have a unique periodic sarcomere structure which produces strong light diffractions. However, inconsistent experimental results have been reported in single fiber diffraction studies. By applying the three-dimensional coupled wave theory in a physical sarcomere model, we found that a variety of experimental observations can be explained if inhomogeneous muscle morphological profiles are considered. We also discovered that the sarcomere structure produced a unique optical reflectance pattern in whole muscle. None of the existing light propagation theories are able to describe this pattern. We developed a Monte Carlo model incorporating the sarcomere diffraction effect. The simulated results quantitatively resemble the unique patterns observed in experiments. We used a set of parameters to quantify the optical reflectance profiles produced by a point incident light in whole muscle. Two parameters, q and B, were obtained by numerically fitting the equi-intensity contours of the reflectance pattern. Two spatial gradients were calculated along the

  8. Abundance, distribution, mobility and oligomeric state of M2 muscarinic acetylcholine receptors in live cardiac muscle

    OpenAIRE

    Nenasheva, Tatiana A.; Neary, Marianne; Gregory I. Mashanov; Birdsall, Nigel J.M.; Breckenridge, Ross A.; Molloy, Justin E.

    2013-01-01

    M2 muscarinic acetylcholine receptors modulate cardiac rhythm via regulation of the inward potassium current. To increase our understanding of M2 receptor physiology we used Total Internal Reflection Fluorescence Microscopy to visualize individual receptors at the plasma membrane of transformed CHOM2 cells, a cardiac cell line (HL-1), primary cardiomyocytes and tissue slices from pre- and post-natal mice. Receptor expression levels between individual cells in dissociated cardiomyocytes and he...

  9. Evaluation of peripheral muscle strength of patients undergoing elective cardiac surgery: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Kelli Maria Souza Santos

    2014-09-01

    Full Text Available Introduction: Peripheral muscle strength has been little explored in the literature in the context of cardiac rehabilitation. Objective: To evaluate the peripheral muscle strength of patients undergoing elective cardiac surgery. Methods: This was a longitudinal observational study. The peripheral muscle strength was measured using isometric dynamometry lower limb (knee extensors and flexors at three different times: preoperatively (M1, the day of discharge (M2 and hospital discharge (M3. Participants received physiotherapy pre and postoperatively during the days of hospitalization during the morning and afternoon. Results: Twenty-two patients were evaluated. The values of peripheral muscle strength of knee extensors preoperative found were about 50% lower than those predicted for the healthy population. When comparing muscle strength prior (M1, with the remaining evaluation, found himself in a fall of 29% for the movement of knee extension and 25% for knee flexion in M2 and a decrease of 10% movement for knee extension and 13% for knee flexion in M3 when comparing with M1. Conclusion: The values of peripheral muscle strength prior of the study patients were lower than predicted for the healthy population of the same age. After the surgical event this reduction is even more remarkable, being reestablished until the time of discharge, to values close to baseline.

  10. CGP 41251, a new potential anticancer drug, improves contractility of rat isolated cardiac muscle subjected to hypoxia.

    Science.gov (United States)

    Kocic, I; Dworakowska, D; Dworakowski, R; Petrusewicz, J

    2001-06-01

    The aim of the present work was to examine the effects of 4'-N-benzoyl staurosporine (CGP 41251), a protein kinase C inhibitor with broad antiproliferative activity in many cell lines, on the rat isolated heart contractility under normoxic and hypoxic conditions. Additionally, we examined the effects of CGP 41251, WB-4101 (alpha1a -adrenoceptor antagonist), chloroethylclonidine (CEC) (alpha1b-adrenoceptor antagonist) and selective damage of endocardial endothelium by Triton X-100 on the protection against hypoxia induced by preconditioning of rat heart tissue. Experiments were performed on rat isolated left ventricular papillary muscle. The following parameters were measured: force of contraction (Fc), velocity of contraction (+dF/dt) and velocity of relaxation (-dF/dt). The temperature of the bath solution was 37 degrees C +/- 0.5 degrees C, and rate of electrical stimulation was 0.5 Hz. At concentrations less than 1 microM CGP 41251 did not cause any changes in contractility of rat heart. At 1 and 3 microM, significant positive inotropic action was observed. Treatment of rat papillary muscle by CGP 41251 at 3 microM reduced decreasing of contractility by simulated hypoxia and reperfusion. Moreover, protective effects of preconditioning was not affected by addition of CGP 41251 neither at 1 nor at 3 microM. Pretreatment with CEC at 3 microM, and selective damage of endocardial endothelium induced by fast (1-s) immersion of papillary muscle in 0.5% Triton X-100, but not pretreatment with WB-4101, abolished the protective effects of preconditioning. The results imply that CGP 41251 improves contractility of heart muscle under normoxic and hypoxic conditions, and does not alter hypoxic preconditioning in rat isolated cardiac tissue. Moreover, it was shown that alpha1b-adrenoceptors and endocardial endothelium are involved in triggering of preconditioning in rat isolated heart muscle.

  11. Neonatal epicardial-derived progenitors aquire myogenic traits in skeletal muscle, but not cardiac muscle

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Jensen, Charlotte H; Skovrind, Ida;

    2016-01-01

    BACKGROUND/OBJECTIVES: Epicardium-derived progenitor cells (EPDCs) differentiate into all heart cell types in the embryonic heart, yet their differentiation into cardiomyocytes in the adult heart is limited and poorly described. This may be due to EPDCs lacking myogenic potential or the inert adu...... that EPDCs may be more myogenic than previously anticipated. But, the heart may lack factors for induction of myogenesis of EPDCs, a scenario that should be taken into consideration when aiming for repair of damaged myocardium by stem cell transplantation.......BACKGROUND/OBJECTIVES: Epicardium-derived progenitor cells (EPDCs) differentiate into all heart cell types in the embryonic heart, yet their differentiation into cardiomyocytes in the adult heart is limited and poorly described. This may be due to EPDCs lacking myogenic potential or the inert adult...... heart missing regenerative signals essential for directed differentiation of EPDCs. Herein, we aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal mouse myocardium, as well as in skeletal muscle. The two latter tissues have an intrinsic capability to develop and regenerate...

  12. A swimming robot actuated by living muscle tissue

    Directory of Open Access Journals (Sweden)

    Herr Hugh

    2004-10-01

    Full Text Available Abstract Biomechatronics is the integration of biological components with artificial devices, in which the biological component confers a significant functional capability to the system, and the artificial component provides specific cellular and tissue interfaces that promote the maintenance and functional adaptation of the biological component. Based upon functional performance, muscle is potentially an excellent mechanical actuator, but the larger challenge of developing muscle-actuated, biomechatronic devices poses many scientific and engineering challenges. As a demonstratory proof of concept, we designed, built, and characterized a swimming robot actuated by two explanted frog semitendinosus muscles and controlled by an embedded microcontroller. Using open loop stimulation protocols, the robot performed basic swimming maneuvers such as starting, stopping, turning (turning radius ~400 mm and straight-line swimming (max speed >1/3 body lengths/second. A broad spectrum antibiotic/antimycotic ringer solution surrounded the muscle actuators for long term maintenance, ex vivo. The robot swam for a total of 4 hours over a 42 hour lifespan (10% duty cycle before its velocity degraded below 75% of its maximum. The development of functional biomechatronic prototypes with integrated musculoskeletal tissues is the first critical step toward the long term objective of controllable, adaptive and robust biomechatronic robots and prostheses.

  13. A swimming robot actuated by living muscle tissue

    Science.gov (United States)

    Herr, Hugh; Dennis, Robert G

    2004-01-01

    Biomechatronics is the integration of biological components with artificial devices, in which the biological component confers a significant functional capability to the system, and the artificial component provides specific cellular and tissue interfaces that promote the maintenance and functional adaptation of the biological component. Based upon functional performance, muscle is potentially an excellent mechanical actuator, but the larger challenge of developing muscle-actuated, biomechatronic devices poses many scientific and engineering challenges. As a demonstratory proof of concept, we designed, built, and characterized a swimming robot actuated by two explanted frog semitendinosus muscles and controlled by an embedded microcontroller. Using open loop stimulation protocols, the robot performed basic swimming maneuvers such as starting, stopping, turning (turning radius ~400 mm) and straight-line swimming (max speed >1/3 body lengths/second). A broad spectrum antibiotic/antimycotic ringer solution surrounded the muscle actuators for long term maintenance, ex vivo. The robot swam for a total of 4 hours over a 42 hour lifespan (10% duty cycle) before its velocity degraded below 75% of its maximum. The development of functional biomechatronic prototypes with integrated musculoskeletal tissues is the first critical step toward the long term objective of controllable, adaptive and robust biomechatronic robots and prostheses. PMID:15679914

  14. Cyclic AMP system in muscle tissue during prolonged hypokinesia

    Science.gov (United States)

    Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

    1980-01-01

    Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

  15. 9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Disposition of thyroid glands and... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle tissue shall not be used for human food. (b) Livestock thyroid glands and laryngeal muscle tissue may...

  16. Effect of xinmailong on ischemic cardiac muscle during hemorrhagic shock

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Xinmailong injection solution was invented at 1988 by prof. Li Shunan in Dali medical college. It was made from the material which has high biological activeness to the cardiac and vascular system. During the experimental shock caused by excessive loss of blood in monkey and dog, it was found by ECG that the T-wave of anterion lead on left chest elevated and became high and sharp after acute blood loss. Arterial blood pressure dropped to 8-5.3 kPa for dog and 8-5.3-2.7 kPa for monkey, changes of T-wave all recovered to near normal level after xinmailong solution was injected intravenously (0.05-0.2 mL/kg). These Results implied that xinmailong might improve the ischemia of myocardium induced by hemorrhagic shock.

  17. Morphological and Tissue Alterations in one Papillary Muscle: an Early Sign of Hypertrophic Cardiomyopathy?

    Directory of Open Access Journals (Sweden)

    Alberto Cresti

    2016-12-01

    Full Text Available Isolated Papillary Muscle (PM hypertrophy has been supposed to be a phenotypic variant of hypertrophic cardiomyopathy. Whether this finding may explain an electrocardiographic pattern of left ventricular hypertrophy has to be demonstrated. A cardiac magnetic resonance imaging may add additional crucial information. Our case was a 26-year-old asymptomatic male cyclist who underwent routine sport medicine screening. His cousin had suddenly died during a bicycle race at 40 years of age, and autopsy had revealed a hypertrophic cardiomyopathy. Screening revealed an electrocardiographic pattern of left ventricular hypertrophy. A multimodal imaging examination was also performed and the only abnormal finding was a hypertrophic anterolateral PM and cardiac magnetic resonance imaging showed fibrotic substitution of its head. An otherwise unexplained electrocardiographic pattern of left ventricular hypertrophy can be justified by an isolated PM hypertrophy. Cardiac magnetic resonance imaging is crucial for precise ventricular wall and papillary thickness measurement. In the presence of an isolated PM hypertrophy, postgadolinium T1 mapping can demonstrate the presence of abnormal tissue and probably fibrosis of the papillary head, which can confirm the presence of a strictly localized form of hypertrophic cardiomyopathy.

  18. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  19. Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease.

    Science.gov (United States)

    Goldfarb, Lev G; Dalakas, Marinos C

    2009-07-01

    Muscle fiber deterioration resulting in progressive skeletal muscle weakness, heart failure, and respiratory distress occurs in more than 20 inherited myopathies. As discussed in this Review, one of the newly identified myopathies is desminopathy, a disease caused by dysfunctional mutations in desmin, a type III intermediate filament protein, or alphaB-crystallin, a chaperone for desmin. The range of clinical manifestations in patients with desminopathy is wide and may overlap with those observed in individuals with other myopathies. Awareness of this disease needs to be heightened, diagnostic criteria reliably outlined, and molecular testing readily available; this would ensure prevention of sudden death from cardiac arrhythmias and other complications.

  20. Multiscale models of skeletal muscle reveal the complex effects of muscular dystrophy on tissue mechanics and damage susceptibility.

    Science.gov (United States)

    Virgilio, Kelley M; Martin, Kyle S; Peirce, Shayn M; Blemker, Silvia S

    2015-04-06

    Computational models have been increasingly used to study the tissue-level constitutive properties of muscle microstructure; however, these models were not created to study or incorporate the influence of disease-associated modifications in muscle. The purpose of this paper was to develop a novel multiscale muscle modelling framework to elucidate the relationship between microstructural disease adaptations and modifications in both mechanical properties of muscle and strain in the cell membrane. We used an agent-based model to randomly generate new muscle fibre geometries and mapped them into a finite-element model representing a cross section of a muscle fascicle. The framework enabled us to explore variability in the shape and arrangement of fibres, as well as to incorporate disease-related changes. We applied this method to reveal the trade-offs between mechanical properties and damage susceptibility in Duchenne muscular dystrophy (DMD). DMD is a fatal genetic disease caused by a lack of the transmembrane protein dystrophin, leading to muscle wasting and death due to cardiac or pulmonary complications. The most prevalent microstructural variations in DMD include: lack of transmembrane proteins, fibrosis, fatty infiltration and variation in fibre cross-sectional area. A parameter analysis of these variations and case study of DMD revealed that the nature of fibrosis and density of transmembrane proteins strongly affected the stiffness of the muscle and susceptibility to membrane damage.

  1. 3D engineered cardiac tissue models of human heart disease: learning more from our mice.

    Science.gov (United States)

    Ralphe, J Carter; de Lange, Willem J

    2013-02-01

    Mouse engineered cardiac tissue constructs (mECTs) are a new tool available to study human forms of genetic heart disease within the laboratory. The cultured strips of cardiac cells generate physiologic calcium transients and twitch force, and respond to electrical pacing and adrenergic stimulation. The mECT can be made using cells from existing mouse models of cardiac disease, providing a robust readout of contractile performance and allowing a rapid assessment of genotype-phenotype correlations and responses to therapies. mECT represents an efficient and economical extension to the existing tools for studying cardiac physiology. Human ECTs generated from iPSCMs represent the next logical step for this technology and offer significant promise of an integrated, fully human, cardiac tissue model.

  2. Sarcomere Imaging by Quantum Dots for the Study of Cardiac Muscle Physiology

    Directory of Open Access Journals (Sweden)

    Fuyu Kobirumaki-Shimozawa

    2012-01-01

    Full Text Available We here review the use of quantum dots (QDs for the imaging of sarcomeric movements in cardiac muscle. QDs are fluorescence substances (CdSe that absorb photons and reemit photons at a different wavelength (depending on the size of the particle; they are efficient in generating long-lasting, narrow symmetric emission profiles, and hence useful in various types of imaging studies. Recently, we developed a novel system in which the length of a particular, single sarcomere in cardiomyocytes can be measured at ~30 nm precision. Moreover, our system enables accurate measurement of sarcomere length in the isolated heart. We propose that QDs are the ideal tool for the study of sarcomere dynamics during excitation-contraction coupling in healthy and diseased cardiac muscle.

  3. Electrical stimulation of cardiac adipose tissue-derived progenitor cells modulates cell phenotype and genetic machinery.

    Science.gov (United States)

    Llucià-Valldeperas, A; Sanchez, B; Soler-Botija, C; Gálvez-Montón, C; Prat-Vidal, C; Roura, S; Rosell-Ferrer, J; Bragos, R; Bayes-Genis, A

    2015-11-01

    A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. Our aim was to examine the effect of electrical stimulation on the cardiodifferentiation potential of cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs). Three different electrical stimulation protocols were tested; the selected protocol consisted of 2 ms monophasic square-wave pulses of 50 mV/cm at 1 Hz over 14 days. Cardiac and subcutaneous ATDPCs were grown on biocompatible patterned surfaces. Cardiomyogenic differentiation was examined by real-time PCR and immunocytofluorescence. In cardiac ATDPCs, MEF2A and GATA-4 were significantly upregulated at day 14 after stimulation, while subcutaneous ATDPCs only exhibited increased Cx43 expression. In response to electrical stimulation, cardiac ATDPCs elongated, and both cardiac and subcutaneous ATDPCs became aligned following the linear surface pattern of the construct. Cardiac ATDPC length increased by 11.3%, while subcutaneous ATDPC length diminished by 11.2% (p = 0.013 and p = 0.030 vs unstimulated controls, respectively). Compared to controls, electrostimulated cells became aligned better to the patterned surfaces when the pattern was perpendicular to the electric field (89.71 ± 28.47º for cardiac ATDPCs and 92.15 ± 15.21º for subcutaneous ATDPCs). Electrical stimulation of cardiac ATDPCs caused changes in cell phenotype and genetic machinery, making them more suitable for cardiac regeneration approaches. Thus, it seems advisable to use electrical cell training before delivery as a cell suspension or within engineered tissue.

  4. Human Cardiac Tissue Engineering: From Pluripotent Stem Cells to Heart Repair

    Science.gov (United States)

    Jackman, Christopher P.; Shadrin, Ilya Y.; Carlson, Aaron L.; Bursac, Nenad

    2014-01-01

    Engineered cardiac tissues hold great promise for use in drug and toxicology screening, in vitro studies of human physiology and disease, and as transplantable tissue grafts for myocardial repair. In this review, we discuss recent progress in cell-based therapy and functional tissue engineering using pluripotent stem cell-derived cardiomyocytes and we describe methods for delivery of cells into the injured heart. While significant hurdles remain, notable advances have been made in the methods to derive large numbers of pure human cardiomyocytes, mature their phenotype, and produce and implant functional cardiac tissues, bringing the field a step closer to widespread in vitro and in vivo applications. PMID:25599018

  5. Dose-dependent effect of Bisphenol-A on insulin signaling molecules in cardiac muscle of adult male rat.

    Science.gov (United States)

    Sivashanmugam, Preethi; Mullainadhan, Vigneswari; Karundevi, Balasubramanian

    2017-03-25

    Environmental contaminant, Bisphenol-A (BPA) is a xenoestrogen, an essential component used for the production of two classes of polymers such as polycarbonate and epoxy resin which disrupts the normal endocrine function. BPA has intense effects on mice endocrine pancreas, an essential tissue involved in glucose metabolism. It disrupts pancreatic β-cell insulin content, induces hyperinsulinemia and insulin resistance in male rats. Cardiac muscle is an insulin responsive organ and insulin has direct effects on glucose transport. The present study was designed to assess the effect of BPA on insulin signaling molecules in the cardiac muscle of adult male Wistar rat. Adult male Wistar rats (200-250 g) were selected and divided into following groups: Group 1: Control (vehicle treated), Group 2: Rats treated with 10 mg BPA/kg b.wt./day for 30 days orally, Group 3: Rats treated with 100 mg BPA/kg b.wt./day for 30 days orally, Group 4: Rats treated with 400 mg BPA/kg b.wt./day for 30 days orally. IR (insulin receptor) and pIR(Tyr1162) proteins were significantly decreased in the high dose group (400 mg). There was no change in IRS1 (insulin receptor substrate-1) and Akt proteins. Whereas, a decrease in pIRS1(Tyr632) (100 mg and 400 mg), pAkt (Ser473) (400 mg) and GLUT4 (glucose transporter 4) (cytosolic and plasma membrane) proteins was observed which may affect the cardiovascular function. It is concluded that BPA exposure has adverse effect on cardiac insulin signal transduction which may affect its function.

  6. Cardiac and Skeletal Muscle Defects in a Mouse Model of Human Barth Syndrome*

    Science.gov (United States)

    Acehan, Devrim; Vaz, Frederic; Houtkooper, Riekelt H.; James, Jeanne; Moore, Vicky; Tokunaga, Chonan; Kulik, Willem; Wansapura, Janaka; Toth, Matthew J.; Strauss, Arnold; Khuchua, Zaza

    2011-01-01

    Barth syndrome is an X-linked genetic disorder caused by mutations in the tafazzin (taz) gene and characterized by dilated cardiomyopathy, exercise intolerance, chronic fatigue, delayed growth, and neutropenia. Tafazzin is a mitochondrial transacylase required for cardiolipin remodeling. Although tafazzin function has been studied in non-mammalian model organisms, mammalian genetic loss of function approaches have not been used. We examined the consequences of tafazzin knockdown on sarcomeric mitochondria and cardiac function in mice. Tafazzin knockdown resulted in a dramatic decrease of tetralinoleoyl cardiolipin in cardiac and skeletal muscles and accumulation of monolysocardiolipins and cardiolipin molecular species with aberrant acyl groups. Electron microscopy revealed pathological changes in mitochondria, myofibrils, and mitochondrion-associated membranes in skeletal and cardiac muscles. Echocardiography and magnetic resonance imaging revealed severe cardiac abnormalities, including left ventricular dilation, left ventricular mass reduction, and depression of fractional shortening and ejection fraction in tafazzin-deficient mice. Tafazzin knockdown mice provide the first mammalian model system for Barth syndrome in which the pathophysiological relationships between altered content of mitochondrial phospholipids, ultrastructural abnormalities, myocardial and mitochondrial dysfunction, and clinical outcome can be completely investigated. PMID:21068380

  7. Cardiac and skeletal muscle scintigraphy in dermato- and polymyositis: clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Buchpiguel, C.A. [Centro de Medicina Nuclear, Dept. de Radiologia, Faculdade de Medicina da USP, Sao Paulo, SP (Brazil); Roizemblatt, S. [Dept. of Rheumatology, Sao Paulo Univ. School of Medicine (Brazil); Pastor, E.H. [Dept. of Rheumatology, Sao Paulo Univ. School of Medicine (Brazil); Hironaka, F.H. [Centro de Medicina Nuclear, Dept. de Radiologia, Faculdade de Medicina da USP, Sao Paulo, SP (Brazil); Cossermelli, W. [Dept. of Rheumatology, Sao Paulo Univ. School of Medicine (Brazil)

    1996-02-01

    To determine the role of scintigraphy in the detection of skeletal and cardiac involvement in dermato- and polymyosits (DM/PM), we studied 30 patients with a confirmed diagnosis of DM/PM (23 females, 7 males; mean age: 35 years). Technetium-99m pyrophosphate ({sup 99m}Tc-DYP) and gallium-67 scans showed similar sensitivity, specificity and accuracy in the detection of skeletal muscle involvement when compared with serum enzymes (70%, 100% and 80%, respectively). Compared with the clinical parameters, {sup 99m}Tc-PYP showed 70% and {sup 67}Ga 65% accuracy. Abnormal PYP cardiac uptake was observed in 57% of patients, whereas abnormal {sup 67}Ga cardiac uptake was seen in only 15%. Electrocardiogrpahy was abnormal in 40%, rest gated blood pool study in 23%, and chest X-ray in 13%. In conclusion, both {sup 99m}Tc-PYP and {sup 67}Ga can be useful in the detection of the active phase of muscle disease. However, {sup 99m}Tc-PYP seems to be more effective than {sup 67}Ga in the early diagnosis of cardiac involvement. (orig.)

  8. Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Kevin M. Lewis

    2016-09-01

    Full Text Available Calsequestrin is glycosylated and phosphorylated during its transit to its final destination in the junctional sarcoplasmic reticulum. To determine the significance and universal profile of these post-translational modifications to mammalian calsequestrin, we characterized, via mass spectrometry, the glycosylation and phosphorylation of skeletal muscle calsequestrin from cattle (B. taurus, lab mice (M. musculus and lab rats (R. norvegicus and cardiac muscle calsequestrin from cattle, lab rats and humans. On average, glycosylation of skeletal calsequestrin consisted of two N-acetylglucosamines and one mannose (GlcNAc2Man1, while cardiac calsequestrin had five additional mannoses (GlcNAc2Man6. Skeletal calsequestrin was not phosphorylated, while the C-terminal tails of cardiac calsequestrin contained between zero to two phosphoryls, indicating that phosphorylation of cardiac calsequestrin may be heterogeneous in vivo. Static light scattering experiments showed that the Ca2+-dependent polymerization capabilities of native bovine skeletal calsequestrin are enhanced, relative to the non-glycosylated, recombinant isoform, which our crystallographic studies suggest may be due to glycosylation providing a dynamic “guiderail”-like scaffold for calsequestrin polymerization. Glycosylation likely increases a polymerization/depolymerization response to changing Ca2+ concentrations, and proper glycosylation, in turn, guarantees both effective Ca2+ storage/buffering of the sarcoplasmic reticulum and localization of calsequestrin (Casq at its target site.

  9. (-)-Stepholodine induced enhancement of cardiac muscle contractions mediated by D1 receptors

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shu-yuan; LIU Zheng; HU Hui-sheng; SHI Zhen; CHEN Long

    2008-01-01

    Objective To investigate the effect of (-)-Stepholidine (SPD) on enhancing D1 receptor mediated contraction of cardiac muscle in isolated rat heart and to examine whether SPD has a direct effect on the heart dopamine D1 receptors. SPD an active ingredient of the Chinese herb Stephania intermedia, binds to dopamine D1 and D2 like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1/5) agonist and a D(2/4) antagonist, which could indicate unique antipsychotic properties. Methods Normal adult rat working hearts were isolated by Langendorff technique. Results SPD significantly increased the cardiac muscle contraction in a dose-dependent manner. The selective D1 dopamine receptor antagonist SCH23390 (1 μM) blocked the SPD induced heart contraction, however, neither the β-receptor antagonist propranolol (1 μM) nor the α1-receptor antagonist prazosin (1 μM) had any effect on blocking SPD induced heart contractions. Moreover, the L-type Ca2+ channel inhibitor nimodipine (1 μM) completely blocked the effect of SPD on cardiac muscle contraction. Conclusions SPD show the effect on enhancing contraction of isolated rat heart through activating L-type Ca2+ channel mediated by heart D1 receptors.

  10. Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury

    DEFF Research Database (Denmark)

    Mackey, Abigail Louise; Kjaer, Michael

    2016-01-01

    the adaptation throughout this process of both the connective tissue structures surrounding the myofibres, and the fibroblasts, the cells responsible for synthesising this connective tissue. However, the few studies investigating muscle connective tissue remodelling demonstrate a strong response that appears...... when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning...

  11. Zebrafish cardiac muscle thick filaments: isolation technique and three-dimensional structure.

    Science.gov (United States)

    González-Solá, Maryví; Al-Khayat, Hind A; Behra, Martine; Kensler, Robert W

    2014-04-15

    To understand how mutations in thick filament proteins such as cardiac myosin binding protein-C or titin, cause familial hypertrophic cardiomyopathies, it is important to determine the structure of the cardiac thick filament. Techniques for the genetic manipulation of the zebrafish are well established and it has become a major model for the study of the cardiovascular system. Our goal is to develop zebrafish as an alternative system to the mammalian heart model for the study of the structure of the cardiac thick filaments and the proteins that form it. We have successfully isolated thick filaments from zebrafish cardiac muscle, using a procedure similar to those for mammalian heart, and analyzed their structure by negative-staining and electron microscopy. The isolated filaments appear well ordered with the characteristic 42.9 nm quasi-helical repeat of the myosin heads expected from x-ray diffraction. We have performed single particle image analysis on the collected electron microscopy images for the C-zone region of these filaments and obtained a three-dimensional reconstruction at 3.5 nm resolution. This reconstruction reveals structure similar to the mammalian thick filament, and demonstrates that zebrafish may provide a useful model for the study of the changes in the cardiac thick filament associated with disease processes.

  12. Gold nanoparticle-decellularized matrix hybrids for cardiac tissue engineering.

    Science.gov (United States)

    Shevach, Michal; Fleischer, Sharon; Shapira, Assaf; Dvir, Tal

    2014-10-01

    Decellularized matrices are valuable scaffolds for engineering functional cardiac patches for treating myocardial infarction. However, the lack of quick and efficient electrical coupling between adjacent cells may jeopardize the success of the treatment. To address this issue, we have deposited gold nanoparticles on fibrous decellularized omental matrices and investigated their morphology, conductivity, and degradation. We have shown that cardiac cells engineered within the hybrid scaffolds exhibited elongated and aligned morphology, massive striation, and organized connexin 43 electrical coupling proteins. Finally, we have shown that the hybrid patches demonstrated superior function as compared to pristine patches, including a stronger contraction force, lower excitation threshold, and faster calcium transients.

  13. Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia.

    Science.gov (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

    2013-02-01

    Familial dysautonomia (Riley-Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement.

  14. Anisotropic x-ray scattering and orientation fields in cardiac tissue cells

    Science.gov (United States)

    Bernhardt, M.; Nicolas, J.-D.; Eckermann, M.; Eltzner, B.; Rehfeldt, F.; Salditt, T.

    2017-01-01

    X-ray diffraction from biomolecular assemblies is a powerful technique which can provide structural information about complex architectures such as the locomotor systems underlying muscle contraction. However, in its conventional form, macromolecular diffraction averages over large ensembles. Progress in x-ray optics has now enabled to probe structures on sub-cellular scales, with the beam confined to a distinct organelle. Here, we use scanning small angle x-ray scattering (scanning SAXS) to probe the diffraction from cytoskeleton networks in cardiac tissue cells. In particular, we focus on actin-myosin composites, which we identify as the dominating contribution to the anisotropic diffraction patterns, by correlation with optical fluorescence microscopy. To this end, we use a principal component analysis approach to quantify direction, degree of orientation, nematic order, and the second moment of the scattering distribution in each scan point. We compare the fiber orientation from micrographs of fluorescently labeled actin fibers to the structure orientation of the x-ray dataset and thus correlate signals of two different measurements: the native electron density distribution of the local probing area versus specifically labeled constituents of the sample. Further, we develop a robust and automated fitting approach based on a power law expansion, in order to describe the local structure factor in each scan point over a broad range of the momentum transfer {q}{{r}}. Finally, we demonstrate how the methodology shown for freeze dried cells in the first part of the paper can be translated to alive cell recordings.

  15. Regulation of Cardiac Hypertrophy: the nuclear option

    NARCIS (Netherlands)

    D.W.D. Kuster (Diederik)

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, c

  16. Engineering muscle tissue for the fetus: getting ready for a strong life

    Directory of Open Access Journals (Sweden)

    George Joseph Christ

    2015-04-01

    Full Text Available Congenital malformations frequently involve either skeletal, smooth or cardiac tissues. When large parts of those tissues are damaged, the repair of the malformations is challenged by the fact that so much autologous tissue is missing. Current treatments require the use of prostheses or other therapies and are associated with a significant morbidity and mortality. Nonetheless, affected children have generally good survival rates and mostly normal schooling. As such, new therapeutic modalities need to represent significant improvements with clear safety profiles. Regenerative medicine and tissue engineering technologies have the potential to dramatically improve the treatment of any disease or disorder involving a lack of viable tissue. With respect to congenital soft tissue anomalies, the development of, for example, implantable muscle constructs would provide not only the usual desired elasticity and contractile proprieties, but should also be able to grow with the fetus and/or in the postnatal life. Such an approach would eliminate the need for multiple surgeries. However, the more widespread clinical applications of regenerative medicine and tissue engineering technologies require identification of the optimal indications, as well as further elucidation of the precise mechanisms and best methods (cells, scaffolds/biomaterials for achieving large functional tissue regeneration in those clinical indications. In short, despite some amazing scientific progress, significant safety and efficacy hurdles remain. However, the rapid preclinical advances in the field bode well for future applications. As such, translational researchers and clinicians alike need be informed and prepared to utilize these new techniques for the benefit of their patients, as soon as they are available. To this end, we review herein, the clinical need(s, potential applications, and the relevant preclinical studies that are currently guiding the field toward novel

  17. Molecular cloning and in silico analysis of the duck (Anas platyrhynchos MEF2A gene cDNA and its expression profile in muscle tissues during fetal development

    Directory of Open Access Journals (Sweden)

    Hehe Liu

    2012-01-01

    Full Text Available The role of myogenic enhancer transcription factor 2a (MEF2A in avian muscle during fetal development is unknown. In this work, we cloned the duck MEF2A cDNA sequence (GenBank accession no. HM460752 and examined its developmental expression profiles in cardiac muscle, non-vascular smooth muscle and skeletal muscle. Duck MEF2A cDNA comprised 1479 bp encoding 492 amino acid residues. In silico analysis showed that MEF2A contained MADS (MCM1, AGAMOUS, DEFICIENS and SRF -serum response factor, MEF2 and mitogen-activated protein kinase (MAPK transcription domains with high homology to related proteins in other species. Modified sites in these domains were conserved among species and several variants were found. Quantitative PCR showed that MEF2A was expressed in all three muscles at each developmental stage examined, with the expression in smooth muscle being higher than in the other muscles. These results indicate that the conserved domains of duck MEF2A, including the MADS and MEF2 domains, are important for MEF2A transcription factor function. The expression of MEF2A in duck smooth muscle and cardiac muscle suggests that MEF2A plays a role in these two tissues.

  18. Early remodeling of rat cardiac muscle induced by swimming training

    Directory of Open Access Journals (Sweden)

    Verzola R.M.M.

    2006-01-01

    Full Text Available The aim of the present investigation was to study the effect of acute swimming training with an anaerobic component on matrix metallopeptidase (MMP activity and myosin heavy chain gene expression in the rat myocardium. Animals (male Wistar rats, weighing approximately 180 g were trained for 6 h/day in 3 sessions of 2 h each for 1 to 5 consecutive days (N = 5 rats per group. Rats swam in basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35ºC. After the training period a significant increase (P < 0.05 was observed in the heart weight normalized to body weight by about 22 and 35% in the groups that trained for 96 and 120 h, respectively. Blood lactate levels were significantly increased (P < 0.05 in all groups after all training sessions, confirming an anaerobic component. However, lactate levels decreased (P < 0.05 with days of training, suggesting that the animals became adapted to this protocol. Myosin heavy chain-ß gene expression, analyzed by real time PCR and normalized with GAPDH gene expression, showed a significant two-fold increase (P < 0.01 after 5 days of training. Zymography analysis of myocardium extracts indicated a single ~60-kDa activity band that was significantly increased (P < 0.05 after 72, 96, and 120 h, indicating an increased expression of MMP-2 and suggesting precocious remodeling. Furthermore, the presence of MMP-2 was confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3. Taken together, our results indicate that in these training conditions, the rat heart undergoes early biochemical and functional changes required for the adaptation to the new physiological condition by tissue remodeling.

  19. Functional evaluation of artificial skeletal muscle tissue constructs fabricated by a magnetic force-based tissue engineering technique.

    Science.gov (United States)

    Yamamoto, Yasunori; Ito, Akira; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

    2011-01-01

    Skeletal muscle tissue engineering is currently applied in a variety of research fields, including regenerative medicine, drug screening, and bioactuator development, all of which require the fabrication of biomimic and functional skeletal muscle tissues. In the present study, magnetite cationic liposomes were used to magnetically label C2C12 myoblast cells for the construction of three-dimensional artificial skeletal muscle tissues by an applied magnetic force. Skeletal muscle functions, such as biochemical and contractile properties, were evaluated for the artificial tissue constructs. Histological studies revealed that elongated and multinucleated myotubes were observed within the tissue. Expression of muscle-specific markers, such as myogenin, myosin heavy chain and tropomyosin, were detected in the tissue constructs by western blot analysis. Further, creatine kinase activity increased during differentiation. In response to electric pulses, the artificial tissue constructs contracted to generate a physical force (the maximum twitch force, 33.2 μN [1.06 mN/mm2]). Rheobase and chronaxie of the tissue were determined as 4.45 V and 0.72 ms, respectively. These results indicate that the artificial skeletal muscle tissue constructs fabricated in this study were physiologically functional and the data obtained for the evaluation of their functional properties may provide useful information for future skeletal muscle tissue engineering studies.

  20. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    Science.gov (United States)

    2011-10-01

    in cardiology since early 50s is the development of an artificial heart that can replace a failing heart. Until today, artificial heart is used only...Engineering Dr. M. Gibb, Head of Cardiology , Carle Hospital Dr. Sherrie Clark, UIUC swine species veterinarian 7 Year 3 Project Goals Interface DFB...sarcomere lengths in the normal dog heart, Circulation Research 21 (1967) 671-678. [5] E.J. DeSouza, W. Ahmed, V. Chan, R. Bahir, T.M. Saif, Cardiac

  1. Micro and Nano-mediated 3D Cardiac Tissue Engineering

    Science.gov (United States)

    2009-10-01

    13-70% positive for CD34, similar to values and ranges found for both excised and liposuction derived human cells. Also similar to human cells... position , policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public...studies. We examined the effects of substrate stiffness on the beating rate and beating force in embryonic chicken cardiac myocytes. Our results

  2. Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yutaka; Matsui; Junko; Morimoto; Toshimitsu; Uede

    2010-01-01

    After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.

  3. DETECTION OF LEPTIN IN MUSCLE TISSUES AND ORGANS OF PIGS

    Directory of Open Access Journals (Sweden)

    Simona Kunová

    2015-02-01

    Full Text Available The aim of this study was detection of gene leptin in muscles, liver and kidneys from pigs of breed Large White. Using Real time PRC method, we determined the Ct values of leptim gene in muscle, liver, kidney. The body weight of pigs ranged from 100 kg to 103 kg. The average body weight was 101.6 kg. The thickness of backfat ranged from 10 to 20 mm, average backfat thickness was 16 mm. The minimal Ct value of leptin gene in liver was 24.05 and the maximal value was 25.79. Average Ct value of leptin gene was 24.84. The minimal Ct value of leptin gene in muscle tissue was 25.83 and the maximal value was 27.05. Average Ct value of leptin gene was 26.41. The Ct value of leptin gene in liver ranged from 24.05 to 25.79. Average Ct value of leptin gene was 24.84. Leptin gene is expressed by porcine preadipocytes and leptin gene expression is highly dependent on dexamethasone induced preadipocyte differentiation. Hormonally driven preadipocyte recruitment and subsequent fat cell size may regulate leptin gene expression in the pig.

  4. Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues.

    Science.gov (United States)

    Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

    2017-01-01

    Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

  5. Moldable elastomeric polyester-carbon nanotube scaffolds for cardiac tissue engineering.

    Science.gov (United States)

    Ahadian, Samad; Davenport Huyer, Locke; Estili, Mehdi; Yee, Bess; Smith, Nathaniel; Xu, Zhensong; Sun, Yu; Radisic, Milica

    2017-04-01

    Polymer biomaterials are used to construct scaffolds in tissue engineering applications to assist in mechanical support, organization, and maturation of tissues. Given the flexibility, electrical conductance, and contractility of native cardiac tissues, it is desirable that polymeric scaffolds for cardiac tissue regeneration exhibit elasticity and high electrical conductivity. Herein, we developed a facile approach to introduce carbon nanotubes (CNTs) into poly(octamethylene maleate (anhydride) 1,2,4-butanetricarboxylate) (124 polymer), and developed an elastomeric scaffold for cardiac tissue engineering that provides electrical conductivity and structural integrity to 124 polymer. 124 polymer-CNT materials were developed by first dispersing CNTs in poly(ethylene glycol) dimethyl ether porogen and mixing with 124 prepolymer for molding into shapes and crosslinking under ultraviolet light. 124 polymers with 0.5% and 0.1% CNT content (wt) exhibited improved conductivity against pristine 124 polymer. With increasing the CNT content, surface moduli of hybrid polymers were increased, while their bulk moduli were decreased. Furthermore, increased swelling of hybrid 124 polymer-CNT materials was observed, suggesting their improved structural support in an aqueous environment. Finally, functional characterization of engineered cardiac tissues using the 124 polymer-CNT scaffolds demonstrated improved excitation threshold in materials with 0.5% CNT content (3.6±0.8V/cm) compared to materials with 0% (5.1±0.8V/cm) and 0.1% (5.0±0.7V/cm), suggesting greater tissue maturity. 124 polymer-CNT materials build on the advantages of 124 polymer elastomer to give a versatile biomaterial for cardiac tissue engineering applications.

  6. Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

    Energy Technology Data Exchange (ETDEWEB)

    Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.; Ertel, P.J.; Bemis, K.G.; Robertson, D.W. (Eli Lilly and Company, Indianapolis, IN (USA))

    1991-01-01

    Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09 microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas.

  7. Dynamic adaptation of tendon and muscle connective tissue to mechanical loading

    DEFF Research Database (Denmark)

    Mackey, Abigail; Heinemeier, Katja Maria; Koskinen, Satu Osmi Anneli

    2008-01-01

    The connective tissue of tendon and skeletal muscle is a crucial structure for force transmission. A dynamic adaptive capacity of these tissues in healthy individuals is evident from reports of altered gene expression and protein levels of the fibrillar and network-forming collagens, when subjected...... in this article provide strong evidence for the highly adaptable nature of connective tissue in muscle and tendon....

  8. Cardiac-induced physiologic noise in tissue is a direct observation of cardiac-induced fluctuations.

    Science.gov (United States)

    Bhattacharyya, Pallab K; Lowe, Mark J

    2004-01-01

    Recent studies have shown that in certain cases, cardiac and respiratory rate fluctuations in BOLD-weighted MRI time courses may be an artifact unique to rapid sampled acquisitions and may not be present in longer repetition-time acquisitions. The implication of this is that, in these cases, cardiac and respiratory rate fluctuations are not aliased into data that undersample these effects and do not affect the resulting time course measurements. In this study, we show that these cases are specific to regions of large cerebrospinal fluid content and are not generally true for gray matter regions of the brain. We demonstrate that in many brain regions of interest, these fluctuations are directly observed as BOLD fluctuations and thus will affect measurements that undersample these effects.

