Science.gov

Sample records for cardiac muscle due

  1. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations

    PubMed Central

    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

    2016-01-01

    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. PMID:26805781

  2. Slow Conduction in Cardiac Muscle

    PubMed Central

    Lieberman, Melvyn; Kootsey, J. Mailen; Johnson, Edward A.; Sawanobori, Tohru

    1973-01-01

    Mechanisms of slow conduction in cardiac muscle are categorized and the most likely identified. Propagating action potentials were obtained experimentally from a synthetically grown strand of cardiac muscle (around 50 μm by 30 mm) and theoretically from a one-dimensional cable model that incorporated varying axial resistance and membrane properties along its length. Action potentials propagated at about 0.3 m/s, but in some synthetic strands there were regions (approximately 100 μm in length) where the velocity decreased to 0.002 m/s. The electrophysiological behavior associated with this slow conduction was similar to that associated with slow conduction in naturally occurring cardiac muscle (notches, Wenckebach phenomena, and block). Theoretically, reasonable changes in specific membrane capacitance, membrane activity, and various changes in geometry were insufficient to account for the observed slow conduction velocities. Conduction velocities as low as 0.009 m/s, however, could be obtained by increasing the resistance (ri) of connections between the cells in the cable; velocities as low as 0.0005 m/s could be obtained by a further increase in ri made possible by a reduction in membrane activity by one-fourth, which in itself decreased conduction velocity by only a factor of 1/1.4. As a result of these findings, several of the mechanisms that have been postulated, previously, are shown to be incapable of accounting for delays such as those which occur in the synthetic strand as well as in the atrioventricular (VA) node. ImagesFIGURE 1FIGURE 2FIGURE 3FIGURE 4 PMID:4709519

  3. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    PubMed

    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. PMID:26826406

  4. Cardiac assistance from skeletal muscle: a reappraisal.

    PubMed

    Salmons, Stanley

    2009-02-01

    Cardiac assistance from skeletal muscle offers an attractive surgical solution to the problem of end-stage heart failure, yet it is widely regarded as a failed approach. I argue here that this is an outdated assessment. Systematic progress has been made over the last 25 years in understanding the relevant basic science. In the light of these advances we should be reconsidering the place of skeletal muscle assist in the surgical armamentarium. PMID:18954996

  5. Cardiac Muscle Studies with Rat Ventricular Strips

    ERIC Educational Resources Information Center

    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…

  6. Stimulating Cardiac Muscle by Light: Cardiac Optogenetics by Cell Delivery

    PubMed Central

    Jia, Zhiheng; Valiunas, Virginijus; Lu, Zongju; Bien, Harold; Liu, Huilin; Wang, Hong-Zhang; Rosati, Barbara; Brink, Peter R.; Cohen, Ira S.; Entcheva, Emilia

    2011-01-01

    Background After the recent cloning of light-sensitive ion channels and their expression in mammalian cells, a new field, optogenetics, emerged in neuroscience, allowing for precise perturbations of neural circuits by light. However, functionality of optogenetic tools has not been fully explored outside neuroscience; and a non-viral, non-embryogenesis based strategy for optogenetics has not been shown before. Methods and Results We demonstrate the utility of optogenetics to cardiac muscle by a tandem cell unit (TCU) strategy, where non-excitable cells carry exogenous light-sensitive ion channels, and when electrically coupled to cardiomyocytes, produce optically-excitable heart tissue. A stable channelrhodopsin2 (ChR2) expressing cell line was developed, characterized and used as a cell delivery system. The TCU strategy was validated in vitro in cell pairs with adult canine myocytes (for a wide range of coupling strengths) and in cardiac syncytium with neonatal rat cardiomyocytes. For the first time, we combined optical excitation and optical imaging to capture light-triggered muscle contractions and high-resolution propagation maps of light-triggered electrical waves, found to be quantitatively indistinguishable from electrically-triggered waves. Conclusions Our results demonstrate feasibility to control excitation and contraction in cardiac muscle by light using the TCU approach. Optical pacing in this case uses less energy, offers superior spatiotemporal control, remote access and can serve not only as an elegant tool in arrhythmia research, but may form the basis for a new generation of light-driven cardiac pacemakers and muscle actuators. The TCU strategy is extendable to (non-viral) stem cell therapy and is directly relevant to in vivo applications. PMID:21828312