  9. A hybrid stimulation strategy for suppression of spiral waves in cardiac tissue

    Energy Technology Data Exchange (ETDEWEB)

    Xu Binbin, E-mail: xubinbin@hotmail.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Jacquir, Sabir, E-mail: sjacquir@u-bourgogne.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Laurent, Gabriel; Bilbault, Jean-Marie [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Binczak, Stephane, E-mail: stbinc@u-bourgogne.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France)

    2011-08-15

    Highlights: > Simulation of a cardiac tissue by a modified 2D FitzHugh-Nagumo model. > Stimulation of monophasic impulsions from a grid of electrodes to the cardiac tissue. > Propose a method by modifying the tissue's sodium channels and electrical stimulation. > The method leading to suppress spiral waves without generating new ones. > Optimal parameters of a successful suppression of spiral waves are investigated. - Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia whose mechanisms are thought to be mainly due to the self perpetuation of spiral waves (SW). To date, available treatment strategies (antiarrhythmic drugs, radiofrequency ablation of the substrate, electrical cardioversion) to restore and to maintain a normal sinus rhythm have limitations and are associated with AF recurrences. The aim of this study was to assess a way of suppressing SW by applying multifocal electrical stimulations in a simulated cardiac tissue using a 2D FitzHugh-Nagumo model specially convenient for AF investigations. We identified stimulation parameters for successful termination of SW. However, SW reinduction, following the electrical stimuli, leads us to develop a hybrid strategy based on sodium channel modification for the simulated tissue.

  10. PGS:Gelatin Nanofibrous Scaffolds with Tunable Mechanical and Structural Properties for Engineering Cardiac Tissues

    Science.gov (United States)

    Kharaziha, Mahshid; Nikkhah, Mehdi; Shin, Su-Ryon; Annabi, Nasim; Masoumi, Nafiseh; Gaharwar, Akhilesh K.; Camci-Unal, Gulden; Khademhosseini, Ali

    2013-01-01

    A significant challenge in cardiac tissue engineering is the development of biomimetic grafts that can potentially promote myocardial repair and regeneration. A number of approaches have used engineered scaffolds to mimic the architecture of the native myocardium tissue and precisely regulate cardiac cell functions. However previous attempts have not been able to simultaneously recapitulate chemical, mechanical, and structural properties of the myocardial extracellular matrix (ECM). In this study, we utilized an electrospinning approach to fabricate elastomeric biodegradable poly(glycerol-sebacate) (PGS):gelatin scaffolds with a wide range of chemical composition, stiffness and anisotropy. Our findings demonstrated that through incorporation of PGS, it is possible to create nanofibrous scaffolds with well-defined anisotropy that mimics the left ventricular myocardium architecture. Furthermore, we studied attachment, proliferation, differentiation and alignment of neonatal rat cardiac fibroblast cells (CFs) as well as protein expression, alignment, and contractile function of cardiomyocyte (CMs) on PGS:gelatin scaffolds with variable amount of PGS. Notably, aligned nanofibrous scaffold, consisting of 33 wt. % PGS, induced optimal synchronous contractions of CMs while significantly enhanced cellular alignment. Overall, our study suggests that the aligned nanofibrous PGS:gelatin scaffold support cardiac cell organization, phenotype and contraction and could potentially be used to develop clinically relevant constructs for cardiac tissue engineering. PMID:23747008

  11. Autologous Minced Muscle Grafts: A Tissue Engineering Therapy for the Volumetric Loss of Skeletal Muscle

    Science.gov (United States)

    2013-07-24

    allotted to one of three time points postinjury: 2, 8, or 16 wk. At these times, tissue was collected for histological and molecular analyses. At 8 and 16...from the CyQUANT kit, and read on a SpectraMax M2 plate reader ( Molecular Devices, Sunnyvale, CA) with excitation at 480 nm and emission at 520 nm. DNA...auto-, homo, and hetero-transplantation]. Biologia (Bratislava) 13: 514–522, 1958. 25. Huijing PA, Jaspers RT. Adaptation of muscle size and myofascial

  12. Real time assessment of RF cardiac tissue ablation with optical spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Demos, S G; Sharareh, S

    2008-03-20

    An optical spectroscopy approach is demonstrated allowing for critical parameters during RF ablation of cardiac tissue to be evaluated in real time. The method is based on incorporating in a typical ablation catheter transmitting and receiving fibers that terminate at the tip of the catheter. By analyzing the spectral characteristics of the NIR diffusely reflected light, information is obtained on such parameters as, catheter-tissue proximity, lesion formation, depth of penetration of the lesion, formation of char during the ablation, formation of coagulum around the ablation site, differentiation of ablated from healthy tissue, and recognition of micro-bubble formation in the tissue.

  13. A pharmacological investigation of the venom extract of the Australian box jellyfish, Chironex fleckeri, in cardiac and vascular tissues.

    Science.gov (United States)

    Hughes, Richard J A; Angus, James A; Winkel, Kenneth D; Wright, Christine E

    2012-02-25

    The pharmacology of Australian box jellyfish, Chironex fleckeri, unpurified (crude) nematocyst venom extract (CVE) was investigated in rat isolated cardiac and vascular tissues and in anaesthetised rats. In small mesenteric arteries CVE (0.01-30 μg/ml) caused contractions (EC(50) 1.15±0.19 μg/ml) that were unaffected by prazosin (0.1 μM), bosentan (10 μM), CGRP(8-37) (1 μM) or tetrodotoxin (1 μM). Box jellyfish antivenom (5-92.6 units/ml) caused rightward shifts of the CVE concentration-response curve with no change in the maximum. In the presence of l-NAME (100 μM) the sensitivity and maximum response to CVE were increased, whilst MgSO(4) (6 mM) decreased both parameters. CVE (1-10 μg/ml) caused inhibition of the contractile response to electrical sympathetic nerve stimulation. Left atrial responses to CVE (0.001-30 μg/ml) were bi-phasic, composed of an initial positive inotropy followed by a marked negative inotropy and atrial standstill. CVE (0.3 μg/ml) elicited a marked decrease in right atrial rate followed by atrial standstill at 3 μg/ml. These responses were unaffected by 1 μM of propranolol, atropine or CGRP(8-37). Antivenom (54 and 73 units/ml) caused rightward shifts of the CVE concentration-response curve and prevented atrial standstill in left and right atria. The effects of CVE do not appear to involve autonomic nerves, post-synaptic α(1)- or β(1)-adrenoceptors, or muscarinic, endothelin or CGRP receptors, but may occur through direct effects on the cardiac and vascular muscle. Box jellyfish antivenom was effective in attenuating CVE-induced responses in isolated cardiac and vascular tissues.

  14. Evaluation of optical imaging and spectroscopy approaches for cardiac tissue depth assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lin, B; Matthews, D; Chernomordik, V; Gandjbakhche, A; Lane, S; Demos, S G

    2008-02-13

    NIR light scattering from ex vivo porcine cardiac tissue was investigated to understand how imaging or point measurement approaches may assist development of methods for tissue depth assessment. Our results indicate an increase of average image intensity as thickness increases up to approximately 2 mm. In a dual fiber spectroscopy configuration, sensitivity up to approximately 3 mm with an increase to 6 mm when spectral ratio between selected wavelengths was obtained. Preliminary Monte Carlo results provided reasonable fit to the experimental data.

  15. Vanadium and cadmium in vivo effects in teleost cardiac muscle: metal accumulation and oxidative stress markers.

    Science.gov (United States)

    Soares, S S; Martins, H; Gutiérrez-Merino, C; Aureliano, M

    2008-03-01

    Several biological studies associate vanadium and cadmium with the production of reactive oxygen species (ROS), leading to lipid peroxidation and antioxidant enzymes alterations. The present study aims to analyse and compare the oxidative stress responses induced by an acute intravenous exposure (1 and 7 days) to a sub-lethal concentration (5 mM) of two vanadium solutions, containing different vanadate n-oligomers (n=1-5 or n=10), and a cadmium solution on the cardiac muscle of the marine teleost Halobatrachus didactylus (Lusitanian toadfish). It was observed that vanadium is mainly accumulated in mitochondria (1.33+/-0.26 microM), primarily when this element was administrated as decameric vanadate, than when administrated as metavanadate (432+/-294 nM), while the highest content of cadmium was found in cytosol (365+/-231 nM). Indeed, decavanadate solution promotes stronger increases in mitochondrial antioxidant enzymes activities (catalase: +120%; superoxide dismutase: +140%) than metavanadate solution. On contrary, cadmium increases cytosolic catalase (+111%) and glutathione peroxidases (+50%) activities. It is also observed that vanadate oligomers induce in vitro prooxidant effects in toadfish heart, with stronger effects induced by metavanadate solution. In summary, vanadate and cadmium are differently accumulated in blood and cardiac subcellular fractions and induced different responses in enzymatic antioxidant defence mechanisms. In the present study, it is described for the first time the effects of equal doses of two different metals intravenously injected in the same fish species and upon the same exposure period allowing to understand the mechanisms of vanadate and cadmium toxicity in fish cardiac muscle.

  16. High expression of nuclear factor 90 (NF90 leads to mitochondrial degradation in skeletal and cardiac muscles.

    Directory of Open Access Journals (Sweden)

    Takuma Higuchi

    Full Text Available While NF90 has been known to participate in transcription, translation and microRNA biogenesis, physiological functions of this protein still remain unclear. To uncover this, we generated transgenic (Tg mice using NF90 cDNA under the control of β-actin promoter. The NF90 Tg mice exhibited a reduction in body weight compared with wild-type mice, and a robust expression of NF90 was detected in skeletal muscle, heart and eye of the Tg mice. To evaluate the NF90 overexpression-induced physiological changes in the tissues, we performed a number of analyses including CT-analysis and hemodynamic test, revealing that the NF90 Tg mice developed skeletal muscular atrophy and heart failure. To explore causes of the abnormalities in the NF90 Tg mice, we performed histological and biochemical analyses for the skeletal and cardiac muscles of the Tg mice. Surprisingly, these analyses demonstrated that mitochondria in those muscular tissues of the Tg mice were degenerated by autophagy. To gain further insight into the cause for the mitochondrial degeneration, we identified NF90-associated factors by peptide mass fingerprinting. Of note, approximately half of the NF90-associated complexes were ribosome-related proteins. Interestingly, protein synthesis rate was significantly suppressed by high-expression of NF90. These observations suggest that NF90 would negatively regulate the function of ribosome via its interaction with the factors involved in the ribosome function. Furthermore, we found that the translations or protein stabilities of PGC-1 and NRF-1, which are critical transcription factors for expression of mitochondrial genes, were significantly depressed in the skeletal muscles of the NF90 Tg mice. Taken together, these findings suggest that the mitochondrial degeneration engaged in the skeletal muscle atrophy and the heart failure in the NF90 Tg mice may be caused by NF90-induced posttranscriptional repression of transcription factors such as PGC-1 and

  17. Measurements of pericardial adipose tissue using contrast enhanced cardiac multidetector computed tomography—comparison with cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Elming, Marie Bayer; Lønborg, Jacob; Rasmussen, Thomas;

    2013-01-01

    Recent studies have suggested that pericardial adipose tissue (PAT) located in close vicinity to the epicardial coronary arteries may play a role in the development of coronary artery disease. PAT has primarily been measured with cardiac magnetic resonance imaging (CMRI) or with non...... tested, and the smallest difference in PAT was noted when -30 to -190 HU were used in MDCT measures. The median difference between MDCT and CMRI for the assessment of PAT was 9 ml (SD 50) suggesting a reasonable robust method for the assessment of PAT in a large-scale study. Pericardial adipose tissue...... and CMRI scans were performed. The optimal fit for measuring PAT using contrast MDCT was developed and validated by the corresponding measures on CMRI. The median for PAT volume in patients was 175 ml (SD 68) and 153 ml (SD 60) measured by MDCT and CMRI respectively. Four different attenuation values were...

  18. Exposure to a Low Lead Concentration Impairs Contractile Machinery in Rat Cardiac Muscle.

    Science.gov (United States)

    Silva, Marito A S C; de Oliveira, Thiago F; Almenara, Camila C P; Broseghini-Filho, Gilson B; Vassallo, Dalton V; Padilha, Alessandra S; Silveira, Edna A

    2015-10-01

    Lead exposure has been considered to be a risk factor for hypertension and cardiovascular disease. Our purpose was to evaluate the effects of low plasma lead concentration on cardiac contractility in isolated papillary muscles. Wistar rats were divided in control group or group treated with 100 ppm of lead acetate in the drinking water for 15 days. Blood pressure (BP) was measured weekly. At the end of the treatment period, the animals were anesthetized and euthanized, and parameters related to isolated papillary muscle contractility were recorded. The lead concentrations in the blood reached 12.3 ± 2 μg/dL. The BP was increased in the group treated with 100 ppm of lead acetate. Lead treatment did not alter force and time derivatives of the force of left ventricular papillary muscles. In addition, the inotropic response induced by an increase in the extracellular Ca(2+) concentration was reduced in the Pb(2+) group. However, the uptake of Ca(2+) by the sarcoplasmic reticulum and the protein expression of SERCA and phospholamban remained unchanged. Postrest contraction was similar in the both groups, and tetanic peak and plateau tension were reduced in lead group. These results demonstrated that the reduction in the inotropic response to calcium does not appear to be caused by changes in the trans-sarcolemmal calcium flux but suggest that an impairment of the contractile machinery might be taking place. Our results demonstrate that even at a concentration below the limit considered to be safe, lead exerts deleterious effects on the cardiac contractile machinery.

  19. Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin beta-4 in the dystrophin deficient mouse.

    Directory of Open Access Journals (Sweden)

    Christopher F Spurney

    Full Text Available Thymosin beta-4 (Tbeta4 is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tbeta4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ and mdx mice, 8-10 weeks old, were treated with 150 microg of Tbeta4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tbeta4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tbeta4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tbeta4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tbeta4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy.

  20. Tolerance to low temperatures of Toxocara cati larvae in chicken muscle tissue

    DEFF Research Database (Denmark)

    Taira, Kensuke; Saitoh, Yasuhide; Okada, Natsuki;

    2012-01-01

    Infectivity of Toxocara cati larvae in muscle tissue of chickens after storage at 4 degrees C and -25 degrees C was assessed in a mouse bioassay to provide information on the risk of meat-borne toxocarosis. Muscle tissue samples of 30-day old T. cati infections were stored at 4 degrees C for 14...

  1. Comparison of prenatal musle tissue expression profiles of two pigs breed differing in muscle characteristics

    NARCIS (Netherlands)

    Cagnazzo, M.; Pas, te M.F.W.; Priem, J.; Wit, de A.A.C.; Pool, M.H.; Davoli, R.; Russo, V.

    2006-01-01

    The objective of this study was to compare purebred Duroc and Pietrain prenatal muscle tissue transcriptome expression levels at different stages of prenatal development to gain insight into the differences in muscle tissue development in these pig breeds. Commercial western pig breeds have been sel

  2. TRPV-1-mediated elimination of residual iPS cells in bioengineered cardiac cell sheet tissues.

    Science.gov (United States)

    Matsuura, Katsuhisa; Seta, Hiroyoshi; Haraguchi, Yuji; Alsayegh, Khaled; Sekine, Hidekazu; Shimizu, Tatsuya; Hagiwara, Nobuhisa; Yamazaki, Kenji; Okano, Teruo

    2016-02-18

    The development of a suitable strategy for eliminating remaining undifferentiated cells is indispensable for the use of human-induced pluripotent stem (iPS) cell-derived cells in regenerative medicine. Here, we show for the first time that TRPV-1 activation through transient culture at 42 °C in combination with agonists is a simple and useful strategy to eliminate iPS cells from bioengineered cardiac cell sheet tissues. When human iPS cells were cultured at 42 °C, almost all cells disappeared by 48 hours through apoptosis. However, iPS cell-derived cardiomyocytes and fibroblasts maintained transcriptional and protein expression levels, and cardiac cell sheets were fabricated after reducing the temperature. TRPV-1 expression in iPS cells was upregulated at 42 °C, and iPS cell death at 42 °C was TRPV-1-dependent. Furthermore, TRPV-1 activation through thermal or agonist treatment eliminated iPS cells in cardiac tissues for a final concentration of 0.4% iPS cell contamination. These findings suggest that the difference in tolerance to TRPV-1 activation between iPS cells and iPS cell-derived cardiac cells could be exploited to eliminate remaining iPS cells in bioengineered cell sheet tissues, which will further reduce the risk of tumour formation.

  3. Fourier transform infrared spectroscopic imaging of cardiac tissue to detect collagen deposition after myocardial infarction

    Science.gov (United States)

    Cheheltani, Rabee; Rosano, Jenna M.; Wang, Bin; Sabri, Abdel Karim; Pleshko, Nancy; Kiani, Mohammad F.

    2012-05-01

    Myocardial infarction often leads to an increase in deposition of fibrillar collagen. Detection and characterization of this cardiac fibrosis is of great interest to investigators and clinicians. Motivated by the significant limitations of conventional staining techniques to visualize collagen deposition in cardiac tissue sections, we have developed a Fourier transform infrared imaging spectroscopy (FT-IRIS) methodology for collagen assessment. The infrared absorbance band centered at 1338 cm-1, which arises from collagen amino acid side chain vibrations, was used to map collagen deposition across heart tissue sections of a rat model of myocardial infarction, and was compared to conventional staining techniques. Comparison of the size of the collagen scar in heart tissue sections as measured with this methodology and that of trichrome staining showed a strong correlation (R=0.93). A Pearson correlation model between local intensity values in FT-IRIS and immuno-histochemical staining of collagen type I also showed a strong correlation (R=0.86). We demonstrate that FT-IRIS methodology can be utilized to visualize cardiac collagen deposition. In addition, given that vibrational spectroscopic data on proteins reflect molecular features, it also has the potential to provide additional information about the molecular structure of cardiac extracellular matrix proteins and their alterations.

  4. Muscle shortening velocity depends on tissue inertia and level of activation during submaximal contractions.

    Science.gov (United States)

    Ross, Stephanie A; Wakeling, James M

    2016-06-01

    In order to perform external work, muscles must do additional internal work to deform their tissue, and in particular, to overcome the inertia due to their internal mass. However, the contribution of the internal mass within a muscle to the mechanical output of that muscle has only rarely been studied. Here, we use a dynamic, multi-element Hill-type muscle model to examine the effects of the inertial mass within muscle on its contractile performance. We find that the maximum strain-rate of muscle is slower for lower activations and larger muscle sizes. As muscle size increases, the ability of the muscle to overcome its inertial load will decrease, as muscle tension is proportional to cross-sectional area and inertial load is proportional to mass. Thus, muscles that are larger in size will have a higher inertial cost to contraction. Similarly, when muscle size and inertial load are held constant, decreasing muscle activation will increase inertial cost to contraction by reducing muscle tension. These results show that inertial loads within muscle contribute to a slowing of muscle contractile velocities (strain-rates), particularly at the submaximal activations that are typical during animal locomotion.

  5. Ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expressions in heart tissues of rats exposed to incense smoke.

    Science.gov (United States)

    Al-Attas, Omar S; Hussain, Tajamul; Ahmed, Mukhtar; Al-Daghri, Nasser; Mohammed, Arif A; De Rosas, Edgard; Gambhir, Dikshit; Sumague, Terrance S

    2015-07-01

    Incense smoke exposure has recently been linked to cardiovascular disease risk, heart rate variability, and endothelial dysfunction. To test the possible underlying mechanisms, oxidative stress, and inflammatory markers, gene expressions of cardiac hypertrophic and xenobiotic-metabolizing enzymes and ultrastructural changes were measured, respectively, using standard, ELISA-based, real-time PCR, and transmission electron microscope procedures in heart tissues of Wistar rats after chronically exposing to Arabian incense. Malondialdehyde, tumor necrosis alpha (TNF)-α, and IL-4 levels were significantly increased, while catalase and glutathione levels were significantly declined in incense smoke-exposed rats. Incense smoke exposure also resulted in a significant increase in atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain, CYP1A1 and CYP1A2 messenger RNAs (mRNAs). Rats exposed to incense smoke displayed marked ultrastructural changes in heart muscle with distinct cardiac hypertrophy, which correlated with the augmented hypertrophic gene expression as well as markers of cardiac damage including creatine kinase-myocardial bound (CK-MB) and lactate dehydrogenase (LDH). Increased oxidative stress, inflammation, altered cardiac hypertrophic gene expression, tissue damage, and architectural changes in the heart may collectively contribute to increased cardiovascular disease risk in individuals exposed to incense smoke. Increased gene expressions of CYP1A1 and CYP1A2 may be instrumental in the incense smoke-induced oxidative stress and inflammation. Thus, incense smoke can be considered as a potential environmental pollutant and its long-term exposure may negatively impact human health.

  6. Tuning of shortening speed in coleoid cephalopod muscle: no evidence for tissue-specific muscle myosin heavy chain isoforms.

    Science.gov (United States)

    Shaffer, Justin F; Kier, William M

    2016-03-01

    The contractile protein myosin II is ubiquitous in muscle. It is widely accepted that animals express tissue-specific myosin isoforms that differ in amino acid sequence and ATPase activity in order to tune muscle contractile velocities. Recent studies, however, suggested that the squid Doryteuthis pealeii might be an exception; members of this species do not express muscle-specific myosin isoforms, but instead alter sarcomeric ultrastructure to adjust contractile velocities. We investigated whether this alternative mechanism of tuning muscle contractile velocity is found in other coleoid cephalopods. We analyzed myosin heavy chain transcript sequences and expression profiles from muscular tissues of a cuttlefish, Sepia officinalis, and an octopus, Octopus bimaculoides, in order to determine if these cephalopods express tissue-specific myosin heavy chain isoforms. We identified transcripts of four and six different myosin heavy chain isoforms in S. officinalis and O. bimaculoides muscular tissues, respectively. Transcripts of all isoforms were expressed in all muscular tissues studied, and thus S. officinalis and O. bimaculoides do not appear to express tissue-specific muscle myosin isoforms. We also examined the sarcomeric ultrastructure in the transverse muscle fibers of the arms of O. bimaculoides and the arms and tentacles of S. officinalis using transmission electron microscopy and found that the fast contracting fibers of the prey capture tentacles of S. officinalis have shorter thick filaments than those found in the slower transverse muscle fibers of the arms of both species. It thus appears that coleoid cephalopods, including the cuttlefish and octopus, may use ultrastructural modifications rather than tissue-specific myosin isoforms to adjust contractile velocities.

  7. NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field.

    Science.gov (United States)

    Wang, Wei; Razy-Krajka, Florian; Siu, Eric; Ketcham, Alexandra; Christiaen, Lionel

    2013-12-01

    The heart and head muscles share common developmental origins and genetic underpinnings in vertebrates, including humans. Parts of the heart and cranio-facial musculature derive from common mesodermal progenitors that express NKX2-5, ISL1, and TBX1. This ontogenetic kinship is dramatically reflected in the DiGeorge/Cardio-Velo-Facial syndrome (DGS/CVFS), where mutations of TBX1 cause malformations in the pharyngeal apparatus and cardiac outflow tract. Cardiac progenitors of the first heart field (FHF) do not require TBX1 and segregate precociously from common progenitors of the second heart field (SHF) and pharyngeal muscles. However, the cellular and molecular mechanisms that govern heart versus pharyngeal muscle specification within this lineage remain elusive. Here, we harness the simplicity of the ascidian larva to show that, following asymmetric cell division of common progenitors, NK4/NKX2-5 promotes GATAa/GATA4/5/6 expression and cardiac specification in the second heart precursors by antagonizing Tbx1/10-mediated inhibition of GATAa and activation of Collier/Olf/EBF (COE), the determinant of atrial siphon muscle (ASM) specification. Our results uncover essential regulatory connections between the conserved cardio-pharyngeal factor Tbx1/10 and muscle determinant COE, as well as a mutual antagonism between NK4 and Tbx1/10 activities upstream of GATAa and COE. The latter cross-antagonism underlies a fundamental heart versus pharyngeal muscle fate choice that occurs in a conserved lineage of cardio-pharyngeal progenitors. We propose that this basic ontogenetic motif underlies cardiac and pharyngeal muscle development and evolution in chordates.

  8. NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2013-12-01

    Full Text Available The heart and head muscles share common developmental origins and genetic underpinnings in vertebrates, including humans. Parts of the heart and cranio-facial musculature derive from common mesodermal progenitors that express NKX2-5, ISL1, and TBX1. This ontogenetic kinship is dramatically reflected in the DiGeorge/Cardio-Velo-Facial syndrome (DGS/CVFS, where mutations of TBX1 cause malformations in the pharyngeal apparatus and cardiac outflow tract. Cardiac progenitors of the first heart field (FHF do not require TBX1 and segregate precociously from common progenitors of the second heart field (SHF and pharyngeal muscles. However, the cellular and molecular mechanisms that govern heart versus pharyngeal muscle specification within this lineage remain elusive. Here, we harness the simplicity of the ascidian larva to show that, following asymmetric cell division of common progenitors, NK4/NKX2-5 promotes GATAa/GATA4/5/6 expression and cardiac specification in the second heart precursors by antagonizing Tbx1/10-mediated inhibition of GATAa and activation of Collier/Olf/EBF (COE, the determinant of atrial siphon muscle (ASM specification. Our results uncover essential regulatory connections between the conserved cardio-pharyngeal factor Tbx1/10 and muscle determinant COE, as well as a mutual antagonism between NK4 and Tbx1/10 activities upstream of GATAa and COE. The latter cross-antagonism underlies a fundamental heart versus pharyngeal muscle fate choice that occurs in a conserved lineage of cardio-pharyngeal progenitors. We propose that this basic ontogenetic motif underlies cardiac and pharyngeal muscle development and evolution in chordates.

  9. Cardiac Time Intervals Measured by Tissue Doppler Imaging M-mode

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Mogelvang, Rasmus; Schnohr, Peter

    2016-01-01

    BACKGROUND: We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons with hypertension and are strong predictors of future ischemic cardiovascular diseases in the general population. METHODS AND RESULTS: In a large community-based population study, cardiac...... function was evaluated in 1915 participants by using both conventional echocardiography and tissue Doppler imaging (TDI). The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET), were obtained by TDI M-mode through the mitral...... leaflet. IVCT/ET, IVRT/ET, and myocardial performance index [MPI=(IVRT+IVCT)/ET] were calculated. After multivariable adjustment for clinical variables the IVRT, IVRT/ET, and MPI, remained significantly impaired in persons with hypertension (n=826) compared with participants without hypertension (n=1082...

  10. Textile-templated electrospun anisotropic scaffolds for regenerative cardiac tissue engineering.

    Science.gov (United States)

    Şenel Ayaz, H Gözde; Perets, Anat; Ayaz, Hasan; Gilroy, Kyle D; Govindaraj, Muthu; Brookstein, David; Lelkes, Peter I

    2014-10-01

    For patients with end-stage heart disease, the access to heart transplantation is limited due to the shortage of donor organs and to the potential for rejection of the donated organ. Therefore, current studies focus on bioengineering approaches for creating biomimetic cardiac patches that will assist in restoring cardiac function, by repairing and/or regenerating the intrinsically anisotropic myocardium. In this paper we present a simplified, straightforward approach for creating bioactive anisotropic cardiac patches, based on a combination of bioengineering and textile-manufacturing techniques in concert with nano-biotechnology based tissue-engineering stratagems. Using knitted conventional textiles, made of cotton or polyester yarns as template targets, we successfully electrospun anisotropic three-dimensional scaffolds from poly(lactic-co-glycolic) acid (PLGA), and thermoplastic polycarbonate-urethane (PCU, Bionate(®)). The surface topography and mechanical properties of textile-templated anisotropic scaffolds significantly differed from those of scaffolds electrospun from the same materials onto conventional 2-D flat-target electrospun scaffolds. Anisotropic textile-templated scaffolds electrospun from both PLGA and PCU, supported the adhesion and proliferation of H9C2 cardiac myoblasts cell line, and guided the cardiac tissue-like anisotropic organization of these cells in vitro. All cell-seeded PCU scaffolds exhibited mechanical properties comparable to those of a human heart, but only the cells on the polyester-templated scaffolds exhibited prolonged spontaneous synchronous contractility on the entire engineered construct for 10 days in vitro at a near physiologic frequency of ∼120 bpm. Taken together, the methods described here take advantage of straightforward established textile manufacturing strategies as an efficient and cost-effective approach to engineering 3D anisotropic, elastomeric PCU scaffolds that can serve as a cardiac patch.

  11. Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

    Science.gov (United States)

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2013-09-03

    Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

  12. An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury.

    Science.gov (United States)

    Aurora, Amit; Roe, Janet L; Corona, Benjamin T; Walters, Thomas J

    2015-10-01

    Extracellular matrix (ECM) derived scaffolds continue to be investigated for the treatment of volumetric muscle loss (VML) injuries. Clinically, ECM scaffolds have been used for lower extremity VML repair; in particular, MatriStem™, a porcine urinary bladder matrix (UBM), has shown improved functional outcomes and vascularization, but limited myogenesis. However, efficacy of the scaffold for the repair of traumatic muscle injuries has not been examined systematically. In this study, we demonstrate that the porcine UBM scaffold when used to repair a rodent gastrocnemius musculotendinous junction (MTJ) and tibialis anterior (TA) VML injury does not support muscle tissue regeneration. In the MTJ model, the scaffold was completely resorbed without tissue remodeling, suggesting that the scaffold may not be suitable for the clinical repair of muscle-tendon injuries. In the TA VML injury, the scaffold remodeled into a fibrotic tissue and showed functional improvement, but not due to muscle fiber regeneration. The inclusion of physical rehabilitation also did not improve functional response or tissue remodeling. We conclude that the porcine UBM scaffold when used to treat VML injuries may hasten the functional recovery through the mechanism of scaffold mediated functional fibrosis. Thus for appreciable muscle regeneration, repair strategies that incorporate myogenic cells, vasculogenic accelerant and a myoconductive scaffold need to be developed.

  13. Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue.

    Science.gov (United States)

    Majumder, Rupamanjari; Pandit, Rahul; Panfilov, A V

    2014-10-01

    Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na(+) current (INa), L-type slow inward Ca(2+) current (ICaL), slow delayed-rectifier current (IKs), rapid delayed-rectifier current (IKr), inward rectifier K(+) current (IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

  14. Human induced pluripotent stem cell-derived beating cardiac tissues on paper.

    Science.gov (United States)

    Wang, Li; Xu, Cong; Zhu, Yujuan; Yu, Yue; Sun, Ning; Zhang, Xiaoqing; Feng, Ke; Qin, Jianhua

    2015-11-21

    There is a growing interest in using paper as a biomaterial scaffold for cell-based applications. In this study, we made the first attempt to fabricate a paper-based array for the culture, proliferation, and direct differentiation of human induced pluripotent stem cells (hiPSCs) into functional beating cardiac tissues and create "a beating heart on paper." This array was simply constructed by binding a cured multi-well polydimethylsiloxane (PDMS) mold with common, commercially available paper substrates. Three types of paper material (print paper, chromatography paper and nitrocellulose membrane) were tested for adhesion, proliferation and differentiation of human-derived iPSCs. We found that hiPSCs grew well on these paper substrates, presenting a three-dimensional (3D)-like morphology with a pluripotent property. The direct differentiation of human iPSCs into functional cardiac tissues on paper was also achieved using our modified differentiation approach. The cardiac tissue retained its functional activities on the coated print paper and chromatography paper with a beating frequency of 40-70 beats per min for up to three months. Interestingly, human iPSCs could be differentiated into retinal pigment epithelium on nitrocellulose membrane under the conditions of cardiac-specific induction, indicating the potential roles of material properties and mechanical cues that are involved in regulating stem cell differentiation. Taken together, these results suggest that different grades of paper could offer great opportunities as bioactive, low-cost, and 3D in vitro platforms for stem cell-based high-throughput drug testing at the tissue/organ level and for tissue engineering applications.

  15. Atomic force microscope observation of branching in single transcript molecules derived from human cardiac muscle

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Jason; Hsueh, Carlin; Gimzewski, James K [Department of Chemistry and Biochemistry, UCLA, 607 Charles Young Drive East, Los Angeles, CA 90095 (United States); Mishra, Bud [Courant Institute of Mathematical Sciences, NYU, 251 Mercer Street, New York, NY 10012 (United States)], E-mail: jreed@chem.ucla.edu, E-mail: gim@chem.ucla.edu

    2008-09-24

    We have used an atomic force microscope to examine a clinically derived sample of single-molecule gene transcripts, in the form of double-stranded cDNA, (c: complementary) obtained from human cardiac muscle without the use of polymerase chain reaction (PCR) amplification. We observed a log-normal distribution of transcript sizes, with most molecules being in the range of 0.4-7.0 kilobase pairs (kb) or 130-2300 nm in contour length, in accordance with the expected distribution of mRNA (m: messenger) sizes in mammalian cells. We observed novel branching structures not previously known to exist in cDNA, and which could have profound negative effects on traditional analysis of cDNA samples through cloning, PCR and DNA sequencing.

  16. Monitoring of Physicochemical Changes in Frozen Fish Muscle Tissue

    Directory of Open Access Journals (Sweden)

    František Ježek

    2011-10-01

    Full Text Available The aim of the study was to monitor physicochemical parameters (pH, nitrogen trimethylamine N-TMA, total volatile basic nitrogen TVBN, free fatty acids FFA, peroxide value and thiobarbituric acid assay TBA of postmortal changes in muscle tissue of silver carp (Hypophthalmichthys molitrix during a period of storage at -18°C. Fresh silver carp samples and samples aft er three, six, nine and 12 months of storage were tested. The degree of acidification during the experiment was insignificant (P > 0.05. Proteolytic changes were almost stopped and TVBN levels remained unchanged (P > 0.05, while N-TMA levels fluctuated significantly (P < 0.01 between months 3 and 12. The essential were lipid hydrolysis and oxidation, which caused a significant increase in FFA values (5.89 ± 0.99% total lipids as oleic acid, peroxides (9.90 ± 2.83 mekv O2.kg-1 and TBA values (50.76 ± 31.52 mg MDA.kg-1. The shelf life recommended for silver carp was set at three months.

  17. Monitoring of Physicochemical Changes in Frozen Fish Muscle Tissue

    Directory of Open Access Journals (Sweden)

    František Ježek

    2011-09-01

    Full Text Available The aim of the study was to monitor physicochemical parameters (pH, nitrogen trimethylamine N-TMA, total volatile basic nitrogen TVBN, free fatty acids FFA, peroxide value and thiobarbituric acid assay TBA of postmortal changes in muscle tissue of silver carp (Hypophthalmichthys molitrix during a period of storage at -18°C. Fresh silver carp samples and samples aft er three, six, nine and 12 months of storage were tested. The degree of acidification during the experiment was insignificant (P > 0.05. Proteolytic changes were almost stopped and TVBN levels remained unchanged (P > 0.05, while N-TMA levels fluctuated significantly (P < 0.01 between months 3 and 12. The essential were lipid hydrolysis and oxidation, which caused a significant increase in FFA values (5.89 ± 0.99% total lipids as oleic acid, peroxides (9.90 ± 2.83 mekv O2.kg-1 and TBA values (50.76 ± 31.52 mg MDA.kg-1. The shelf life recommended for silver carp was set at three months.

  18. Serial block face scanning electron microscopy for the study of cardiac muscle ultrastructure at nanoscale resolutions.

    Science.gov (United States)

    Pinali, Christian; Kitmitto, Ashraf

    2014-11-01

    Electron microscopy techniques have made a significant contribution towards understanding muscle physiology since the 1950s. Subsequent advances in hardware and software have led to major breakthroughs in terms of image resolution as well as the ability to generate three-dimensional (3D) data essential for linking structure to function and dysfunction. In this methodological review we consider the application of a relatively new technique, serial block face scanning electron microscopy (SBF-SEM), for the study of cardiac muscle morphology. Employing SBF-SEM we have generated 3D data for cardiac myocytes within the myocardium with a voxel size of ~15 nm in the X-Y plane and 50 nm in the Z-direction. We describe how SBF-SEM can be used in conjunction with selective staining techniques to reveal the 3D cellular organisation and the relationship between the t-tubule (t-t) and sarcoplasmic reticulum (SR) networks. These methods describe how SBF-SEM can be used to provide qualitative data to investigate the organisation of the dyad, a specialised calcium microdomain formed between the t-ts and the junctional portion of the SR (jSR). We further describe how image analysis methods may be applied to interrogate the 3D volumes to provide quantitative data such as the volume of the cell occupied by the t-t and SR membranes and the volumes and surface area of jSR patches. We consider the strengths and weaknesses of the SBF-SEM technique, pitfalls in sample preparation together with tips and methods for image analysis. By providing a 'big picture' view at high resolutions, in comparison to conventional confocal microscopy, SBF-SEM represents a paradigm shift for imaging cellular networks in their native environment.

  19. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction

    Energy Technology Data Exchange (ETDEWEB)

    Muthu, Priya; Wang, Li; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Huang, Wenrui; Hernandez, Olga M.; Kawai, Masataka; Irving, Thomas C.; Szczesna-Cordary, Danuta (IIT); (Iowa); (Miami-MED)

    2012-04-02

    The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-{Delta}43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing ({approx} 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I{sub 1,1}/I{sub 1,0}, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-{Delta}43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-{Delta}43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

  20. Heart Rate Changes in Response to Mechanical Pressure Stimulation of Skeletal Muscles Are Mediated by Cardiac Sympathetic Nerve Activity

    Science.gov (United States)

    Watanabe, Nobuhiro; Hotta, Harumi

    2017-01-01

    Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm2) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: −56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = −0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: −9 to +3 bpm, p mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = −0.62, p = 0.0066). These results suggest that cardiac sympathetic nerve activity regulates HR responses to muscle mechanical pressure stimulation and the direction of HR

  1. Development and application of human virtual excitable tissues and organs: from premature birth to sudden cardiac death.

    Science.gov (United States)

    Holden, Arun V

    2010-12-01

    The electrical activity of cardiac and uterine tissues has been reconstructed by detailed computer models in the form of virtual tissues. Virtual tissues are biophysically and anatomically detailed, and represent quantitatively predictive models of the physiological and pathophysiological behaviours of tissue within an isolated organ. The cell excitation properties are quantitatively reproduced by equations that describe the kinetics of a few dozen proteins. These equations are derived from experimental measurements of membrane potentials, ionic currents, fluxes, and concentrations. Some of the measurements were taken from human cells and human ion channel proteins expressed in non-human cells, but they were mostly taken from cells of other animal species. Data on tissue geometry and architecture are obtained from the diffusion tensor magnetic resonance imaging of ex vivo or post mortem tissue, and are used to compute the spread of current in the tissue. Cardiac virtual tissues are well established and reproduce normal and pathological patterns of cardiac excitation within the atria or ventricles of the human heart. They have been applied to increase the understanding of normal cardiac electrophysiology, to evaluate the candidate mechanisms for re-entrant arrhythmias that lead to sudden cardiac death, and to predict the tissue level effects of mutant or pharmacologically-modified ion channels. The human full-term virtual uterus is still in development. This virtual tissue reproduces the in vitro behaviour of uterine tissue biopsies, and provides possible mechanisms for premature labour.

  2. Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.

    Science.gov (United States)

    Duffy, Rebecca M; Feinberg, Adam W

    2014-01-01

    Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs.

  3. Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering.

    Science.gov (United States)

    Boonen, Kristel J M; Langelaan, Marloes L P; Polak, Roderick B; van der Schaft, Daisy W J; Baaijens, Frank P T; Post, Mark J

    2010-05-28

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications for regenerative medicine, in vitro physiological model systems, and in vitro meat production. Besides conventional biochemical cues to promote muscle tissue maturation in vitro, biophysical stimuli are necessary to reach the desired functionality and texture of the engineered tissue. Stretch, caused by active movements of the body, is an important factor present in the niche of muscle progenitor cells in vivo. We therefore investigated the effects of uniaxial ramp stretch (2%) followed by uniaxial intermittent dynamic stretch (4%) on C2C12 and murine muscle progenitor cells in a 2D and 3D environment and found that stretch negatively influenced maturation in all cases, demonstrated by decreased expression of MRFs and sarcomere proteins at the RNA level and a delay in the formation of cross striations. We therefore conclude that the current protocol is not recommended for skeletal muscle tissue engineering purposes.

  4. OPTOGENETICS: A NOVEL APPROACH IN PACING HAERT TISSUE AND ENGENDER PROPAGATING CARDIAC IMPULSES

    Directory of Open Access Journals (Sweden)

    Pasam Naga Abhinay

    2012-04-01

    Full Text Available The cardiac pacemaker controls the rhythmicity of heart contractions and these can be substituted by battery-operated devices as last resource. Optogenetics involves insertion of light-sensitive proteins into human embryonic stem cell to encode DNA making mammalian tissues light-sensitive. The first discovered protein of this type is Channelrhodopsin2 (ChR2, which is widely used in neuroscience. The limitation of electrical stimulation of heart, a standard technique can be overcome by using ChR2.The various methods involved in optogenetics and energy needs were discussed in this section. Initially, optogenetics is confined only to neuronal system, later on extended to heart and other organs. This method involves precise localized stimulation and constant prolonged depolarization of cardiomyocytes and cardiac tissue resulting in alterations of pacemaking, Ca2+ homeostasis, electrical coupling and arrhythmogenic spontaneous extra beats.

  5. Contribution of elastic tissues to the mechanics and energetics of muscle function during movement.

    Science.gov (United States)

    Roberts, Thomas J

    2016-01-01

    Muscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle.

  6. Coordinated gene expression between skeletal muscle and intramuscular adipose tissue in growing beef cattle.

    Science.gov (United States)

    Roberts, S L; Lancaster, P A; DeSilva, U; Horn, G W; Krehbiel, C R

    2015-09-01

    Previous research indicates that metabolism and fiber type of skeletal muscle is related to intramuscular lipid content. It is hypothesized that changes in skeletal muscle gene expression influence adipose tissue development. The objective of this study was to determine differences in the metabolism and intercellular signaling of skeletal muscle fibers within the same muscle group that could be responsible for the initiation of intramuscular adipose tissue development and differentiation. Longissimus dorsi muscle samples were collected from steers ( = 12; 385 d of age; 378 kg BW) grazing wheat pasture. Longissimus muscle samples were dissected under magnification and sorted into 3 categories based on visual stage of adipose tissue development: immature intramuscular adipose tissue (MM), intermediate intramuscular adipose tissue (ME), and mature intramuscular adipose tissue (MA). Additionally, muscle fibers lying adjacent to each intramuscular adipose tissue (IM) category and those not associated with IM tissue were collected and stored separately. Quantitative real-time PCR was used to determine relative fold change in genes involved in metabolism, angiogenesis, formation of extracellular matrix, and intercellular signaling pathways in both LM and IM samples. Gene expression data were analyzed using a GLM that included the fixed effect of tissue. Pearson correlation coefficients were also computed between gene expression in LM and IM tissue samples that were at the same stage of development. and γ mRNA expression were 3.56- and 1.97-fold greater ( development categories. Genes associated with metabolism and angiogenesis in LM tissue showed no differences among stages of development. Myostatin expression did not change in LM tissue; however, expression of and mRNA decreased ( tissue had a strong positive correlation ( ≥ 0.69) with angiogenic growth factors in LM associated with MM IM; however, no correlation was observed in ME or MA IM. These data indicate a

  7. Gene expression in cardiac tissues from infants with idiopathic conotruncal defects

    Directory of Open Access Journals (Sweden)

    Lofland Gary K

    2011-01-01

    Full Text Available Abstract Background Tetralogy of Fallot (TOF is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot. Methods We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions and compared gene expression patterns to normally developing subjects. Results We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation. However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003 appeared to be generally suppressed. Conclusions The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.

  8. Methods for demonstration of enzyme activity in muscle fibres at the muscle/bone interface in demineralized tissue

    DEFF Research Database (Denmark)

    Kirkeby, S; Vilmann, H

    1981-01-01

    A method for demonstration of activity for ATPase and various oxidative enzymes (succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase) in muscle/bone sections of fixed and demineralized tissue has been developed. It was found that it is possible to preserve...... considerable amounts of the above mentioned enzymes in the muscle fibres at the muscle/bone interfaces. The best results were obtained after 20 min fixation, and 2-3 weeks of storage in MgNa2EDTA containing media. As the same technique previously has been used to describe patterns of resorption and deposition...

  9. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs

    DEFF Research Database (Denmark)

    Tous, Nuria; Theil, Peter Kappel; Lauridsen, Charlotte

    2012-01-01

    in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P tissues studied (P fat. Transcription of genes related to FA synthesis was reduced by CLA in SM muscle and liver (SREBP1......, both P fat. Saturated FA were increased in all studied tissues (P ....01), while monosaturated and polyunsaturated FA were reduced in a tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner....

  10. Effects of muscle electrical stimulation on peak VO2 in cardiac transplant patients.

    Science.gov (United States)

    Vaquero, A F; Chicharro, J L; Gil, L; Ruiz, M P; Sánchez, V; Lucía, A; Urrea, S; Gómez, M A

    1998-07-01

    Peak oxygen consumption (peak VO2) has become a critical component in the evaluation of heart transplant recipients (HTR). In these patients, peak VO2 remains low after cardiac transplantation mainly because of persisting peripheral limitations in the working muscles. Muscular electrical stimulation, on the other hand, has been shown to enhance the oxidative capacity of healthy muscle. It was the purpose of our investigation to study the effects of ES on the peak VO2 of HTR. Fourteen (11 males and 3 females) HTR (age: 57+/-7yr, mean +/- SD; height: 163+/-7 cm, weight: 70.5+/-8.6 kg) were selected as subjects and each of them was randomly assigned to one of two groups: (a) group EXP (n = 7), receiving electrical stimulation on both quadriceps muscles during a period of 8 weeks, and (b) group CONT (n = 7), not receiving electrical stimulation. Before (PRE) and after (POST) the aforementioned 8-week period, respectively, all the subjects performed a cardiopulmonary exercise test (ramp protocol) on a cycle ergometer for peak VO2 determination. PRE values of peak VO2 were similar in both groups (17.1+/-2.0 vs 16.9+/-3.8ml x kg(-1) x min(-1) in EXP and CONT, respectively). However, peak values of VO2 significantly increased in EXP (p < 0.05) after the period of electrical stimulation (POST peak VO2: 18.7+/-2.0ml x kg(-1)), whereas no change was observed in CONT (POST peak VO2: 16.2+/-3.2 ml x kg(-1) x min(-1)). In conclusion, electrical stimulation could therefore be used to improve the functional capacity of HTR, and might be included in the rehabilitation programs of this population group.

  11. Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    Adam; M; Noyes; Kirandeep; Dua; Ramprakash; Devadoss; Lovely; Chhabra

    2014-01-01

    Type-2 diabetes mellitus(T2DM) plays a central role in the development of cardiovascular disease(CVD). However, its relationship to epicardial adipose tissue(EAT) and pericardial adipose tissue(PAT) in particular is important in the pathophysiology of coronary artery disease. Owing to its close proximity to the heart and coronary vasculature, EAT exerts a direct metabolic impact by secreting proinflammatory adipokines and free fatty acids, which promote CVD locally. In this review, we have discussed the relationship between T2 DM and cardiac fat deposits, particularly EAT and PAT, which together exert a big impact on the cardiovascular health.

  12. Subcutaneous Tissue Thickness is an Independent Predictor of Image Noise in Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Staniak, Henrique Lane; Sharovsky, Rodolfo [Hospital Universitário - Universidade de São Paulo, São Paulo, SP (Brazil); Pereira, Alexandre Costa [Hospital das Clínicas - Universidade de São Paulo, São Paulo, SP (Brazil); Castro, Cláudio Campi de; Benseñor, Isabela M.; Lotufo, Paulo A. [Hospital Universitário - Universidade de São Paulo, São Paulo, SP (Brazil); Faculdade de Medicina - Universidade de São Paulo, São Paulo, SP (Brazil); Bittencourt, Márcio Sommer, E-mail: msbittencourt@mail.harvard.edu [Hospital Universitário - Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-01-15

    Few data on the definition of simple robust parameters to predict image noise in cardiac computed tomography (CT) exist. To evaluate the value of a simple measure of subcutaneous tissue as a predictor of image noise in cardiac CT. 86 patients underwent prospective ECG-gated coronary computed tomographic angiography (CTA) and coronary calcium scoring (CAC) with 120 kV and 150 mA. The image quality was objectively measured by the image noise in the aorta in the cardiac CTA, and low noise was defined as noise < 30HU. The chest anteroposterior diameter and lateral width, the image noise in the aorta and the skin-sternum (SS) thickness were measured as predictors of cardiac CTA noise. The association of the predictors and image noise was performed by using Pearson correlation. The mean radiation dose was 3.5 ± 1.5 mSv. The mean image noise in CT was 36.3 ± 8.5 HU, and the mean image noise in non-contrast scan was 17.7 ± 4.4 HU. All predictors were independently associated with cardiac CTA noise. The best predictors were SS thickness, with a correlation of 0.70 (p < 0.001), and noise in the non-contrast images, with a correlation of 0.73 (p < 0.001). When evaluating the ability to predict low image noise, the areas under the ROC curve for the non-contrast noise and for the SS thickness were 0.837 and 0.864, respectively. Both SS thickness and CAC noise are simple accurate predictors of cardiac CTA image noise. Those parameters can be incorporated in standard CT protocols to adequately adjust radiation exposure.

  13. Fluorescence of muscle and connective tissue from cod and salmon

    DEFF Research Database (Denmark)

    Andersen, Charlotte Møller; Wold, J.P.

    2003-01-01

    Autofluorescence of salmon and cod muscle was measured and compared with autofluorescence of collagen type I and type V. Similarities between fluorescence of fish muscle and collagen were found in that the same peaks were obtained around 390, 430, and 480 nm, These similarities are supported by p...

  14. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( muscle-wasting disorders.

  15. Monoclonal antibodies to desmin: evidence for stage-dependent intermediate filament immunoreactivity during cardiac and skeletal muscle development.

    Science.gov (United States)

    Fischman, D A; Danto, S I

    1985-01-01

    Monoclonal antibodies reactive with desmin (D3 and D76) have been generated and their specificities validated by immunoblots, RIAs, and immunocytochemistry. No cross-reaction with other IFPs has been observed. The McAbs recognized different epitopes but both reside in the amino-terminal rod domain of desmin. Whereas McAb D3 produces a staining pattern characteristic of desmin throughout the development of cardiac and skeletal muscles, McAb D76 was selectively unreactive with certain regions of early (three days in ovo) embryonic cardiac anlage, with cultured cardiac myocytes derived from 7-day-old embryos, and with skeletal myotubes in early stages of myogenesis in vitro. Positive reactivity of D76 was seen at stages of myofibrillogenesis when the sarcomeres assume lateral alignment. Evidence was presented that differential reactivity of D76 did not result from the biosynthesis of a new desmin isoform or the post-translational modification of an existing protein. We suggest that the appearance of D76 immunoreactivity during striated muscle development represents an unmasking of the epitope by some IF-associated protein. Since this transition during skeletal muscle differentiation occurs during lateral alignment of the myofibrils, this antibody may serve as a useful probe for exploring this reorganization of the contractile apparatus during myogenesis and muscle regeneration.

  16. Magnetization Transfer MR Imaging to Monitor Muscle Tissue Formation during Myogenic in Vivo Differentiation of Muscle Precursor Cells.

    Science.gov (United States)

    Rottmar, Markus; Haralampieva, Deana; Salemi, Souzan; Eberhardt, Christian; Wurnig, Moritz C; Boss, Andreas; Eberli, Daniel

    2016-11-01

    Purpose To determine whether magnetization transfer (MT) magnetic resonance (MR) imaging may serve as a quantitative measure of the degree of fiber formation during differentiation of muscle precursor cells into engineered muscle tissue as a potential noninvasive monitoring tool in mice. Materials and Methods The study was approved by the local ethics committee (no. StV 01/2008) and the local Veterinary Office (license no. 99/2013). Human muscle progenitor cells (hMPCs) derived from rectus abdominis muscles were subcutaneously injected into CD-1 nude mice (CD-1 nude mice, Crl:CD1-Foxn1(nu); Charles River Laboratories, Wilmington, Mass) for development of muscle tissue. The mice underwent MR imaging examinations at 4.7 T at days 1, 3, 7, 14, 21, and 28 after cell transplantation by using a gradient-echo sequence with an MT prepulse and systematic variation of the off-resonance frequency (50-37 500 Hz) at an amplitude of 800°. Direct saturation was estimated from a Bloch equation simulation. The MT ratio (MTR) was correlated to immunohistochemistry findings, Western blot results, and results of myography. Data were analyzed by using one-way or two-way analysis of variance with the Sidak or Tukey multiple comparisons test. Results In the reference skeletal muscle, highest MT was found for 2500 Hz off-resonance frequency with an MTR ± standard deviation of 57.5% ± 3.5. The developing muscle tissue exhibited increasing MT values during the 28 days of myogenic in vivo differentiation and did not reach the values of native skeletal muscle. Mean values of MTR (2500 Hz) for hMPCs were 27.6% ± 6.3 (day 1), 24.7% ± 8.7 (day 3), 28.2% ± 5.7 (day 7), 35.9% ± 5.0 (day 14), 37.0% ± 7.9 (day 21), and 39.9% ± 8.1 (day 28). The results from MT MR imaging correlated qualitatively well with muscle tissue expression of specific skeletal markers, as well as muscle contractility. Conclusion MT MR imaging may be used to noninvasively monitor the process of myogenic in vivo

  17. Rules of tissue packing involving different cell types: human muscle organization.

    Science.gov (United States)

    Sánchez-Gutiérrez, Daniel; Sáez, Aurora; Gómez-Gálvez, Pedro; Paradas, Carmen; Escudero, Luis M

    2017-01-10

    Natural packed tissues are assembled as tessellations of polygonal cells. These include skeletal muscles and epithelial sheets. Skeletal muscles appear as a mosaic composed of two different types of cells: the "slow" and "fast" fibres. Their relative distribution is important for the muscle function but little is known about how the fibre arrangement is established and maintained. In this work we capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that the biceps brachii muscle presents a particular arrangement, based on the different sizes of slow and fast fibres. By contrast, in the quadriceps muscle an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into natural tessellations. These findings establish a new framework for the analysis of any packed tissue where two or more cell types exist.

  18. Tissue temperature transients in resting contra-lateral leg muscle tissue during isolated knee extension.

    Science.gov (United States)

    Kenny, Glen P; Reardon, Frank D; Ducharme, Michel B; Reardon, Mark L; Zaleski, Wytek

    2002-12-01

    This study was designed to evaluate the role of non-active tissue in the retention and dissipation of heat during and following intense isolated muscle activity. Six subjects performed an incremental isotonic test (constant angular velocity, increases in force output) on a KIN-COM isokinetic apparatus to determine their maximal oxygen consumption during single knee extensions (VO2sp). In a subsequent session, a thin wire multi-sensor temperature probe was inserted into the left vastus medialis under ultrasound guidance at a specific internal marker. The deepest temperature sensor (tip, Tmu10) was located approximately 10 mm from the femur and deep femoral artery with 2 additional sensors located at 15 (Tmu25) and 30 (Tmu40) mm from the tip. Implant site was midway between and medial to a line joining the anterior superior iliac spine and base of patella. Esophageal temperature (Tes) temperature was measured as an index of core temperature. Subjects rested in a supine position for 60 min followed by 30 min of seated rest in an ambient condition of 22 degree C. Subjects then performed 15 min of isolated single right knee extensions against a dynamic resistance on a KIN COM corresponding to 60% of VO2sp at 60 degree x sec(-1). Exercise was followed by 60 min of seated rest. Resting Tes was 37 degree C while Tmu10, Tmu25, and Tmu40 were 36.58, 36.55 and 36.45 degree C, respectively. Exercise resulted in a Tes increase of 0.31 C above pre-exercise resting. Tmu of the non-exercising leg increased 0.23, 0.19 and 0.09 degree C for Tmu10, Tmu25, and Tmu40, respectively. While Tes decreased to baseline values within approximately 15 min of end-exercise, Tmu10 reached resting values following approximately 40 min of recovery. These results suggest that during isolated muscle activity, convective heat transfer by the blood to non-active muscle tissue may have a significant role in maintaining resting core temperature.

  19. Interdigitated array of Pt electrodes for electrical stimulation and engineering of aligned muscle tissue.

    Science.gov (United States)

    Ahadian, Samad; Ramón-Azcón, Javier; Ostrovidov, Serge; Camci-Unal, Gulden; Hosseini, Vahid; Kaji, Hirokazu; Ino, Kosuke; Shiku, Hitoshi; Khademhosseini, Ali; Matsue, Tomokazu

    2012-09-21

    Engineered skeletal muscle tissues could be useful for applications in tissue engineering, drug screening, and bio-robotics. It is well-known that skeletal muscle cells are able to differentiate under electrical stimulation (ES), with an increase in myosin production, along with the formation of myofibers and contractile proteins. In this study, we describe the use of an interdigitated array of electrodes as a novel platform to electrically stimulate engineered muscle tissues. The resulting muscle myofibers were analyzed and quantified in terms of their myotube characteristics and gene expression. The engineered muscle tissues stimulated through the interdigitated array of electrodes demonstrated superior performance and maturation compared to the corresponding tissues stimulated through a conventional setup (i.e., through Pt wires in close proximity to the muscle tissue). In particular, the ES of muscle tissue (voltage 6 V, frequency 1 Hz and duration 10 ms for 1 day) through the interdigitated array of electrodes resulted in a higher degree of C2C12 myotube alignment (∼80%) as compared to ES using Pt wires (∼65%). In addition, higher amounts of C2C12 myotube coverage area, myotube length, muscle transcription factors and protein biomarkers were found for myotubes stimulated through the interdigitated array of electrodes compared to those stimulated using the Pt wires. Due to the wide array of potential applications of ES for two- and three-dimensional (2D and 3D) engineered tissues, the suggested platform could be employed for a variety of cell and tissue structures to more efficiently investigate their response to electrical fields.

  20. Muscle connective tissue content of endurance-trained and inactive individuals

    DEFF Research Database (Denmark)

    Mackey, Abigail; Donnelly, A E; Roper, H P

    2005-01-01

    Although it is known that exercise exerts a positive regulatory effect on collagen synthesis, the effects of endurance training on muscle endomysial connective tissue in man are not so well documented. To investigate this, a single muscle biopsy was collected from two groups of volunteers...

  1. Study of the response of the penile corporal tissue and cavernosus muscles to micturition

    Directory of Open Access Journals (Sweden)

    El Sibai Olfat

    2008-03-01

    Full Text Available Abstract Background The reaction of the corpora cavernosa (CC, the corpus spongiosum (CS, the bulbocavernosus (BCM and ischiocavernosus (ICM muscles to passage of urine through the urethra during micturition is not known. We investigated the hypothesis that the passage of urine through the urethra stimulates the corporal tissue and cavernosus muscles. Methods In 30 healthy men (mean age 42.8 ± 11.7 years, the electromyographic activity (EMG of the CC, CS, BCM, and ICM were recorded before and during micturition, and on interruption of and straining during micturition. These tests were repeated after individual anesthetization of urethra, corporal tissue, and cavernosus muscles. Results During micturition, the slow wave variables (frequency, amplitude, conduction velocity of the CC and CS decreased while the motor unit action potentials of the BCM and ICM increased; these EMG changes were mild and returned to the basal values on interruption or termination of micturition. Micturition after individual anesthetization of urethra, corporal tissue and cavernosal muscles did not effect significant EMG changes in these structures, while saline administration produced changes similar to those occurring before saline administration. Conclusion The decrease of sinusoidal and increase of cavernosus muscles' EMG activity during micturition apparently denotes sinusoidal relaxation and cavernosus muscles contraction. Sinusoidal muscle relaxation and cavernosus muscles contraction upon micturition are suggested to be mediated through a 'urethro-corporocavernosal reflex'. These sinusoidal and cavernosus muscle changes appear to produce a mild degree of penile tumescence and stretch which might assist in urinary flow during micturition.

  2. Evidence for a Border-Collision Bifurcation in Paced Cardiac Tissue

    Science.gov (United States)

    Berger, Carolyn

    2005-11-01

    Bifurcations in the electrical response of cardiac tissue can destabilize spatial-temporal waves of electrical activity in the heart, leading to tachycardia or even fibrillation. Therefore, it is important to characterize the types of bifurcations occurring in cardiac tissue. Our goal is to classify the bifurcation that occurs in cardiac cells when a change in pacing rate induces a transition from 1:1 to 2:2 phase-locked behavior. Current mathematical models predict that the bifurcation mediating the transition is a supercritical pitchfork type. For such a bifurcation, small random noise is predicted to be amplified by greater amounts as the bifurcation is approached (Weisenfeld). However, our experimental observations of paced bullfrog myocardium driven by small beat-to-beat alternations in the pacing rate (rather than driven by noise) displays de-amplification as the bifurcation is approached. To explain this surprising result, we hypothesize that the transition to 2:2 behavior is mediated by border-collision bifurcation, which is predicted to show little noise amplification. Wiesenfeld, K. Phys. Rev. A 32, 1744 (1985).

  3. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    Science.gov (United States)

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

  4. Effect of Twisted Fiber Anisotropy in Cardiac Tissue on Ablation with Pulsed Electric Fields

    Science.gov (United States)

    Xie, Fei; Zemlin, Christian W.

    2016-01-01

    Background Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart. Methods We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered how tissue thickness, degree of anisotropy, and electrode configuration affect the geometry of the ablated volume. We considered two electrode configurations: two parallel needles inserted into the myocardium (“penetrating needles” configuration) and one circular electrode each on epi- and endocardium, opposing each other (“epi-endo” configuration). Results For thick tissues (10 mm) and moderate anisotropy ratio (a = 2), we find that the geometry of the ablated volume is almost unaffected by twisted anisotropy, i.e. it is approximately translationally symmetric from epi- to endocardium, for both electrode configurations. Higher anisotropy ratio (a = 10) leads to substantial variation in ablation width across the wall; these variations were more pronounced for the penetrating needle configuration than for the epi-endo configuration. For thinner tissues (4 mm, typical for human atria) and higher anisotropy ratio (a = 10), the epi-endo configuration yielded approximately translationally symmetric ablation volumes, while the penetrating electrodes configuration was much more sensitive to fiber twist. Conclusions These results suggest that the epi-endo configuration will be reliable for ablation of atrial fibrillation, independently of fiber orientation, while the penetrating electrode configuration may experience problems when the

  5. Active and passive behaviors of soft tissues: Pelvic floor muscles

    OpenAIRE

    Areias, P.; Pato, M. P. M.

    2010-01-01

    A new active-contraction visco-elastic numerical model of the pelvic floor (skeletal) muscle is presented. Our model includes all elements that represent the muscle constitutive behavior, contraction and relaxation. In contrast with the previous models, the activation function can be null. The complete equations are shown and exactly linearized. Small verification and validation tests are performed and the pelvis is modeled using the data from the intra-abdominal pressure tests.

  6. Modelling the effect of gap junctions on tissue-level cardiac electrophysiology

    CERN Document Server

    Bruce, Doug; Whiteley, Jonathan P

    2012-01-01

    When modelling tissue-level cardiac electrophysiology, continuum approximations to the discrete cell-level equations are used to maintain computational tractability. One of the most commonly used models is represented by the bidomain equations, the derivation of which relies on a homogenisation technique to construct a suitable approximation to the discrete model. This derivation does not explicitly account for the presence of gap junctions connecting one cell to another. It has been seen experimentally [Rohr, Cardiovasc. Res. 2004] that these gap junctions have a marked effect on the propagation of the action potential, specifically as the upstroke of the wave passes through the gap junction. In this paper we explicitly include gap junctions in a both a 2D discrete model of cardiac electrophysiology, and the corresponding continuum model, on a simplified cell geometry. Using these models we compare the results of simulations using both continuum and discrete systems. We see that the form of the action potent...

  7. Wave trains induced by circularly polarized electric fields in cardiac tissues.

    Science.gov (United States)

    Feng, Xia; Gao, Xiang; Tang, Juan-Mei; Pan, Jun-Ting; Zhang, Hong

    2015-08-25

    Clinically, cardiac fibrillation caused by spiral and turbulent waves can be terminated by globally resetting electric activity in cardiac tissues with a single high-voltage electric shock, but it is usually associated with severe side effects. Presently, a promising alternative uses wave emission from heterogeneities induced by a sequence of low-voltage uniform electric field pulses. Nevertheless, this method can only emit waves locally near obstacles in turbulent waves and thereby requires multiple obstacles to globally synchronize myocardium and thus to terminate fibrillation. Here we propose a new approach using wave emission from heterogeneities induced by a low-voltage circularly polarized electric field (i.e., a rotating uniform electric field). We find that, this approach can generate circular wave trains near obstacles and they propagate outwardly. We study the characteristics of such circular wave trains and further find that, the higher-frequency circular wave trains can effectively suppress spiral turbulence.

  8. Unidirectional Pinning and Hysteresis of Spatially Discordant Alternans in Cardiac Tissue

    CERN Document Server

    Skardal, Per Sebastian; Restrepo, Juan G

    2011-01-01

    Spatially discordant alternans is a widely observed pattern of voltage and calcium signals in cardiac tissue that can precipitate lethal cardiac arrhythmia. Using spatially coupled iterative maps of the beat-to-beat dynamics, we explore this pattern's dynamics in the regime of a calcium-dominated period-doubling instability at the single cell level. We find a novel nonlinear bifurcation associated with the formation of a discontinuous jump in the amplitude of calcium alternans at nodal lines separating discordant regions. We show that this jump unidirectionally pins nodal lines by preventing their motion away from the pacing site following a pacing rate decrease, but permitting motion towards this site following a rate increase. This unidirectional pinning leads to strongly history-dependent nodal line motion that is strongly arrhythmogenic.

  9. In situ regeneration of skeletal muscle tissue through host cell recruitment.

    Science.gov (United States)

    Ju, Young Min; Atala, Anthony; Yoo, James J; Lee, Sang Jin

    2014-10-01

    Standard reconstructive procedures for restoring normal function after skeletal muscle defects involve the use of existing host tissues such as muscular flaps. In many instances, this approach is not feasible and delays the rehabilitation process and restoration of tissue function. Currently, cell-based tissue engineering strategies have been used for reconstruction; however, donor tissue biopsy and ex vivo cell manipulation are required prior to implantation. The present study aimed to overcome these limitations by demonstrating mobilization of muscle cells into a target-specific site for in situ muscle regeneration. First, we investigated whether host muscle cells could be mobilized into an implanted scaffold. Poly(l-lactic acid) (PLLA) scaffolds were implanted in the tibialis anterior (TA) muscle of rats, and the retrieved scaffolds were characterized by examining host cell infiltration in the scaffolds. The host cell infiltrates, including Pax7+ cells, gradually increased with time. Second, we demonstrated that host muscle cells could be enriched by a myogenic factor released from the scaffolds. Gelatin-based scaffolds containing a myogenic factor were implanted in the TA muscle of rats, and the Pax7+ cell infiltration and newly formed muscle fibers were examined. By the second week after implantation, the Pax7+ cell infiltrates and muscle formation were significantly accelerated within the scaffolds containing insulin-like growth factor 1 (IGF-1). Our data suggest an ability of host stem cells to be recruited into the scaffolds with the capability of differentiating to muscle cells. In addition, the myogenic factor effectively promoted host cell recruitment, which resulted in accelerating muscle regeneration in situ.

  10. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends.

    Science.gov (United States)

    Qazi, Taimoor H; Mooney, David J; Pumberger, Matthias; Geissler, Sven; Duda, Georg N

    2015-01-01

    Skeletal muscles have a robust capacity to regenerate, but under compromised conditions, such as severe trauma, the loss of muscle functionality is inevitable. Research carried out in the field of skeletal muscle tissue engineering has elucidated multiple intrinsic mechanisms of skeletal muscle repair, and has thus sought to identify various types of cells and bioactive factors which play an important role during regeneration. In order to maximize the potential therapeutic effects of cells and growth factors, several biomaterial based strategies have been developed and successfully implemented in animal muscle injury models. A suitable biomaterial can be utilized as a template to guide tissue reorganization, as a matrix that provides optimum micro-environmental conditions to cells, as a delivery vehicle to carry bioactive factors which can be released in a controlled manner, and as local niches to orchestrate in situ tissue regeneration. A myriad of biomaterials, varying in geometrical structure, physical form, chemical properties, and biofunctionality have been investigated for skeletal muscle tissue engineering applications. In the current review, we present a detailed summary of studies where the use of biomaterials favorably influenced muscle repair. Biomaterials in the form of porous three-dimensional scaffolds, hydrogels, fibrous meshes, and patterned substrates with defined topographies, have each displayed unique benefits, and are discussed herein. Additionally, several biomaterial based approaches aimed specifically at stimulating vascularization, innervation, and inducing contractility in regenerating muscle tissues are also discussed. Finally, we outline promising future trends in the field of muscle regeneration involving a deeper understanding of the endogenous healing cascades and utilization of this knowledge for the development of multifunctional, hybrid, biomaterials which support and enable muscle regeneration under compromised conditions.

  11. Regeneration of the skin and muscle tissue in rainbow trout (Oncorhynchus mykiss) following mechanical injury

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Nielsen, Michael Engelbrecht

    Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation......, proliferation and remodelling. We investigated the expression of genes traditionally being important in these processes untill 7 days after the tissue damage in order to find inducible genetic markers following mechanical injury....

  12. Use-dependence of ryanodine effects on postrest contraction in ferret cardiac muscle.

    Science.gov (United States)

    Malecot, C O; Katzung, B G

    1987-04-01

    During an investigation of the effect of ryanodine on contractions in cardiac muscle, it was found that long rest periods removed all or most of the drug's effect. Therefore, we studied the kinetics of block development and recovery from block produced by low concentrations of ryanodine (1-100 pM) on the postrest contractions of ferret papillary muscle. At 100 pM, ryanodine depressed steady-state contraction amplitude slightly (4.2 +/- 1.1% mean +/- SEM, n = 10) but strongly inhibited (40-80%) the first contraction (postrest contraction) elicited on restimulation of the preparation after rest periods of 1 second to 5 minutes. Under control conditions, the nearly maximal potentiation of the twitch occurring after a standard test rest period (30 seconds of rest) was not affected by a preceding conditioning rest of up to 20 minutes. In the presence of 100 pM ryanodine, a conditioning rest increased the amplitude of the twitch elicited after a test rest, and the test rest contraction recovered toward control (drug-free) amplitude monoexponentially (time constant, 582 +/- 105 seconds). Block of postrest contraction could be reinduced by stimulation and occurred faster when higher rates were used (time constants, 758 seconds at 1 Hz and 107 +/- 26 seconds at 3 Hz). Since rest potentiation of twitch tension is believed to be mostly dependent on extra calcium released from the sarcoplasmic reticulum, the results suggest that the ryanodine-induced blockade of calcium release from the sarcoplasmic reticulum is use-dependent and recovers during diastole.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Vascularization strategies of engineered tissues and their application in cardiac regeneration.

    Science.gov (United States)

    Sun, Xuetao; Altalhi, Wafa; Nunes, Sara S

    2016-01-15

    The primary function of vascular networks is to transport blood and deliver oxygen and nutrients to tissues, which occurs at the interface of the microvasculature. Therefore, the formation of the vessels at the microcirculatory level, or angiogenesis, is critical for tissue regeneration and repair. Current strategies for vascularization of engineered tissues have incorporated multi-disciplinary approaches including engineered biomaterials, cells and angiogenic factors. Pre-vascularization of scaffolds composed of native matrix, synthetic polymers, or other biological materials can be achieved through the use of single cells in mono or co-culture, in combination or not with angiogenic factors or by the use of isolated vessels. The advance of these methods, together with a growing understanding of the biology behind vascularization, has facilitated the development of vascularization strategies for engineered tissues with therapeutic potential for tissue regeneration and repair. Here, we review the different cell-based strategies utilized to pre-vascularize engineered tissues and in making more complex vascularized cardiac tissues for regenerative medicine applications.

  14. Cardiac strength-interval curves calculated using a bidomain tissue with a parsimonious ionic current

    Science.gov (United States)

    Roth, Bradley J.

    2017-01-01

    The strength-interval curve plays a major role in understanding how cardiac tissue responds to an electrical stimulus. This complex behavior has been studied previously using the bidomain formulation incorporating the Beeler-Reuter and Luo-Rudy dynamic ionic current models. The complexity of these models renders the interpretation and extrapolation of simulation results problematic. Here we utilize a recently developed parsimonious ionic current model with only two currents—a sodium current that activates rapidly upon depolarization INa and a time-independent inwardly rectifying repolarization current IK—which reproduces many experimentally measured action potential waveforms. Bidomain tissue simulations with this ionic current model reproduce the distinctive dip in the anodal (but not cathodal) strength-interval curve. Studying model variants elucidates the necessary and sufficient physiological conditions to predict the polarity dependent dip: a voltage and time dependent INa, a nonlinear rectifying repolarization current, and bidomain tissue with unequal anisotropy ratios. PMID:28222136

  15. "The state of the heart": Recent advances in engineering human cardiac tissue from pluripotent stem cells.

    Science.gov (United States)

    Sirabella, Dario; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2015-08-01

    The pressing need for effective cell therapy for the heart has led to the investigation of suitable cell sources for tissue replacement. In recent years, human pluripotent stem cell research expanded tremendously, in particular since the derivation of human-induced pluripotent stem cells. In parallel, bioengineering technologies have led to novel approaches for in vitro cell culture. The combination of these two fields holds potential for in vitro generation of high-fidelity heart tissue, both for basic research and for therapeutic applications. However, this new multidisciplinary science is still at an early stage. Many questions need to be answered and improvements need to be made before clinical applications become a reality. Here we discuss the current status of human stem cell differentiation into cardiomyocytes and the combined use of bioengineering approaches for cardiac tissue formation and maturation in developmental studies, disease modeling, drug testing, and regenerative medicine.

  16. Action potential duration heterogeneity of cardiac tissue can be evaluated from cell properties using Gaussian Green's function approach.

    Directory of Open Access Journals (Sweden)

    Arne Defauw

    Full Text Available Action potential duration (APD heterogeneity of cardiac tissue is one of the most important factors underlying initiation of deadly cardiac arrhythmias. In many cases such heterogeneity can be measured at tissue level only, while it originates from differences between the individual cardiac cells. The extent of heterogeneity at tissue and single cell level can differ substantially and in many cases it is important to know the relation between them. Here we study effects from cell coupling on APD heterogeneity in cardiac tissue in numerical simulations using the ionic TP06 model for human cardiac tissue. We show that the effect of cell coupling on APD heterogeneity can be described mathematically using a Gaussian Green's function approach. This relates the problem of electrotonic interactions to a wide range of classical problems in physics, chemistry and biology, for which robust methods exist. We show that, both for determining effects of tissue heterogeneity from cell heterogeneity (forward problem as well as for determining cell properties from tissue level measurements (inverse problem, this approach is promising. We illustrate the solution of the forward and inverse problem on several examples of 1D and 2D systems.

  17. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-12-01

    Full Text Available Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06 but less than half of the native postnatal day 12 (0.90 ± 0.06 and adult (0.91 ± 0.04 myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal

  18. OCT Study of Optical Clearing of Muscle Tissue in vitro with 40% Glucose Solution

    Science.gov (United States)

    Genina, E. A.; Bashkatov, A. N.; Kozintseva, M. D.; Tuchin, V. V.

    2016-01-01

    The technique of -optical clearing of biological tissues- is aimed at improving the quality of visualization of structures hidden deep in tissue. In this study, we measured the diffusion coefficient of glucose in bovine skeletal muscle tissue by optical coherence tomography (OCT) in vitro and determined changes that took place in the imaging contrast of muscle fibers, the optical depth of coherent probing, and detection under the influence of aqueous 40% solution of glucose. It was shown that, within 90 min, when the depth of coherent probing increased by 14%, the contrast of OCT images increased fourfold and the depth of coherent detection of structural elements of the tissue increased by 2.4 times. The diffusion coefficient of glucose in the muscle tissue was (2.98 ± 0.94) × 10-6 cm2/s.

  19. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    Science.gov (United States)

    Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

  20. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy

    Science.gov (United States)

    Huang, Chao; Sachse, Frank B.; Hitchcock, Robert W.; Kaza, Aditya K.

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2±0.3% and 98.0±0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2±0.3% and 94.0±2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease. PMID:26808149

  1. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    Directory of Open Access Journals (Sweden)

    Chao Huang

    Full Text Available Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000. We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81 and nodal tissue (n = 81. In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively. Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

  2. Physical exercise regulates p53 activity targeting SCO2 and increases mitochondrial COX biogenesis in cardiac muscle with age.

    Directory of Open Access Journals (Sweden)

    Zhengtang Qi

    Full Text Available The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-μ (PFTμ, sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2, p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTμ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle.

  3. Influence of cardiac tissue anisotropy on re-entrant activation in computational models of ventricular fibrillation

    Science.gov (United States)

    Clayton, Richard H.

    2009-06-01

    The aim of this study was to establish the role played by anisotropic diffusion in (i) the number of filaments and epicardial phase singularities that sustain ventricular fibrillation in the heart, (ii) the lifetimes of filaments and phase singularities, and (iii) the creation and annihilation dynamics of filaments and phase singularities. A simplified monodomain model of cardiac tissue was used, with membrane excitation described by a simplified 3-variable model. The model was configured so that a single re-entrant wave was unstable, and fragmented into multiple re-entrant waves. Re-entry was then initiated in tissue slabs with varying anisotropy ratio. The main findings of this computational study are: (i) anisotropy ratio influenced the number of filaments sustaining simulated ventricular fibrillation, with more filaments present in simulations with smaller values of transverse diffusion coefficient, (ii) each re-entrant filament was associated with around 0.9 phase singularities on the surface of the slab geometry, (iii) phase singularities were longer lived than filaments, and (iv) the creation and annihilation of filaments and phase singularities were linear functions of the number of filaments and phase singularities, and these relationships were independent of the anisotropy ratio. This study underscores the important role played by tissue anisotropy in cardiac ventricular fibrillation.

  4. Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy.

    Science.gov (United States)

    Sun, Guilian; Haginoya, Kazuhiro; Wu, Yanling; Chiba, Yoko; Nakanishi, Tohru; Onuma, Akira; Sato, Yuko; Takigawa, Masaharu; Iinuma, Kazuie; Tsuchiya, Shigeru

    2008-04-15

    The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-beta1 (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy.

  5. Controlling activation site density by low-energy far-field stimulation in cardiac tissue

    Science.gov (United States)

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2012-06-01

    Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites (“virtual electrodes”) in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

  6. Total mercury in liver and muscle tissue of two coastal sharks from the northwest of Mexico.

    Science.gov (United States)

    Hurtado-Banda, Rocío; Gomez-Alvarez, Agustín; Márquez-Farías, J Fernando; Cordoba-Figueroa, Marcial; Navarro-García, Gerardo; Medina-Juárez, Luis Angel

    2012-06-01

    Total mercury (THg) in liver and muscle of three costal sharks from Mexico were evaluated. The highest concentrations of THg in muscle tissue of juveniles were found in Sphyrna lewini (0.82 ± 0.33 mg kg(-1) wet basis). Rhizoprionodon longurio adults had the highest concentrations (0.92 ± 1.03 mg kg(-1)). THg concentrations in liver were low compared to those found in muscle tissue; higher levels were found in liver of juvenile S. lewini (0.250 ± 0.07 mg kg(-1)). Results showed that 35 % of muscle tissue samples are above the precautionary limit (0.50 mg kg(-1) of THg) and a 7 % exceeded the maximum limit for human consumption (1 mg kg(-1)).

  7. Erythropoietin improves functional and histological recovery of traumatized skeletal muscle tissue.

    Science.gov (United States)

    Rotter, Robert; Menshykova, Marija; Winkler, Tobias; Matziolis, Georg; Stratos, Ioannis; Schoen, Matthias; Bittorf, Thomas; Mittlmeier, Thomas; Vollmar, Brigitte

    2008-12-01

    Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic cytokine with anti-inflammatory and anti-apoptotic properties. Here, we evaluated for the first time the EPO-dependent regeneration capacity in an in vivo rat model of skeletal muscle trauma. A myoblast cell line was used to study the effect of EPO on serum deprivation-induced cell apoptosis in vitro. A crush injury was performed to the left soleus muscle in 80 rats treated with either EPO or saline. Muscle recovery was assessed by analysis of contraction capacities. Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved caspase-3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42 posttrauma served for assessment of local microcirculation, tissue integrity, and cell proliferation. Serum deprivation-induced myoblast apoptosis of 23.9 +/- 1.5% was reduced by EPO to 17.2 +/- 0.8%. Contraction force analysis in the EPO-treated animals revealed significantly improved muscle strength with 10-20% higher values of twitch and tetanic forces over the 42-day observation period. EPO-treated muscle tissue displayed improved functional capillary density as well as reduced leukocytic response and consecutively macromolecular leakage over day 14. Concomitantly, muscle histology showed significantly increased numbers of BrdU-positive satellite cells and interstitial cells as well as slightly lower counts of cleaved caspase-3-positive interstitial cells. EPO results in faster and better regeneration of skeletal muscle tissue after severe trauma and goes along with improved microcirculation. Thus, EPO, a compound established as clinically safe, may represent a promising therapeutic option to optimize the posttraumatic course of muscle tissue healing.

  8. Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species.

    Science.gov (United States)

    O'Bryhim, Jason R; Adams, Douglas H; Spaet, Julia L Y; Mills, Gary; Lance, Stacey L

    2017-04-01

    Mercury (Hg) exposure poses a threat to both fish and human health. Sharks are known to bioaccumulate Hg, however, little is known regarding how Hg is distributed between different tissue groups (e.g. muscle regions, organs). Here we evaluated total mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two different shark species, bonnethead (Sphyrna tiburo) and silky shark (Carcharhinus falciformis) to determine the relationships of THg concentrations between and within tissue groups. Total Hg concentrations were highest in the eight muscle regions with no significant differences in THg concentrations between the different muscle regions and muscle types (red and white). Results from tissue collected from any muscle region would be representative of all muscle sample locations. Total Hg concentrations were lowest in samples taken from the fin inner core of the first dorsal, pectoral, and caudal (lower lobe) fins. Mercury concentrations for samples taken from the trailing margin of the dorsal, pectoral, and caudal fins (upper and lower lobe) were also not significantly different from each other for both species. Significant relationships were found between THg concentrations in dorsal axial muscle tissue and the fin inner core, liver, kidney, spleen and heart for both species as well as the THg concentrations between the dorsal fin trailing margin and the heart for the silky shark and all other sampled tissue types for the bonnethead shark. Our results suggest that biopsy sampling of dorsal muscle can provide data that can effectively estimate THg concentrations in specific organs without using more invasive, or lethal methods.