  7. Pediatric Cardiac Arrest Due to Trauma.

    PubMed

    Kjellemo, Hugo; Hansen, Andreas E; Øines, Dennis A; Nilsen, Thor O; Wik, Lars

    2016-01-01

    Survival from pediatric cardiac arrest due to trauma has been reported to be 0.0%-8.8%. Some argue that resuscitation efforts in the case of trauma-related cardiac arrests are futile. We describe a successful outcome in the case of a child who suffered cardiac arrest caused by external traumatic airway obstruction. Our case illustrates how to deal with pediatric traumatic cardiac arrests in an out-of-hospital environment. It also illustrates how good clinical treatment in these situations may be supported by correct treatment after hospital admission when it is impossible to ventilate the patient to provide sufficient oxygen delivery to vital organs. This case relates to a lifeless child of 3-5 years, blue, and trapped by an electrically operated garage door. The first ambulance arrived to find several men trying to bend the frame and the door apart in order to extricate the child, who was hanging in the air with head and neck squeezed between the horizontally-moving garage door and the vertical door frame. One paramedic found a car jack and used it to push the door and the frame apart, allowing the lifeless child to be extricated. Basic life support was then initiated. Intubation was performed by the anesthesiologist without drugs. With FiO2 1.0 the first documented SaO2 was <50%. Restoration of Spontaneous Circulation was achieved after thirty minutes, and she was transported to the hospital. After a few hours she was put on venous-arterial ECMO for 5.5 days and discharged home after two months. Outpatient examinations during the rest of 2013 were positive, and the child found not to be suffering from any injuries, either physical or mental. The last follow-up in October 2014 demonstrated she had made a 100% recovery and she started school in August 2014. PMID:26930137

  8. The phosphorylation of troponin I from cardiac muscle.

    PubMed Central

    Cole, H A; Perry, S V

    1975-01-01

    1. Troponin I isolated from fresh cardiac muscle by affinity chromatography contains about 1.9 mol of covalently bound phosphate/mol. Similar preparations of white-skeletal-muscle troponin I contain about 0.5 mol of phosphate/mol. 2. A 3':5'-cyclic AMP-dependent protein kinase and a protein phosphatase are associated with troponin isolated from cardiac muscle. 3. Bovine cardiac 3':5'-cyclic AMP-dependent protein kinase catalyses the phosphorylation of cardiac troponin I 30 times faster than white-skeletal-muscle troponin I. 4. Troponin I is the only component of cardiac troponin phosphorylated at a significant rate by the endogenous or a bovine cardiac 3':5'-cyclic AMP-dependent protein kinase. 5. Phosphorylase kinase catalyses the phosphorylation of cardiac troponin I at similar or slightly faster rates than white-skeletal-muscle troponin I. 6. Troponin C inhibits the phosphorylation of cardiac and skeletal troponin I catalysed by phosphorylase kinase and the phosphorylation of white skeletal troponin I catalysed by 3':5'-cyclic AMP-dependent protein kinase; the phosphorylation of cardiac troponin I catalysed by the latter enzyme is not inhibited. Images Fig. 1. PMID:173290

  9. A viscoplastic model for the active component in cardiac muscle.

    PubMed

    Rubin, M B

    2016-08-01

    The HMK model (Hunter et al. in Prog Biophys Mol Biol 69:289-331, 1998) proposes mechanobiological equations for the influence of intracellular calcium concentration [Formula: see text] on the evolution of bound calcium concentration [Formula: see text] and the tropomyosin kinetics parameter z, which model processes in the active component of the tension in cardiac muscle. The inelastic response due to actin-myosin crossbridge kinetics is modeled in the HMK model with a function Q that depends on the history of the rate of total stretch of the muscle fiber. Here, an alternative model is proposed which models the active component of the muscle fiber as a viscoplastic material. In particular, an evolution equation is proposed for the elastic stretch [Formula: see text] in the active component. Specific forms of the constitutive equations are proposed and used to match experimental data. The proposed viscoplastic formulation allows for separate modeling of three processes: the high rate deactivation of crossbridges causing rapid reduction in active tension; the high but lower rate reactivation of crossbridges causing recovery of active tension; and the low rate relaxation effects characterizing the Hill model of muscles. PMID:26476735

  10. Muscle ring finger 1 mediates cardiac atrophy in vivo.

    PubMed

    Willis, Monte S; Rojas, Mauricio; Li, Luge; Selzman, Craig H; Tang, Ru-Hang; Stansfield, William E; Rodriguez, Jessica E; Glass, David J; Patterson, Cam

    2009-04-01

    Pathological cardiac hypertrophy, induced by various etiologies such as high blood pressure and aortic stenosis, develops in response to increased afterload and represents a common intermediary in the development of heart failure. Understandably then, the reversal of pathological cardiac hypertrophy is associated with a significant reduction in cardiovascular event risk and represents an important, yet underdeveloped, target of therapeutic research. Recently, we determined that muscle ring finger-1 (MuRF1), a muscle-specific protein, inhibits the development of experimentally induced pathological; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression. This prompted us to investigate the role of MuRF1 in two independent mouse models of cardiac atrophy: 1) cardiac hypertrophy regression after reversal of transaortic constriction (TAC) reversal and 2) dexamethasone-induced atrophy. Using echocardiographic, histological, and gene expression analyses, we found that upon TAC release, cardiac mass and cardiomyocyte cross-sectional areas in MuRF1(-/-) mice decreased approximately 70% less than in wild type mice in the 4 wk after release. This was in striking contrast to wild-type mice, who returned to baseline cardiac mass and cardiomyocyte size within 4 days of TAC release. Despite these differences in atrophic remodeling, the transcriptional activation of cardiac hypertrophy measured by beta-myosin heavy chain, smooth muscle actin, and brain natriuretic peptide was attenuated similarly in both MuRF1(-/-) and wild-type hearts after TAC release. In the second model, MuRF1(-/-) mice also displayed resistance to dexamethasone-induced cardiac atrophy, as determined by echocardiographic analysis. This study demonstrates, for the first time, that MuRF1 is essential for cardiac atrophy in vivo, both in the setting of therapeutic

  11. Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy

    NASA Technical Reports Server (NTRS)

    Mathur, A. B.; Collinsworth, A. M.; Reichert, W. M.; Kraus, W. E.; Truskey, G. A.