  9. Relationships of mercury concentrations across tissue types, muscle regions and fins for two shark species

    KAUST Repository

    O'Bryhim, Jason R.

    2017-01-31

    Mercury (Hg) exposure poses a threat to both fish and human health. Sharks are known to bioaccumulate Hg, however, little is known regarding how Hg is distributed between different tissue groups (e.g. muscle regions, organs). Here we evaluated total mercury (THg) concentrations from eight muscle regions, four fins (first dorsal, left and right pectorals, caudal-from both the inner core and trailing margin of each fin), and five internal organs (liver, kidney, spleen, heart, epigonal organ) from two different shark species, bonnethead (Sphyrna tiburo) and silky shark (Carcharhinus falciformis) to determine the relationships of THg concentrations between and within tissue groups. Total Hg concentrations were highest in the eight muscle regions with no significant differences in THg concentrations between the different muscle regions and muscle types (red and white). Results from tissue collected from any muscle region would be representative of all muscle sample locations. Total Hg concentrations were lowest in samples taken from the fin inner core of the first dorsal, pectoral, and caudal (lower lobe) fins. Mercury concentrations for samples taken from the trailing margin of the dorsal, pectoral, and caudal fins (upper and lower lobe) were also not significantly different from each other for both species. Significant relationships were found between THg concentrations in dorsal axial muscle tissue and the fin inner core, liver, kidney, spleen and heart for both species as well as the THg concentrations between the dorsal fin trailing margin and the heart for the silky shark and all other sampled tissue types for the bonnethead shark. Our results suggest that biopsy sampling of dorsal muscle can provide data that can effectively estimate THg concentrations in specific organs without using more invasive, or lethal methods.

  10. Unpinning of rotating spiral waves in cardiac tissues by circularly polarized electric fields

    Science.gov (United States)

    Feng, Xia; Gao, Xiang; Pan, De-Bei; Li, Bing-Wei; Zhang, Hong

    2014-04-01

    Spiral waves anchored to obstacles in cardiac tissues may cause lethal arrhythmia. To unpin these anchored spirals, comparing to high-voltage side-effect traditional therapies, wave emission from heterogeneities (WEH) induced by the uniform electric field (UEF) has provided a low-voltage alternative. Here we provide a new approach using WEH induced by the circularly polarized electric field (CPEF), which has higher success rate and larger application scope than UEF, even with a lower voltage. And we also study the distribution of the membrane potential near an obstacle induced by CPEF to analyze its mechanism of unpinning. We hope this promising approach may provide a better alternative to terminate arrhythmia.

  11. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats.

    Science.gov (United States)

    Jumabay, Medet; Matsumoto, Taro; Yokoyama, Shin-ichiro; Kano, Koichiro; Kusumi, Yoshiaki; Masuko, Takayuki; Mitsumata, Masako; Saito, Satoshi; Hirayama, Atsushi; Mugishima, Hideo; Fukuda, Noboru

    2009-11-01

    Adipose tissue-derived stem cells have been demonstrated to differentiate into cardiomyocytes and vascular endothelial cells. Here we investigate whether mature adipocyte-derived dedifferentiated fat (DFAT) cells can differentiate to cardiomyocytes in vitro and in vivo by establishing DFAT cell lines via ceiling culture of mature adipocytes. DFAT cells were obtained by dedifferentiation of mature adipocytes from GFP-transgenic rats. We evaluated the differentiating ability of DFAT cells into cardiomyocytes by detection of the cardiac phenotype markers in immunocytochemical and RT-PCR analyses in vitro. We also examined effects of the transplantation of DFAT cells into the infarcted heart of rats on cardiomyocytes regeneration and angiogenesis. DFAT cells expressed cardiac phenotype markers when cocultured with cardiomyocytes and also when grown in MethoCult medium in the absence of cardiomyocytes, indicating that DFAT cells have the potential to differentiate to cardiomyocyte lineage. In a rat acute myocardial infarction model, transplanted DFAT cells were efficiently accumulated in infarcted myocardium and expressed cardiac sarcomeric actin at 8 weeks after the cell transplantation. The transplantation of DFAT cells significantly (pDFAT cells have the ability to differentiate to cardiomyocyte-like cells in vitro and in vivo. In addition, transplantation of DFAT cells led to neovascuralization in rats with myocardial infarction. We propose that DFAT cells represent a promising candidate cell source for cardiomyocyte regeneration in severe ischemic heart disease.

  12. Injection of duck recombinant follistatin fusion protein into duck muscle tissues stimulates satellite cell proliferation and muscle fiber hypertrophy.

    Science.gov (United States)

    Liu, He-he; Wang, Ji-wen; Yu, Hai-yue; Zhang, Rong-ping; Chen, Xi; Jin, Hai-bo; Dai, Fei; Li, Liang; Xu, Feng

    2012-06-01

    Follistatin (FST) can inhibit the expression of myostatin, which is a predominant inhibitor of muscle development. The potential application of myostatin-based technology has been prompted in different ways in agriculture. We previously constructed an expression vector of duck FST and isolated the FST fusion protein. After the protein was purified and refolded, it was added to the medium of duck myoblasts cultured in vitro. The results show that the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide value of the myoblasts in the duck FST treatment group is higher than that in the control group, which indicates that the duck FST fusion protein exhibits the biological activities that can accelerate myoblast proliferation. To further investigate the roles of duck FST on muscle development, we injected the protein into the duck muscle tissues in vivo. The results show that both the duck muscle fiber cross-sectional area and the satellite cell activation frequency are influenced more in the FST treatment group than they are in the control group. In addition to these phenomena, expression of MyoD and Myf5 were increased, and the expression of myostatin was decreased. Together, these results suggest the potential for using duck FST fusion protein to inhibit myostatin activity and subsequently to enhance muscle growth in vivo. The mechanism by which FST regulates muscle development in the duck is similar to that in mammals and fishes.

  13. Infectivity of Trichinella spp. recovered from decaying mouse and fox muscle tissue

    DEFF Research Database (Denmark)

    Von Koller, J.; Kapel, C.M.O.; Enemark, Heidi L.;

    2001-01-01

    The tolerance to degradation processes in meat of nine Trichinella genotypes was studied in mouse and fox tissue, respectively. Minced muscle tissue with Trichinella larvae of different age was stored at room temperature at 100 % relative humidity. During storage weekly sub samples of the minced...

  14. Connective tissue growth factor induces extracellular matrix in asthmatic airway smooth muscle

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K; Ge, Qi; Poniris, Maree; Boustany, Sarah; Twigg, Stephen M; Black, Judith L

    2006-01-01

    Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in airway smooth muscle cells isolated from patients with ast

  15. On the Behaviour of Porcine Adipose and Skeletal Muscle Tissues under Shock Compression

    Science.gov (United States)

    2012-09-01

    presented by Ono et al. for the m. biceps femoris (a likely component within the commercial porcine muscle tissue tested here) correspond to maximum fibre... tendinous deposits found within the material. Whilst comprising the same biological make-up as the non-processed variant of the tissue (actin and myosin

  16. Passive muscle stiffness may be influenced by active contractility of intramuscular connective tissue.

    Science.gov (United States)

    Schleip, Robert; Naylor, Ian L; Ursu, Daniel; Melzer, Werner; Zorn, Adjo; Wilke, Hans-Joachim; Lehmann-Horn, Frank; Klingler, Werner

    2006-01-01

    The article introduces the hypothesis that intramuscular connective tissue, in particular the fascial layer known as the perimysium, may be capable of active contraction and consequently influence passive muscle stiffness, especially in tonic muscles. Passive muscle stiffness is also referred to as passive elasticity, passive muscular compliance, passive extensibility, resting tension, or passive muscle tone. Evidence for the hypothesis is based on five indications: (1) tonic muscles contain more perimysium and are therefore stiffer than phasic muscles; (2) the specific collagen arrangement of the perimysium is designed to fit a load-bearing function; (3) morphological considerations as well as histological observations in our laboratory suggest that the perimysium is characterized by a high density of myofibroblasts, a class of fibroblasts with smooth muscle-like contractile kinetics; (4) in vitro contraction tests with fascia have demonstrated that fascia, due to the presence of myofibroblasts, is able to actively contract, and that the resulting contraction forces may be strong enough to influence musculoskeletal dynamics; (5) the pronounced increase of the perimysium in muscle immobilization and in the surgical treatment of distraction osteogenesis indicates that perimysial stiffness adapts to mechanical stimulation and hence influences passive muscle stiffness. In conclusion, the perimysium seems capable of response to mechanostimulation with a myofibroblast facilitated active tissue contraction, thereby adapting passive muscle stiffness to increased tensional demands, especially in tonic musculature. If verified, this new concept may lead to novel pharmaceutical or mechanical approaches to complement existing treatments of pathologies which are accompanied by an increase or decrease of passive muscle stiffness (e.g., muscle fibroses such as torticollis, peri-partum pelvic pain due to pelvic instability, and many others). Methods for testing this new concept

  17. Calprotectin is released from human skeletal muscle tissue during exercise

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian

    2008-01-01

    in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...... as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of approximately 50......% of peak power output and arterial-femoral venous differences were obtained. Arterial plasma concentrations for calprotectin increased 2-fold compared to rest and there was a net release of calprotectin from the working muscle. In conclusion, IL-6 infusion and muscle contractions induce expression of S100A...

  18. In vitro terahertz monitoring of muscle tissue dehydration under the action of hyperosmotic agents

    Energy Technology Data Exchange (ETDEWEB)

    Kolesnikov, A S; Kolesnikova, E A; Popov, A P; Tuchin, V V [N.G. Chernyshevsky Saratov State University, Saratov (Russian Federation); Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation)

    2014-07-31

    Dehydration of muscle tissue in vitro under the action of biologically compatible hyperosmotic agents is studied using a laser terahertz spectrometer in the frequency range from 0.25 to 2.5 THz. Broadband terahertz absorption and reflection spectra of the bovine skeletal muscle tissue were obtained under the action of glycerol, polyethylene glycol with the molecular weight 600 (PEG-600), and propylene glycol. The presented results are proposed for application in developing the methods of image contrast enhancement and increasing the depth of biological tissue probing with terahertz radiation. (laser biophotonics)

  19. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

  20. The current status of iPS cells in cardiac research and their potential for tissue engineering and regenerative medicine.

    Science.gov (United States)

    Martins, Ana M; Vunjak-Novakovic, Gordana; Reis, Rui L

    2014-04-01

    The recent availability of human cardiomyocytes derived from induced pluripotent stem (iPS) cells opens new opportunities to build in vitro models of cardiac disease, screening for new drugs, and patient-specific cardiac therapy. Notably, the use of iPS cells enables studies in the wide pool of genotypes and phenotypes. We describe progress in reprogramming of induced pluripotent stem (iPS) cells towards the cardiac lineage/differentiation. The focus is on challenges of cardiac disease modeling using iPS cells and their potential to produce safe, effective and affordable therapies/applications with the emphasis of cardiac tissue engineering. We also discuss implications of human iPS cells to biological research and some of the future needs.

  1. Regulation of tissue crosstalk by skeletal muscle-derived myonectin and other myokines.

    Science.gov (United States)

    Seldin, Marcus M; Wong, G William

    2012-10-01

    The integrated control of animal physiology requires intimate tissue crosstalk, a vital task mediated by circulating humoral factors. As one type of these factors, adipose tissue-derived adipokines have recently garnered attention as important regulators of systemic insulin sensitivity and metabolic homeostasis. However, the realization that skeletal muscle also secretes a variety of biologically and metabolically active polypeptide factors (collectively called myokines) has provided a new conceptual framework to understand the critical role skeletal muscle plays in coordinating whole-body energy balance. Here, we highlight recent progress made in the myokine field and discuss possible roles of myonectin, which we have recently identified as a potential postprandial signal derived from skeletal muscle to integrate metabolic processes in other tissues, such as adipose and liver; one of its roles is to promote fatty acid uptake into cells. Myonectin is also likely an important mediator in inter-tissue crosstalk.

  2. Muscle and tendon connective tissue adaptation to unloading, exercise and NSAID.

    Science.gov (United States)

    Dideriksen, Kasper

    2014-04-01

    The extracellular matrix network of skeletal muscle and tendon connective tissue is primarily composed of collagen and connects the muscle contractile protein to the bones in the human body. The mechanical properties of the connective tissue are important for the effectiveness of which the muscle force is transformed into movement. Periods of unloading and exercise affect the synthesis rate of connective tissue collagen protein, whereas only sparse information exits regarding collagen protein degradation. It is likely, though, that changes in both collagen protein synthesis and degradation are required for remodeling of the connective tissue internal structure that ultimately results in altered mechanical properties of the connective tissue. Both unloading and exercise lead to increased production of growth factors and inflammatory mediators that are involved in connective tissue remodeling. Despite the fact that non-steroidal anti-inflammatory drugs seem to inhibit the healing process of connective tissue and the stimulating effect of exercise on connective tissue protein synthesis, these drugs are often consumed in relation to connective tissue injury and soreness. However, the potential effect of non-steroidal anti-inflammatory drugs on connective tissue needs further investigation.

  3. Histone deacetylase 8 regulates cortactin deacetylation and contraction in smooth muscle tissues.

    Science.gov (United States)

    Li, Jia; Chen, Shu; Cleary, Rachel A; Wang, Ruping; Gannon, Olivia J; Seto, Edward; Tang, Dale D

    2014-08-01

    Histone deacetylases (HDACs) are a family of enzymes that mediate nucleosomal histone deacetylation and gene expression. Some members of the HDAC family have also been implicated in nonhistone protein deacetylation, which modulates cell-cycle control, differentiation, and cell migration. However, the role of HDACs in smooth muscle contraction is largely unknown. Here, HDAC8 was localized both in the cytoplasm and the nucleus of mouse and human smooth muscle cells. Knockdown of HDAC8 by lentivirus-encoding HDAC8 shRNA inhibited force development in response to acetylcholine. Treatment of smooth muscle tissues with HDAC8 inhibitor XXIV (OSU-HDAC-44) induced relaxation of precontracted smooth muscle tissues. In addition, cortactin is an actin-regulatory protein that undergoes deacetylation during migration of NIH 3T3 cells. In this study, acetylcholine stimulation induced cortactin deacetylation in mouse and human smooth muscle tissues, as evidenced by immunoblot analysis using antibody against acetylated lysine. Knockdown of HDAC8 by RNAi or treatment with the inhibitor attenuated cortactin deacetylation and actin polymerization without affecting myosin activation. Furthermore, expression of a charge-neutralizing cortactin mutant inhibited contraction and actin dynamics during contractile activation. These results suggest a novel mechanism for the regulation of smooth muscle contraction. In response to contractile stimulation, HDAC8 may mediate cortactin deacetylation, which subsequently promotes actin filament polymerization and smooth muscle contraction.

  4. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Tingqing Guo

    Full Text Available Myostatin (Mstn is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/- mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/- mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/- mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/- mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/- mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/- mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

  5. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering

    Science.gov (United States)

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun

    2016-06-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE.

  6. The Dip in the Anodal Strength-Interval Curve in Cardiac Tissue

    Science.gov (United States)

    Kandel, Sunil; Roth, Bradley J.

    2012-10-01

    Heart disease -- specifically ventricular fibrillation -- is the leading cause of death in the United States. The most common treatment for this lethal arrhythmia is defibrillation: application of a strong electrical shock that resets the heart to its normal rhythm. The goal of this project is to obtain a better understanding of how anodal (hyperpolarizing) shocks affect the heart by using numerical simulations. To accomplish this goal, we will test four hypotheses to find the response of refractory tissue to an anodal shock. We will use bidomain model; the state-of-the-art mathematical description of how cardiac tissue responds to an electric shock. The innovative feature of this proposal is to integrate the bidomain model with an ion channel model (Luo-Rudy model, 1994) that includes intracellular calcium dynamics to get a detailed calculation of the mechanism of the excitation and to understand the electrical behavior of the heart, which is important for pacing and defibrillation.

  7. Engineering skeletal muscle tissues from murine myoblast progenitor cells and application of electrical stimulation.

    Science.gov (United States)

    van der Schaft, Daisy W J; van Spreeuwel, Ariane C C; Boonen, Kristel J M; Langelaan, Marloes L P; Bouten, Carlijn V C; Baaijens, Frank P T

    2013-03-19

    Engineered muscle tissues can be used for several different purposes, which include the production of tissues for use as a disease model in vitro, e.g. to study pressure ulcers, for regenerative medicine and as a meat alternative (1). The first reported 3D muscle constructs have been made many years ago and pioneers in the field are Vandenburgh and colleagues (2,3). Advances made in muscle tissue engineering are not only the result from the vast gain in knowledge of biochemical factors, stem cells and progenitor cells, but are in particular based on insights gained by researchers that physical factors play essential roles in the control of cell behavior and tissue development. State-of-the-art engineered muscle constructs currently consist of cell-populated hydrogel constructs. In our lab these generally consist of murine myoblast progenitor cells, isolated from murine hind limb muscles or a murine myoblast cell line C2C12, mixed with a mixture of collagen/Matrigel and plated between two anchoring points, mimicking the muscle ligaments. Other cells may be considered as well, e.g. alternative cell lines such as L6 rat myoblasts (4), neonatal muscle derived progenitor cells (5), cells derived from adult muscle tissues from other species such as human (6) or even induced pluripotent stem cells (iPS cells) (7). Cell contractility causes alignment of the cells along the long axis of the construct (8,9) and differentiation of the muscle progenitor cells after approximately one week of culture. Moreover, the application of electrical stimulation can enhance the process of differentiation to some extent (8). Because of its limited size (8 x 2 x 0.5 mm) the complete tissue can be analyzed using confocal microscopy to monitor e.g. viability, differentiation and cell alignment. Depending on the specific application the requirements for the engineered muscle tissue will vary; e.g. use for regenerative medicine requires the up scaling of tissue size and vascularization, while

  8. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

    Directory of Open Access Journals (Sweden)

    Amy Y Hsiao

    Full Text Available The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

  9. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

    Science.gov (United States)

    Hsiao, Amy Y; Okitsu, Teru; Onoe, Hiroaki; Kiyosawa, Mahiro; Teramae, Hiroki; Iwanaga, Shintaroh; Kazama, Tomohiko; Matsumoto, Taro; Takeuchi, Shoji

    2015-01-01

    The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

  10. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    Directory of Open Access Journals (Sweden)

    Marcelo G. Pereira

    2014-09-01

    Full Text Available This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA. Young male Wistar rats were supplemented with leucine (1.35 g/kg per day; then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA of regenerating myofibers (p > 0.05 from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I and Smad2/3 in regenerating muscles (p < 0.05. Leucine also reduced neonatal myosin heavy chain (MyHC-n (p < 0.05, increased adult MyHC-II expression (p < 0.05 and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05. Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

  11. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Baei, Payam [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Jalili-Firoozinezhad, Sasan [Department of Biomedicine and Surgery, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel (Switzerland); Department of Bioengineeringand IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa (Portugal); Rajabi-Zeleti, Sareh [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad [Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser, E-mail: Nasser.Aghdami@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of)

    2016-06-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m{sup −1} was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

  12. Feasibility of a nanomaterial-tissue patch for vascular and cardiac reconstruction.

    Science.gov (United States)

    Ostdiek, Allison M; Ivey, Jan R; Hansen, Sarah A; Gopaldas, Raja; Grant, Sheila A

    2016-04-01

    Vascular and cardiac reconstruction involves the use of biological patches to treat trauma and defects. An in vivo study was performed to determine the remodeling and biologic effects of novel nanostructured vascular patches with and without gold nanoparticles. Porcine vascular tissue was decellularized and conjugated with gold nanoparticles to evaluate if integration would occur while avoiding rupture and stenosis. Swine underwent a bilateral patch angioplasty of the carotid arteries with experimental patches on the right and control patches of bovine pericardium on the left. Animals were sacrificed after surgery and at 3 and 9 weeks. Ultrasound was performed during surgery, every 3 weeks, and before euthanasia. Endothelial regeneration was examined using Evans Blue dye and histology using Trichrome and H&E. There was a 100% success rate of implantation with 0% mortality. All patches were patent on ultrasound. At 3 weeks, experimental patches had regenerating endothelial cell growth and normal healing responses. At 9 weeks, the experimental patches demonstrated excellent integration. Histology demonstrated cellular in-growth into the experimental patches and no major immune reactions. This is one of the first studies to demonstrate the feasibility of nanomaterial-tissue patches for vascular and cardiac reconstruction.

  13. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering.

    Science.gov (United States)

    Gelmi, Amy; Cieslar-Pobuda, Artur; de Muinck, Ebo; Los, Marek; Rafat, Mehrdad; Jager, Edwin W H

    2016-06-01

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

  14. An Autologous Muscle Tissue Expansion Approach for the Treatment of Volumetric Muscle Loss

    Science.gov (United States)

    2015-07-01

    MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release, distribution unlimited 13. SUPPLEMENTARY NOTES 14...Alexaflour 488 and 596 labeled secondary antibodies (1:200–1:500; Invitro- gen) were used for detection. Morphological assessment Whole muscle H&E cross...sections were analyzed for total fiber number and muscle fiber morphological characteristics. Total fiber number was analyzed by manually counting each

  15. Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Veld, Joyce; Vossen, Josephina A.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); De Amorim Bernstein, Karen [Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Francis H Burr Proton Therapy Center, Boston, MA (United States); Halpern, Elkan F. [Massachusetts General Hospital and Harvard Medical School, Institute of Technology Assessment, Boston, MA (United States)

    2016-12-15

    To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. (orig.)

  16. Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy.

    Science.gov (United States)

    Min, Kisuk; Kwon, Oh-Sung; Smuder, Ashley J; Wiggs, Michael P; Sollanek, Kurt J; Christou, Demetra D; Yoo, Jeung-Ki; Hwang, Moon-Hyon; Szeto, Hazel H; Kavazis, Andreas N; Powers, Scott K

    2015-04-15

    Although doxorubicin (DOX) is a highly effective anti-tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX-mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX-induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial-targeted anti-oxidant to prevent DOX-induced increases in mitochondrial ROS emission, whereas a highly-selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX-mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX-induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX-induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX-induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX-induced myopathy in both cardiac and skeletal muscle fibres.

  17. Propagation velocity profile in a cross-section of a cardiac muscle bundle from PSpice simulation

    Directory of Open Access Journals (Sweden)

    Sperelakis Nicholas

    2006-08-01

    Full Text Available Abstract Background The effect of depth on propagation velocity within a bundle of cardiac muscle fibers is likely to be an important factor in the genesis of some heart arrhythmias. Model and methods The velocity profile of simulated action potentials propagated down a bundle of parallel cardiac muscle fibers was examined in a cross-section of the bundle using a PSpice model. The model (20 × 10 consisted of 20 chains in parallel, each chain being 10 cells in length. All 20 chains were stimulated simultaneously at the left end of the bundle using rectangular current pulses (0.25 nA, 0.25 ms duration applied intracellularly. The simulated bundle was symmetrical at the top and bottom (including two grounds, and voltage markers were placed intracellularly only in cells 1, 5 and 10 of each chain to limit the total number of traces to 60. All electrical parameters were standard values; the variables were (1 the number of longitudinal gap-junction (G-j channels (0, 1, 10, 100, (2 the longitudinal resistance between the parallel chains (Rol2 (reflecting the closeness of the packing of the chains, and (3 the bundle termination resistance at the two ends of the bundle (RBT. The standard values for Rol2 and RBT were 200 KΩ. Results The velocity profile was bell-shaped when there was 0 or only 1 gj-channel. With standard Rol2 and RBT values, the velocity at the surface of the bundle (θ1 and θ20 was more than double (2.15 × that at the core of the bundle (θ10, θ11. This surface:core ratio of velocities was dependent on the values of Rol2 and RBT. When Rol2 was lowered 10-fold, θ1 increased slightly and θ2decreased slightly. When there were 100 gj-channels, the velocity profile was flat, i.e. the velocity at the core was about the same as that at the surface. Both velocities were more than 10-fold higher than in the absence of gj-channels. Varying Rol2 and RBT had almost no effect. When there were 10 gj-channels, the cross-sectional velocity profile

  18. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...... indicate that during 1h of exercise the liver utilizes carbohydrates for oxidation rather than gluconeogenesis and that gluconeogenic activity during 1h of exercise is not regulated through increases in protein content. The aim of study III was to investigate the role of skeletal muscle derived IL-6...

  19. Stem Cells and Tissue Niche: Two Faces of the Same Coin of Muscle Regeneration

    Science.gov (United States)

    Scicchitano, Bianca Maria; Sica, Gigliola; Musarò, Antonio

    2016-01-01

    Capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program. However, muscle regeneration is severely compromised in several pathological conditions. It is likely that the restricted tissue repair program under pathological conditions is due to either progressive loss of stem cell populations or to missing signals that limit the damaged tissues to efficiently activate a regenerative program. It is therefore plausible that loss of control over these cell fates might lead to a pathological cell transdifferentiation, limiting the ability of a pathological muscle to sustain an efficient regenerative process. The critical role of microenvironment on stem cells activity and muscle regeneration is discussed. PMID:28078070

  20. Stem cells and tissue niche: two faces of the same coin of muscle regeneration

    Directory of Open Access Journals (Sweden)

    Bianca Maria Scicchitano

    2016-11-01

    Full Text Available Capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program. However, muscle regeneration is severely compromised in several pathological conditions. It is likely that the restricted tissue repair program under pathological conditions is due to either progressive loss of stem cell populations or to missing signals that limit the damaged tissues to efficiently activate a regenerative program. It is therefore plausible that loss of control over these cell fates might lead to a pathological cell transdifferentiation, limiting the ability of a pathological muscle to sustain an efficient regenerative process. The critical role of microenvironment on stem cells activity and muscle regeneration is discussed.

  1. Central injection of GalR1 agonist M617 facilitates GLUT4 expression in cardiac muscle of type 2 diabetic rats.

    Science.gov (United States)

    Fang, Penghua; Shi, Mingyi; Zhu, Yan; Zhang, Zhenwen; Bo, Ping

    2015-05-01

    Although galanin has been shown to increase GLUT4 expression in the cardiac muscle of rats, there is no literature available about the effect of GalR1 on GLUT4 expression in the cardiac muscle of type 2 diabetic rats. The aim of this study was to determine whether intracerebroventricular injection of GalR1 agonist M617 would elevate GLUT4 expression in the cardiac muscle of type 2 diabetic rats. The rats tested were divided into four groups: rats from healthy and type 2 diabetic drug groups were injected with 10nM/kg/d M617 in 5μl artificial cerebrospinal fluid for 21days, while control received 5μl vehicle injections. The blood samples were analyzed for glucose and insulin concentration. Cardiac muscle was collected and processed for determination of GLUT4 mRNA expression and GLUT4 protein levels. The present findings showed that fasting blood glucose levels in both M617 treatment groups were lower compared with each control. The insulin levels in both M617 treatment groups were decreased compared with each control. Moreover, the GLUT4 content in the cardiac muscle in both drug groups was higher compared with each control. M617 treatment increased GLUT4 mRNA expression and GLUT4 protein levels compared with each control group. These observations suggest that GalR1 agonist M617, acting through its central GalR1, can promote GLUT4 expression and enhance GLUT4 content in the cardiac muscle of type 2 diabetic rats. Central GalR1 may play a significant role in regulation of glucose metabolic homeostasis in the cardiac muscle of type 2 diabetic rats.

  2. Effects of Dexamethasone on Satellite Cells and Tissue Engineered Skeletal Muscle Units.

    Science.gov (United States)

    Syverud, Brian C; VanDusen, Keith W; Larkin, Lisa M

    2016-03-01

    Tissue engineered skeletal muscle has potential for application as a graft source for repairing soft tissue injuries, a model for testing pharmaceuticals, and a biomechanical actuator system for soft robots. However, engineered muscle to date has not produced forces comparable to native muscle, limiting its potential for repair and for use as an in vitro model for pharmaceutical testing. In this study, we examined the trophic effects of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation and fusion into myotubes, on our tissue engineered three-dimensional skeletal muscle units (SMUs). Using our established SMU fabrication protocol, muscle isolates were cultured with three experimental DEX concentrations (5, 10, and 25 nM) and compared to untreated controls. Following seeding onto a laminin-coated Sylgard substrate, the administration of DEX was initiated on day 0 or day 6 in growth medium or on day 9 after the switch to differentiation medium and was sustained until the completion of SMU fabrication. During this process, total cell proliferation was measured with a BrdU assay, and myogenesis and structural advancement of muscle cells were observed through immunostaining for MyoD, myogenin, desmin, and α-actinin. After SMU formation, isometric tetanic force production was measured to quantify function. The histological and functional assessment of the SMU showed that the administration of 10 nM DEX beginning on either day 0 or day 6 yielded optimal SMUs. These optimized SMUs exhibited formation of advanced sarcomeric structure and significant increases in myotube diameter and myotube fusion index, compared with untreated controls. Additionally, the optimized SMUs matured functionally, as indicated by a fivefold rise in force production. In conclusion, we have demonstrated that the addition of DEX to our process of engineering skeletal muscle tissue improves myogenesis, advances muscle structure, and increases force production in the

  3. Isolation of Endothelial Cells and Vascular Smooth Muscle Cells from Internal Mammary Artery Tissue

    Science.gov (United States)

    Moss, Stephanie C.; Bates, Michael; Parrino, Patrick E.; Woods, T. Cooper

    2007-01-01

    Analyses of vascular smooth muscle cell and endothelial cell function through tissue culture techniques are often employed to investigate the underlying mechanisms regulating cardiovascular disease. As diseases such as diabetes mellitus and chronic kidney disease increase a patient's risk of cardiovascular disease, the development of methods for examining the effects of these diseases on vascular smooth muscle cells and endothelial cells is needed. Commercial sources of endothelial cells and vascular smooth muscle cells generally provide minimal donor information and are in limited supply. This study was designed to determine if vascular smooth muscle cells and endothelial cells could be isolated from human internal mammary arteries obtained from donors undergoing coronary artery bypass graft surgery. As coronary artery bypass graft surgery is a commonly performed procedure, this method would provide a new source for these cells that when combined with the donor's medical history will greatly enhance our studies of the effects of complicating diseases on vascular biology. Internal mammary artery tissue was obtained from patients undergoing coronary artery bypass graft surgery. Through a simple method employing two separate tissue digestions, vascular smooth muscle cells and endothelial cells were isolated and characterized. The isolated vascular smooth muscle cells and endothelial cells exhibited the expected morphology and were able to be passaged for further analysis. The vascular smooth muscle cells exhibited positive staining for α-smooth muscle actin and the endothelial cells exhibited positive staining for CD31. The overall purity of the isolations was > 95%. This method allows for the isolation of endothelial cells and vascular smooth muscle cells from internal mammary arteries, providing a new tool for investigations into the interplay of vascular diseases and complicating diseases such as diabetes and kidney disease. PMID:21603530

  4. Exploring PTX3 expression in Sus scrofa cardiac tissue using RNA sequencing.

    Science.gov (United States)

    Cabiati, Manuela; Caselli, Chiara; Savelli, Sara; Prescimone, Tommaso; Lionetti, Vincenzo; Giannessi, Daniela; Del Ry, Silvia

    2012-02-10

    The prototypic long pentraxin PTX3 is a novel vascular inflammatory marker sharing similarities with the classic short pentraxin (C-reactive protein). PTX3 is rapidly produced and released by several cell types in response to local inflammation of the cardiovascular system. Plasma PTX3 levels are very low in normal conditions and increase in heart failure (HF) patients with advancing NYHA functional class, but its exact role during HF pathogenetic mechanisms is not yet established. No data about PTX3 cardiac expression in normal and pathological conditions are currently available, either in human or in large-size animals. Of the latter, the pig has a central role in "in vivo" clinical settings but its genome has not been completely sequenced and the PTX3 gene sequence is still lacking. The aim of this study was to sequence the PTX3 in Sus scrofa, whose sequence is not yet present in GenBank. Utilizing our knowledge of this sequence, PTX3 mRNA expression was evaluated in cardiac tissue of normal (n=6) and HF pigs (n=5), obtained from the four chambers. To sequence PTX3 gene in S. scrofa, the high homology between Homo sapiens and S. scrofa was exploited. Pig PTX3 mRNA was sequenced using polymerase chain reaction primers designed from human consensus sequences. The DNA, obtained from different RT-PCR reactions, was sequenced using the Sanger method. S. scrofa PTX3 mRNA, 1-336 bp, was submitted to GenBank (ID: GQ412351). The sequence obtained from pig cardiac tissue shared an 84% sequence identity with human homolog. The presence of PTX3 mRNA expression was detected in all the cardiac chambers sharing an increase after 3 weeks of pacing compared to controls (p=0.036 HF right atrium vs. N; p=0.022, HF left ventricle vs. N). Knowledge of the PTX3 sequence could be a useful starting point for future studies devoted to better understanding the specific role of this molecule in the pathogenesis of cardiovascular diseases.

  5. Reentry produced by small-scale heterogeneities in a discrete model of cardiac tissue

    Science.gov (United States)

    Alonso, Sergio; Bär, Markus

    2016-06-01

    Reentries are reexcitations of cardiac tissue after the passing of an excitation wave which can cause dangerous arrhythmias like tachycardia or life-threatening heart failures like fibrillation. The heart is formed by a network of cells connected by gap junctions. Under ischemic conditions some of the cells lose their connections, because gap junctions are blocked and the excitability is decreased. We model a circular region of the tissue where a fraction of connections among individual cells are removed and substituted by non-conducting material in a two-dimensional (2D) discrete model of a heterogeneous excitable medium with local kinetics based on electrophysiology. Thus, two neighbouring cells are connected (disconnected) with a probability ϕ (1 - ϕ). Such a region is assumed to be surrounded by homogeneous tissue. The circular heterogeneous area is shown to act as a source of new waves which reenter into the tissue and reexcitate the whole domain. We employ the Fenton-Karma equations to model the action potential for the local kinetics of the discrete nodes to study the statistics of the reentries in two dimensional networks with different topologies. We conclude that the probability of reentry is determined by the proximity of the fraction of disrupted connections between neighboring nodes (“cells”) in the heterogeneous region to the percolation threshold.

  6. Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue.

    Science.gov (United States)

    Watt, Matthew J; Holmes, Anna G; Pinnamaneni, Srijan K; Garnham, Andrew P; Steinberg, Gregory R; Kemp, Bruce E; Febbraio, Mark A

    2006-03-01

    Hormone-sensitive lipase (HSL) is important for the degradation of triacylglycerol in adipose and muscle tissue, but the tissue-specific regulation of this enzyme is not fully understood. We investigated the effects of adrenergic stimulation and AMPK activation in vitro and in circumstances where AMPK activity and catecholamines are physiologically elevated in humans in vivo (during physical exercise) on HSL activity and phosphorylation at Ser(563) and Ser(660), the PKA regulatory sites, and Ser(565), the AMPK regulatory site. In human experiments, skeletal muscle, subcutaneous adipose and venous blood samples were obtained before, at 15 and 90 min during, and 120 min after exercise. Skeletal muscle HSL activity was increased by approximately 80% at 15 min compared with rest and returned to resting rates at the cessation of and 120 min after exercise. Consistent with changes in plasma epinephrine, skeletal muscle HSL Ser(563) and Ser(660) phosphorylation were increased by 27% at 15 min (P HSL Ser(565) phosphorylation and AMPK signaling were increased at 90 min during, and after, exercise. Phosphorylation of adipose tissue HSL paralleled changes in skeletal muscle in vivo, except HSL Ser(660) was elevated 80% in adipose compared with 35% in skeletal muscle during exercise. Studies in L6 myotubes and 3T3-L1 adipocytes revealed important tissue differences in the regulation of HSL. AMPK inhibited epinephrine-induced HSL activity in L6 myotubes and was associated with reduced HSL Ser(660) but not Ser(563) phosphorylation. HSL activity was reduced in L6 myotubes expressing constitutively active AMPK, confirming the inhibitory effects of AMPK on HSL activity. Conversely, in 3T3-L1 adipocytes, AMPK activation after epinephrine stimulation did not prevent HSL activity or glycerol release, which coincided with maintenance of HSL Ser(660) phosphorylation. Taken together, these data indicate that HSL activity is maintained in the face of AMPK activation as a result of

  7. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Chunlei Miao

    2017-01-01

    Full Text Available Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious.

  8. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Science.gov (United States)

    Miao, Chunlei; Zhou, Lulu; Tian, Lufeng; Zhang, Yingjie; Zhang, Wei; Yang, Fanghong; Liu, Tianyi

    2017-01-01

    Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious. PMID:28210626

  9. Multisite Tissue Oxygenation Monitoring Indicates Organ-Specific Flow Distribution and Oxygen Delivery Related to Low Cardiac Output in Preterm Infants With Clinical Sepsis

    NARCIS (Netherlands)

    van der Laan, Michelle E.; Roofthooft, Marcus T. R.; Fries, Marian W. A.; Schat, Trijntje E.; Bos, Arend F.; Berger, Rolf M. F.; Kooi, Elisabeth M. W.

    2016-01-01

    Objectives: Cardiac output may be compromised in preterm infants with sepsis. Whether low cardiac output is associated with low tissue oxygen supply in these patients is unclear. The aim of the current study was to assess the association between cardiac output, assessed by echocardiography, and tiss

  10. Changes in joint angle, muscle-tendon complex length, muscle contractile tissue displacement, and modulation of EMG activity during acute whole-body vibration.

    Science.gov (United States)

    Cochrane, Darryl J; Loram, Ian D; Stannard, Stephen R; Rittweger, Jörn

    2009-09-01

    It has been suggested that vibration causes small changes in muscle length, but to the best of our knowledge, these have yet to be demonstrated during whole-body vibration (WBV). This was an observational study to determine whether acute WBV would result in muscle lengthening. We hypothesized that acute WBV would increase electromyography (EMG) activity concurrently with measurable changes in muscle contractile length. Nine healthy males performed two conditions on a Galileo vibration machine for 15 s at 0 HZ (resting) and 6 HZ at a set knee angle of 18 degrees. Muscle tendon complex length, contractile tissue displacement of the medial gastrocnemius muscle, and EMG of soleus, tibialis anterior, and vastus lateralis muscles were measured. At 6 HZ the medial gastrocnemius (MG) muscle tendon complex (MTC) amplitude (375 microm) was significantly greater (P EMG modulation were found for all muscles during the 6 HZ compared to the 0 HZ condition. The major finding was that approximately 50% of the elongation occurred within the muscle itself and was associated with preceding changes in EMG. This indicates muscle lengthening may be a prerequisite for eliciting stretch reflexes. In conclusion, there is a temporal association between EMG activity and muscle contractile tissue displacement where low-frequency WBV results in small muscle length changes and increases muscle activation.

  11. Methylation-sensitive amplification polymorphism analysis of fat and muscle tissues in pigs.

    Science.gov (United States)

    Ma, J D; Li, M Z; Zhou, S L; Zhou, C W; Li, X W

    2012-09-26

    DNA methylation may be involved in regulating the expression of protein-coding genes, resulting in different fat and muscle phenotypes. Using a methylation-sensitive amplified polymorphism approach, we obtained 7423 bands by selective amplification of genomic DNA from six different fat depots and two heterogeneous muscle types from Duroc/Landrace/Yorkshire cross-bred pigs. The degrees of DNA methylation, determined by the percentages of hemi- and fully methylated sites relative to the total number of CCGG sites, were similar in male and female pigs for each specific tissue [χ(2) test; P (two-tailed) > 0.05]. Gender bias was therefore ignored. There were significant differences in the degree of DNA methylation among the eight tissue types [χ(2) test; P(total) (two-tailed) = 0.009]. However, similar degrees of methylation were observed among the six fat depots [χ(2) test; P(fat) (two-tailed) = 0.24 > 0.05]and between the two muscle types [χ(2) test; P(muscle) (two-tailed) = 0.76 > 0.05]. We conclude that the degree of DNA methylation differs between porcine fat and muscle tissue, but that the methylation status of a particular tissue type is similar, despite being deposited at different body sites.

  12. Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy.

    Science.gov (United States)

    Chen, Na; Chen, Meimei; Liu, Shupeng; Guo, Qiang; Chen, Zhenyi; Wang, Tingyun

    2014-01-01

    This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

  13. Fatty acid composition of muscle and adipose tissue of beef cattle

    Directory of Open Access Journals (Sweden)

    Ivan Jurić

    2010-01-01

    Full Text Available The fatty acid (FA composition of muscle and adipose tissue was investigated in intensively fed beef cattle. Heifers had more intramuscular fat with higher proportion of monounsaturated FA, while bulls had higher proportion of polyunsaturated FA (PUFA. The same was found in adipose tissue accompanied by higher proportion of saturated FA (SFA in bulls. The PUFA/SFA ratio was close to recommendation for human diet only in bulls’ muscle, while n-6/n-3 PUFA ratios were generally higher than recommended. The observed FA variability between sexes was due to the differences in fatness. To improve the nutritional value, the n-3 PUFA in beef should be increased.

  14. Comparative transcriptome profiling of longissimus muscle tissues from Qianhua Mutton Merino and Small Tail Han sheep.