    2001-01-01

    This study evaluated the hypothesis that, due to functional and structural differences, the apparent elastic modulus and viscous behavior of cardiac and skeletal muscle and vascular endothelium would differ. To accurately determine the elastic modulus, the contribution of probe velocity, indentation depth, and the assumed shape of the probe were examined. Hysteresis was observed at high indentation velocities arising from viscous effects. Irreversible deformation was not observed for endothelial cells and hysteresis was negligible below 1 microm/s. For skeletal muscle and cardiac muscle cells, hysteresis was negligible below 0.25 microm/s. Viscous dissipation for endothelial and cardiac muscle cells was higher than for skeletal muscle cells. The calculated elastic modulus was most sensitive to the assumed probe geometry for the first 60 nm of indentation for the three cell types. Modeling the probe as a blunt cone-spherical cap resulted in variation in elastic modulus with indentation depth that was less than that calculated by treating the probe as a conical tip. Substrate contributions were negligible since the elastic modulus reached a steady value for indentations above 60 nm and the probe never indented more than 10% of the cell thickness. Cardiac cells were the stiffest (100.3+/-10.7 kPa), the skeletal muscle cells were intermediate (24.7+/-3.5 kPa), and the endothelial cells were the softest with a range of elastic moduli (1.4+/-0.1 to 6.8+/-0.4 kPa) depending on the location of the cell surface tested. Cardiac and skeletal muscle exhibited nonlinear elastic behavior. These passive mechanical properties are generally consistent with the function of these different cell types.

  12. Fast skeletal muscle troponin T increases the cooperativity of transgenic mouse cardiac muscle contraction

    PubMed Central

    Huang, Qi-Quan; Brozovich, Frank V; Jin, Jian-Ping

    1999-01-01

    To investigate the functional significance of different troponin T (TnT) isoforms in the Ca2+ activation of muscle contraction, transgenic mice have been constructed with a chicken fast skeletal muscle TnT transgene driven by a cardiac α-myosin heavy chain gene promoter. Cardiac muscle-specific expression of the fast skeletal muscle TnT has been obtained with significant myofibril incorporation. Expression of the endogenous cardiac muscle thin filament regulatory proteins, such as troponin I and tropomyosin, was not altered in the transgenic mouse heart, providing an authentic system for the functional characterization of TnT isoforms. Cardiac muscle contractility was analysed for the force vs. Ca2+ relationship in skinned ventricular trabeculae of transgenic mice in comparison with wild-type litter-mates. The results showed unchanged pCa50 values (5.1 ± 0.04 and 5.1 ± 0.1, respectively) but significantly steeper slopes (the Hill coefficient was 2.0 ± 0.2 vs. 1.0 ± 0.2, P < 0.05). The results demonstrate that the structural and functional variation of different TnT isoforms may contribute to the difference in responsiveness and overall cooperativity of the thin filament-based Ca2+ regulation between cardiac and skeletal muscles. PMID:10517814

  13. Prevalence of Rate-Dependent Behaviors in Cardiac Muscle

    NASA Astrophysics Data System (ADS)

    Hall, G. Martin; Bahar, Sonya; Gauthier, Daniel J.

    1999-04-01

    We explore the rate-dependent dynamic response of periodically paced bullfrog (Rana catesbeiana) cardiac muscle. Alternans (2:2 behavior) occur in 35% of animals and 2:1<-->1:1 bistability in 74% of animals. In addition, we observe 2:2<-->2:1 bistablility. We discuss the implications of these results for two map-based models of cardiac dynamics. The high prevalence of bistability suggests that this dynamical behavior must be accounted for in the design of closed-loop feedback protocols to stabilize cardiac dynamics.

  14. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    PubMed Central

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

  15. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle.

    PubMed

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

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

    PubMed

    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. PMID:26795479

  17. Familial cardiac valvulopathy due to filamin A mutation.

    PubMed

    Bernstein, Jonathan A; Bernstein, Daniel; Hehr, Ute; Hudgins, Louanne

    2011-09-01

    We report on the clinical findings in siblings affected by the recently characterized X-linked form of hereditary cardiac valvular dystrophy or cardiac valve disease (OMIM 314400) due to mutations in the FLNA gene and review the literature on this condition. Although FLNA related cardiac valve disease is presumed to be a rare disorder, it is likely underdiagnosed. Several features of this condition may aid in its identification. FLNA related valvular disease can be recognized on the basis of its distinctive inheritance, early age of onset, and frequent multi-valve involvement. PMID:21815255

  18. Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice.

    PubMed

    Spurney, Christopher F; Sali, Arpana; Guerron, Alfredo D; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P; Nagaraju, Kanneboyina

    2011-03-01

    Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmd(mdx)/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

  19. Experimental Control of Cardiac Muscle Alternans

    NASA Astrophysics Data System (ADS)

    Hall, G. Martin; Gauthier, Daniel J.