    Science.gov (United States)

    Sun, Limin; Bai, Man; Xiang, Lujie; Zhang, Guishan; Ma, Wei; Jiang, Huaizhi

    2016-09-20

    The Qianhua Mutton Merino (QHMM) is a new sheep (Ovis aries) variety with better meat performance compared with the traditional local variety Small Tail Han (STH) sheep. We aimed to evaluate the transcriptome regulators associated with muscle growth and development between the QHMM and STH. We used RNA-Seq to obtain the transcriptome profiles of the longissimus muscle from the QHMM and STH. The results showed that 960 genes were differentially expressed (405 were up-regulated and 555 were down-regulated). Among these, 463 differently expressed genes (DEGs) were probably associated with muscle growth and development and were involved in biological processes such as skeletal muscle tissue development and muscle cell differentiation; molecular functions such as catalytic activity and oxidoreductase activity; cellular components such as mitochondrion and sarcoplasmic reticulum; and pathways such as metabolic pathways and citrate cycle. From the potential genes, a gene-act-network and co-expression-network closely related to muscle growth and development were identified and established. Finally, the expressions of nine genes were validated by real-time PCR. The results suggested that some DEGs, including MRFs, GXP1 and STAC3, play crucial roles in muscle growth and development processes. This genome-wide transcriptome analysis of QHMM and STH muscle is reported for the first time.

  15. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    Science.gov (United States)

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-06

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  16. A new three-variable mathematical model of action potential propagation in cardiac tissue.

    Science.gov (United States)

    Fenton, Flavio; Karma, Alain

    1996-03-01

    Modeling the electrical activity of the heart, and the complex signaling patterns which underly dangerous arrhythmias such as tachycardia and fibrillation, requires a quantitative model of action potential (AP) propagation. At present, there exist detailed ionic models of the Hodgkin-Huxley form that accurately reproduce dynamical features of the AP at a single cell level (e.g. Luo-Rudy, 1994). However, such models are not computationally tractable to study propagation in two and three-dimensional tissues of many resistively coupled cells. At the other extreme, there exists generic models of excitable media, such as the well-known FitzHugh-Nagumo model, which are only qualitative and do not reproduce essential dynamical features of cardiac AP. A new three-variable model is introduced which bridges the gap between these two types of models. It reproduces quantitatively important `mesoscopic' dynamical properties which are specific to cardiac AP, namely restitution and dispersion. At the same time, it remains computationally tractable and makes it possible to study the effect of these properties on the initiation, dynamics, and stability of complex reentrant excitations in two and three dimensions. Preliminary numerical results of the effect of restitution and dispersion on two-dimensional reentry (i.e. spiral waves) are presented.

  17. Automated segmentation of muscle and adipose tissue on CT images for human body composition analysis

    Science.gov (United States)

    Chung, Howard; Cobzas, Dana; Birdsell, Laura; Lieffers, Jessica; Baracos, Vickie

    2009-02-01

    The ability to compute body composition in cancer patients lends itself to determining the specific clinical outcomes associated with fat and lean tissue stores. For example, a wasting syndrome of advanced disease associates with shortened survival. Moreover, certain tissue compartments represent sites for drug distribution and are likely determinants of chemotherapy efficacy and toxicity. CT images are abundant, but these cannot be fully exploited unless there exist practical and fast approaches for tissue quantification. Here we propose a fully automated method for segmenting muscle, visceral and subcutaneous adipose tissues, taking the approach of shape modeling for the analysis of skeletal muscle. Muscle shape is represented using PCA encoded Free Form Deformations with respect to a mean shape. The shape model is learned from manually segmented images and used in conjunction with a tissue appearance prior. VAT and SAT are segmented based on the final deformed muscle shape. In comparing the automatic and manual methods, coefficients of variation (COV) (1 - 2%), were similar to or smaller than inter- and intra-observer COVs reported for manual segmentation.

  18. Topographic Mapping and Compression Elasticity Analysis of Skinned Cardiac Muscle Fibers in Vitro with Atomic Force Microscopy and Nanoindentation

    OpenAIRE

    2009-01-01

    Surface topography and compression elasticity of bovine cardiac muscle fibers in rigor and relaxing state has been studied with atomic force microscopy. Characteristic sarcomere patterns running along the longitudinal axis of the fibers were clearly observed, and Z-lines, M-lines, I-bands, and A-bands can be distinguished through comparing with TEM images and force curves. AFM height images of fibers had shown a sarcomere length of 1.22±0.02μm (n=5) in rigor with a significant 9% increase in ...

  19. Gene control of acupuncture and moxibustion preconditioning on apoptosis in ischemic cardiac muscle of rats with re-perfusion

    Institute of Scientific and Technical Information of China (English)

    SUN Zhong-ren; LI Xiao-ning; ZHAO Yu-hui; TIAN Yan-yan; XU Li

    2008-01-01

    In order to explore the effect of acupuncture preconditioning on rats' cell apoptosis with cardiac muscle re-perfusion damage and bcl-2mRNA genes, we used differentiating acupuncture and moxibustion preconditioning among groups, then compared acupuncture and moxibustion preconditioning with ischemic preconditioning. The experimental results show that acupuncture and moxibustion preconditioning makes more bcl-2mRNA genes expressed and produces less cell apeptosis, furthermore, groups of acupuncture and moxibustion preconditioning for twice a day are more effective than those of ischemic preconditioning.

  20. Prognostic value of cardiac time intervals measured by tissue Doppler imaging M-mode in the general population

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Mogelvang, Rasmus; Jensen, Jan Skov

    2015-01-01

    OBJECTIVE: Tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to estimate the cardiac time intervals. The aim was to evaluate the usability of the cardiac time intervals in predicting major cardiovascular events (MACE) in the general population. METHODS......: In a large prospective community-based study, cardiac function was evaluated in 1915 participants by both conventional echocardiography and TDI. The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT) and ejection time (ET), were obtained by TDI M...... echocardiographic parameters resulted in a significant increase in the c-statistics (0.76 vs 0.75 ptime intervals that include...

  1. Unstable spiral waves and local Euclidean symmetry in a model of cardiac tissue

    Energy Technology Data Exchange (ETDEWEB)

    Marcotte, Christopher D.; Grigoriev, Roman O. [School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States)

    2015-06-15

    This paper investigates the properties of unstable single-spiral wave solutions arising in the Karma model of two-dimensional cardiac tissue. In particular, we discuss how such solutions can be computed numerically on domains of arbitrary shape and study how their stability, rotational frequency, and spatial drift depend on the size of the domain as well as the position of the spiral core with respect to the boundaries. We also discuss how the breaking of local Euclidean symmetry due to finite size effects as well as the spatial discretization of the model is reflected in the structure and dynamics of spiral waves. This analysis allows identification of a self-sustaining process responsible for maintaining the state of spiral chaos featuring multiple interacting spirals.

  2. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

    DEFF Research Database (Denmark)

    Mulla, N A; Simonsen, L; Bülow, J

    2000-01-01

    , a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... in lipolysis, but it began to increase about 1 h post-exercise and remained elevated for the following 2 h. The increase in post-exercise non-esterified fatty acid (NEFA) mobilization was greater after 60% exercise than after 40 % exercise. It is concluded that the lipolytic rate in abdominal subcutaneous...

  3. ELECTROACTIVE AND NANOSTRUCTURED POLYMERS AS SCAFFOLD MATERIALS FOR NEURONAL AND CARDIAC TISSUE ENGINEERING

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Conducting polymer, polyaniline (PANI), has been studied as a novel electroactive and electrically conductive material for tissue engineering applications. The biocompatibility of the conductive polymer can be improved by (I) covalently grafting various adhesive peptides onto the surface of prefabricated conducting polymer flms or into the polymer structures during the synthesis, (ii) co-electrospinning or blending with natural proteins to form conducting nanofibers or films, and (iii) preparing conducting polymers using biopolymers, such as collagen, as templates. In this paper, we mainly describe and review the approaches of covalently attaching oligopeptides to PANI and electrospinning PANI-gelatin blend nanofibers. The employment of such modified conducting polymers as substrates for enhanced cell attachment, proliferation and differentiation has been investigated with neuronal PC-12 cells and H9c2 cardiac myoblasts. For the electrospun PANIgelatin fibers, depending on the concentrations of PANI, H9c2 cells initially displayed different morphologies on the fibrous substrates, but after one week all cultures reached confluence of similar densities and morphologies. Furthermore, we observed, that conductive PANI, when maintained in an aqueous physiologic environment, retained a significant level of electrical conductivity for at least 100 h, even though this conductivity was decreasing over time. Preliminary data show that the application of micro-current stimulates the differentiation of PC-12 cells. All the results demonstrate the potential for using PANI as an electroactive polymer in the culture of excitable cells and open the possibility of using this material as an electroactive scaffold for cardiac and/or neuronal tissue engineering applications that require biocompatibility of conductive polymers.

  4. Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue.

    Directory of Open Access Journals (Sweden)

    Darryl R Davis

    Full Text Available BACKGROUND: At least four laboratories have shown that endogenous cardiac progenitor cells (CPCs can be grown directly from adult heart tissue in primary culture, as cardiospheres or their progeny (cardiosphere-derived cells, CDCs. Indeed, CDCs are already being tested in a clinical trial for cardiac regeneration. Nevertheless, the validity of the cardiosphere strategy to generate CPCs has been called into question by reports based on variant methods. In those reports, cardiospheres are argued to be cardiomyogenic only because of retained cardiomyocytes, and stem cell activity has been proposed to reflect hematological contamination. We use a variety of approaches (including genetic lineage tracing to show that neither artifact is applicable to cardiospheres and CDCs grown using established methods, and we further document the stem cell characteristics (namely, clonogenicity and multilineage potential of CDCs. METHODOLOGY/PRINCIPAL FINDINGS: CPCs were expanded from human endomyocardial biopsies (n = 160, adult bi-transgenic MerCreMer-Z/EG mice (n = 6, adult C57BL/6 mice (n = 18, adult GFP(+ C57BL/6 transgenic mice (n = 3, Yucatan mini pigs (n = 67, adult SCID beige mice (n = 8, and adult Wistar-Kyoto rats (n = 80. Cellular yield was enhanced by collagenase digestion and process standardization; yield was reduced in altered media and in specific animal strains. Heparinization/retrograde organ perfusion did not alter the ability to generate outgrowth from myocardial sample. The initial outgrowth from myocardial samples was enriched for sub-populations of CPCs (c-Kit(+, endothelial cells (CD31(+, CD34(+, and mesenchymal cells (CD90(+. Lineage tracing using MerCreMer-Z/EG transgenic mice revealed that the presence of cardiomyocytes in the cellular outgrowth is not required for the generation of CPCs. Rat CDCs are shown to be clonogenic, and cloned CDCs exhibit spontaneous multineage potential. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that

  5. Hypoxia Promotes Proliferation of Human Myogenic Satellite Cells : A Potential Benefactor in Tissue Engineering of Skeletal Muscle

    NARCIS (Netherlands)

    Koning, Merel; Werker, Paul M. N.; van Luyn, Marja J. A.; Harmsen, Martin C.

    2011-01-01

    Facial paralysis is a physically, psychologically, and socially disabling condition. Innovative treatment strategies based on regenerative medicine, in particular tissue engineering of skeletal muscle, are promising for treatment of patients with facial paralysis. The natural source for tissue-engin

  6. Gel stretch method: a new method to measure constitutive properties of cardiac muscle cells

    Science.gov (United States)

    Zile, M. R.; Cowles, M. K.; Buckley, J. M.; Richardson, K.; Cowles, B. A.; Baicu, C. F.; Cooper G, I. V.; Gharpuray, V.

    1998-01-01

    Diastolic dysfunction is an important cause of congestive heart failure; however, the basic mechanisms causing diastolic congestive heart failure are not fully understood, especially the role of the cardiac muscle cell, or cardiocyte, in this process. Before the role of the cardiocyte in this pathophysiology can be defined, methods for measuring cardiocyte constitutive properties must be developed and validated. Thus this study was designed to evaluate a new method to characterize cardiocyte constitutive properties, the gel stretch method. Cardiocytes were isolated enzymatically from normal feline hearts and embedded in a 2% agarose gel containing HEPES-Krebs buffer and laminin. This gel was cast in a shape that allowed it to be placed in a stretching device. The ends of the gel were held between a movable roller and fixed plates that acted as mandibles. Distance between the right and left mandibles was increased using a stepper motor system. The force applied to the gel was measured by a force transducer. The resultant cardiocyte strain was determined by imaging the cells with a microscope, capturing the images with a CCD camera, and measuring cardiocyte and sarcomere length changes. Cardiocyte stress was characterized with a finite-element method. These measurements of cardiocyte stress and strain were used to determine cardiocyte stiffness. Two variables affecting cardiocyte stiffness were measured, the passive elastic spring and viscous damping. The passive spring was assessed by increasing the force on the gel at 1 g/min, modeling the resultant stress vs. strain relationship as an exponential [sigma = A/k(ekepsilon - 1)]. In normal cardiocytes, A = 23.0 kN/m2 and k = 16. Viscous damping was assessed by examining the loop area between the stress vs. strain relationship during 1 g/min increases and decreases in force. Normal cardiocytes had a finite loop area = 1.39 kN/m2, indicating the presence of viscous damping. Thus the gel stretch method provided accurate

  7. Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling

    NARCIS (Netherlands)

    Schwab, Bettina C.; Seemann, Gunnar; Lasher, Richard A.; Torres, Natalia S.; Wülfers, Eike M.; Arp, Maren; Carruth, Eric D.; Bridge, John H.B.; Sachse, Frank B.

    2013-01-01

    Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization bas

  8. Roles of chondroitin sulfate proteoglycan 4 in fibrogenic/adipogenic differentiation in skeletal muscle tissues.

    Science.gov (United States)

    Takeuchi, Shiho; Nakano, Shin-Ichi; Nakamura, Katsuyuki; Ozoe, Atsufumi; Chien, Peggie; Yoshihara, Hidehito; Hakuno, Fumihiko; Matsuwaki, Takashi; Saeki, Yasushi; Takahashi, Shin-Ichiro; Yamanouchi, Keitaro; Nishihara, Masugi

    2016-10-01

    Intramuscular adipose tissue and fibrous tissue are observed in some skeletal muscle pathologies such as Duchenne muscular dystrophy and sarcopenia, and affect muscle strength and myogenesis. They originate from common fibrogenic/adipogenic cells in the skeletal muscle. Thus, elucidating the regulatory mechanisms underlying fibrogenic/adipogenic cell differentiation is an important step toward the mediation of these disorders. Previously, we established a highly adipogenic progenitor clone, 2G11, from rat skeletal muscle and showed that basic fibroblast growth factor (bFGF) is pro-adipogenic in these cells. Here, we demonstrated that 2G11 cells give rise to fibroblasts upon transforming growth factor (TGF)-β1 stimulation, indicating that they possess mesenchymal progenitor cells (MPC)-like characteristics. The previously reported MPC marker PDGFRα is expressed in other cell populations. Accordingly, we produced monoclonal antibodies that specifically bind to 2G11 cell surface antigens and identified chondroitin sulfate proteoglycan 4 (CSPG4) as a potential MPC marker. Based on an RNA interference analysis, we found that CSPG4 is involved in both the pro-adipogenic effect of bFGF and in TGF-β-induced alpha smooth muscle actin expression and stress fiber formation. By establishing an additional marker for MPC detection and characterizing its role in fibrogenic/adipogenic differentiation, these results will facilitate the development of effective treatments for skeletal muscle pathologies.

  9. Oxidative stress in toadfish (Halobactrachus didactylus) cardiac muscle. Acute exposure to vanadate oligomers.

    Science.gov (United States)

    Aureliano, M; Joaquim, N; Sousa, A; Martins, H; Coucelo, J M

    2002-06-07

    Vanadate solutions as "metavanadate" (containing ortho and metavanadate species) and "decavanadate" (containing mainly decameric species) (5 mM; 1 mg/kg) were injected intraperitoneously in Halobatrachus didactylus (toadfish), in order to evaluate the contribution of decameric vanadate species to vanadium (V) intoxication on the cardiac tissue. Following short-term exposure (1 and 7 days), different changes on antioxidant enzyme activities-superoxide dismutase (SOD), catalase (CAT), selenium-glutathione peroxidase (Se-GPx), total glutathione peroxidase (GPx), lipid peroxidation and subcellular vanadium distribution were observed in mitochondrial and cytosolic fractions of heart ventricle toadfish. After 1 day of vanadium intoxication, SOD, CAT and Se-GPx activities were decreased up to 25%, by both vanadate solutions, except mitochondrial CAT activity that increased (+23%) upon decavanadate administration. After 7 days of exposure, decavanadate versus metavanadate solutions promoted different effects mainly on cytosolic CAT activity (-56% versus -5%), mitochondrial CAT activity (-10% versus +10%) and total GPx activity (+1% versus -35%), whereas lipid peroxidation products were significantly increased (+82%) upon 500 microM decavanadate intoxication. Accumulation of vanadium in total (0.137+/-0.011 microg/g) and mitochondrial (0.022+/-0.001 microg/g) fractions was observed upon 7 days of metavanadate exposure, whereas for decavanadate, the concentration of vanadium increased in cytosolic (0.020+/-0.005 microg/g) and mitochondrial (0.021+/-0.009 microg/g) fractions. It is concluded that decameric vanadate species are responsible for a strong increase on lipid peroxidation and a decrease in cytosolic catalase activity thus contributing to oxidative stress responses upon vanadate intoxication, in the toadfish heart.

  10. Modeling the response of normal and ischemic cardiac tissue to electrical stimulation

    Science.gov (United States)

    Kandel, Sunil Mani

    Heart disease, the leading cause of death worldwide, is often caused by ventricular fibrillation. A common treatment for this lethal arrhythmia is defibrillation: a strong electrical shock that resets the heart to its normal rhythm. To design better defibrillators, we need a better understanding of both fibrillation and defibrillation. Fundamental mysteries remain regarding the mechanism of how the heart responds to a shock, particularly anodal shocks and the resultant hyperpolarization. Virtual anodes play critical roles in defibrillation, and one cannot build better defibrillators until these mechanisms are understood. We are using mathematical modeling to numerically simulate observed phenomena, and are exploring fundamental mechanisms responsible for the heart's electrical behavior. Such simulations clarify mechanisms and identify key parameters. We investigate how systolic tissue responds to an anodal shock and how refractory tissue reacts to hyperpolarization by studying the dip in the anodal strength-interval curve. This dip is due to electrotonic interaction between regions of depolarization and hyperpolarization following a shock. The dominance of the electrotonic mechanism over calcium interactions implies the importance of the spatial distribution of virtual electrodes. We also investigate the response of localized ischemic tissue to an anodal shock by modeling a regional elevation of extracellular potassium concentration. This heterogeneity leads to action potential instability, 2:1 conduction block (alternans), and reflection-like reentry at the boarder of the normal and ischemic regions. This kind of reflection (reentry) occurs due to the delay between proximal and distal segments to re-excite the proximal segment. Our numerical simulations are based on the bidomain model, the state-of-the-art mathematical description of how cardiac tissue responds to shocks. The dynamic LuoRudy model describes the active properties of the membrane. To model ischemia

  11. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs.

    Science.gov (United States)

    Tous, N; Theil, P K; Lauridsen, C; Lizardo, R; Vilà, B; Esteve-Garcia, E

    2012-12-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA, and slaughtered at an average BW of 117 ± 4.9 kg. Transcription of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP1), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P tissues studied (P fat. Transcription of genes related to FA synthesis was reduced by CLA in SM muscle and liver (SREBP1, both P fat. Saturated FA were increased in all studied tissues (P tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner.

  12. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter H; Bojsen-Møller, Kirstine N; Dirksen, Carsten

    2015-01-01

    12 months post-surgery. Adipose tissue from glucose tolerant subjects was the most responsive to RYGB compared to type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin sensitive phenotype of skeletal muscle......Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose...... tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 week, 3 and 12 months after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 months post...

  13. Short-term immobilization and recovery affect skeletal muscle but not collagen tissue turnover in humans

    DEFF Research Database (Denmark)

    Christensen, Britt; Dyrberg, Eva; Aagaard, Per

    2008-01-01

    of 6% (5,413 to 5,077 mm(2)) in cross-sectional area (CSA) of the triceps surae muscles and a mean decrease of 9% (261 to 238 N.m) in strength of the immobilized calf muscles. Two weeks of recovery resulted in a 6% increased in CSA (to 5,367 mm(2)), whereas strength remained suppressed (240 N...... muscle size and strength, while tendon size and collagen turnover were unchanged. While recovery resulted in an increase in muscle size, strength was unchanged. No significant difference in tendon size could be detected between the two legs after 2 wk of recovery, although collagen synthesis......Not much is known about the effects of immobilization and subsequent recovery on tendon connective tissue. In the present study, healthy young men had their nondominant leg immobilized for a 2-wk period, followed by a recovery period of the same length. Immobilization resulted in a mean decrease...

  14. Evaluation of tissue and urinary survivin expression in non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    S. Sharaf

    2012-12-01

    Conclusion: Urinary survivin is a useful marker for non-invasive detection of non-muscle-invasive bladder cancer recurrence. Its detection is better using ELISA technique than WB and there is no correlation between its expression in tissue and urine.

  15. Cloning and analysis of differentially expressed ESTs in swine muscle tissue

    Institute of Scientific and Technical Information of China (English)

    LI Chongsheng; CHEN Yaosheng; WANG Chong; LI Jiaqi

    2006-01-01

    The obvious difference in muscle growth and meat quality traits exists between Chinese indigenous pig and exotic pigs. In order to study the reason of these phenotypic differences and search the potential gene related to growth and meat quality traits, silver-stained mRNA differential display technique was used to detect the difference with mRNA of loin-eye muscle tissue from maturity pigs of Lantang in Guangdong Province and Large Yorkshire. One of the newly discovered expressed sequence tag (ESTsp3) was analyzed by using bioinformatic technique. The results showed: (1) nearly 2000 cDNA fragments were detected with 30 primer pairs, and 6 differentially expressed ESTs in the loin-eye muscle tissues from the two breeds were isolated and obtained. The differential fragments were cloned and sequenced. The all sequences were recorded in the GenBank. (2) The 786 bp fragment of ESTsp3 was obtained with in silico elongation system, the ORF analysis revealed that it existed as an 83 aa complete open reading frame, and the elongation sequences were verified by RT-PCR. The analysis of in silico expression profile showed that ESTsp3 is expressed in various growth stages and in most tissues and organs, such as soft tissue, skin, skeletal muscle and kidney, but with variant expression quantity.

  16. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E;

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...... cancer when using Doppler tissue imaging of longitudinal left ventricular function....

  17. Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration

    NARCIS (Netherlands)

    Meek, MF; den Dunnen, WFA; Schakenraad, JM; Robinson, PH

    1999-01-01

    The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated u

  18. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  19. Oxidative stress and DNA damage signalling in skeletal muscle in pressure-induced deep tissue injury.

    Science.gov (United States)

    Sin, Thomas K; Pei, Xiao M; Teng, Bee T; Tam, Eric W; Yung, Benjamin Y; Siu, Parco M

    2013-02-01

    The molecular mechanisms that contribute to the pathogenesis of pressure-induced deep tissue injury are largely unknown. This study tested the hypothesis that oxidative stress and DNA damage signalling mechanism in skeletal muscle are involved in deep tissue injury. Adult Sprague Dawley rats were subject to an experimental protocol to induce deep tissue injury. Two compression cycles with a static pressure of 100 mmHg was applied to an area of 1.5 cm(2) over the mid-tibialis region of right limb of the rats. The left uncompressed limb served as intra-animal control. Muscle tissues underneath compression region were collected for examination. Our analyses indicated that pathohistological characteristics including rounding contour of myofibres and extensive nuclei accumulation were apparently shown in compressed muscles. The elevation of 8OHdG immunopositively stained nuclei indicated the presence of oxidative DNA damage. Increase in oxidative stress was revealed by showing significant elevation of 4HNE and decreases in mRNA abundance of SOD1, catalase and GPx, and protein content of SOD2 in compressed muscles relative to control muscles. Increase in nitrosative stress was demonstrated by significant elevation of nitrotyrosine and NOS2 mRNA content. The activation of tumor suppressor p53 signalling was indicated by the remarkable increases in protein contents of total p53 and serine-15 phosphorylated p53. The transcript expression of the DNA-repairing enzyme, Rad23A, was significantly suppressed in compressed muscles. Our time-course study indicated that increased oxidative/nitrosative stress and proapoptotic signalling were maintained in muscles receiving increasing amount of compression cycles and post-compression time. Furthermore, resveratrol was found to attenuate the histological damage, oxidative/nitrosative stress and proapoptotic signalling in response to prolonged moderate compression. In conclusion, our findings are consistent with the hypothesis that

  20. Development and Implementation of Discrete Polymeric Microstructural Cues for Applications in Cardiac Tissue Engineering

    Science.gov (United States)

    Pinney, James Richardson

    Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. Despite care in the acute setting of MI, subsequent development of scar tissue and a lack of treatments for this maladaptive response lead to a poor prognosis. This has increased burdens on the cost of healthcare due to chronic disability. Here a novel therapeutic strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructural cues to attenuate the fibrotic response and improve functional outcomes is presented. Additionally, applications of integrated chemical functionalizations into discrete, micro-scale polymer structures are discussed in the realm of tissue engineering in order to impart enhancements in in vivo localization, three-dimensional manipulation and drug delivery. Polymeric microstructures, termed "microrods" and "microcubes", were fabricated using photolithographic techniques and studied in three-dimensional culture models of the fibrotic environment and by direct injection into the infarct zone of adult Sprague-Dawley rats. In vitro gene expression and functional and histological results were analyzed, showing a dose-dependent down-regulation fibrotic indicators and improvement in cardiac function. Furthermore, iron oxide nanoparticles and functionalized fluorocarbons were incorporated into the polymeric microdevices to promote in situ visualization by magnetic resonance imaging as well as to facilitate the manipulation and alignment of microstructural cues in a tissue-realistic environment. Lastly, successful encapsulation of native MGF peptide within microrods is demonstrated with release over two weeks as a proof of concept in the ability to locally deliver myogenic or supportive pharmacotherapeutics to the injured myocardium. This work demonstrates the efficacy and versatility of discrete microtopographical cues to attenuate the fibrotic response after MI and suggests a novel

  1. 3D Printed Polycaprolactone Carbon Nanotube Composite Scaffolds for Cardiac Tissue Engineering.

    Science.gov (United States)

    Ho, Chee Meng Benjamin; Mishra, Abhinay; Lin, Pearlyn Teo Pei; Ng, Sum Huan; Yeong, Wai Yee; Kim, Young-Jin; Yoon, Yong-Jin

    2016-11-28

    Fabrication of tissue engineering scaffolds with the use of novel 3D printing has gained lot of attention, however systematic investigation of biomaterials for 3D printing have not been widely explored. In this report, well-defined structures of polycaprolactone (PCL) and PCL- carbon nanotube (PCL-CNT) composite scaffolds have been designed and fabricated using a 3D printer. Conditions for 3D printing has been optimized while the effects of varying CNT percentages with PCL matrix on the thermal, mechanical and biological properties of the printed scaffolds are studied. Raman spectroscopy is used to characterise the functionalized CNTs and its interactions with PCL matrix. Mechanical properties of the composites are characterised using nanoindentation. Maximum peak load, elastic modulus and hardness increases with increasing CNT content. Differential scanning calorimetry (DSC) studies reveal the thermal and crystalline behaviour of PCL and its CNT composites. Biodegradation studies are performed in Pseudomonas Lipase enzymatic media, showing its specificity and effect on degradation rate. Cell imaging and viability studies of H9c2 cells from rat origin on the scaffolds are performed using fluorescence imaging and MTT assay, respectively. PCL and its CNT composites are able to show cell proliferation and have the potential to be used in cardiac tissue engineering.

  2. Alginate-polyester comacromer based hydrogels as physiochemically and biologically favorable entities for cardiac tissue engineering.

    Science.gov (United States)

    Thankam, Finosh G; Muthu, Jayabalan

    2015-11-01

    The physiochemical and biological responses of tissue engineering hydrogels are crucial in determining their desired performance. A hybrid comacromer was synthesized by copolymerizing alginate and poly(mannitol fumarate-co-sebacate) (pFMSA). Three bimodal hydrogels pFMSA-AA, pFMSA-MA and pFMSA-NMBA were synthesized by crosslinking with Ca(2+) and vinyl monomers acrylic acid (AA), methacrylic acid (MA) and N,N'-methylene bisacrylamide (NMBA), respectively. Though all the hydrogels were cytocompatible and exhibited a normal cell cycle profile, pFMSA-AA exhibited superior physiochemical properties viz non-freezable water content (58.34%) and water absorption per unit mass (0.97 g water/g gel) and pore length (19.92±3.91 μm) in comparing with other two hydrogels. The increased non-freezable water content and water absorption of pFMSA-AA hydrogels greatly influenced its biological performance, which was evident from long-term viability assay and cell cycle proliferation. The physiochemical and biological favorability of pFMSA-AA hydrogels signifies its suitability for cardiac tissue engineering.

  3. The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

    DEFF Research Database (Denmark)

    Larsen, Steen; Danielsen, J H; Søndergård, Stine Dam

    2015-01-01

    on mitochondrial fat oxidation in skeletal muscle and adipose tissue. Mitochondrial oxidative phosphorylation (OXPHOS) capacity, mitochondrial substrate sensitivity (Km (app) ), and mitochondrial content were measured in skeletal muscle and adipose tissue in healthy overweight subjects before and after 6 weeks...... of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. Km (app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal...... muscle, but not in adipose tissue. Furthermore, mitochondrial fat oxidation was not improved in either skeletal muscle or adipose tissue....

  4. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    Science.gov (United States)

    Canuto, K. S.; Sergio, L. P. S.; Paoli, F.; Mencalha, A. L.; Fonseca, A. S.

    2016-03-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases.

  5. A DIC Based Technique to Measure the Contraction of a Skeletal Muscle Engineered Tissue

    Directory of Open Access Journals (Sweden)

    Emanuele Rizzuto

    2016-01-01

    Full Text Available Tissue engineering is a multidisciplinary science based on the application of engineering approaches to biologic tissue formation. Engineered tissue internal organization represents a key aspect to increase biofunctionality before transplant and, as regarding skeletal muscles, the potential of generating contractile forces is dependent on the internal fiber organization and is reflected by some macroscopic parameters, such as the spontaneous contraction. Here we propose the application of digital image correlation (DIC as an independent tool for an accurate and noninvasive measurement of engineered muscle tissue spontaneous contraction. To validate the proposed technique we referred to the X-MET, a promising 3-dimensional model of skeletal muscle. The images acquired through a high speed camera were correlated with a custom-made algorithm and the longitudinal strain predictions were employed for measuring the spontaneous contraction. The spontaneous contraction reference values were obtained by studying the force response. The relative error between the spontaneous contraction frequencies computed in both ways was always lower than 0.15%. In conclusion, the use of a DIC based system allows for an accurate and noninvasive measurement of biological tissues’ spontaneous contraction, in addition to the measurement of tissue strain field on any desired region of interest during electrical stimulation.

  6. Prediction of peak forces for a shortening smooth muscle tissue subjected to vibration.

    Science.gov (United States)

    Pidaparti, Ramana M; Dhanaraj, Nandhini; Meiss, Richard A

    2008-01-01

    The objective of the present study is to investigate the peak forces for a tracheal smooth muscle tissue subjected to an applied longitudinal vibration following isotonic shortening. A non-linear finite element analysis was carried out to simulate the vibratory response under experimental conditions that corresponds to forced length oscillations at 33 Hz for 1 second. The stiffness change and hysteresis estimated from the experimental data was used in the analysis. The finite element results of peak forces are compared to the experimental data obtained. The comparison of results indicate that the approach and the vibratory response obtained may be useful for describing the cross-bridge de-attachments within the cells as well as connective tissue connections characteristic of tracheal smooth muscle tissue.

  7. Selection, processing and clinical application of muscle-skeletal tissue; Seleccion, Procesamiento y Aplicacion Clinica de Tejido Musculo-Esqueletico

    Energy Technology Data Exchange (ETDEWEB)

    Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G. [ININ, Carretera Mexico-Toluca s/n, 52750 La Marquesa, Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: dlz@nuclear.inin. mx

    2007-07-01

    Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

  8. Fast activation of Ca2+-ATPases in plasma membranes from cardiac muscle and from ascites carcinoma cells: a possible function of endogenous calmodulin.

    Science.gov (United States)

    Wetzker, R; Klinger, R; Haase, H; Vetter, R; Böhmer, F D

    1987-01-01

    Content of endogenous calmodulin, binding of calmodulin to, and Ca2+-ATPase activity in plasma membranes of cardiac muscle. Ehrlich ascites carcinoma (EAC) cells and erythrocytes were examined. The content of endogenous calmodulin in cardiac and EAC cells was shown to be considerably higher than in erythrocyte membranes. Ca2+-independent binding of calmodulin to cardiac and EAC cell membranes was found to be realized by some low molecular weight proteins. Ca2+-ATPases in cardiac and EAC cell membranes differ from those in erythrocytes with respect to their activation by Ca2+ and calmodulin. The erythrocyte enzyme is strongly stimulated by exogenous calmodulin and reaches its maximum activity about 2 min after Ca2+-addition. In contrast, the Ca2+-ATPases in cardiac and EAC cell plasma membranes cannot be considerably stimulated by exogenous calmodulin and are instantaneously activated by Ca2+.

  9. [The expression of the sperm-specific lactate dehydrogenase gene Ldh-c in plateau pika (Ochotona curzoniae) cardiac muscle and its effect on the anaerobic glycolysis].

    Science.gov (United States)

    Li, Xiao; Wei, Lian; Wang, Yang; Xu, Li-Na; Wei, Lin-Na; Wei, Deng-Bang

    2015-06-25

    The plateau pika (Ochotona curzoniae) has a strong adaptability to hypoxic plateau environment. We found that the sperm-specific lactate dehydrogenase (LDH-C4) gene Ldh-c expressed in plateau pika cardiac muscle. In order to shed light on the effect of LDH-C4 on the anaerobic glycolysis in plateau pika cardiac muscle, 20 pikas were randomly divided into the inhibitor group and the control group, and the sample size of each group was 10. The pikas of inhibitor group were injected with 1 mL 1 mol/L N-isopropyl oxamate, a specific LDH-C4 inhibitor, in biceps femoris muscle of hind legs, each leg with 500 μL. The pikas of control group were injected with the same volume of normal saline (0.9% NaCl). The mRNA and protein expression levels of Ldh-c gene in plateau pika cardiac muscle were determined by real-time PCR and Western blot. The activities of LDH, and the contents of lactate (LD) and ATP in cardiac muscle were compared between the inhibitor group and the control group. The results showed that 1) the expression levels of Ldh-c mRNA and protein were 0.47 ± 0.06 and 0.68 ± 0.08, respectively; 2) 30 min after injection of 1 mL 1 mol/L N-isopropyl oxamate in biceps femoris muscle, the concentration of N-isopropyl oxamate in blood was 0.08 mmol/L; 3) in cardiac muscle of the inhibitor group and the control group, the LDH activities were (6.18 ± 0.48) U/mg and (9.08 ± 0.58) U/mg, the contents of LD were (0.21 ± 0.03) mmol/g and (0.26 ± 0.04) mmol/g, and the contents of ATP were (4.40 ± 0.69) nmol/mg and (6.18 ± 0.73) nmol/mg (P < 0.01); 5) the inhibition rates of N-isopropyl oxamate to LDH, LD and ATP were 31.98%, 20.90% and 28.70%, respectively. The results suggest that Ldh-c expresses in cardiac muscle of plateau pika, and the pika cardiac muscle may get at least 28% ATP for its activities by LDH-C4 catalyzed anaerobic glycolysis, which reduces the dependence on oxygen and enhances the adaptation to the hypoxic environments.

  10. Gene expression profiling of muscle tissue in Brahman steers during nutritional restriction.

    Science.gov (United States)

    Byrne, K A; Wang, Y H; Lehnert, S A; Harper, G S; McWilliam, S M; Bruce, H L; Reverter, A

    2005-01-01

    Expression profiling using microarrays allows for the detailed characterization of the gene networks that regulate an animal's response to environmental stresses. During nutritional restriction, processes such as protein turnover, connective tissue remodeling, and muscle atrophy take place in the skeletal muscle of the animal. These processes and their regulation are of interest in the context of managing livestock for optimal production efficiency and product quality. Here we expand on recent research applying complementary DNA (cDNA) microarray technology to the study of the effect of nutritional restriction on bovine skeletal muscle. Using a custom cDNA microarray of 9,274 probes from cattle muscle and s.c. fat libraries, we examined the differential gene expression profile of the LM from 10 Brahman steers under three different dietary treatments. The statistical approach was based on mixed-model ANOVA and model-based clustering of the BLUP solutions for the gene x diet interaction effect. From the results, we defined a transcript profile of 156 differentially expressed array elements between the weight loss and weight gain diet substrates. After sequence and annotation analyses, the 57 upregulated elements represented 29 unique genes, and the 99 downregulated elements represented 28 unique genes. Most of these co-regulated genes cluster into groups with distinct biological function related to protein turnover and cytoskeletal metabolism and contribute to our mechanistic understanding of the processes associated with remodeling of muscle tissue in response to nutritional stress.

  11. Interactive Hierarchical-Flow Segmentation of Scar Tissue From Late-Enhancement Cardiac MR Images.

    Science.gov (United States)

    Rajchl, Martin; Yuan, Jing; White, James A; Ukwatta, Eranga; Stirrat, John; Nambakhsh, Cyrus M S; Li, Feng P; Peters, Terry M

    2014-01-01

    We propose a novel multi-region image segmentation approach to extract myocardial scar tissue from 3-D whole-heart cardiac late-enhancement magnetic resonance images in an interactive manner. For this purpose, we developed a graphical user interface to initialize a fast max-flow-based segmentation algorithm and segment scar accurately with progressive interaction. We propose a partially-ordered Potts (POP) model to multi-region segmentation to properly encode the known spatial consistency of cardiac regions. Its generalization introduces a custom label/region order constraint to Potts model to multi-region segmentation. The combinatorial optimization problem associated with the proposed POP model is solved by means of convex relaxation, for which a novel multi-level continuous max-flow formulation, i.e., the hierarchical continuous max-flow (HMF) model, is proposed and studied. We demonstrate that the proposed HMF model is dual or equivalent to the convex relaxed POP model and introduces a new and efficient hierarchical continuous max-flow based algorithm by modern convex optimization theory. In practice, the introduced hierarchical continuous max-flow based algorithm can be implemented on the parallel GPU to achieve significant acceleration in numerics. Experiments are performed in 50 whole heart 3-D LE datasets, 35 with left-ventricular and 15 with right-ventricular scar. The experimental results are compared to full-width-at-half-maximum and Signal-threshold to reference-mean methods using manual expert myocardial segmentations and operator variabilities and the effect of user interaction are assessed. The results indicate a substantial reduction in image processing time with robust accuracy for detection of myocardial scar. This is achieved without the need for additional region constraints and using a single optimization procedure, substantially reducing the potential for error.

  12. Skeletal muscle

    Science.gov (United States)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  13. Effects of Mg2+ on Ca2+ handling by the sarcoplasmic reticulum in skinned skeletal and cardiac muscle fibres.

    Science.gov (United States)

    Kabbara, A A; Stephenson, D G

    1994-10-01

    The influence of myoplasmic Mg2+ (0.05-10 mM) on Ca2+ accumulation (net Ca2+ flux) and Ca2+ uptake (pump-driven Ca2+ influx) by the intact sarcoplasmic reticulum (SR) was studied in skinned fibres from the toad iliofibularis muscle (twitch portion), rat extensor digitorum longus (EDL) muscle (fast twitch), rat soleus muscle (slow twitch) and rat cardiac trabeculae. Ca2+ accumulation was optimal between 1 and 3 mM Mg2+ in toad fibres and reached a plateau between 1 and 10 mM Mg2+ in the rat EDL fibres and between 3 and 10 mM Mg2+ in the rat cardiac fibres. In soleus fibres, optimal Ca2+ accumulation occurred at 10 mM Mg2+. The same trend was obtained with all preparations at 0.3 and 1 microM Ca2+. Experiments with 2,5-di-(tert-butyl)-1,4-benzohydroquinone, a specific inhibitor of the Ca2+ pump, revealed a marked Ca2+ efflux from the SR of toad iliofibularis fibres in the presence of 0.2 microM Ca2+ and 1 mM Mg2+. Further experiments indicated that the SR Ca2+ leak could be blocked by 10 microM ruthenium red without affecting the SR Ca2+ pump and this allowed separation between SR Ca2+ uptake and SR Ca2+ accumulation. At 0.3 microM Ca2+, Ca2+ uptake was optimal with 1 mM Mg2+ in the toad iliofibularis and rat EDL fibres and between 1 and 10 mM Mg2+ in the rat soleus and trabeculae preparations. At higher [Ca2+] (1 microM), Ca2+ uptake was optimal with 1 mM Mg2+ in the iliofibularis fibres and between 1 and 3 mM Mg2+ in the EDL fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Porous polycaprolactone scaffold for cardiac tissue engineering fabricated by selective laser sintering.