    2002-05-01

    We demonstrate that alternans in small pieces of in vitro paced bullfrog (Rana Catesbeiana) myocardium can be suppressed by making minute adjustments to the pacing period in response to real time measurements of the action potential duration. Control is possible over a large range of physiological conditions over many animals and the self-referencing control protocol can automatically adjust to changes in the pacing interval. Our results suggest the feasibility of developing low-energy methods for maintaining normal cardiac function.

  20. Cardiac autoimmunity in HIV related heart muscle disease

    PubMed Central

    Currie, P; Goldman, J; Caforio, A; Jacob, A; Baig, M; Brettle, R; Haven, A; Boon, N; McKenna, W

    1998-01-01

    Objective—To assess the frequency of circulating cardiac specific autoantibodies in HIV positive patients with and without echocardiographic evidence of left ventricular dysfunction.
Subjects—74 HIV positive patients including 28 with echocardiographic evidence of heart muscle disease, 52 HIV negative people at low risk of HIV infection, and 14 HIV negative drug users who had all undergone non-invasive cardiac assessment were studied along with a group of 200 healthy blood donors.
Results—Cardiac autoantibodies detected by indirect immunofluorescence (serum dilution 1/10) were more common in the HIV positive patients (15%), particularly the HIV heart muscle disease group (21%), than in HIV negative controls (3.5%) (both p < 0.001). By ELISA (dilution 1/320), abnormal anti-α myosin autoantibody concentrations were found more often in HIV patients with heart muscle disease (43%) than in HIV positive patients with normal hearts (19%) or in HIV negative controls (3%) (p < 0.05 and p < 0.001, respectively). Anti-α myosin autoantibody concentrations were greater in HIV positive patients than in HIV negative controls, regardless of cardiac status ((mean SD) 0.253 (0.155) v 0.170 (0.076); p = 0.003). In particular the mean antibody concentration was higher in the HIV heart muscle disease patients (0.291 (0.160) v 0.170 (0.076); p = 0.001) than in HIV negative controls. On follow up, six subjects with normal echocardiograms but raised autoantibody concentrations had died after a median of 298 days, three with left ventricular abnormalities at necropsy. This compared with a median survival of 536 days for 21 HIV positive patients with normal cardiological and immunological results.
Conclusions—There is an increased frequency of circulating cardiac specific autoantibodies in HIV positive individuals, particularly those with heart muscle disease. The data support a role for cardiac autoimmunity in the pathogenesis of HIV related heart

  1. Transcriptional activation of muscle atrophy promotes cardiac muscle remodeling during mammalian hibernation

    PubMed Central

    Zhang, Yichi; Aguilar, Oscar A.

    2016-01-01

    Background. Mammalian hibernation in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) is characterized by dramatic changes on a physiological and molecular level. During hibernation, mammalian hearts show a propensity to hypertrophy due to the need for increasing contractility to pump colder and more viscous blood. While cardiac hypertrophy is quite often a process characterized by decompensation, the ground squirrel studied is an excellent model of cardiac plasticity and cardioprotection under conditions of hypothermia and ischemia. The forkhead box O (Foxo) family of proteins and myogenin (MyoG) are transcription factors that control protein degradation and muscle atrophy by regulating the expression of the E3 ubiquitin ligases, MAFbx and MuRF1. These ligases are part of the ubiquitin proteasome system by transferring ubiquitin to proteins and targeting these proteins for degradation. Regulation of Foxo1 and 3a occurs through phosphorylation at different residues. The threonine-24 (Thr-24) and serine-319 (Ser-319) residues on Foxo1, and the Thr-32 residue on Foxo3a are phosphorylated by Akt, leading to cytoplasmic localization of Foxo. We propose that the described mechanism contributes to the changes taking place in cardiac muscle throughout hibernation. Methods. Total and phosphorylated protein levels of Foxo1 and Foxo3a, as well as total protein levels of MyoG, MAFbx, and MuRF1, were studied using immunoblotting. Results. Immunoblotting results demonstrated upregulations in Foxo1 and Foxo3a total protein levels (1.3- and 4.5-fold increases relative to euthermic control, for Foxo1 and 3a respectively) during late torpor, and protein levels remained elevated throughout the rest of torpor and at interbout arousal. We also observed decreases in inactive, phosphorylated Foxo1 and 3a proteins during throughout torpor, where levels of p-Foxo1 Ser319 and Thr24, as well as p-Foxo3a Thr32 decreased by at least 45% throughout torpor. MyoG was upregulated only

  2. Transcriptional activation of muscle atrophy promotes cardiac muscle remodeling during mammalian hibernation.

    PubMed

    Zhang, Yichi; Aguilar, Oscar A; Storey, Kenneth B

    2016-01-01

    Background. Mammalian hibernation in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) is characterized by dramatic changes on a physiological and molecular level. During hibernation, mammalian hearts show a propensity to hypertrophy due to the need for increasing contractility to pump colder and more viscous blood. While cardiac hypertrophy is quite often a process characterized by decompensation, the ground squirrel studied is an excellent model of cardiac plasticity and cardioprotection under conditions of hypothermia and ischemia. The forkhead box O (Foxo) family of proteins and myogenin (MyoG) are transcription factors that control protein degradation and muscle atrophy by regulating the expression of the E3 ubiquitin ligases, MAFbx and MuRF1. These ligases are part of the ubiquitin proteasome system by transferring ubiquitin to proteins and targeting these proteins for degradation. Regulation of Foxo1 and 3a occurs through phosphorylation at different residues. The threonine-24 (Thr-24) and serine-319 (Ser-319) residues on Foxo1, and the Thr-32 residue on Foxo3a are phosphorylated by Akt, leading to cytoplasmic localization of Foxo. We propose that the described mechanism contributes to the changes taking place in cardiac muscle throughout hibernation. Methods. Total and phosphorylated protein levels of Foxo1 and Foxo3a, as well as total protein levels of MyoG, MAFbx, and MuRF1, were studied using immunoblotting. Results. Immunoblotting results demonstrated upregulations in Foxo1 and Foxo3a total protein levels (1.3- and 4.5-fold increases relative to euthermic control, for Foxo1 and 3a respectively) during late torpor, and protein levels remained elevated throughout the rest of torpor and at interbout arousal. We also observed decreases in inactive, phosphorylated Foxo1 and 3a proteins during throughout torpor, where levels of p-Foxo1 Ser(319) and Thr(24), as well as p-Foxo3a Thr(32) decreased by at least 45% throughout torpor. MyoG was

  3. Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle.

    PubMed

    Preedy, V R; Patel, V B; Reilly, M E; Richardson, P J; Falkous, G; Mantle, D

    1999-08-01

    setting. In the rat, circulating troponin-T release increases in the presence of ethanol, a mechanism ascribed to free radical mediated damage, as it is prevented with the xanthine oxidase inhibitor and beta-blocker, propranolol. However, whilst propranolol prevents the release of troponin-T, it does not prevent the fall in whole cardiac protein synthesis, suggestive of localized ischemic damage due to ethanol. PMID:10430553

  4. Transplantation of a tissue-engineered human vascularized cardiac muscle.

    PubMed

    Lesman, Ayelet; Habib, Manhal; Caspi, Oren; Gepstein, Amira; Arbel, Gil; Levenberg, Shulamit; Gepstein, Lior

    2010-01-01

    Myocardial regeneration strategies have been hampered by the lack of sources for human cardiomyocytes (CMs) and by the significant donor cell loss following transplantation. We assessed the ability of a three-dimensional tissue-engineered human vascularized cardiac muscle to engraft in the in vivo rat heart and to promote functional vascularization. Human embryonic stem cell-derived CMs alone or with human endothelial cells (human umbilical vein endothelial cells) and embryonic fibroblasts (triculture constructs) were seeded onto biodegradable porous scaffolds. The resulting tissue constructs were transplanted to the in vivo rat heart and formed cardiac tissue grafts. Immunostaining studies for human-specific CD31 and alpha-smooth muscle actin demonstrated the formation of both donor (human) and host (rat)-derived vasculature within the engrafted triculture tissue constructs. Intraventricular injection of fluorescent microspheres or lectin resulted in their incorporation by human-derived vessels, confirming their functional integration with host coronary vasculature. Finally, the number of blood vessels was significantly greater in the triculture tissue constructs (60.3 +/- 8/mm(3), p < 0.05) when compared with scaffolds containing only CMs (39.0 +/- 14.4/mm(3)). In conclusion, a tissue-engineered human vascularized cardiac muscle can be established ex vivo and transplanted in vivo to form stable grafts. By utilizing a multicellular preparation we were able to increase biograft vascularization and to show that the preexisting human vessels can become functional and contribute to tissue perfusion. PMID:19642856

  5. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    PubMed

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located. PMID:26585961

  6. Sarcoglycans in human skeletal muscle and human cardiac muscle: a confocal laser scanning microscope study.

    PubMed

    Anastasi, G; Cutroneo, G; Trimarchi, F; Rizzo, G; Bramanti, P; Bruschetta, D; Fugazzotto, D; Cinelli, M P; Soscia, A; Santoro, G; Favaloro, A

    2003-01-01

    Sarcoglycans are a subcomplex of transmembrane proteins which are part of the dystrophin-glycoprotein complex. They are expressed in the skeletal, cardiac and smooth muscle. Although numerous studies have been conducted on the sarcoglycan subcomplex in skeletal and cardiac muscle, the manner of the distribution and localization of these proteins along the nonjunctional sarcolemma is not clear. We therefore carried out an indirect immunofluorescence study on surgical biopsies of normal human skeletal muscle and of healthy human atrial myocardium biopsies of patients affected by valvulopathy. Our results indicate that, in skeletal muscle, sarcoglycans have a costameric distribution and all colocalize with each other. Only in a few cases did the alpha-sarcoglycan not colocalize with other sarcoglycans. In addition, these glycoproteins can be localized in different fibers either in the regions of the sarcolemma over band I or band A. In cardiac muscle, our results show a costameric distribution of all proteins examined and, unlike in skeletal muscle, they show a constant colocalization of all sarcoglycans with each other, along with a consistent localization of these proteins in the region of the sarcolemma over band I. In our opinion, this situation seems to confirm the hypothesis of a correlation between the region of the sarcolemma occupied by costameric proteins and the metabolic type, fast or slow, of the muscular fibers. These data, besides opening a new line of research in understanding interactions between the sarcoglycans and other transmembrane proteins, could also be extended to skeletal and cardiac muscles affected by neuromuscular and cardiovascular pathologies to understand possible structural alterations. PMID:12566627