    Science.gov (United States)

    Yeong, W Y; Sudarmadji, N; Yu, H Y; Chua, C K; Leong, K F; Venkatraman, S S; Boey, Y C F; Tan, L P

    2010-06-01

    An advanced manufacturing technique, selective laser sintering (SLS), was utilized to fabricate a porous polycaprolactone (PCL) scaffold designed with an automated algorithm in a parametric library system named the "computer-aided system for tissue scaffolds" (CASTS). Tensile stiffness of the sintered PCL strut was in the range of 0.43+/-0.15MPa when a laser power of 3W and scanning speed of 150 in s(-1) was used. A series of compressive mechanical characterizations was performed on the parametric scaffold design and an empirical formula was presented to predict the compressive stiffness of the scaffold as a function of total porosity. In this work, the porosity of the scaffold was selected to be 85%, with micropores (40-100mum) throughout the scaffold. The compressive stiffness of the scaffold was 345kPa. The feasibility of using the scaffold for cardiac tissue engineering was investigated by culturing C2C12 myoblast cells in vitro for 21days. Fluorescence images showed cells were located throughout the scaffold. High density of cells at 1.2x10(6)cellsml(-1) was recorded after 4days of culture. Fusion and differentiation of C2C12 were observed as early as 6days in vitro and was confirmed with myosin heavy chain immunostaining after 11days of cell culture. A steady population of cells was then maintained throughout 21days of culturing. This work demonstrated the feasibility of tailoring the mechanical property of the scaffold for soft tissue engineering using CASTS and SLS. The macroarchitecture of the scaffold can be modified efficiently to fabricate scaffolds with different macropore sizes or changing the elemental cell design in CASTS. Further process and design optimization could be carried out in the future to fabricate scaffolds that match the tensile strength of native myocardium, which is of the order of tens of kPa.

  15. Creation of a bioreactor for the application of variable amplitude mechanical stimulation of fibrin gel-based engineered cardiac tissue.

    Science.gov (United States)

    Morgan, Kathy Y; Black, Lauren D

    2014-01-01

    This chapter details the creation of three-dimensional fibrin hydrogels as an engineered myocardial tissue and introduces a mechanical stretch bioreactor system that allows for the cycle-to-cycle variable amplitude mechanical stretch of the constructs as a method of conditioning the constructs to be more similar to native tissue. Though mechanical stimulation has been established as a standard method of improving construct development, most studies have been performed under constant frequency and constant amplitude, even though variability is a critical aspect of healthy cardiac physiology. The introduction of variability in other organ systems has demonstrated beneficial effects to cell function in vitro. We hypothesize that the introduction of variability in engineered cardiac tissue could have a similar effect.

  16. Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

    Science.gov (United States)

    Purslow, P P; Archile-Contreras, A C; Cha, M C

    2012-03-01

    Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the

  17. Cruzipain induces autoimmune response against skeletal muscle and tissue damage in mice.

    Science.gov (United States)

    Giordanengo, L; Fretes, R; Díaz, H; Cano, R; Bacile, A; Vottero-Cima, E; Gea, S

    2000-09-01

    The goal of the current study was to investigate whether cruzipain, a major Trypanosoma cruzi antigen, is able to induce in mice an autoimmune response and skeletal muscle damage. We demonstrate that immunization with cruzipain triggers immunoglobulin G antibody binding to a 210-kDa antigen from a syngeneic skeletal muscle extract. The absorption of immune sera with purified myosin completely eliminated this reactivity, confirming that the protein identified is really myosin. We also found that spleen cells from immunized mice proliferated in response to a skeletal muscle extract rich in myosin and to purified myosin. Cells from control mice did not proliferate against any of the antigens tested. In addition, we observed an increase in plasma creatine kinase activity, a biochemical marker of muscle damage. Histological studies showed inflammatory infiltrates and myopathic changes in skeletal muscle of immunized animals. Electromyographic studies of these mice revealed changes such as are found in inflammatory or necrotic myopathy. Altogether, our results suggest that this experimental model provides strong evidence for a pathogenic role of anticruzipain immune response in the development of muscle tissue damage.

  18. 4-Aminopyridine induces positive lusitropic effects and prevents the negative inotropic action of phenylephrine in the rat cardiac tissue subjected to ischaemia.

    Science.gov (United States)

    Kocić, I; Dworakowska, D; Dworakowski, R

    1999-09-01

    The effects of 4-aminopyridine (4-AP) at concentration of 1 mM on the contractility of rat isolated papillary muscle subjected to simulated ischaemia has been evaluated. Additionally, the effects of 4-AP on the phenylephrine inotropic action (a selective agonist of alpha1-adrenergic receptor) on rat isolated cardiac tissue underwent simulated ischaemia and reperfusion was studied. Experiments were performed on rat isolated papillary muscles obtained from left ventricle. The following parameters have been measured: force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and the ratio between time to peak contraction (ttp) and relaxation time at the level of 10% of total contraction amplitude (tt10) as an index of lusitropic effects. Simulated ischaemia lasting 45 min was induced by replacement of standard normoxic solution by no-substrat one gassing with 95% N2/5%CO2. Although 4-AP exerted a slight, but significant positive inotropic action itself, pretreatment with 1 mM of this compound significantly depressed a recovery of Fc and +dF/dt, but improves recovery of -dF/dt in the rat papillary muscle during reperfusion as compared with control group of preparations. Moreover, the paradoxical negative inotropic action of phenylephrine observed in rat stunned papillary muscle was prevented in preparations previously treated by 4-AP. These findings suggest that an inhibition of outward K+ current (probably transient outward and rapid component of delayed rectifying currents at 1 mM of 4-AP) aggravates ischaemia-induced failure in contractility but prevents changes in alpha1-adrenergic receptor signaling pathway occuring during ischaemia.

  19. The assessment of cardiac functions by tissue Doppler-derived myocardial performance index in patients with Behcet's disease.

    Science.gov (United States)

    Tavil, Yusuf; Ozturk, Mehmet Akif; Sen, Nihat; Kaya, Mehmet Gungor; Hizal, Fatma; Poyraz, Fatih; Turfan, Murat; Onder, Meltem; Gurer, Mehmet Ali; Cengel, Atiye

    2008-03-01

    Vascular involvement is one of the major characteristics of Behcet's disease (BD). However, there are controversial findings regarding cardiac involvement in BD. Although early reports demonstrated that there is diastolic dysfunction in BD, conflicting results were found in the following trials. Hence, a new method for more objectively estimating the cardiac functions is needed. For this aim, we used high-usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in BD patients because this method was superior to other conventional echocardiographic techniques. The study population included 42 patients with BD (19 men, 23 women; mean age, 35 +/- 10 years, mean disease duration, 2.7 +/- 1.6 years) and 30 healthy subjects (14 men, 16 women; mean age, 38 +/- 7 years). Cardiac functions were determined using echocardiography, comprising standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Peak systolic myocardial velocity at mitral annulus, early diastolic mitral annular velocity (Em), late diastolic mitral annular velocity (Am), Em/Am, and myocardial performance index (MPI) were calculated by TDI. The conventional echocardiographic parameters and tissue Doppler measurements were similar between the groups. Tissue Doppler derived mitral relaxation time was longer (75 +/- 13 vs 63 +/- 16 msn, p = 0.021) in patients with BD. There was statistically significant difference between the two groups regarding left ventricular MPI (0.458 +/- 0.072 vs 0.416 +/- 0.068%, p = 0.016), which were calculated from tissue Doppler systolic time intervals. There was also significant correlation between the disease duration and MPI (r = 0.38, p = 0.017). We have demonstrated that tissue Doppler-derived myocardial left ventricular relaxation time and MPI were impaired in BD patients, although systolic and diastolic function parameters were comparable in the patients and controls.

  20. Post-mortem stability of RNA in skeletal muscle and adipose tissue and the tissue-specific expression of myostatin, perilipin and associated factors in the horse.

    Science.gov (United States)

    Morrison, Philippa K; Bing, Chen; Harris, Patricia A; Maltin, Charlotte A; Grove-White, Dai; Argo, Caroline McG

    2014-01-01

    Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue

  1. LOCALISED MUSCLE TISSUE OXYGENATION DURING DYNAMIC EXERCISE WITH WHOLE BODY VIBRATION

    Directory of Open Access Journals (Sweden)

    Daniel Robbins

    2012-06-01

    Full Text Available Despite increasing use of whole body vibration during exercise an understanding of the exact role of vibration and the supporting physiological mechanisms is still limited. An important aspect of exercise analysis is the utilisation of oxygen, however, there have been limited studies considering tissue oxygenation parameters, particularly during dynamic whole body vibration (WBV exercise. The aim of this study was to determine the effect of adding WBV during heel raise exercises and assessing changes in tissue oxygenation parameters of the lateral gastrocnemius using Near Infra Red Spectroscopy (NIRS. Twenty healthy subjects completed ten alternating sets of 15 heel raises (vibration vs. no vibration. Synchronous oxygenation and motion data were captured prior to exercise to determine baseline levels, for the duration of the exercise and 20 sec post exercise for the recovery period. Both vibration and no vibration conditions elicited a characteristic increase in deoxyhaemoglobin and decreases in oxyhaemoglobin, total haemoglobin, tissue oxygenation index and normalised tissue haemoglobin index which are indicative of local tissue hypoxia. However, the addition of vibration elicited significantly lower (p < 0. 001 depletions in oxyhaemoglobin, total haemoglobin, normalised tissue haemoglobin index but no significant differences in deoxyhaemoglobin. These findings suggest that addition of vibration to exercise does not increase the cost of the exercise for the lateral gastrocnemius muscle, but does decrease the reduction in local muscle oxygenation parameters, potentially resulting from increased blood flow to the calf or a vasospastic response in the feet. However, further studies are needed to establish the mechanisms underlying these findings

  2. Effects of nanosized lithium carbonate particles on intact muscle tissue and tumor growth.

    Science.gov (United States)

    Bgatova, N P; Borodin, Yu I; Makarova, V V; Pozhidaeva, A A; Rachkovskaya, L N; Konenkov, V I

    2014-05-01

    The effects of nanosized lithium carbonate particles on muscle tissue structure and development of experimental hepatocarcinoma-29 transplanted into the hip were studied in CBA mice. Necrotic changes in all structural components of the muscle were detected after intramuscular injection of nanosized lithium carbonate particles to intact animals. Regeneration of the muscle fibers after lithium carbonate treatment was associated with a significant increase in macrophage count, number of microvessels, activation of fibroblasts, and complete recovery of the organ structure. Injection of lithium carbonate nanoparticles at the periphery of tumor growth caused tumor cell necrosis, destruction of the vascular bed, and attraction of neutrophils and macrophages to the tumor focus. After the preparation was discontinued, the tumor developed with lesser number of vessels, smaller tumor cells, and lesser deformation of the cell nuclei structure.

  3. [Viscoelastic properties of isolated papillary muscle: contributions of connective tissue skeleton and intracellular matrix].

    Science.gov (United States)

    Protsenko, Iu L; Kobelev, A V; Lukin, O N; Balakin, A A; Smoliuk, L T

    2009-07-01

    Peculiarities of viscoelastic behavior of rabbit papillary muscle in passive state are studied by transversal versus longitudinal deformation curves, stress-strain and hysteresis curves, and stress relaxation curves under ramp stretching. The papillary muscle was chosen because of mostly longitudinal orientation of fibers and its elongated shape, which both make it as an appropriate model for uniaxial tests. The problem of evaluation of connective tissue protein structures and intracellular matrix contribution into the properties under consideration is solved by using the maceration method to remove intracellular structures. The different contribution of intracellular and extracellular protein features into total properties of a papillary muscle leads to nonlinearity of myocardial viscoelastic properties, such as the increase of differential elastic module and relaxation time with deformation.

  4. Ultrasonic tissue characterization of the upper trapezius muscle in patients with myofascial pain syndrome.

    Science.gov (United States)

    Turo, Diego; Otto, Paul; Shah, Jay P; Heimur, Juliana; Gebreab, Tadesse; Armstrong, Katherine; Gerber, Lynn H; Sikdar, Siddhartha

    2012-01-01

    Myofascial trigger points (MTrPs) are palpable, tender nodules in skeletal muscle that produce symptomatic referred pain when palpated. MTrPs are characteristic findings in myofascial pain syndrome (MPS). The role of MTrPs in the pathophysiology of MPS is unknown. Objective characterization and quantitative measurement of the properties of MTrPs can improve their localization and diagnosis, as well as lead to clinical outcome measures. MTrPs associated with soft tissue neck pain are often found in the upper trapezius muscle. We have previously demonstrated that MTrPs can be visualized using ultrasound imaging. The goal of this study was to evaluate whether texture-based image analysis can differentiate structural heterogeneity of symptomatic MTrPs and normal muscle.

  5. Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in rat cardiac tissues

    Directory of Open Access Journals (Sweden)

    Seyed M. Nabavi

    2012-12-01

    Full Text Available This study aim to evaluate the protective effect of silymarin on sodium fluoride-induced oxidative stress in rat cardiac tissues. Animals were pretreated with silymarin at 20 and 10 mg/kg prior to sodium fluoride consumption (600 ppm through drinking water. Vitamin C at 10 mg/kg was used as standard antioxidant. There was a significant increase in thiobarbituric acid reactive substances level (59.36 ± 2.19 nmol MDA eq/g tissue along with a decrease in antioxidant enzymes activity (64.27 ± 1.98 U/g tissue for superoxide dismutase activity and 29.17 ± 1.01 µmol/min/mg protein for catalase activity and reduced glutathione level (3.8 ± 0.15 µg/mg protein in the tissues homogenates of the sodium fluoride-intoxicated rats. Silymarin administration to animals before sodium fluoride consumption modified the levels of biochemical parameters.Este estudo objetiva avaliar o efeito protetor da silimarina em fluoreto de sódio induzida por estresse oxidativo em tecido cardíaco de ratos. Os animais foram pré-tratados com silimarina a 20 e 10 mg/kg antes do consumo de fluoreto de sódio (600 ppm através da água de beber. A vitamina C a 10 mg/kg foi utilizada como antioxidante padrão. Houve um aumento significativo no nível de substâncias tiobarbitúrico reativo de ácido (59,36 ± 2.19 nmol MDA eq/g tecido, juntamente com uma diminuição da atividade de enzimas antioxidantes (64,27 ± 1,98 U/g tecido para a atividade de superóxido dismutase e 29,7 ± 1,01 mmol/min/mg de proteína para a atividade da catalase e nível de glutationa reduzida (3,8 ± 0,15 mg/mg de proteína nos homogeneizados de tecidos dos fluoreto de sódio-intoxicados ratos. Administração de silimarina a animais, antes do consumo de fluoreto de sódio modifou os níveis de parâmetros bioquímicos.

  6. The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue.

    Science.gov (United States)

    Larsen, S; Danielsen, J H; Søndergård, S D; Søgaard, D; Vigelsoe, A; Dybboe, R; Skaaby, S; Dela, F; Helge, J W

    2015-02-01

    High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak)]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT on mitochondrial fat oxidation in skeletal muscle and adipose tissue. Mitochondrial oxidative phosphorylation (OXPHOS) capacity, mitochondrial substrate sensitivity (K(m)(app)), and mitochondrial content were measured in skeletal muscle and adipose tissue in healthy overweight subjects before and after 6 weeks of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. K(m)(app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal muscle and adipose tissue. Maximal OXPHOS capacity with complex I- and II-linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO2peak. Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal muscle, but not in adipose tissue. Furthermore, mitochondrial fat oxidation was not improved in either skeletal muscle or adipose tissue.

  7. Correlation between the distribution of smooth muscle or non muscle myosins and alpha-smooth muscle actin in normal and pathological soft tissues.

    Science.gov (United States)

    Benzonana, G; Skalli, O; Gabbiani, G

    1988-01-01

    The distribution of smooth muscle (SM) and non muscle myosins was compared with that of alpha-SM actin in various normal and pathological tissues and in cultured cells by means of indirect immunofluorescence using a monoclonal antibody specific for alpha-SM actin [anti-alpha sm-1, Skalli et al., 1986b] and two polyclonal antibodies raised against bovine aortic myosin (ABAM) and human platelet myosin (AHPM), respectively. In normal tissues ABAM stained vascular and parenchymal smooth muscle cells (SMC), myoepithelial cells and myoid cells of the testis in a pattern similar to that reported by other authors with antisera raised against non vascular SM myosin. Cells stained with ABAM were always positive for anti-alpha sm-1. In human and experimental atheromatous plaques, most cells were positive for AHPM; a variable proportion was also stained for ABAM plus anti-alpha sm-1. Myofibroblasts from rat granulation tissue, Dupuytren's nodule and stroma from breast carcinoma were constantly positive for AHPM and negative for ABAM; however, myofibroblasts from Dupuytren's nodule and breast carcinoma were anti-alpha sm-1 positive. Early primary cultures of rat aortic SMC were positive for ABAM and anti-alpha sm-1 and became negative for ABAM and positive for AHPM after a few days in culture. They remained positive for AHPM and anti-alpha sm-1 after passages; the staining of AHPM and anti-alpha sm-1 appeared to be colocalized along the same stress fibers. These results may be relevant for the understanding of SMC function and adaptation, and show that in non malignant SMC proliferation, alpha-SM actin represents a more general marker of SM origin than SM myosin.

  8. Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration.

    Science.gov (United States)

    Zeng, Bin; Tong, Suiyang; Ren, Xiaofeng; Xia, Hao

    2016-08-01

    Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were co-localized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2'-deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury.

  9. Intramuscular Connective Tissue Differences in Spastic and Control Muscle: A Mechanical and Histological Study

    Science.gov (United States)

    de Bruin, Marije; Smeulders, Mark J.; Kreulen, Michiel; Huijing, Peter A.; Jaspers, Richard T

    2014-01-01

    Cerebral palsy (CP) of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU) from CP patients (n = 29) and healthy controls (n = 10). The sarcomere slack length (mean 2.5 µm, SEM 0.05) and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190) in spastic muscle than in controls (2572 µm2, SEM 322). However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold), i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23) did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients. PMID:24977410

  10. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study.

    Directory of Open Access Journals (Sweden)

    Marije de Bruin

    Full Text Available Cerebral palsy (CP of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU from CP patients (n = 29 and healthy controls (n = 10. The sarcomere slack length (mean 2.5 µm, SEM 0.05 and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190 in spastic muscle than in controls (2572 µm2, SEM 322. However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold, i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23 did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients.

  11. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study.

    Science.gov (United States)

    de Bruin, Marije; Smeulders, Mark J; Kreulen, Michiel; Huijing, Peter A; Jaspers, Richard T

    2014-01-01

    Cerebral palsy (CP) of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU) from CP patients (n = 29) and healthy controls (n = 10). The sarcomere slack length (mean 2.5 µm, SEM 0.05) and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190) in spastic muscle than in controls (2572 µm2, SEM 322). However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold), i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23) did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients.

  12. In vitro construction and in vivo regeneration of esophageal bilamellar muscle tissue.

    Science.gov (United States)

    Hou, Lei; Gong, Changfeng; Zhu, Yabin

    2016-04-01

    In order to induce esophageal muscle cells' orientation, the silicon wafer with prototype 1 and prototype 2 was designed. Prototype 1 has micro-channels of 200 µm width and 30 µm depth with 30 µm wide wall as the interval. Prototype 2 has channels of 100 µm width and 30 µm depth with a discontinuous wall which has 30 µm gap for each 100 µm channel. The poly(ester urethane) scaffolds with pattern prototype 1 and prototype 2 were fabricated using solution casting method and abbreviated as PU1 and PU2, respectively. Silk fibroin was grafted individually on PU1 and PU2 surface (PU1-SF, PU2-SF) using our previous protocol, aiming at improving scaffolds' biocompatibility. The primary esophageal smooth muscle cell was seeded to evaluate the scaffolds' cytocompatibility in vitro. Characterizations like MTT assay, immunocytochemistry, scanning electron microscope, and Western blotting were applied. After that, poly(ester urethane) scaffolds with double patterns, prototype 1 on the exterior, and prototype 2 in the lumen were implanted into the rabbit esophagous to test the regeneration of the muscle tissue. Results from these preliminary tests showed that the growth and differentiation of primary smooth muscle cells were promoted, but also the muscle tissue with endocircular and exolongitudinal architecture was in regenerating, against non-constitution in the animals without the patterned scaffold or with poly(ester urethane) plane membrane at the defaulted sites. This micro-channel pattern together with silk fibroin grafting and vascular endothelial growth factor coating greatly promoted the regeneration of esophageal muscle with normal histological structure.

  13. Electrical Resistance as A Measure of Soft Tissue Injuryfrom Delayed Onset Muscle Soreness

    Institute of Scientific and Technical Information of China (English)

    Timothy Hui; Jerrold Petrofsky; Iman Akef Khowailed

    2014-01-01

    Assessment of muscle damage relies commonly on subjective sensation of pain. The purpose of this research was to test thevalidity of microcurrent conductance on skin over injured tissue to quantify soft tissue injury and recovery following heavy exercisecompared to other indexes of muscle soreness. A randomized, controlled, single-blinded, 1-week trial on 60 subjects.Setting-University Interventions: Subjects did 3 sets of squats for 5 min each. There were 3 groups of 20 subjects. One did nothing andone had heat applied for 8 h post exercise. The final group had heat 24 h after exercise. Tissue resistance and muscle strength force tomove the knee, analog visual pain scale. In the control group, microcurrent continually decreased, eventually decreasing 32% by thethird day post exercise. When heat was given immediately following exercise, microcurrent was 26% greater (P 〈 0.001). The painscale rose to 3.1/10 as opposed to 5.4/10 for controls. Strength and muscle elasticity stayed mostly constant after heat as opposed to a28% decrease in strength and increase in stiffness in the control subjects. For 24 h delayed heat, microcurrent was 14% greater(P 〈 0.02), and was unchanged for the first 24 h when no therapy was given. Pain scale rose to 4.8/10. Stiffness was unchanged whilemuscle strength decreased the same as controls. Microcurrent shows agreement with loss of strength, and stiffness from DOMS but notthe subjective pain measure. It appears that microcurrent is a good measure of muscle damage.

  14. Role of O2 in regulating tissue respiration in dog muscle working in situ

    Science.gov (United States)

    Hogan, M. C.; Arthur, P. G.; Bebout, D. E.; Hochachka, P. W.; Wagner, P. D.

    1992-01-01

    This study was designed to investigate the role of tissue oxygenation in some of the factors that are thought to regulate muscle respiration and metabolism. Tissue oxygenation was altered by reductions in O2 delivery (muscle blood flow x arterial O2 content), induced by decreases in arterial PO2 (PaO2). O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius at rest and while working at two stimulation intensities (isometric tetanic contractions at 0.5 and 1 contractions/s) on three separate occasions, with only the level of PaO2 (78, 30, and 21 Torr) being different for each occasion. Muscle blood flow was held constant (pump perfusion) at each work intensity for the three different levels of PaO2. Muscle biopsies were obtained at the end of each rest and work period. Muscle VO2 was significantly less (P less than 0.05) at both stimulation intensities for the hypoxemic conditions, whereas [ATP] was reduced only during the highest work intensity during both hypoxemic conditions (31% reduction at 21 Torr PaO2 and 17% at 30 Torr). For each level of PaO2, the relationships between the changes that occurred in VO2 and levels of phosphocreatine, ADP, and ATP/ADP.P(i) as the stimulation intensity was increased were significantly correlated; however, the slopes and intercepts of these lines were significantly different for each PaO2. Thus a greater change in any of the proposed regulators of tissue respiration (e.g., phosphocreatine, ADP) was required to achieve a given VO2 as PaO2 was decreased.(ABSTRACT TRUNCATED AT 250 WORDS).

  15. Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration.

    Science.gov (United States)

    Emmert, Maximilian Y; Hitchcock, Robert W; Hoerstrup, Simon P

    2014-04-01

    Ischemic Heart Disease (IHD) still represents the "Number One Killer" worldwide accounting for the death of numerous patients. However the capacity for self-regeneration of the adult heart is very limited and the loss of cardiomyocytes in the infarcted heart leads to continuous adverse cardiac-remodeling which often leads to heart-failure (HF). The concept of regenerative medicine comprising cell-based therapies, bio-engineering technologies and hybrid solutions has been proposed as a promising next-generation approach to address IHD and HF. Numerous strategies are under investigation evaluating the potential of regenerative medicine on the failing myocardium including classical cell-therapy concepts, three-dimensional culture techniques and tissue-engineering approaches. While most of these regenerative strategies have shown great potential in experimental studies, the translation into a clinical setting has either been limited or too rapid leaving many key questions unanswered. This review summarizes the current state-of-the-art, important challenges and future research directions as to regenerative approaches addressing IHD and resulting HF.

  16. Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity

    Directory of Open Access Journals (Sweden)

    Schwartz Robert J

    2007-11-01

    Full Text Available Abstract Background Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs, it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects 123. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. Results We have observed cardiovascular abnormalities including outflow tract and aortic arch arterial defects in genetically compromised Folr1 knockout mice. In order to investigate the molecular mechanisms underlying the failure to complete development of outflow tract and aortic arch arteries in the Folr1 knockout mouse model, we examined tissue-specific gene expression difference between Folr1 nullizygous embryos and morphologically normal heterozygous embryos during early cardiac development (14-somite stage, heart tube looping (28-somite stage, and outflow track septation (38-somite stage. Microarray analysis was performed as a primary screening, followed by investigation using quantitative real-time PCR assays. Gene ontology analysis highlighted the following ontology groups: cell migration, cell motility and localization of cells, structural constituent of cytoskeleton, cell-cell adhesion, oxidoreductase, protein folding and mRNA processing. This study provided preliminary data and suggested potential candidate genes for further description and investigation. Conclusion The results suggested that Folr1 gene ablation and abnormal folate homeostasis altered gene expression in developing heart and conotruncal tissues. These changes affected normal cytoskeleton structures, cell migration and

  17. Sexual Dimorphism in the Alterations of Cardiac Muscle Mitochondrial Bioenergetics Associated to the Ageing Process.

    Science.gov (United States)

    Colom, Bartomeu; Oliver, Jordi; Garcia-Palmer, Francisco J

    2015-11-01

    The incidence of cardiac disease is age and sex dependent, but the mechanisms governing these associations remain poorly understood. Mitochondria are the organelles in charge of producing energy for the cells, and their malfunction has been linked to cardiovascular disease and heart failure. Interestingly, heart mitochondrial content and functionality are also age and sex dependent. Here we investigated the combinatory effects of age and sex in mitochondrial bioenergetics that could help to understand their role on cardiac disease. Cardiac mitochondria from 6- and 24-month-old male and female Wistar rats were isolated, and the enzymatic activities of the oxidative-phosphorylative complexes I, III, and IV and ATPase, as well as the protein levels of complex IV, β-ATPase, and mitochondrial transcription factor A (TFAM), were measured. Furthermore, heart DNA content, citrate synthase activity, mitochondrial protein content, oxygen consumption, and H2O2 generation were also determined. Results showed a reduction in heart mitochondrial mass and functionality with age that correlated with increased H2O2 generation. Moreover, sex-dependent differences were found in several of these parameters. In particular, old females exhibited a significant loss of mitochondrial function and increased relative H2O2 production compared with their male counterparts. The results demonstrate a sex dimorphism in the age-associated defects on cardiac mitochondrial function.

  18. Nuclear Factor of Activated T cells (NFAT): key regulator of cardiac hypertrophy and skeletal muscle adaptation

    NARCIS (Netherlands)

    Bourajjaj, M.

    2008-01-01

    Despite significant progress in the prevention and treatment of cardiovascular diseases, heart failure is still a leading cause of morbidity and mortality in industrial countries. Sustained cardiac hypertrophy, which is defined as an increase in heart size resulting from an increase in cardiomyocyte

  19. Motor imagery muscle contraction strength influences spinal motor neuron excitability and cardiac sympathetic nerve activity

    OpenAIRE

    2015-01-01

    [Purpose] The aim of this study was to investigate the changes in spinal motor neuron excitability and autonomic nervous system activity during motor imagery of isometric thenar muscle activity at 10% and 50% maximal voluntary contraction (MVC). [Methods] The F-waves and low frequency/high frequency (LF/HF) ratio were recorded at rest, during motor imagery, and post-trial. For motor imagery trials, subjects were instructed to imagine thenar muscle activity at 10% and 50% MVC while holding the...

  20. FGF signaling supports Drosophila fertility by regulating development of ovarian muscle tissues.

    Science.gov (United States)

    Irizarry, Jihyun; Stathopoulos, Angelike

    2015-08-01

    The thisbe (ths) gene encodes a Drosophila fibroblast growth factor (FGF), and mutant females are viable but sterile suggesting a link between FGF signaling and fertility. Ovaries exhibit abnormal morphology including lack of epithelial sheaths and muscle tissues that surround ovarioles. Here we investigated how FGF influences Drosophila ovary morphogenesis and identified several roles. Heartless (Htl) FGF receptor was found to be expressed within somatic cells at the larval and pupal stages, and phenotypes were uncovered using RNAi. Differentiation of terminal filament cells was affected, but this effect did not alter the ovariole number. In addition, proliferation of epithelial sheath progenitors, the apical cells, was decreased in both htl and ths mutants, while ectopic expression of the Ths ligand led to these cells' over-proliferation suggesting that FGF signaling supports ovarian muscle sheath formation by controlling apical cell number in the developing gonad. Additionally, live imaging of adult ovaries was used to show that htl RNAi mutants, hypomorphic mutants in which epithelial sheaths are present, exhibit abnormal muscle contractions. Collectively, our results demonstrate that proper formation of ovarian muscle tissues is regulated by FGF signaling in the larval and pupal stages through control of apical cell proliferation and is required to support fertility.

  1. Skeletal Muscle Regeneration on Protein-Grafted and Microchannel-Patterned Scaffold for Hypopharyngeal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Zhisen Shen

    2013-01-01

    Full Text Available In the field of tissue engineering, polymeric materials with high biocompatibility like polylactic acid and polyglycolic acid have been widely used for fabricating living constructs. For hypopharynx tissue engineering, skeletal muscle is one important functional part of the whole organ, which assembles the unidirectionally aligned myotubes. In this study, a polyurethane (PU scaffold with microchannel patterns was used to provide aligning guidance for the seeded human myoblasts. Due to the low hydrophilicity of PU, the scaffold was grafted with silk fibroin (PU-SF or gelatin (PU-Gel to improve its cell adhesion properties. Scaffolds were observed to degrade slowly over time, and their mechanical properties and hydrophilicities were improved through the surface grafting. Also, the myoblasts seeded on PU-SF had the higher proliferative rate and better differentiation compared with those on the control or PU-Gel. Our results demonstrate that polyurethane scaffolds seeded with myoblasts hold promise to guide hypopharynx muscle regeneration.

  2. Skeletal muscle regeneration on protein-grafted and microchannel-patterned scaffold for hypopharyngeal tissue engineering.

    Science.gov (United States)

    Shen, Zhisen; Guo, Shanshan; Ye, Dong; Chen, Jingjing; Kang, Cheng; Qiu, Shejie; Lu, Dakai; Li, Qun; Xu, Kunjie; Lv, Jingjing; Zhu, Yabin

    2013-01-01

    In the field of tissue engineering, polymeric materials with high biocompatibility like polylactic acid and polyglycolic acid have been widely used for fabricating living constructs. For hypopharynx tissue engineering, skeletal muscle is one important functional part of the whole organ, which assembles the unidirectionally aligned myotubes. In this study, a polyurethane (PU) scaffold with microchannel patterns was used to provide aligning guidance for the seeded human myoblasts. Due to the low hydrophilicity of PU, the scaffold was grafted with silk fibroin (PU-SF) or gelatin (PU-Gel) to improve its cell adhesion properties. Scaffolds were observed to degrade slowly over time, and their mechanical properties and hydrophilicities were improved through the surface grafting. Also, the myoblasts seeded on PU-SF had the higher proliferative rate and better differentiation compared with those on the control or PU-Gel. Our results demonstrate that polyurethane scaffolds seeded with myoblasts hold promise to guide hypopharynx muscle regeneration.

  3. Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice

    Directory of Open Access Journals (Sweden)

    Hsu Cheng-chin

    2009-08-01

    Full Text Available Abstract Background Caffeic acid (CA and ellagic acid (EA are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined. Methods Diabetic mice were divided into three groups (15 mice per group: diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured. Results The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p p p p p p p Conclusion These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.

  4. Ice recrystallization in a model system and in frozen muscle tissue.

    Science.gov (United States)

    Martino, M N; Zaritzky, N E

    1989-04-01

    Recrystallization produces modifications on ice crystal sizes during storage and transport of frozen foods, reducing the advantages obtained by quick freezing and inducing physicochemical changes which alter their quality and shorten their shelf life. This process involves the growth of the larger crystals at the expense of the smaller ones, being the interfacial energy, the driving force of the phenomenon. In the present work recrystallization was analyzed using direct microscopic observation of ice crystals in a model solution (0.28 N NaCl) and indirect observation of frozen muscle tissue. The model solution allowed visualization of the interface behavior; from the analysis of the ice crystal frequency distributions, relationships between shape and size of the grains were established. A kinetic model based on the average system curvature was proposed obtaining a satisfactory fitness of the experimental data. Values of the kinetic constants determined at different temperatures allowed the estimation of the process activation energy. In muscle tissues isothermal freeze-substitution was used to observe the holes left by the ice in frozen semitendinous beef muscle stored at -5, -10, -15, and -20 degrees C during long periods of time. A different evolution of the mean ice crystal diameter was observed with respect to the model system. In meat samples, at long storage times, a limit diameter value was reached; this situation has been proved to be independent of temperature and initial size (freezing rate); a theoretical expression based on tissue characteristic parameters was proposed for its evaluation. Activation energy for recrystallization in muscle tissue was also determined, being comparable to values for protein denaturation and quality losses.

  5. CT evaluation of soft tissue and muscle infection and inflammation: A systematic compartmental approach

    Energy Technology Data Exchange (ETDEWEB)

    Beauchamp, N.J. Jr. [Dept. of Radiology, and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD (United States); Scott, W.W. Jr. [Dept. of Radiology, and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD (United States); Gottlieb, L.M. [Dept. of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD (United States); Fishman, E.K. [Dept. of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD (United States)

    1995-07-01

    This essay presents a systematic approach to the evaluation of soft tissue and muscle infection by defining the various pathologic processes and then illustrating them through a series of CT studies with corresponding schematic diagrams. The specific processes discussed are cellulitis, lymphangitis/lymphedema, necrotizing fascitis, myositis/myonecrosis, and abscess. Key points in the differential diagnosis of these entities are discussed and illustrated. The clinical management of the specific pathologic processes is also discussed. (orig./MG)

  6. Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

    Directory of Open Access Journals (Sweden)

    Wagner Silva Dantas

    2013-01-01

    Full Text Available Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

  7. Morphological changes in muscle tissue of patients with infantile Pompe's disease receiving enzyme replacement therapy.

    Science.gov (United States)

    Winkel, Léon P F; Kamphoven, Joep H J; van den Hout, Hannerieke J M P; Severijnen, Lies A; van Doorn, Pieter A; Reuser, Arnold J J; van der Ploeg, Ans T

    2003-06-01

    Pompe's disease (glycogen storage disease type II) is an autosomal recessive myopathy caused by lysosomal alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) is currently under development for this disease. We evaluated the morphological changes in muscle tissue of four children with infantile Pompe's disease who received recombinant human alpha-glucosidase from rabbit milk for 72 weeks. The patients were 2.5-8 months of age at entry. Prior to treatment, all patients showed lysosomal glycogen storage in skeletal and smooth muscle cells, vascular endothelium, Schwann cells, and perineurium. The first response to treatment was noticed in vascular endothelium and in peripheral nerves after 12 weeks of treatment at an enzyme dose of 15-20 mg/kg. Increasing the dose to 40 mg/kg led, after 72 weeks of treatment, to a reduction of glycogen storage and substantial improvement of muscle architecture in the least affected patient. Not all patients responded equally well, possibly due to differences in degree of glycogen storage and concomitant muscle pathology at the start of treatment. We conclude that intravenous administration of recombinant human alpha-glucosidase from rabbit milk can improve muscle morphology in classic infantile Pompe's disease when treatment is started before irreversible damage has occurred.

  8. Effects of acute static, ballistic, and PNF stretching exercise on the muscle and tendon tissue properties.

    Science.gov (United States)

    Konrad, A; Stafilidis, S; Tilp, M

    2016-07-01

    The purpose of this study was to investigate the influence of a single static, ballistic, or proprioceptive neuromuscular facilitation (PNF) stretching exercise on the various muscle-tendon parameters of the lower leg and to detect possible differences in the effects between the methods. Volunteers (n = 122) were randomly divided into static, ballistic, and PNF stretching groups and a control group. Before and after the 4 × 30 s stretching intervention, we determined the maximum dorsiflexion range of motion (RoM) with the corresponding fascicle length and pennation angle of the gastrocnemius medialis. Passive resistive torque (PRT) and maximum voluntary contraction (MVC) were measured with a dynamometer. Observation of muscle-tendon junction (MTJ) displacement with ultrasound allowed us to determine the length changes in the tendon and muscle, respectively, and hence to calculate stiffness. Although RoM increased (static: +4.3%, ballistic: +4.5%, PNF: +3.5%), PRT (static: -11.4%, ballistic: -11.5%, PNF: -13,7%), muscle stiffness (static: -13.1%, ballistic: -20.3%, PNF: -20.2%), and muscle-tendon stiffness (static: -11.3%, ballistic: -10.5%, PNF: -13.7%) decreased significantly in all the stretching groups. Only in the PNF stretching group, the pennation angle in the stretched position (-4.2%) and plantar flexor MVC (-4.6%) decreased significantly. Multivariate analysis showed no clinically relevant difference between the stretching groups. The increase in RoM and the decrease in PRT and muscle-tendon stiffness could be explained by more compliant muscle tissue following a single static, ballistic, or PNF stretching exercise.

  9. Infectivity of Trichinella spp. recovered from decaying mouse and fox muscle tissue

    Directory of Open Access Journals (Sweden)

    Von Köller J.

    2001-06-01

    Full Text Available The tolerance to degradation processes in meat of nine Trichinella genotypes was studied in mouse and fox tissue, respectively. Minced muscle tissue with Trichinella larvae of different age was stored at room temperature at 100 % relative humidity. During storage weekly sub samples of the minced meat were digested and released larvae were inoculated in mice to evaluate the Reproductive Capacity Index (RCI. The RCI decreased with the length of storage, but the larvae from older infections appeared better adapted to tolerate the degradation processes. The African species T. nelsoni had a relative higher tolerance to elevated temperature during storage and the unencysted species T. pseudospiralis was the most vulnerable genotype.

  10. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Juan Antonio Marchal

    2013-03-01

    Full Text Available Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i skin; (ii cartilage; (iii bone; (iv nerve; and (v cardiac.

  11. Enantioselective gas chromatographic separation of methylsulfonyl PCBs in seal blubber, pelican muscle and human adipose tissues

    Energy Technology Data Exchange (ETDEWEB)

    Karasek, L.; Rosmus, J. [Veterinary Institute Prague (Czech Republic). Dept. of Chemistry; Hajslova, J. [Institute of Chemical Technology (Czech Republic). Dept. of Food Chemistry and Analysis; Huehnerfuss, H. [Hamburg Univ. (Germany). Inst. fuer Organische Chemie

    2004-09-15

    Methyl sulfone derivatives are known to represent primary metabolic products of PCBs (MeSO2- CB) and DDE (MeSO2-DDE). These metabolites are formed via mercapturic acid pathway and belong to persistent, lipophilic compounds which accumulate in the adipose, lung, liver and kidney tissues of mammals exposed to PCBs. In 1976 Jenssen and Jansson reported the identification of PCB methyl sulfones as metabolites of PCBs in Baltic grey seal blubber. Methyl sulfones are moderately polar compounds that are only slightly less hydrophobic than the parent PCBs, and their partition coefficients fulfill the requirements for bioaccumulation. The highest concentrations have been found in kidney and lung tissues of seals, otters, beluga whales, polar bears, fishes and in human tissues. In the present investigation two samples of seal blubber, two pelican muscles and eleven human adipose tissue samples were analysed with regard to their concentrations of PCB parent compounds as well as to the respective chiral methylsulfonyl metabolites.

  12. Chronic impairment of leg muscle blood flow following cardiac catheterization in childhood. [/sup 133/Xe clearance measurements

    Energy Technology Data Exchange (ETDEWEB)

    Skovranek, J.; Samanek, M.

    1979-01-01

    In 99 patients with congenital heart defects or chronic respiratory disease without clinical symptoms of disturbances in peripheral circulation, resting and maximal blood flow in the anterior tibial muscle of both extremities were investigated 2.7 yrs (average) after cardiac catheterization. The method used involved /sup 133/Xe clearance. Resting blood flow was normal and no difference could be demonstrated between the extremity originally used for catheterization and the contralateral control extremity. No disturbance in maximal blood flow could be proved in the extremity used for catheterization by the venous route only. Maximal blood flow was significantly lower in that extremity where the femoral artery had been catheterized or cannulated for pressure measurement and blood sampling. The disturbance in maximal flow was shown regardless of whether the arterial catheterization involved the Seldinger percutaneous technique, arteriotomy, or mere cannulation of the femoral artery. The values in the involved extremity did not differ significantly from the values in a healthy population.