  7. In utero Undernutrition Programs Skeletal and Cardiac Muscle Metabolism

    PubMed Central

    Beauchamp, Brittany; Harper, Mary-Ellen

    2016-01-01

    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. PMID:26779032

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

    PubMed Central

    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 on Ca2+ microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle. PMID:21385997

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

    PubMed

    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. PMID:20824529

  10. Hierarchical Internal Variables Reflecting Microstructural Properties: Application to Cardiac Muscle Contraction

    NASA Astrophysics Data System (ADS)

    Engelbrecht, Jüri; Vendelin, Marko; Maugin, Gérard A.

    2000-09-01

    The formalism of internal state variables is proposed for describing the processes of deformation in muscles. Due to the complicated hierarchical microstructure of soft tissues where macroscopic stress states depend upon the sliding of molecules and ion concentrations, the internal variables are switched in successively forming a certain hierarchy. This hierarchy is a general property for complicated materials with different microscopic processes influencing the macroscopic behaviour. Based on that property a novel concept of hierarchical internal variables is defined (up to the knowledge of authors first time) and embedded into the framework of the existing formalism. The discussion based on an example of cardiac muscle contraction illustrates the advantages of this approach.

  11. The nuclear membranes in hypertrophied human cardiac muscle cells.

    PubMed Central

    Ferrans, V. J.; Jones, M.; Maron, B. J.; Roberts, W. C.

    1975-01-01

    Nuclear membranes of cardiac muscle cells were studied in 134 patients with cardiac hypertrophy of various causes. Abnormalities observed consisted of: a) increased foldings and convolutions; b) nuclear pseudoinclusions formed by cytoplasmic organelles protruding into saccular invaginations of the nuclear membranes, and c) intranuclear tubules. The increased foldings and convolutions of the nuclear membranes and the nuclear pseudoinclusions appear to result from synthesis of nuclear membranes in excess of that needed to accommodate the increase in nuclear volume which occurs in hypertrophy. Intranuclear tubules were found in 6 patients and consisted of tubular invaginations, 400 to 650 A in diameter, of the inner nuclear membranes into the nucleoplasm. Some of these tubules were straight and cylindrical, and were associated with a peripheral layer of marginated chromatin; others were not associated with chromatin, appeared coiled and followed irregular courses. Intranuclear tubules in cardiac muscle cells probably represent an extreme cellular response to the stimulus of hypertrophy. Images Fig 21 Fig 11 Fig 12 Fig 13 Fig 14 Fig 1 Fig 15 Fig 2 Figs 3 and 4 Fig 5 Fig 16 Fig 17 Fig 6 Fig 18 Fig 7 Fig 8 Fig 9 Fig 10 Fig 19 Fig 20 PMID:164122

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

    PubMed Central

    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

    2012-01-01

    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. PMID:23112163

  13. [Tolerance of +Gz accelerations in chronic compensated cardiac muscle disease].

    PubMed

    Suvorov, P M; Bykova, Iu I

    1975-01-01

    The functional potentialities of the cardiovascular system were investigated during an exposure of people with compensated chronic diseases of the cardiac muscle to acceleration (+Gz). The test subjects were exposed to acceleration of 3 and 5 g for 30 sec with an interval of 5 min. The parameters of hemodynamics, ECG and visual perception were recorded. The systolic blood volume, cardiac output and specific peripheral resistance were derived from the Bremser-Ranke formula. Seventy one subjects with heart diseases and 23 healthy subjects were examined. The subjects with myocardiodystrophy and myocarditic cardiosclerosis (12+/-16) showed a reduced tolerance to accelerations. During an exposure the subjects with atherosclerotic cardiosclerosis showed a higher pressure in vessels of ear conch than the healthy subjects. The myocardiodystrophic subjects frequently (20%) exhibited an inversion of electrocardiographic T2. The subjects with heart diseases (27-33%) showed extrasystolic disturbances. The results may be used in medical expertise of pilots. PMID:1214489

  14. Impaired cardiac reserve and severely diminished skeletal muscle O₂ utilization mediate exercise intolerance in Barth syndrome.

    PubMed

    Spencer, Carolyn T; Byrne, Barry J; Bryant, Randall M; Margossian, Renee; Maisenbacher, Melissa; Breitenger, Petar; Benni, Paul B; Redfearn, Sharon; Marcus, Edward; Cade, W Todd

    2011-11-01

    Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O(2) extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O(2) extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O(2) extraction. Adjusting for age, peak O(2) consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg(-1)·min(-1), P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O(2) saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS. PMID:21873497

  15. Complicated axillary lymphadenectomy due to a pectoralis quartus muscle.

    PubMed

    Totlis, T; Iosifidou, R; Pavlidou, F; Sofidis, G; Natsis, K; Bousoulegas, A

    2012-01-01

    During lymphadenectomy in the left axilla of a 38-year-old woman with a 1.4 cm invasive ductal breast carcinoma an accessory muscle was found. Due to the presence of the anomalous muscle the lymphadenectomy was carried out with difficulty through a limited field. Based on its anatomical characteristics, the supernumerary muscle was recognized as the pectoralis quartus. To our knowledge this is the first report of a pectoralis quartus muscle as a surgical finding. The surgeon should be aware of the possible presence of this anomaly as well as its anatomical characteristics in order to avoid any complications. PMID:22844841

  16. Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

    PubMed Central

    Park, Song-Young; Gifford, Jayson R.; Andtbacka, Robert H. I.; Trinity, Joel D.; Hyngstrom, John R.; Garten, Ryan S.; Diakos, Nikolaos A.; Ives, Stephen J.; Dela, Flemming; Larsen, Steen; Drakos, Stavros

    2014-01-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s−1·mg−1, P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g−1·min−1, P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s−1·mg−1, P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production. PMID:24906913

  17. Proteomic responses of skeletal and cardiac muscle to exercise

    PubMed Central

    Burniston, Jatin G.; Hoffman, Eric P.

    2016-01-01

    Summary Regular exercise is effective in the prevention of chronic diseases and confers a lower risk of death in individuals displaying risk factors such as hypertension and dyslipidaemia. Thus, knowledge of the molecular responses to exercise provides a valuable contrast for interpreting investigations of disease and can highlight novel therapeutic targets. While exercise is an everyday experience and can be conceptualized in simple terms, exercise is a complex physiological phenomena and investigation of exercise responses requires sophisticated analytical techniques and careful standardization of the exercise stimulus. Proteomic investigation of exercise is in its infancy but the ability to link changes in function with comprehensive changes in protein expression and post-translational modification holds great promise for advancing physiology. This review highlights recent pioneering work investigating the effects of exercise in skeletal and cardiac muscle that has uncovered novel mechanisms underling the benefits of physical activity. PMID:21679117

  18. Inclusion body myositis, muscle blood vessel and cardiac amyloidosis, and transthyretin Val122Ile allele.

    PubMed

    Askanas, V; Engel, W K; Alvarez, R B; Frangione, B; Ghiso, J; Vidal, R

    2000-04-01

    Typical of sporadic inclusion body myositis muscle biopsies are vacuolated muscle fibers containing intracellular amyloid deposits and accumulations of "Alzheimer-characteristic" proteins. There is no muscle blood vessel or cardiac amyloidosis. We report on a 70-year-old African-American man homozygous for the transthyretin Val122Ile allele who has both sporadic inclusion body myositis and cardiac amyloidosis. His unique pathological features included transthyretin immunoreactivity in prominent muscle blood vessel amyloid and congophilic amyloid deposits within vacuolated muscle fibers. PMID:10762172

  19. A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription.

    PubMed Central

    Grépin, C; Dagnino, L; Robitaille, L; Haberstroh, L; Antakly, T; Nemer, M

    1994-01-01

    In contrast to skeletal muscle, the mechanisms responsible for activation and maintenance of tissue-specific transcription in cardiac muscle remain poorly understood. A family of hormone-encoding genes is expressed in a highly specific manner in cardiac but not skeletal myocytes. This includes the A- and B-type natriuretic peptide (ANP and BNP) genes, which encode peptide hormones with crucial roles in the regulation of blood volume and pressure. Since these genes are markers of cardiac cells, we have used them to probe the mechanisms for cardiac muscle-specific transcription. Cloning and functional analysis of the rat BNP upstream sequences revealed unexpected structural resemblance to erythroid but not to muscle-specific promoters and enhancers, including a requirement for regulatory elements containing GATA motifs. A cDNA clone corresponding to a member of the GATA family of transcription factors was isolated from a cardiomyocyte cDNA library. Transcription of this GATA gene is restricted mostly to the heart and is undetectable in skeletal muscle. Within the heart, GATA transcripts are localized in ANP- and BNP-expressing myocytes, and forced expression of the GATA protein in heterologous cells markedly activates transcription from the natural cardiac muscle-specific ANP and BNP promoters. This GATA-dependent pathway defines the first mechanism for cardiac muscle-specific transcription. Moreover, the present findings reveal striking similarities between the mechanisms controlling gene expression in hematopoietic and cardiac cells and may have important implications for studies of cardiogenesis. Images PMID:8164667

  20. Cardiac arrest due to airway obstruction in hereditary angioedema.

    PubMed

    Fuse, Takashi; Nakada, Taka-aki; Taniguchi, Masashi; Mizushima, Yasuaki; Matsuoka, Tetsuya

    2015-12-01

    Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency of functional C1 esterase inhibitor that causes swelling attacks in various body tissues. We hereby report a case of out-of-hospital cardiac arrest due to airway obstruction in HAE. Cutaneous swelling and abdominal pain attacks caused by gastrointestinal wall swelling are common symptoms in HAE, whereas laryngeal swelling is rare. Emergency physicians may have few chances to experience cases of life-threatening laryngeal edema resulting in a delay from symptom onset to the diagnosis of HAE. Hereditary angioedema is diagnosed by performing complement blood tests. Because safe and effective treatment options are available for the life-threatening swellings in HAE, the diagnosis potentially reduces the risk of asphyxiation in patients and their blood relatives. PMID:25913082