  13. Human umbilical cord stem cell encapsulation in novel macroporous and injectable fibrin for muscle tissue engineering

    Science.gov (United States)

    Liu, Jun; Xu, Hockin H.K.; Zhou, Hongzhi; Weir, Michael D.; Chen, Qianming; Trotman, Carroll Ann

    2012-01-01

    There has been little research on the seeding of human umbilical cord mesenchymal stem cells (hUCMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were: (i) to seed hUCMSCs in a fibrin hydrogel containing fast-degradable microbeads (dMBs) to create macropores to enhance cell viability; and (ii) to investigate the encapsulated cell proliferation and myogenic differentiation for muscle tissue engineering. Mass fractions of 0–80% of dMBs were tested, and 35% of dMBs in fibrin was shown to avoid fibrin shrinkage while creating macropores and promoting cell viability. This construct was referred to as “dMB35”. Fibrin without dMBs was termed “dMB0”. Microbead degradation created macropores in fibrin and improved cell viability. The percentage of live cells in dMB35 reached 91% at 16 days, higher than the 81% in dMB0 (p muscle tissue engineering applications. PMID:22902812

  14. Skeletal muscle regeneration via engineered tissue culture over electrospun nanofibrous chitosan/PVA scaffold.

    Science.gov (United States)

    Kheradmandi, Mahsa; Vasheghani-Farahani, Ebrahim; Ghiaseddin, Ali; Ganji, Fariba

    2016-07-01

    Skeletal muscle tissue shows a remarkable potential in regeneration of injured tissue. However, in some of chronic and volumetric muscle damages, the native tissue is incapable to repair and remodeling the trauma. In the same condition, stem-cell therapy increased regeneration in situations of deficient muscle repair, but the major problem seems to be the lack of ability to attachment and survive of injected cells on the exact location. In this study, chitosan/poly(vinyl alcohol) nanofibrous scaffold was studied to promote cell attachment and provide mechanical support during regeneration. Scaffold was characterized using scanning electron microscope, X-ray diffraction, and tensile test. Degradation and swelling behavior of scaffold were studied for 20 days. The cell-scaffold interaction was characterized by MTT assay for 10 days and in vivo biocompatibility of scaffold in a rabbit model was evaluated. Results showed that cells had a good viability, adhesion, growth, and spread on the scaffold, which make this mat a desirable engineered muscular graft. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1720-1727, 2016.

  15. Determination and Difference Analysis of DNA Methylation Content Both in Blood and Muscle Tissue of Pigs

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this experiment, DNA samples from parental lines Large White, Landrace, and Meishan pigs, and their hybrids Large White×Landrace, Landrace×Large White, Large White×Meishan, and Meishan×Large White pigs were used for the determination of DNA methylation content in both blood and muscle tissue. The differences about DNA methylation content between parental lines and their hybrids were analyzed. These will offer theoretical support from molecular level for heterosis. High performance liquid chromatography (HPLC) was firstly used to detect DNA methylation content. The average DNA methylation content in 163 DNA samples of muscle tissue was 16.92%, whereas, the average DNA methylation content in 182 samples of blood was 6.49%, the difference between which was especially prominent (P 0.05); and the differences between reciprocal cross hybrids in both hybrid systems were not significant (P > 0.05), but between different hybrid systems, the hybrids had a significant difference (P<0.05). The average methylation content in muscle samples was higher than that in blood samples, and the methylation in different tissues was different.

  16. Cadmium accumulation in soil, fodder, grain, organs and muscle tissue of cattle in West Siberia (Russia

    Directory of Open Access Journals (Sweden)

    Kirill Nikolaevich Narozhnykh

    2017-01-01

    Full Text Available The content of cadmium in the soil, fodder, grain, organs and muscle tissue of animals from two ecological zones of the Novosibirsk Region, marked by different prevalent breeds of cattle – Hereford breed (beef cattle and Black-and-White breed (dairy cattle – was studied. The concentrations of elements in the soil, fodder, and grain were measured by flame atomic absorption, using Kvant-2A spectrometer, and expressed on a dry weight basis. The cadmium content in soil, fodder, and grain did not exceed maximum permissible concentrations (MPC. The chemical composition of organs and muscle tissue was analyzed by atomic absorption spectrometry, using Shimadzu AA-7000 spectrometer. Average cadmium content in liver, kidneys, spleen, heart, lungs and muscle tissue over the populations was determined for Hereford and Black-and-White cattle. The cadmium levels in forage and soil from the first and second zones were not different. Maximal cadmium content was observed in kidneys of the animals of the studied breeds, whereas minimal content was observed in heart. Interbreed differences in cadmium content in lungs, liver, spleen, and heart were determined. The West Siberia territories are suitable for yielding ecologically safe production, concerning the content of cadmium in the soil, fodder, grain, meat and by-products of cattle.

  17. The Effect of Fructose-1,6-diphosphate and HTK Solution on Protecting Primary Cardiac Muscle Cells of Rat with Cold Preservation

    Institute of Scientific and Technical Information of China (English)

    SHI Xiaofeng; CHENG Jun; XIA Suisheng

    2005-01-01

    Summary: In this study we tried to investigate the effect of fructose-1,6-diphosphate and HTK solution on protecting primary cardiac muscle cells of rat with cold preservation. The primary cardiac muscle cells of rat were cultured in vitro with four preservation solutions respectively: 0.9 % sodium chloride solution (group A), FDP (group B), HTK solution (group C) and a mixture of FDP and HTK solution (group D). The cells were preserved for 6, 8 and 10 h at 0-4 ℃. The values of AST and LDH-L and the Na+-K+ ATPase activity in cardiac muscle cells were detected, and the survival rate of cardiac muscle cells was detected with trypan blue staining. The values of AST and LDH-L in group C and group D were remarkable lower those in group A and group B (P<0.001), while the Na+-K+ ATPase activity and the survival rate of cells in group C and group D were much higher than those in group A and group B (P<0.001). The values of AST and LDH-L after 6 hours in group D decreased much more than those in group C (P<0.01), while the Na+-K+ ATPase activity and the survival rate of cells in group D improved more than those in group C (P<0.01). Both of the HTK solution and the mixture of HTK and FDP solution have an evident effect on protecting the primary cardiac muscle cells of rat in vitro with cold preservation, Compared with the HTK solution, the mixture solution has a better short-term protective effect.

  18. Tissue Deformation Index as a Reliable Measure of Lateral Abdominal Muscle Activation on M-Mode Sonography.

    Science.gov (United States)

    Biały, Maciej; Adamczyk, Wacław; Gnat, Rafael; Stranc, Tomasz

    2017-03-24

    The aim of this article is to present a novel method of evaluating the activity of lateral abdominal muscles using M-mode sonography. The method leads to calculation of the tissue deformation index, representing the percent change in lateral abdominal muscle thickness over time. The objectives of this study were as follows: (1) to establish the mean tissue deformation index values for individual lateral abdominal muscles; and (2) to establish the reliability of the tissue deformation index. In a group of 34 healthy young volunteers (mean age, 24.03 years; body mass, 68.89 kg; body height, 174.25 cm), the reflex response of the lateral abdominal muscles to postural perturbation in the form of rapid arm abduction was recorded in 2 series, with 6 repetitions each, and the tissue deformation index was calculated. The mean tissue deformation index values formed a gradient, increasing from deep to superficial lateral abdominal muscles: 0.06%/ms for transversus abdominis, 0.11%/ms for oblique internal, and 0.16 for oblique external muscles. The tissue deformation index values differed significantly among individual lateral abdominal muscles (all paired comparisons, P  0.8).

  19. Host-derived smooth muscle cells accumulate in cardiac allografts: role of inflammation and monocyte chemoattractant protein 1.

    Directory of Open Access Journals (Sweden)

    Piotr Religa

    Full Text Available Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35+/-2.3% of cells in arterioles (range, 0.08-12.51%. As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41+/-1.03, p = 0.034 and the number of leukocytes (19.1+/-12.7 per 20 high-power fields, p = 0.01. The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1 released from leukocytes was crucial for SMC migration. After heart allotransplantation, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts.

  20. Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

    Science.gov (United States)

    Bojakowski, Krzysztof; Soin, Joanna; Nozynski, Jerzy; Zakliczynski, Michal; Gaciong, Zbigniew; Zembala, Marian; Söderberg-Nauclér, Cecilia

    2009-01-01

    Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35±2.3% of cells in arterioles (range, 0.08–12.51%). As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41±1.03, p = 0.034) and the number of leukocytes (19.1±12.7 per 20 high-power fields, p = 0.01). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1) released from leukocytes was crucial for SMC migration. After heart allotransplantion, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts. PMID:19142231

  1. Mechanical Dyssynchrony by Tissue Doppler Cross-Correlation is Associated with Risk for Complex Ventricular Arrhythmias after Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Tayal, Bhupendar; Gorcsan, John; Delgado-Montero, Antonia;

    2015-01-01

    BACKGROUND: Tissue Doppler cross-correlation analysis has been shown to be associated with long-term survival after cardiac resynchronization defibrillator therapy (CRT-D). Its association with ventricular arrhythmia (VA) is unknown. METHODS: From two centers 151 CRT-D patients (New York Heart.......0; 95% CI, 1.8-13.5; P = .002). CONCLUSIONS: Persistent and new mechanical dyssynchrony after CRT-D was associated with subsequent complex VA. Dyssynchrony after CRT-D is a marker of poor prognosis....

  2. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    Science.gov (United States)

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.

  3. Development of Electrically Conductive Double-Network Hydrogels via One-Step Facile Strategy for Cardiac Tissue Engineering.

    Science.gov (United States)

    Yang, Boguang; Yao, Fanglian; Hao, Tong; Fang, Wancai; Ye, Lei; Zhang, Yabin; Wang, Yan; Li, Junjie; Wang, Changyong

    2016-02-18

    Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of electrical conductivity of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one-step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chemical crosslinked poly(thiophene-3-acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo-crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mechanical, and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its conductivity (≈10(-4) S cm(-1)) falls in the range of reported conductivities for native myocardium tissue. To assess their biological activity, the brown adipose-derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without electrical stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, electrical stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.

  4. Antioxidant therapy reduces oxidative and inflammatory tissue damage in patients subjected to cardiac surgery with extracorporeal circulation.

    Science.gov (United States)

    Castillo, Rodrigo; Rodrigo, Ramón; Perez, Felipe; Cereceda, Mauricio; Asenjo, René; Zamorano, Jaime; Navarrete, Roberto; Villalabeitia, Eli; Sanz, Juan; Baeza, Cristián; Aguayo, Rubén

    2011-04-01

    Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol therapy reduces oxidative and inflammatory cardiac tissue damage. This trial assigned 95 either-sex patients to supplementation with n-3 PUFA (2 g/day), or matching placebo groups, 7 days before on-pump surgery. Antioxidant vitamins C (1 g/day) and E (400 IU/day) or placebo were added from 2 days before surgery until discharge. Blood and atrial tissue samples were obtained during the intervention. Reduced/oxidized glutathione (GSH/GSSG) ratio, malondialdehyde (MDA) and protein carbonylation were determined in atrial tissue. Leucocyte count and high-sensitivity C-reactive protein (hs-CRP) in blood plus nuclear factor (NF)-κappaB activation in atrial tissue served for inflammation assessment. Lipid peroxidation and protein carbonylation were 27.5 and 24% lower in supplemented patients (p < 0.01). GSH/GSSG ratio was 38.1% higher in supplemented patients compared with placebo (p < 0.01). Leucocyte count and serum hs-CRP levels were markedly lower throughout the protocol in supplemented patients (p < 0.01). Atrial tissue NF-κB DNA activation in supplemented patients was 22.5% lower than that in placebo patients (p < 0.05). The combined n-3 PUFA-antioxidant vitamin protocol therapy here proposed reduced the oxidative stress and inflammation biomarkers, in patients undergoing on-pump cardiac surgery.

  5. Eliminating cardiac contamination from myoelectric control signals developed by targeted muscle reinnervation.

    Science.gov (United States)

    Zhou, Ping; Kuiken, Todd A

    2006-12-01

    The electrocardiogram (ECG) artifact is a major noise contaminating the myoelectric control signals when using shoulder disarticulation prosthesis. This is an even more significant problem with targeted muscle reinnervation to develop additional myoelectric sites for improved prosthesis control in a bilateral amputee at shoulder disarticulation level. This study aims at removal of ECG artifacts from the myoelectric prosthesis control signals produced from targeted muscle reinnervation. Three ECG artifact removal methods based on template subtracting, wavelet thresholding and adaptive filtering were investigated, respectively. Surface EMG signals were recorded from the reinnervated pectoralis muscles of the amputee. As a key parameter for clinical myoelectric prosthesis control, the amplitude measurement of the signal was used as a performance indicator to evaluate the proposed methods. The feasibility of the different methods for clinical application was also investigated with consideration of the clinical speed requirements and memory limitations of commercial prosthesis controllers.

  6. Periaortic Fat Tissue: A Predictor of Cardiac Valvular Calcification, Malnutrition, Inflammation, and Atherosclerosis Components in Hemodialysis Patients.

    Science.gov (United States)

    Genctoy, Gultekin; Eldem, Olcay; Ergun, Tarkan; Arikan, Serap

    2015-09-01

    Cardiac valvular calcification (CVC) in end-stage renal disease is shown to be a component of malnutrition, inflammation, atherosclerosis, calcification (MIAC) syndrome. Thoracic periaortic fat tissue (T-PAFT) is shown to be increased in patients with end-stage renal disease (ESRD), and has positive correlation with MIAC. Negative correlation between CVC and vitamin D is shown in hemodialysis (HD) patients. In this study, we investigated a relationship between body composition, T-PAFT, metabolic and inflammatory parameters, and CVC in HD patients. Seventy-six HD patients (49M) were included. CVC is defined as bright echoes of >1 mm on one or more cusps on echocardiography. Results were expressed as the number of calcified valves (0,1,2). Calcium, phosphorus, parathyroid hormone (PTH), C-reactive protein (CRP), albumin and 25-hydroxy vitamin D levels were studied from predialysis blood samples. T-PAFT was calculated using a method with manual definition of borders on images from multislice computed tomography. Basal metabolic rate, muscle mass, total and truncal fat mass were measured by bioimpedance analysis. There were 65.8% of patients who had CVC. Patients with CVC were older (63.5 ± 14.6 ± 17, P = 0.02). T-PAFT (1599 ± 596, 739.7 ± 179 mm(2) , P = 0.001) and CRP (15.8 ± 11; 11.1 ± 13.2 mg/dL; P = 0.04) were higher in the group with CVC. T-PAFT had positive correlations with CRP, MIAC, body mass index (BMI) and number of calcified valves, negative correlation with left ventricular ejection fraction, and no correlation with albumin, calcium, phosphorus, and PTH. The logistic regression analysis revealed that T-PAFT was a significant predictor of CVC. In this study, T-PAFT showed a positive correlation with inflammation, CVC, and MIAC score in HD patients. T-PAFT was a significant predictor of CVC.

  7. Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells.

    Science.gov (United States)

    Babij, P; Zhao, J; White, S; Woodcock-Mitchell, J; Mitchell, J; Absher, M; Baldor, L; Periasamy, M; Low, R B

    1993-08-01

    RNA and protein analyses were used to detect expression of SM1 and SM2 smooth muscle myosin heavy chain (MHC) in cultured adult rat lung connective tissue cells (RL-90). Smooth muscle MHC mRNA expression in confluent cells grown in 10% serum was approximately 50% of the level in adult stomach. Similar results were obtained in cells cultured at low density (25% confluency) in 1% serum. However, in low-density cultures transferred to 10% serum for 24 h, the level of MHC mRNA decreased to approximately 20% of that in adult stomach. Smooth muscle alpha-actin showed a pattern of expression similar to that for smooth muscle MHC. Expression of nonmuscle MHC-A mRNA was higher in all culture conditions compared to stomach. MHC-A mRNA expression was less in low-density cultures in low serum and increased when low-density cultures were transferred to 10% serum for 24 h. MHC-B mRNA expression was less in low- vs. high-density cultures. In contrast to MHC-A, however, MHC-B mRNA expression in low-density cultures was higher in low serum. Immunofluorescence and immunoblotting with SM1-specific antibody demonstrated the presence of the SM1 protein isoform as well as reactivity to a protein band migrating slightly faster than SM2. These results demonstrate that cultured rat lung connective tissue cells express smooth muscle MHC and that expression is modulated by culture conditions.

  8. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher

    2002-01-01

    increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P muscular activity increases the interstitial concentrations...... of bradykinin and adenosine in both skeletal muscle and the connective tissue around its adjacent tendon. These findings support a role for bradykinin and adenosine in exercise-induced hyperaemia in skeletal muscle and suggest that bradykinin and adenosine are potential regulators of blood flow in peritendinous...

  9. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    Directory of Open Access Journals (Sweden)

    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  10. Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

    Science.gov (United States)

    Danoviz, Maria E.; Nakamuta, Juliana S.; Marques, Fabio L. N.; dos Santos, Leonardo; Alvarenga, Erica C.; dos Santos, Alexandra A.; Antonio, Ednei L.; Schettert, Isolmar T.; Tucci, Paulo J.; Krieger, Jose E.

    2010-01-01

    Background Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers. PMID:20711471

  11. ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.

    Science.gov (United States)

    Han, Arum; Zhao, Hu; Li, Jingyuan; Pelikan, Richard; Chai, Yang

    2014-08-01

    The development of the craniofacial muscles requires reciprocal interactions with surrounding craniofacial tissues that originate from cranial neural crest cells (CNCCs). However, the molecular mechanism involved in the tissue-tissue interactions between CNCCs and muscle progenitors during craniofacial muscle development is largely unknown. In the current study, we address how CNCCs regulate the development of the tongue and other craniofacial muscles using Wnt1-Cre; Alk5(fl/fl) mice, in which loss of Alk5 in CNCCs results in severely disrupted muscle formation. We found that Bmp4 is responsible for reduced proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5(fl/fl) mice during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1-Cre; Alk5(fl/fl) mice and are critical for differentiation of the myogenic cells. Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together, our results indicate that CNCCs play critical roles in controlling craniofacial myogenic proliferation and differentiation through tissue-tissue interactions.

  12. Simulation of steady state and transient cardiac muscle response experiments with a Huxley-based contraction model.

    Science.gov (United States)

    Negroni, Jorge A; Lascano, Elena C

    2008-08-01

    A cardiac muscle model is presented with the purpose of representing a wide range of mechanical experiments at constant and transient Ca(2+) concentration. Modifications of a previous model were: weak and power attached crossbridge states, a troponin system involving three consecutive regulatory troponin-tropomyosin units acting together in Ca(2+) kinetics and detachment constants depending on crossbridge length. This model improved cooperativity (Hill coefficient close to 4) and the force-velocity relationship, and incorporated the representation of the four phases of muscle response to length and force steps, isotonic shortening and isosarcometric contractions, preserving previous satisfactory results. Moreover, experimentally reported effects, such as length dependence on Ca(2+) affinity, the decreased cooperativity at higher Ca(2+) concentrations, temperature effects on the stiffness-frequency relationship and the isometric internal shortening due to series elasticity, were obtained. In conclusion, the model is more comprehensive than a previous version because it is able to represent a wider variety of steady state experiments, the mechanical variables in twitches can be adequately related to intracellular Ca(2+), and all the simulations were performed with the same set of parameters.

  13. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice

    DEFF Research Database (Denmark)

    Meijer, Rick I; Bakker, Wineke; Alta, Caro-Lynn A F

    2013-01-01

    Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation...

  14. The Value of Conventional Echocardiographic and Tissue Doppler Imaging in the Diagnosis of Cardiac Amyloidosis

    Institute of Scientific and Technical Information of China (English)

    Li ZHANG; Mingxing XIE; Xinfang WANG; Yali YANG; Junhong HUANG; Ming CHENG; Feixiang XIANG; Qing LU

    2008-01-01

    Transthoracic echocardiographic characteristics of 17 cases of cardiac amyloidosis (CA),a rare disease in China, were analyzed in order to improve the understanding of the disease. Seventeen cases of biopsy-proven CA, admitted to Wuhan Union Hospital from June 1994 to September 2008 were retrospectively reviewed. Twenty normal volunteers served as control group. Left atrial and ventricular functions and mitral inflow velocity were measured by two-dimensional, and Doppler echocardiography, and tissue Doppler imaging (TDI)-derived peak systolic wall motion velocities (Sv), peak early diastolic wall motion velocities (Ev), and peak late diastolic wall motion (Av) were measured at the septunm. Lateral, inferior and anterior comers of mitral annulus from the apical 4- and 2 chamber views. Compared with the control group, the interventricular septal thickness (IVSd), the left ventricular posterior wall (LVPWd), right ventricular transverse diameter (RVTDd) near the end of diastole and the interauricular septum thickness (IASs), left atrial anteroposterior diameter (LAADs), right atrial transverse diameter (RATDs) near the end of systole were increased significantly (all P<0.05) and left ventricular ejection fraction (LVEF) decreased (P<0.05) in the CA group.Compared with the control group, Sv, Ev at each wall and Av at almost all walls were significantly decreased in the CA group. In the CA group, Myocardial echoes of interventricular septum and free wall of left ventricle were enhanced evidently and distributed unevenly. The echoes presented as ground glass-like images, with some spotty hyper echoes. Both atria were enlarged, and LVEF decreased, with diastolic function impaired, and mild-moderate hydropericardium found in the CA group. It was concluded that echocardiography was a relatively sensitive and highly specific non-invasive method for the diagnosis of CA.

  15. Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy

    DEFF Research Database (Denmark)

    Witting, Nanna; Kruuse, Christina; Nyhuus, Bo

    2014-01-01

    OBJECTIVE: Patients with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy lack neuronal nitric oxide synthase (nNOS). nNOS mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosp...

  16. Comparison of Metabolic Network between Muscle and Intramuscular Adipose Tissues in Hanwoo Beef Cattle Using a Systems Biology Approach.

    Science.gov (United States)

    Lee, Hyun-Jeong; Park, Hye-Sun; Kim, Woonsu; Yoon, Duhak; Seo, Seongwon

    2014-01-01

    The interrelationship between muscle and adipose tissues plays a major role in determining the quality of carcass traits. The objective of this study was to compare metabolic differences between muscle and intramuscular adipose (IMA) tissues in the longissimus dorsi (LD) of Hanwoo (Bos taurus coreanae) using the RNA-seq technology and a systems biology approach. The LD sections between the 6th and 7th ribs were removed from nine (each of three cows, steers, and bulls) Hanwoo beef cattle (carcass weight of 430.2 ± 40.66 kg) immediately after slaughter. The total mRNA from muscle, IMA, and subcutaneous adipose and omental adipose tissues were isolated and sequenced. The reads that passed quality control were mapped onto the bovine reference genome (build bosTau6), and differentially expressed genes across tissues were identified. The KEGG pathway enrichment tests revealed the opposite direction of metabolic regulation between muscle and IMA. Metabolic gene network analysis clearly indicated that oxidative metabolism was upregulated in muscle and downregulated in IMA. Interestingly, pathways for regulating cell adhesion, structure, and integrity and chemokine signaling pathway were upregulated in IMA and downregulated in muscle. It is thus inferred that IMA may play an important role in the regulation of development and structure of the LD tissues and muscle/adipose communication.

  17. Influence of menstrual cycle phase on muscle metaboreflex control of cardiac baroreflex sensitivity, heart rate and blood pressure in humans.

    Science.gov (United States)

    Hartwich, Doreen; Aldred, Sarah; Fisher, James P

    2013-01-01

    We sought to determine whether menstrual cycle phase influences muscle metaboreflex control of spontaneous cardiac baroreflex sensitivity (cBRS), blood pressure (BP) and heart rate (HR). Twenty-three young women not taking oral contraceptives were studied during the early (EF; low oestrogen, low progesterone) and late follicular menstrual phases (LF; high oestrogen, low progesterone). Protocol 1 consisted of leg cycling at low (21 ± 2 W) and moderate workloads (71 ± 3 W) in free-flow conditions and with partial flow restriction (bilateral thigh-cuff inflation at 100 mmHg) to activate the muscle metaboreflex. Protocol 2 consisted of rhythmic hand-grip exercise with incremental upper arm-cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia. Leg cycling decreased cBRS (EF, 20 ± 5, 6 ± 1 and 1 ± 0.1 ms mmHg(-1); and LF, 19 ± 3, 6 ± 0.4, 1 ± 0.1 ms mmHg(-1) during rest, low- and moderate-intensity leg cycling, respectively) and increased HR in an intensity-dependent manner, while BP remained unchanged. Partial flow restriction during leg cycling decreased cBRS, and increased HR and BP. During post-exercise ischaemia, HR and BP remained elevated, while cBRS remained suppressed (EF, 4.2 ± 0.6 ms mmHg(-1); and LF, 4.7 ± 0.5 ms mmHg(-1); P < 0.05 versus rest). Cardiac baroreflex sensitivity was unchanged during hand-grip with and without partial flow restriction and post-exercise ischaemia. No differences in cBRS, HR or BP responses were observed between EF and LF at any time during either protocol. These data indicate that endogenous fluctuations in oestrogen between the EF and LF phases of the menstrual cycle do not influence muscle metaboreflex control of cBRS, BP or HR in young women.

  18. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Timothy J Cashman

    Full Text Available Hypertrophic cardiomyopathy (HCM is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS, which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and

  19. THE CONTENT OF SOME COMPONENTS OF METABOLISM IN MUSCLE TISSUE OF BREAM ABRAMIS BRAMA (L.

    Directory of Open Access Journals (Sweden)

    Ekaterina Flerova

    2014-02-01

    Full Text Available Physiological condition is one of the most important characteristic used for evaluating single individuals, populations and fish stocks in general. The data on a number of physiological indicators of bream the Gorky water reservoir were presented. Amount of moisture, dry matter in the muscular tissue was determined of using two-stage determination of total moisture. Simple lipids were determined by extraction with petroleum-ether. The analysis of the results suggests that the indices of water, dry matter and simple lipids content in muscular tissue of mature males, females and juvenile individuals of bream were close. Decrease of water amount in the muscle tissue, increase of dry matter end lipids takes place along with bream ageing.

  20. Validation of Continuously Tagged MRI for the Measurement of Dynamic 3D Skeletal Muscle Tissue Deformation

    CERN Document Server

    Moerman, Kevin M; Simms, Ciaran K; Lamerichs, Rolf M; Stoker, Jaap; Nederveen, Aart J

    2016-01-01

    A SPAMM tagged MRI methodology is presented allowing continuous (3.3-3.6 Hz) sampling of 3D dynamic soft tissue deformation using non-segmented 3D acquisitions. The 3D deformation is reconstructed by the combination of 3 mutually orthogonal tagging directions, thus requiring only 3 repeated motion cycles. In addition a fully automatic post-processing framework is presented employing Gabor scale-space and filter-bank analysis for tag extrema segmentation and triangulated surface fitting aided by Gabor filter bank derived surface normals. Deformation is derived following tracking of tag surface triplet triangle intersections. The dynamic deformation measurements were validated using indentation tests (~20 mm deep at 12 mm/s) on a silicone gel soft tissue phantom containing contrasting markers which provide a reference measure of deformation. In addition, the techniques were evaluated in-vivo for dynamic skeletal muscle tissue deformation measurement during indentation of the biceps region of the upper arm in a ...

  1. Communication channel modeling of human forearm with muscle fiber tissue characteristics.

    Science.gov (United States)

    Zhang, Shuang; Pun, Sio Hang; Mak, Peng Un; Qin, Yu-Ping; Liu, Yi-He; Vai, Mang I

    2016-09-14

    Human-Body Communication (HBC) is a wireless communication method using the human body tissue as a transmission medium for signals. This paper on the basis of human muscle fiber tissues' characteristics, it is first proposed to establish the analytical model of galvanic coupling human-body communication channel. In this model, the parallel and the transverse electrical characteristics of muscular tissue are fully considered, and the model accurately presents the transmission mechanism of galvanic coupling human-body communication signals in the channel. At last, through compare with the experimental results and calculation results, the maximum error of the model is 22.4% and the average error is 14.2% within the frequency range.

  2. Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue.

    Science.gov (United States)

    Prohaska, Bianca K; Tsang, Paul C W; Driggers, William B; Hoffmayer, Eric R; Wheeler, Carolyn R; Brown, A Christine; Sulikowski, James A

    2013-01-01

    Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs.

  3. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

    Science.gov (United States)

    Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance.

  4. Differential regulation of oxytocin receptor in various adipose tissue depots and skeletal muscle types in obese Zucker rats.

    Science.gov (United States)

    Gajdosechova, L; Krskova, K; Olszanecki, R; Zorad, S

    2015-07-01

    Multifunctional peptide oxytocin currently undergoes intensive research due to its proposed anti-obesity properties. Until now, little is known about regulation of oxytocin receptor in metabolically active tissues in obesity. The aim of the present study was to measure expression of oxytocin receptor upon obese phenotype with respect to the variety among adipose tissue and skeletal muscles with distinct anatomical localisation. Total homogenates were prepared from epididymal, retroperitoneal and inguinal adipose tissues as well as quadriceps and soleus muscle from lean and obese Zucker rats. Oxytocin receptor protein was determined by immunoblot. Interestingly, elevated oxytocin receptor was observed in epididymal adipose tissue of obese rats in contrast to its downregulation in subcutaneous and no change in retroperitoneal fat. In lean animals, oxytocin receptor protein was expressed at similar levels in all adipose depots. This uniformity was not observed in the case of skeletal muscle in which fibre type composition seems to be determinant of oxytocin receptor expression. Quadriceps muscle with the predominance of glycolytic fibres exhibits higher oxytocin receptor expression than almost exclusively oxidative soleus muscle. Oxytocin receptor protein levels were decreased in both skeletal muscles analysed upon obese phenotype. The present work demonstrates that even under identical endocrine circumstances, oxytocin receptor is differentially regulated in adipose tissue of obese rats depending on fat depot localisation. These results also imply which tissues may be preferentially targeted by oxytocin treatment in metabolic disease.

  5. Bioreactors as Engineering Support to Treat Cardiac Muscle and Vascular Disease

    Directory of Open Access Journals (Sweden)

    Diana Massai

    2013-01-01

    Full Text Available Cardiovascular disease is the leading cause of morbidity and mortality in the Western World. The inability of fully differentiated, load-bearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. For the effective production of organized and functional cardiovascular engineered constructs in vitro, a suitable dynamic environment is essential, and can be achieved and maintained within bioreactors. Bioreactors are technological devices that, while monitoring and controlling the culture environment and stimulating the construct, attempt to mimic the physiological milieu. In this study, a review of the current state of the art of bioreactor solutions for cardiovascular tissue engineering is presented, with emphasis on bioreactors and biophysical stimuli adopted for investigating the mechanisms influencing cardiovascular tissue development, and for eventually generating suitable cardiovascular tissue replacements.

  6. Comparative cardiac pathological changes of Atlantic salmon (Salmo salar L.) affected with heart and skeletal muscle inflammation (HSMI), cardiomyopathy syndrome (CMS) and pancreas disease (PD)

    DEFF Research Database (Denmark)

    Yousaf, Muhammad Naveed; Koppang, Erling Olaf; Skjødt, Karsten

    2013-01-01

    The heart is considered the powerhouse of the cardiovascular system. Heart and skeletal muscle inflammation (HSMI), cardiomyopathy syndrome (CMS) and pancreas disease (PD) are cardiac diseases of marine farmed Atlantic salmon (Salmo salar) which commonly affect the heart in addition to the skeletal......) and TUNEL, and moderate levels of caspase 3 immuno-reactivity suggested a high cell turnover where DNA damage/repair might be occurring in the diseased hearts. Interestingly, the apparently similar cardiac diseases exhibited differences in the immunopathological responses in Atlantic salmon....

  7. In Vivo Imaging of Far-red Fluorescent Proteins after DNA Electrotransfer to Muscle Tissue

    Directory of Open Access Journals (Sweden)

    Hojman Pernille

    2009-04-01

    Full Text Available Abstract DNA electrotransfer to muscle tissue yields long-term, high levels of gene expression; showing great promise for future gene therapy. We want to characterize the novel far-red fluorescent protein Katushka as a marker for gene expression using time domain fluorescence in vivo imaging. Highly efficient transgenic expression was observed after DNA electrotransfer with 100-fold increase in fluorescent intensity. The fluorescent signal peaked 1 week after transfection and returned to background level within 4 weeks. Katushka expression was not as stable as GFP expression, which was detectable for 8 weeks. Depth and 3D analysis proved that the expression was located in the target muscle. In vivo bio-imaging using the novel Katushka fluorescent protein enables excellent evaluation of the transfection efficacy, and spatial distribution, but lacks long-term stability.

  8. Familial amyloidotic polyneuropathy with muscle, vitreous, leptomeningeal, and cardiac involvement: Phenotypic, pathological, and MRI description

    Directory of Open Access Journals (Sweden)

    Prashantha D

    2010-01-01

    Full Text Available Familial amyloidotic polyneuropathy (FAN type 1 is a rare systemic disease that causes severe and disabling peripheral neuropathy. We describe the phenotypic, radiological, and pathological characteristics of a patient with familial amyloid polyneuropathy type 1 who had evidence of motor-sensory-autonomic neuropathy, ocular vitreous deposits, diffuse leptomeningeal involvement, and hypertrophic cardiomyopathy. Muscle involvement, an infrequently reported feature, was also observed. Early recognition of the disease has significant therapeutic implications.

  9. Myosin types and fiber types in cardiac muscle. II. Atrial myocardium

    OpenAIRE

    1982-01-01

    Antibodies were produced against myosins isolated from the left atrial myocardium (anti-bAm) and the left ventricular myocardium (anti-bVm) of the bovine heart. Cross-reactive antibodies were removed by cross- absorption. Absorbed anti-bAm and anti-bVm were specific for the myosin heavy chains when tested by enzyme immunoassay combined with SDS gel electrophoresis. Indirect immunofluorescence was used to determine the reactivity of atrial muscle fibers to the two antibodies. Three populations...

  10. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    Science.gov (United States)

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

  11. The proliferative potential of human cardiac stem cells was unaffected after a long-term cryopreservation of tissue blocks

    Science.gov (United States)

    Iguchi, Nobuo; Cho, Yasunori; Inoue, Masaki; Murakami, Tsutomu; Tabata, Minoru; Takanashi, Shuichiro; Tomoike, Hitonobu

    2017-01-01

    Background Human c-kit-positive cardiac stem cells (CSCs) have been used to treat patients suffering from ischemic cardiomyopathy. This study aimed to investigate whether a long-term storage of cardiac tissues would influence the growth potential of the subsequently isolated CSCs. Methods A total of 34 fresh samples were obtained from various cardiac regions [right atrium (RA), left atrium (LA), and/or left ventricle (LV)] of 21 patients. From 12 of these patients, 18 samples kept frozen for ~2 years were employed to prepare and characterize the CSCs. After confirming the specificity of the cell sorting by c-kit immunolabeling, the growth rate (number of doublings per day), BrdU positivity, and colony forming unit (CFU) were measured in each CSC population; the values were compared among distinct cardiac regions as well as between fresh and frozen tissues from which CSCs were derived. Results Among independent measurements indicating growth potential, the growth rate and BrdU positivity remarkably correlated in freshly prepared CSCs. The cells obtained from every examined region displayed a high proliferative capacity with the growth rate of 0.48±0.19 and the BrdU positivity of 15.0%±7.6%. The right atrial CSCs tended to show a greater growth than those in the other two areas. Similarly, the CSCs were isolated from tissue blocks, cryopreserved for ~2 years, and compared with CSCs derived from the fresh specimens of the same patients. Importantly, we were able to obtain and culture CSCs from every frozen material, and their proliferative potential, represented by the growth rate of 0.47±0.22 and the BrdU positivity of 13.7%±7.9%, was not inferior to that of the freshly prepared cells. Conclusions The long-term cryopreservation of cardiac tissues did not affect the growth potential of the derivative CSCs. Our findings should expand the therapeutic applications of these cells over a longer time span. PMID:28251120

  12. Insulin action in muscle and adipose tissue in type 2diabetes: The significance of blood flow

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Under normal metabolic conditions insulin stimulatesmicrovascular perfusion (capillary recruitment) ofskeletal muscle and subcutaneous adipose tissue andthus increases blood flow mainly after meal ingestionor physical exercise. This helps the delivery of insulinitself but also that of substrates and of other signallingmolecules to multiple tissues beds and facilitatesglucose disposal and lipid kinetics. This effect is impairedin insulin resistance and type 2 diabetes early in thedevelopment of metabolic dysregulation and reflectsearly-onset endothelial dysfunction. Failure of insulinto increase muscle and adipose tissue blood flowresults in decreased glucose handling. In fat depots, ablunted postprandial blood flow response will result inan insufficient suppression of lipolysis and an increasedspill over of fatty acids in the circulation, leading toa more pronounced insulin resistant state in skeletalmuscle. This defect in blood flow response is apparenteven in the prediabetic state, implying that it is afacet of insulin resistance and exists long before overthyperglycaemia develops. The following review intendsto summarize the contribution of blood flow impairmentto the development of the atherogenic dysglycemia anddyslipidaemia.

  13. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  14. Effects of Acupuncture Pretreatment on Ischemic Cardiac Muscle Cell Apoptosis and Gene Expression in Ischemia-reperfusion Rats

    Institute of Scientific and Technical Information of China (English)

    赵宇辉; 孙忠人; 崔学军

    2009-01-01

    目的:针灸预处理对缺血心肌具有保护作用.通过观察针刺预处理对心肌缺血再灌注损伤大鼠心肌细胞凋亡及HSP70mPNA表达的影响,探讨针刺预处理的心肌保护机制.方法:64只Wistar大鼠随机分为8组,即正常对照组,假手术组,缺血再灌注组,缺血预处理组,手捻针预处理日1次组,电针预处理日1次组,手捻针预处理日2次组,电针预处理日2次组.建立大鼠心肌缺血再灌注模型,采用原位杂交法测定心肌HSP70mRNA的表达,TUNEL法检测细胞凋亡.结果:与正常对照组、假手术组比较,缺血再灌注组细胞凋亡增加,HSP70 mRNA表达增加;与缺血再灌注组比较,针刺预处理使心肌细胞凋亡减少、HSP70mRNA表达增加,且针刺预处理日2次组作用强于针刺预处理日1次组和缺血预处理组.结论:针刺预处理能够抑制心肌缺血再灌注损伤大鼠心肌细胞凋亡,上调心肌HSP70mRNA的表达.针刺预处理每日2次的作用强于针剌预处理每日1次.%Objective:To investigate the protective effects of acupuncture pretreatment on ischemic myocardium,the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac muscle cell apoptosis and the expression of HSP70 mRNA of ischemia-reperfusion injury rats treated with acupuncture pretreatment.Methods:Sixty-four Wistar rats were randomly divided into eight groups:control group,sham surgery group,ischemia-repertusion group,ischemia pretreatment group,manual acupuncture pretreatment group(once a day),electroacupuncture pretreatment group(once a day),manual acupuncture pretreatment group(twice a day),and electroacupuncture pretreatment group(twice a day).The reperfusion model of rat myocardial ischemia was made.Expression of HSP70 mRNA was assayed by in situ hyrbridization,and cell apoptosis by TUNEL.Results:Compared with those in the control group and the sham surgery group,the apoptosis and the expression of HSP70 m

  15. Mercury and selenium concentrations in muscle tissue of different species of predatory freshwater fish and correlation between these elements.

    Science.gov (United States)

    Strapáč, Imrich; Sokol, Jozef; Žatko, Daniel; Baranová, Mária

    2012-01-01

    Concentrations of total mercury and selenium were determined in 49 and 42 muscle tissue samples, respectively, of six species of predatory freshwater fish, dace (Leuciscus leuciscus), pike perch (Sander lucioperca), pike (Esox lucius), European catfish (Silurus glanis), rainbow trout (Oncorhynchus mykiss) and asp (Aspius aspius). Muscle selenium concentration did not correlate with the corresponding total mercury concentration (R² < 0.198) in all examined predatory fish species. There was an inverse correlation between the ratio Se/Hg content and the total mercury content in the muscle tissues of dace, pike perch, pike, European catfish and asp. The muscle tissue of rainbow trout exhibits a linear correlation between the ratio Se/Hg content and the total mercury content. The total mercury concentration of all examined samples did not exceed the hygienic limit for Hg for predatory fish.

  16. Physiologic Basis and Pathophysiologic Implications of the Diastolic Properties of the Cardiac Muscle

    Directory of Open Access Journals (Sweden)

    João Ferreira-Martins

    2010-01-01

    Full Text Available Although systole was for long considered the core of cardiac function, hemodynamic performance is evenly dependent on appropriate systolic and diastolic functions. The recognition that isolated diastolic dysfunction is the major culprit for approximately fifty percent of all heart failure cases imposes a deeper understanding of its underlying mechanisms so that better diagnostic and therapeutic strategies can be designed. Risk factors leading to diastolic dysfunction affect myocardial relaxation and/or its material properties by disrupting the homeostasis of cardiomyocytes as well as their relation with surrounding matrix and vascular structures. As a consequence, slower ventricular relaxation and higher myocardial stiffness may result in higher ventricular filling pressures and in the risk of hemodynamic decompensation. Thus, determining the mechanisms of diastolic function and their implications in the pathophysiology of heart failure with normal ejection fraction has become a prominent field in basic and clinical research.

  17. Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice.

    Directory of Open Access Journals (Sweden)

    Takashi Ito

    Full Text Available Taurine (2-aminoethanesulfonic acid is found in milimolar concentrations in mammalian tissues. One of its main functions is osmoregulation; however, it also exhibits cytoprotective activity by diminishing injury caused by stress and disease. Taurine depletion is associated with several defects, many of which are found in the aging animal, suggesting that taurine might exert anti-aging actions. Therefore, in the present study, we examined the hypothesis that taurine depletion accelerates aging by reducing longevity and accelerating aging-associated tissue damage. Tissue taurine depletion in taurine transporter knockout (TauTKO mouse was found to shorten lifespan and accelerate skeletal muscle histological and functional defects, including an increase in central nuclei containing myotubes, a reduction in mitochondrial complex 1 activity and an induction in an aging biomarker, Cyclin-dependent kinase 4 inhibitor A (p16INK4a. Tissue taurine depletion also enhances unfolded protein response (UPR, which may be associated with an improvement in protein folding by taurine. Our data reveal that tissue taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding.

  18. Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated With Cardiac and Skeletal Muscle Pathology.

    Science.gov (United States)

    Sato, Yohei; Kobayashi, Hiroshi; Higuchi, Takashi; Shimada, Yohta; Ida, Hiroyuki; Ohashi, Toya

    2016-08-18

    : Pompe disease (PD) is a lysosomal storage disease that is caused by a deficiency of the acid α-glucosidase, which results in glycogen accumulation in the lysosome. The major clinical symptoms of PD include skeletal muscle weakness, respiratory failure, and cardiac hypertrophy. Based on its severity and symptom onset, PD is classified into infantile and late-onset forms. Lysosomal accumulation of glycogen can promote many types of cellular dysfunction, such as autophagic dysfunction, endoplasmic reticulum stress, and abnormal calcium signaling within skeletal muscle. However, the disease mechanism underlying PD cardiomyopathy is not fully understood. Several researchers have shown that PD induced pluripotent stem cell (iPSC)-derived cardiomyocytes successfully replicate the disease phenotype and are useful disease models. We have analyzed the metabolomic profile of late-onset PD iPSC-derived cardiomyocytes and found that oxidative stress and mitochondrial dysfunction are likely associated with cardiac complications. Furthermore, we have validated that these disease-specific changes were also observed in the cardiomyocytes and skeletal muscle of a genetically engineered murine PD model. Oxidative stress may contribute to skeletal muscle and cardiomyocyte dysfunction in PD mice; however, NF-E2-related factor 2 was downregulated in cardiomyocytes and skeletal muscle, despite evidence of oxidative stress. We hypothesized that oxidative stress and an impaired antioxidative stress response mechanism may underlie the molecular pathology of late-onset PD.

  19. Optimizing seeding and culture methods to engineer smooth muscle tissue on biodegradable polymer matrices.

    Science.gov (United States)

    Kim, B S; Putnam, A J; Kulik, T J; Mooney, D J

    1998-01-05

    The engineering of functional smooth muscle (SM) tissue is critical if one hopes to successfully replace the large number of tissues containing an SM component with engineered equivalents. This study reports on the effects of SM cell (SMC) seeding and culture conditions on the cellularity and composition of SM tissues engineered using biodegradable matrices (5 x 5 mm, 2-mm thick) of polyglycolic acid (PGA) fibers. Cells were seeded by injecting a cell suspension into polymer matrices in tissue culture dishes (static seeding), by stirring polymer matrices and a cell suspension in spinner flasks (stirred seeding), or by agitating polymer matrices and a cell suspension in tubes with an orbital shaker (agitated seeding). The density of SMCs adherent to these matrices was a function of cell concentration in the seeding solution, but under all conditions a larger number (approximately 1 order of magnitude) and more uniform distribution of SMCs adherent to the matrices were obtained with dynamic versus static seeding methods. The dynamic seeding methods, as compared to the static method, also ultimately resulted in new tissues that had a higher cellularity, more uniform cell distribution, and greater elastin deposition. The effects of culture conditions were next studied by culturing cell-polymer constructs in a stirred bioreactor versus static culture conditions. The stirred culture of SMC-seeded polymer matrices resulted in tissues with a cell density of 6.4 +/- 0.8 x 10(8) cells/cm3 after 5 weeks, compared to 2.0 +/- 1.1 x 10(8) cells/cm3 with static culture. The elastin and collagen synthesis rates and deposition within the engineered tissues were also increased by culture in the bioreactors. The elastin content after 5-week culture in the stirred bioreactor was 24 +/- 3%, and both the elastin content and the cellularity of these tissues are comparable to those of native SM tissue. New tissues were also created in vivo when dynamically seeded polymer matrices were

  20. Mathematical models based on transfer functions to estimate tissue temperature during RF cardiac ablation in real time.

    Science.gov (United States)

    Alba-Martínez, Jose; Trujillo, Macarena; Blasco-Gimenez, Ramon; Berjano, Enrique

    2012-01-01

    Radiofrequency cardiac ablation (RFCA) has been used to treat certain types of cardiac arrhythmias by producing a thermal lesion. Even though a tissue temperature higher than 50ºC is required to destroy the target, thermal mapping is not currently used during RFCA. Our aim was thus to develop mathematical models capable of estimating tissue temperature from tissue characteristics acquired or estimated at the beginning of the procedure (electrical conductivity, thermal conductivity, specific heat and density) and the applied voltage at any time. Biological tissue was considered as a system with an input (applied voltage) and output (tissue temperature), and so the mathematical models were based on transfer functions relating these variables. We used theoretical models based on finite element method to verify the mathematical models. Firstly, we solved finite element models to identify the transfer functions between the temperature at a depth of 4 mm and a constant applied voltage using a 7Fr and 4 mm electrode. The results showed that the relationships can be expressed as first-order transfer functions. Changes in electrical conductivity only affected the static gain of the system, while specific heat variations produced a change in the dynamic system response. In contrast, variations in thermal conductivity modified both the static gain and the dynamic system response. Finally, to assess the performance of the transfer functions obtained, we conducted a new set of computer simulations using a controlled temperature protocol and considering the temperature dependence of the thermal and electrical conductivities, i.e. conditions closer to those found in clinical use. The results showed that the difference between the values estimated from transfer functions and the temperatures obtained from finite element models was less than 4ºC, which suggests that the proposed method could be used to estimate tissue temperature in real time.

  1. Biphasic Electrical Field Stimulation Aids in Tissue Engineering of Multicell-Type Cardiac Organoids

    Science.gov (United States)

    Chiu, Loraine L.Y.; Iyer, Rohin K.; King, John-Paul

    2011-01-01

    The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence. PMID:18783322

  2. Biphasic electrical field stimulation aids in tissue engineering of multicell-type cardiac organoids.

    Science.gov (United States)

    Chiu, Loraine L Y; Iyer, Rohin K; King, John-Paul; Radisic, Milica

    2011-06-01

    The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence.

  3. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland.

    Science.gov (United States)

    Alves, Susana P; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J B; Almeida, André M

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases.

  4. Comparison of the stable carbon and nitrogen isotopic values of gill and white muscle tissue of fish

    NARCIS (Netherlands)

    Svensson, E.; Freitas, V.; Schouten, S.; Middelburg, J.J.; van der Veer, H.W.; Sinninghe Damsté, J.S.

    2014-01-01

    The potential use of stable carbon and nitrogen isotope ratios (δ13C, δ15N) of fish gills for studies on fish feeding ecology was evaluated by comparing the δ13C and δ15N of gill tissue with the more commonly used white muscle tissue. To account for the effect of lipid content on the δ13C signatures

  5. Comparison of the stable carbon and nitrogen isotopic values of gill and white muscle tissue of fish

    NARCIS (Netherlands)

    Svensson, E.; Freitas, V.; Schouten, S.; Middelburg, J.J.; van der Veer, H.W.; Sinninghe Damsté, J.S.

    2014-01-01

    The potential use of stable carbon and nitrogen isotope ratios (d13C, d15N) of fish gills for studies on fish feeding ecology was evaluated by comparing the d13C and d15N of gill tissue with the more commonly used white muscle tissue. To account for the effect of lipid content on the d13C signatures

  6. Biochemical and biomolecular aspects of oxidative stress due to acute and severe hypoxia in human muscle tissue.

    Science.gov (United States)

    Corbucci, G G; Sessego, R; Velluti, C; Salvi, M

    1995-01-01

    Mitochondrial oxidative stress was investigated in severe and acute hypoxia and in reperfusion applied to human muscle tissues. The biochemical and biomolecular relationship between the response of the respiratory-chain enzymic complexes and the metabolism of specific hypoxia stress proteins (HSP) suggest an adaptive mechanism which antagonizes the oxidative damage due to acute and severe tissue hypoxia.

  7. Mechanically relevant consequences of the composite laminate-like design of the abdominal wall muscles and connective tissues.

    Science.gov (United States)

    Brown, Stephen H M

    2012-05-01

    Together, three abdominal wall muscles (external oblique, internal oblique and transversus abdominis) form a tightly bound muscular sheet that has been likened to a composite-laminate structure. Previous work has demonstrated the ability of force generated by these three muscles to be passed between one another through connective tissue linkages. Muscle fibres in each muscle are obliquely oriented with respect to its neighbouring muscles. It is proposed here is that this unique morphology of the abdominal wall muscles functions, through the application of constraining forces amongst the muscles, to increase force- and stiffness-generating capabilities. This paper presents a mathematical formulation of the stress-strain relationship for a transversely isotropic fibrous composite, and establishes a strengthening and stiffening effect when stress can be transferred between the fibrous layers. Application of empirical mechanical properties to this formulation demonstrates this effect for the abdominal wall muscles and, in greater proportion, for the anterior aponeurosis of the abdominal wall. This has implications for increasing the stiffness and passive load bearing ability of the abdominal wall muscles, and has the potential to modulate the whole muscle force-length and force-velocity relationships during contraction.

  8. The Effects of Environmental Factors on Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells and Esophagus Tissues Engineering

    DEFF Research Database (Denmark)

    Wang, Fang

    Adipose-derived stem cells (ASCs) are increasingly being used for regenerative medicine and tissue engineering. Smooth muscle cells (SMCs) can be differentiated from ASCs. Oxygen is a key factor influencing the stem cell differentiation. Tissue engineered esophagus has been a preferred solution...... of esophagus was studied. Our results showed that both SMCs and ASCs could attach on the porcine esophageal acellular matrix (EAM) scaffold in vitro after 24 hours and survive until 7 days. Thus ASCs might be a substitute for SMCs in the construction of tissue engineered esophageal muscle layer....

  9. Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

    DEFF Research Database (Denmark)

    Carey, A.; Wolsk, Emil; Bruce, C.;

    2006-01-01

    was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR. Methods  Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset...... (PPARGC1A), carnitine palmitoyltransferase 1B and solute carrier family 2 (facilitated glucose transporter), member 4 (formerly known as glucose transporter 4/GLUT4), was higher in adipose tissue, but lower in skeletal muscle of diabetic patients than in that of control subjects. In addition, uncoupling...

  10. Predicting Effects of Tropomyosin Mutations on Cardiac Muscle Contraction through Myofilament Modeling

    Directory of Open Access Journals (Sweden)

    Lorenzo Rakesh Sewanan

    2016-10-01

    Full Text Available Point mutations to the human gene TPM1 have been implicated in the development of both hypertrophic and dilated cardiomyopathies. Such observations have led to studies investigating the link between single residue changes and the biophysical behavior of the tropomyosin molecule. However, the degree to which these molecular perturbations explain the performance of intact sarcomeres containing mutant tropomyosin remains uncertain. Here, we present a modeling approach that integrates various aspects of tropomyosin’s molecular properties into a cohesive paradigm representing their impact on muscle function. In particular, we considered the effects of tropomyosin mutations on (1 persistence length, (2 equilibrium between thin filament blocked and closed regulatory states, and (3 the crossbridge duty cycle. After demonstrating the ability of the new model to capture Ca-dependent myofilament responses during both dynamic and steady-state activation, we used it to capture the effects of hypertrophic cardiomyopathy (HCM related E180G and D175N mutations on skinned myofiber mechanics. Our analysis indicates that the fiber-level effects of the two mutations can be accurately described by a combination of changes to the three tropomyosin properties represented in the model. Subsequently, we used the model to predict mutation effects on muscle twitch. Both mutations led to increased twitch contractility as a consequence of diminished cooperative inhibition between thin filament regulatory units. Overall, simulations suggest that a common twitch phenotype for HCM-linked tropomyosin mutations includes both increased contractility and elevated diastolic tension.

  11. Myosin types and fiber types in cardiac muscle. II. Atrial myocardium.

    Science.gov (United States)

    Gorza, L; Sartore, S; Schiaffino, S

    1982-12-01

    Antibodies were produced against myosins isolated from the left atrial myocardium (anti-bAm) and the left ventricular myocardium (anti-bVm) of the bovine heart. Cross-reactive antibodies were removed by cross-absorption. Absorbed anti-bAm and anti-bVm were specific for the myosin heavy chains when tested by enzyme immunoassay combined with SDS gel electrophoresis. Indirect immunofluorescence was used to determine the reactivity of atrial muscle fibers to the two antibodies. Three populations of atrial muscle fibers were distinguished in the bovine heart: (a) fibers reactive with anti-bAm and unreactive with anti-bVm, like most fibers in the left atrium; (b) fibers reactive with both antibodies, especially numerous in the right atrium; (c) fibers reactive with anti-bVm and unreactive with anti-bAm, present only in the interatrial septum and in specific regions of the right atrium, such as the crista terminalis. These findings can be accounted for by postulating the existence of two distinct types of atrial myosin heavy chains, one of which is antigenically related to ventricular myosin. The tendency for fibers labeled by anti-bVm to occur frequently in bundles and their preferential distribution in the crista terminalis, namely along one of the main conduction pathways between the sinus node and the atrioventricular node, and in the interatrial septum, where different internodal tracts are known to converge, suggests that these fibers may be specialized for faster conduction.

  12. Application of exogenous enzymes to beef muscle of high and low-connective tissue.

    Science.gov (United States)

    Sullivan, G A; Calkins, C R

    2010-08-01

    Exogenous enzymes tenderize meat through proteolysis. Triceps brachii and Supraspinatus were randomly assigned to the seven enzyme treatments, papain, ficin, bromelain, homogenized fresh ginger, Bacillus subtilis protease, and two Aspergillus oryzae proteases or control to determine the extent of tenderization (Warner-Bratzler shear and sensory evaluation) and mode of action (myofibrillar or collagen degradation). Sensory evaluation showed improvement (P<0.0009) for tenderness and connective tissue component and all except ginger had a lower shear force than the control (P<0.003). Ginger produced more off-flavor than all other treatments (P<0.0001). Only papain increased soluble collagen (P<0.0001). Control samples were only significantly less than ficin for water soluble (P=0.0002) and A. oryzae concentrate for salt soluble proteins (P=0.0148). All enzyme treatments can increase tenderness via myofibrillar and collagenous protein degradation with no difference among high and low-connective tissue muscles.

  13. On the Automated Segmentation of Epicardial and Mediastinal Cardiac Adipose Tissues Using Classification Algorithms.

    Science.gov (United States)

    Rodrigues, Érick Oliveira; Cordeiro de Morais, Felipe Fernandes; Conci, Aura

    2015-01-01

    The quantification of fat depots on the surroundings of the heart is an accurate procedure for evaluating health risk factors correlated with several diseases. However, this type of evaluation is not widely employed in clinical practice due to the required human workload. This work proposes a novel technique for the automatic segmentation of cardiac fat pads. The technique is based on applying classification algorithms to the segmentation of cardiac CT images. Furthermore, we extensively evaluate the performance of several algorithms on this task and discuss which provided better predictive models. Experimental results have shown that the mean accuracy for the classification of epicardial and mediastinal fats has been 98.4% with a mean true positive rate of 96.2%. On average, the Dice similarity index, regarding the segmented patients and the ground truth, was equal to 96.8%. Therfore, our technique has achieved the most accurate results for the automatic segmentation of cardiac fats, to date.

  14. Staphylococcus aureus Panton-Valentine leukocidin contributes to inflammation and muscle tissue injury.

    Directory of Open Access Journals (Sweden)

    Ching Wen Tseng

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA threatens public health worldwide, and epidemiologic data suggest that the Panton-Valentine Leukocidin (PVL expressed by most CA-MRSA strains could contribute to severe human infections, particularly in young and immunocompetent hosts. PVL is proposed to induce cytolysis or apoptosis of phagocytes. However, recent comparisons of isogenic CA-MRSA strains with or without PVL have revealed no differences in human PMN cytolytic activity. Furthermore, many of the mouse studies performed to date have failed to demonstrate a virulence role for PVL, thereby provoking the question: does PVL have a mechanistic role in human infection? In this report, we evaluated the contribution of PVL to severe skin and soft tissue infection. We generated PVL mutants in CA-MRSA strains isolated from patients with necrotizing fasciitis and used these tools to evaluate the pathogenic role of PVL in vivo. In a model of necrotizing soft tissue infection, we found PVL caused significant damage of muscle but not the skin. Muscle injury was linked to induction of pro-inflammatory chemokines KC, MIP-2, and RANTES, and recruitment of neutrophils. Tissue damage was most prominent in young mice and in those strains of mice that more effectively cleared S. aureus, and was not significant in older mice and mouse strains that had a more limited immune response to the pathogen. PVL mediated injury could be blocked by pretreatment with anti-PVL antibodies. Our data provide new insights into CA-MRSA pathogenesis, epidemiology and therapeutics. PVL could contribute to the increased incidence of myositis in CA-MRSA infection, and the toxin could mediate tissue injury by mechanisms other than direct killing of phagocytes.

  15. Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program

    Directory of Open Access Journals (Sweden)

    Bárbara Maria Hermes

    2015-08-01

    Full Text Available Abstract Objective: To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program. Methods: A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II cardiac rehabilitation program: inspiratory muscle training program associated with combined training (aerobic and resistance group (GCR + IMT, n=12 and combined training with respiratory exercises group (GCR, n=12, over a period of 12 weeks, with two sessions per week. Before and after intervention, the following measurements were obtained: maximal inspiratory and expiratory pressures (PImax and PEmax, peak oxygen consumption (peak VO2 and quality of life scores. Data were compared between pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student's t-test, except the categorical variables, which were compared using the Chi-square test. Values of P<0.05 were considered statistically significant. Results: Compared to GCR, the GCR + IMT group showed larger increments in PImax (P<0.001, PEmax (P<0.001, peak VO2 (P<0.001 and quality of life scores (P<0.001. Conclusion: The present study demonstrated that the addition of inspiratory muscle training, even when applied for a short period, may potentiate the effects of combined aerobic and resistance training, becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation.

  16. Three dimensional graphene scaffold for cardiac tissue engineering and in-situ electrical recording.

    Science.gov (United States)

    Ameri, S K; Singh, P K; D'Angelo, R; Stoppel, W; Black, L; Sonkusale, S R

    2016-08-01

    In this paper, we present a three-dimensional graphene foam made of few layers of CVD grown graphene as a scaffold for growing cardiac cells and recording their electrical activity. Our results show that graphene foam not only provides an excellent extra-cellular matrix (ECM) for the culture of such electrogenic cells but also enables recording of its extracellular electrical activity in-situ. Recording is possible due to graphene's excellent conductivity. In this paper, we present our results on the fabrication of the graphene scaffold and initial studies on the culture of cardiac cell lines such as HL-1 and recording of their real-time electrical activity.

  17. The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle

    DEFF Research Database (Denmark)

    Enevoldsen, L H; Stallknecht, B; Langfort, J

    2001-01-01

    1. Adrenaline-stimulated lipolysis in adipose tissue may increase with training. The rate-limiting step in adipose tissue lipolysis is catalysed by the enzyme hormone-sensitive lipase (HSL). We studied the effect of exercise training on the activity of the total and the activated form of HSL......, n = 12) or sedentary (S, n = 12). Then RE and ME adipose tissue and the EDL and soleus muscles were incubated for 20 min with 4.4 microM adrenaline. 3. HSL enzyme activities in adipose tissue were higher in T compared with S rats. Furthermore, in RE adipose tissue, training also doubled HSL protein...... not differ between T and S rats (P > 0.05). 4. In conclusion, training increased the amount of HSL and the sensitivity of HSL to stimulation by adrenaline in intra-abdominal adipose tissue, the extent of the change differing between anatomical locations. In contrast, in skeletal muscle the amount of HSL...

  18. Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

    Energy Technology Data Exchange (ETDEWEB)

    Samnick, Samuel E-mail: rassam@uniklinik-saarland.de; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

    2004-05-01

    In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the {sup 99m}Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ({sup 99m}Tc-FBPBAT) with those of the clinically established meta-[{sup 123}I]iodobenzylguanidine ({sup 123}I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various {alpha}- and {beta}-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of {sup 99m}Tc-FBPBAT and {sup 123}I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, {sup 99m}Tc-FBPBAT showed the higher uptake, relative to {sup 123}I-MIBG, at any given cell concentration. The cellular uptake of {sup 99m}Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the {sup 123}I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of {sup 123}I-MIBG is mediated by the uptake-I carrier, whereas {alpha}{sub 1}- and {beta}{sub 1}-adrenoceptors were predominantly involved in the uptake of {sup 99m}Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that {sup 99m}Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with {sup 123}I

  19. Stem Cell Differentiation Toward the Myogenic Lineage for Muscle Tissue Regeneration: A Focus on Muscular Dystrophy.

    Science.gov (United States)

    Ostrovidov, Serge; Shi, Xuetao; Sadeghian, Ramin Banan; Salehi, Sahar; Fujie, Toshinori; Bae, Hojae; Ramalingam, Murugan; Khademhosseini, Ali

    2015-12-01

    Skeletal muscle tissue engineering is one of the important ways for regenerating functionally defective muscles. Among the myopathies, the Duchenne muscular dystrophy (DMD) is a progressive disease due to mutations of the dystrophin gene leading to progressive myofiber degeneration with severe symptoms. Although current therapies in muscular dystrophy are still very challenging, important progress has been made in materials science and in cellular technologies with the use of stem cells. It is therefore useful to review these advances and the results obtained in a clinical point of view. This article focuses on the differentiation of stem cells into myoblasts, and their application in muscular dystrophy. After an overview of the different stem cells that can be induced to differentiate into the myogenic lineage, we introduce scaffolding materials used for muscular tissue engineering. We then described some widely used methods to differentiate different types of stem cell into myoblasts. We highlight recent insights obtained in therapies for muscular dystrophy. Finally, we conclude with a discussion on stem cell technology. We discussed in parallel the benefits brought by the evolution of the materials and by the expansion of cell sources which can differentiate into myoblasts. We also discussed on future challenges for clinical applications and how to accelerate the translation from the research to the clinic in the frame of DMD.

  20. Fatty acid composition of muscle and adipose tissues of organic and conventional Blanca Andaluza suckling kids

    Directory of Open Access Journals (Sweden)

    F. De la Vega

    2013-01-01

    Full Text Available Interest in the preservation of autochthonous breeds such as the Blanca Andaluza goat (meat breed, raised under grazing-based management, has recently increased among Spanish farmers. A study of the possibilities of transformation to organic production needs to analyze the quality of their products. The aim of this study was to evaluate the fatty acid (FA composition of muscle and adipose tissues of Blanca Andaluza goat kids under organic and conventional grazing–based management system. Twenty-four twin kids (12 males, 12 females were selected from each system. The FA profile was determined in the longissimus thoracis muscle, kidney and pelvic fat. The percentages of C17:0, C17:1, C20:1, C20:4 n-6, C22:2 and several n-3 FAs were higher in organic meat; C12:0, C18:1 trans-11, CLA and C20:5 n-3 were lower in organic meat. The fat depots from the conventional kids showed lower percentages of C12:0, C14:0, C15:0, C17:0, C17:1, C18:3 n-3 and atherogenicity index, and higher percentage of C18:0. In the pelvic fat, the conventional kids displayed lower percentages of C16:0, C18:2 n-6 cis, PUFA, n-3 and n-6 FAs, and greater percentages of C18:1 n-9 cis and MUFA. The conventional kids displayed a major n6:n3 ratio in the kidney fat. No gender differences were observed. Significant differences were found only in some FA percentages of muscle and adipose tissues of suckling kids raised in organic and conventional livestock production systems, and due to this reason conventional grazing–based management farms could easily be transformed into organic production.

  1. Genome-wide association analyses for fatty acid composition in porcine muscle and abdominal fat tissues.

    Directory of Open Access Journals (Sweden)

    Bin Yang

    Full Text Available Fatty acid composition is an important phenotypic trait in pigs as it affects nutritional, technical and sensory quality of pork. Here, we reported a genome-wide association study (GWAS for fatty acid composition in the longissimus muscle and abdominal fat tissues of 591 White Duroc×Erhualian F2 animals and in muscle samples of 282 Chinese Sutai pigs. A total of 46 loci surpassing the suggestive significance level were identified on 15 pig chromosomes (SSC for 12 fatty acids, revealing the complex genetic architecture of fatty acid composition in pigs. Of the 46 loci, 15 on SSC5, 7, 14 and 16 reached the genome-wide significance level. The two most significant SNPs were ss131535508 (P = 2.48×10(-25 at 41.39 Mb on SSC16 for C20∶0 in abdominal fat and ss478935891 (P = 3.29×10(-13 at 121.31 Mb on SSC14 for muscle C18∶0. A meta-analysis of GWAS identified 4 novel loci and enhanced the association strength at 6 loci compared to those evidenced in a single population, suggesting the presence of common underlying variants. The longissimus muscle and abdominal fat showed consistent association profiles at most of the identified loci and distinct association signals at several loci. All loci have specific effects on fatty acid composition, except for two loci on SSC4 and SSC7 affecting multiple fatness traits. Several promising candidate genes were found in the neighboring regions of the lead SNPs at the genome-wide significant loci, such as SCD for C18∶0 and C16∶1 on SSC14 and ELOVL7 for C20∶0 on SSC16. The findings provide insights into the molecular basis of fatty acid composition in pigs, and would benefit the final identification of the underlying mutations.

  2. Digital image analysis of striated skeletal muscle tissue injury during reperfusion after induced ischemia

    Science.gov (United States)

    Rosero Salazar, Doris Haydee; Salazar Monsalve, Liliana

    2015-01-01

    Conditions such as surgical procedures or vascular diseases produce arterial ischemia and reperfusion injuries, which generate changes in peripheral tissues and organs, for instance, in striated skeletal muscle. To determine such changes, we conducted an experimental method in which 42 male Wistar rat were selected, to be undergone to tourniquet application on the right forelimb and left hind limb, to induce ischemia during one and three hours, followed by reperfusion periods starting at one hour and it was prolonged up to 32 days. Extensor carpi radialis longus and soleus respectively, were obtained to be processed for histochemical and morphometric analysis. By means of image processing and detection of regions of interest, variations of areas occupied by muscle fibers and intramuscular extracellular matrix (IM-ECM) throughout reperfusion were observed. In extensor carpi radialis longus, results shown reduction in the area occupied by muscle fibers; this change is significant between one hour and three hours ischemia followed by 16 hours, 48 hours and 32 days reperfusión (p˂0.005). To compare only periods of reperfusión that continued to three hours ischemia, were found significant differences, as well. For area occupied by IM-ECM, were identified increments in extensor carpi radialis longus by three hours ischemia and eight to 16 days reperfusion; in soleus, was observed difference by one hour ischemia with 42 hours reperfusion, and three hours ischemia followed by four days reperfusion (p˂0.005). Skeletal muscle develops adaptive changes in longer reperfusion, to deal with induced injury. Descriptions beyond 32 days reperfusion, can determine recovering normal pattern.

  3. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations.

    Science.gov (United States)

    Lalani, Seema R; Liu, Pengfei; Rosenfeld, Jill A; Watkin, Levi B; Chiang, Theodore; Leduc, Magalie S; Zhu, Wenmiao; Ding, Yan; Pan, Shujuan; Vetrini, Francesco; Miyake, Christina Y; Shinawi, Marwan; Gambin, Tomasz; Eldomery, Mohammad K; Akdemir, Zeynep Hande Coban; Emrick, Lisa; Wilnai, Yael; Schelley, Susan; Koenig, Mary Kay; Memon, Nada; Farach, Laura S; Coe, Bradley P; Azamian, Mahshid; Hernandez, Patricia; Zapata, Gladys; Jhangiani, Shalini N; Muzny, Donna M; Lotze, Timothy; Clark, Gary; Wilfong, Angus; Northrup, Hope; Adesina, Adekunle; Bacino, Carlos A; Scaglia, Fernando; Bonnen, Penelope E; Crosson, Jane; Duis, Jessica; Maegawa, Gustavo H B; Coman, David; Inwood, Anita; McGill, Jim; Boerwinkle, Eric; Graham, Brett; Beaudet, Art; Eng, Christine M; Hanchard, Neil A; Xia, Fan; Orange, Jordan S; Gibbs, Richard A; Lupski, James R; Yang, Yaping

    2016-02-01

    The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ∼34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations.

  4. The Effect of Xin Mai Tong Capsules in Protecting Survival Cardiac Muscles of the Patients with Acute Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    Qiu Ruixiang; Feng Jun; Meng Jun

    2005-01-01

    To study the effect of Composite Xin Mai Tong capsules (复方心脉通胶囊 CXMT) in protecting survival cardiac muscles in patients with acute myocardial infarction (AMI) after percutaneous transluminal coronary angioplasty (PTCA) operation. The treatment with Composite XMT capsules started 3 days prior to the operation and continued for a period of 4 weeks; and its effect on the number of segments of nuclide resting ventricular myocardial imaging, the nuclide defect extension score (ES) and nuclide defect severity score (SS),and the level of vascular endothelial growth factor (VEGF) of circulatory blood were determined and compared with that of the control group. More segments originally scored 1 turning to be scored 2 in nuclide imaging were seen in the treatment group than in the control group; and smaller ES and less SS seen in the former than in the latter group (P<0.05). Composite XMT capsules play an active role in myocardial salvage by promoting its metabolism and expression of circulatory VEGF. Its angiogenesis-like action helps establish collateral flow and has a positive role in myocardial salvage.

  5. Modelling the effect of repositioning on the evolution of skeletal muscle damage in deep tissue injury.

    Science.gov (United States)

    Demol, Jan; Deun, Dorien Van; Haex, Bart; Oosterwyck, Hans Van; Sloten, Jos Vander

    2013-04-01

    Deep tissue injury (DTI) is a localized area of tissue necrosis that originates in the subcutaneous layers under an intact skin and tends to develop when soft tissue is compressed for a prolonged period of time. In clinical practice, DTI is particularly common in bedridden patients and remains a serious issue in todays health care. Repositioning is generally considered to be an effective preventive measure of pressure ulcers. However, limited experimental research and no computational studies have been undertaken on this method. In this study, a methodology was developed to evaluate the influence of different repositioning intervals on the location, size and severity of DTI in bedridden patients. The spatiotemporal evolution of compressive stresses and skeletal muscle viability during the first 48 h of DTI onset was simulated for repositioning schemes in which a patient is turned every 2, 3, 4 or 6 h. The model was able to reproduce important experimental findings, including the morphology and location of DTI in human patients as well as the discrepancy between the internal tissue loads and the contact pressure at the interface with the environment. In addition, the model indicated that the severity and size of DTI were reduced by shortening the repositioning intervals. In conclusion, the computational framework presented in this study provides a promising modelling approach that can help to objectively select the appropriate repositioning scheme that is effective and efficient in the prevention of DTI.

  6. Monitoring late radiation damage in normal muscle tissue with electrical impedance spectroscopy

    Science.gov (United States)

    Osterman, Kendra Sunshine

    During radiation treatment for cancer, normal tissue will be exposed to radiation and it is the response of this tissue and the risk of complications that limits the prescribed dose and the efficacy of treatment. The response to radiation exposure is dose, time and tissue-type dependent and has been studied extensively in animal and human systems. However, there remains significant heterogeneity among individuals. Systematic and quantitative monitoring of tissue response with electrical impedance spectroscopy (EIS) might providing insight into early warning signs of late effects which could be used to alter the course of therapy on an individual patient basis. The implementation of EIS in three clinically relevant radiation settings is described. A kilovolt unit (orthovoltage, x-ray), a linear accelerator (x-ray), and an implantable radionuclide source (high dose rate, iridium-192 seed) were employed for the irradiation of muscle in the hind leg of rats. Doses of 70 Gy, 90 Gy, and 150 Gy were delivered with orthovoltage, nominal doses of 70 and 90 Gy which translate to doses of approximately 50 and 63 Gy at a 5mm distance from the center were employed with the linear accelerator, and doses of 26 and 52 Gy, at 5mm, were employed with the HDR system. The responses were monitored from 1--4 months post-irradiation. In all cases, EIS was capable of detecting a dose and time response, suggesting that EIS may indeed have a role to play in three of the most common irradiation procedures.

  7. Exercise and Type 2 Diabetes Mellitus : Changes in Tissue-specific Fat Distribution and Cardiac Function

    NARCIS (Netherlands)

    Jonker, Jacqueline T.; de Mol, Pieter; de Vries, Suzanna T.; Widya, Ralph L.; Hammer, Sebastiaan; van Schinkel, Linda D.; van der Meer, Rutger W.; Gans, Rijk O. B.; Webb, Andrew G.; Kan, Hermien E.; de Koning, Eelco J. P.; Bilo, Henk J. G.; Lamb, Hildo J.

    2013-01-01

    Purpose: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Materials and Methods: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics

  8. alpha-Smooth muscle actin-expressing cells and lubricin in periprosthetic tissue.

    Science.gov (United States)

    Funakoshi, Tadanao; Martin, Scott D; Wolf, Bryce T; Schmid, Thomas M; Thornhill, Thomas S; Spector, Myron

    2010-05-01

    The objective of the study was to evaluate the distributions of (1) cells expressing the contractile actin isoform, alpha-smooth muscle actin (alpha-SMA) and (2) a lubricating and antiadhesion glycoprotein, lubricin, in the tissue around loose joint replacement prostheses in human subjects. Periprostehtic tissue resected at revision arthroplasty of noncemented glenoid components of total shoulder arthroplasties was obtained from 10 patients. Samples of periprosthetic tissue were stained with monoclonal antibodies to alpha-SMA and lubricin. alpha-SMA was found in cells, principally of fibroblast morphology, in many of the fields of view (FOVs) in samples from all patients. Moderate correlations were observed between the percentage of FOVs containing alpha-SMA-expressing cells and the percentages of FOVs containing polyethylene (R(2) = 0.79) and metallic (R(2) = 0.75) particles. Lubricin was identified (1) as a discrete layer on the surface, (2) within the extracellular matrix, and (3) intracellularly. These lubricin-positive features were found in samples from all patients. Strong correlations were noted between the percentages of FOVs with matrix and intracellular lubricin staining (R(2) = 0.97) and between the percentages of FOVs with surface and matrix staining for lubricin (R(2) = 0.96). Having established the presence of alpha-SMA and lubricin in periprosthetic tissue, hypotheses regarding their role in the development and persistence of periprosthetic tissue can be synthesized for future study: for example, alpha-SMA-enabled contracture of the fibrous periprosthetic tissue results in its densification, and lubricin-coated surfaces interfere with integrative repair processes necessary for resorption and remodeling.

  9. Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes

    Science.gov (United States)

    Banerjee, Ranjan; He, Jun; Spaniel, Carolyn; Quintana, Megan T.; Wang, Zhongjing; Bain, James; Newgard, Christopher B.; Muehlbauer, Michael J.; Willis, Monte S.

    2017-01-01

    The muscle-specific ubiquitin ligases MuRF1, MuRF2, MuRF3 have been reported to have overlapping substrate specificities, interacting with each other as well as proteins involved in metabolism and cardiac function. In the heart, all three MuRF family proteins have proven critical to cardiac responses to ischemia and heart failure. The non-targeted metabolomics analysis of MuRF1-/-, MuRF2-/-, and MuRF3-/- hearts was initiated to investigate the hypothesis that MuRF1, MuRF2, and MuRF3 have a similarly altered metabolome, representing alterations in overlapping metabolic processes. Ventricular tissue was flash frozen and quantitatively analyzed by GC/MS using a library built upon the Fiehn GC/MS Metabolomics RTL Library. Non-targeted metabolomic analysis identified significant differences (via VIP statistical analysis) in taurine, myoinositol, and stearic acid for the three MuRF-/- phenotypes relative to their matched controls. Moreover, pathway enrichment analysis demonstrated that MuRF1-/- had significant changes in metabolite(s) involved in taurine metabolism and primary acid biosynthesis while MuRF2-/- had changes associated with ascorbic acid/aldarate metabolism (via VIP and t-test analysis vs. sibling-matched wildtype controls). By identifying the functional metabolic consequences of MuRF1, MuRF2, and MuRF3 in the intact heart, non-targeted metabolomics analysis discovered common pathways functionally affected by cardiac MuRF family proteins in vivo. These novel metabolomics findings will aid in guiding the molecular studies delineating the mechanisms that MuRF family proteins regulate metabolic pathways. Understanding these mechanism is an important key to understanding MuRF family proteins' protective effects on the heart during cardiac disease.

  10. Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.

    Science.gov (United States)

    Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

    2012-08-01

    Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness.

  11. Insulin-resistant subjects have normal angiogenic response to aerobic exercise training in skeletal muscle, but not in adipose tissue

    OpenAIRE

    Walton, R. Grace; Finlin, Brian S.; Mula, Jyothi; Long, Douglas E.; Zhu, Beibei; Fry, Christopher S; Westgate, Philip M.; Lee, Jonah D.; Bennett, Tamara; Kern, Philip A.; Peterson, Charlotte A.

    2015-01-01

    Reduced vessel density in adipose tissue and skeletal muscle is associated with obesity and may result in decreased perfusion, decreased oxygen consumption, and insulin resistance. In the presence of VEGFA, Angiopoietin-2 (Angpt2) and Angiopoietin-1 (Angpt1) are central determinants of angiogenesis, with greater Angpt2:Angpt1 ratios promoting angiogenesis. In skeletal muscle, exercise training stimulates angiogenesis and modulates transcription of VEGFA, Angpt1, and Angpt2. However, it remain...

  12. New method for determining total calcium content in tissue applied to skeletal muscle with and without calsequestrin

    Science.gov (United States)

    Lamboley, Cédric R.H.; Kake Guena, Sandrine A.; Touré, Fatou; Hébert, Camille; Yaddaden, Louiza; Nadeau, Stephanie; Bouchard, Patrice; Wei-LaPierre, Lan; Lainé, Jean; Rousseau, Eric C.; Frenette, Jérôme; Protasi, Feliciano; Dirksen, Robert T.

    2015-01-01

    We describe a new method for determining the concentration of total Ca in whole skeletal muscle samples ([CaT]WM in units of mmoles/kg wet weight) using the Ca-dependent UV absorbance spectra of the Ca chelator BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). Muscle tissue was homogenized in a solution containing 0.15 mM BAPTA and 0.5% sodium dodecyl sulfate (to permeabilize membranes and denature proteins) and then centrifuged. The solution volume was adjusted so that BAPTA captured essentially all of the Ca. [CaT]WM was obtained with Beer’s law from the absorbance change produced by adding 1 mM EGTA to capture Ca from BAPTA. Results from mouse, rat, and frog muscles were reasonably consistent with results obtained using other methods for estimating total [Ca] in whole muscles and in single muscle fibers. Results with external Ca removed before determining [CaT]WM indicate that most of the Ca was intracellular, indicative of a lack of bound Ca in the extracellular space. In both fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) muscles from mice, [CaT]WM increased approximately linearly with decreasing muscle weight, increasing approximately twofold with a twofold decrease in muscle weight. This suggests that the Ca concentration of smaller muscles might be increased relative to that in larger muscles, thereby increasing the specific force to compensate for the smaller mass. Knocking out the high capacity Ca-binding protein calsequestrin (CSQ) did not significantly reduce [CaT]WM in mouse EDL or soleus muscle. However, in EDL muscles lacking CSQ, muscle weights were significantly lower than in wild-type (WT) muscles and the values of [CaT]WM were, on average, about half the expected WT values, taking into account the above [CaT]WM versus muscle weight relationship. Because greater reductions in [CaT]WM would be predicted in both muscle types, we hypothesize that there is a substantial increase in Ca bound to other sites

  13. Gene Expression Profile of Human Skeletal Muscle and Adipose Tissue of Chinese Han Patients with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    YAN-LI YANG; RUO-LAN XIANG; CHANG YANG; XIAO-JUN LIU; WEN-JUN SHEN; JIN ZUO; YONG-SHENG CHANG; FU-DE FANG

    2009-01-01

    Objective To study the differential patterns of gene expression in skeletal muscle and adipose tissue between type 2 diabetes mellitus (T2DM) patients and healthy subjects using DNA microarray analysis. Methods T2DM patiens were divided into female group, young male group and old male group. DNA microarray analysis and quantitative real-time PCR were carried out to analyze the relation between gene expressions and T2DM. Results The mRNA expression of 298, 578, and 350 genes was changed in the skeletal muscle of diabetes mellitus patients compared with control subjects. The 1320, 1143, and 2847 genes were modified in adipose tissue of the three groups. Among the genes surveyed, the change of 25 and 39 gene transcripts in skeletal muscle and adipose tissue was ≥2 folds. These differentially expressed genes were classified into 15 categories according to their functions. Conclusion New genes are found and T2DM can be prevented or cured.

  14. Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Barillet, Sabrina, E-mail: sabrina.barillet@free.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Larno, Valerie, E-mail: valerie.larno@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Floriani, Magali, E-mail: magali.floriani@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Devaux, Alain, E-mail: alain.devaux@entpe.fr [INRA, EFPA Department, 54280, Champenoux and Environmental Science Laboratory, ENTPE, 69518 Vaulx en Velin cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.fr [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological Protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France)

    2010-11-01

    Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

  15. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    Science.gov (United States)

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3