  1. Development of aerobic and anaerobic metabolism in cardiac and skeletal muscles from harp and hooded seals.

    PubMed

    Burns, J M; Skomp, N; Bishop, N; Lestyk, K; Hammill, M

    2010-03-01

    In diving animals, skeletal muscle adaptations to extend underwater time despite selective vasoconstriction include elevated myoglobin (Mb) concentrations, high acid buffering ability (beta) and high aerobic and anaerobic enzyme activities. However, because cardiac muscle is perfused during dives, it may rely less heavily on Mb, beta and anaerobic pathways to support contractile activity. In addition, because cardiac tissue must sustain contractile activity even before birth, it may be more physiologically mature at birth and/or develop faster than skeletal muscles. To test these hypotheses, we measured Mb levels, beta and the activities of citrate synthase (CS), beta-hydroxyacyl-CoA dehydrogenase (HOAD) and lactate dehydrogenase (LDH) in cardiac and skeletal muscle samples from 72 harp and hooded seals, ranging in age from fetuses to adults. Results indicate that in adults cardiac muscle had lower Mb levels (14.7%), beta (55.5%) and LDH activity (36.2%) but higher CS (459.6%) and HOAD (371.3%) activities (all P<0.05) than skeletal muscle. In addition, while the cardiac muscle of young seals had significantly lower [Mb] (44.7%) beta (80.7%) and LDH activity (89.5%) than adults (all P<0.05), it was relatively more mature at birth and weaning than skeletal muscle. These patterns are similar to those in terrestrial species, suggesting that seal hearts do not exhibit unique adaptations to the challenges of an aquatic existence. PMID:20154189

  2. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages

    SciTech Connect

    Arsic, Nikola; Mamaeva, Daria; Lamb, Ned J.; Fernandez, Anne

    2008-04-01

    Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal {beta} III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders.

  3. Modelling diffusive O(2) supply to isolated preparations of mammalian skeletal and cardiac muscle.

    PubMed

    Barclay, C J

    2005-01-01

    The purpose of this study was to use A. V. Hill's equation describing diffusion of O(2) into cylindrical muscles to assess the adequacy of O(2) supply for commonly used isolated preparations of mammalian cardiac and skeletal muscles. The diffusion equation was solved numerically to give the maximum, steady state O(2) diffusion distances (i.e. the distance from the surface of the muscle to the radial location where P(O(2)) is 0) for both resting and contracting muscles and for a range of temperatures. Non-steady state solutions for the rest-to-work transition were also determined to estimate how long contractile activity could be continued before anoxia develops at the muscle centre. The influence on muscle oxygenation of myoglobin-facilitated O(2) diffusion was also assessed. The analysis was performed for typical sized, whole muscles from adult rats and mice, for frog sartorius muscle and for a range of temperatures. Muscle O(2) consumption rates were taken from the literature. The results indicated that (1) diffusive O(2) supply would be adequate to support resting metabolism of soleus and EDL muscles of rat and mouse but may not be adequate to support the transient high resting metabolic rate of papillary muscles shortly after dissection, (2) during steady contractile activity of soleus and EDL muscles, particularly those from the rat, over a reasonable range of duty cycles, adequate O(2) supply could only be ensured if the radii of preparations was substantially smaller than those of whole muscles and (3) for cardiac muscles, diffusive O(2) supply could only support steady-state metabolism at twitch frequencies <1 Hz for whole papillary muscles from rat and <3 Hz for those from mouse. Reducing experimental temperature markedly enhances O(2) supply to skeletal, but not cardiac, muscle. O(2) supply from myoglobin had only minimal effects on oxygenation under typical isolated muscle conditions. PMID:16322911

  4. Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

    PubMed Central

    Quattrocelli, Mattia; Swinnen, Melissa; Giacomazzi, Giorgia; Camps, Jordi; Barthélemy, Ines; Ceccarelli, Gabriele; Caluwé, Ellen; Grosemans, Hanne; Thorrez, Lieven; Pelizzo, Gloria; Muijtjens, Manja; Verfaillie, Catherine M.; Blot, Stephane; Janssens, Stefan; Sampaolesi, Maurilio

    2015-01-01

    Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles. PMID:26571398

  5. Effect of swimming on myostatin expression in white and red gastrocnemius muscle and in cardiac muscle of rats.

    PubMed

    Matsakas, Antonios; Bozzo, Cyrille; Cacciani, Nicola; Caliaro, Francesca; Reggiani, Carlo; Mascarello, Francesco; Patruno, Marco

    2006-11-01

    The aim of this study was to test the hypothesis that swimming training might impact differentially myostatin expression in skeletal muscles, depending on fibre type composition, and in cardiac muscle of rats. Myostatin expression was analysed by real time reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry of the red deep portion (mainly composed of slow and type II A fibres) and in the superficial, white portion (composed of fast type II X and II B fibres) of the gastrocnemius muscle in adult male Wistar rats: (i) subjected to two consecutive swimming bouts for 3 h; (ii) subjected to intensive swimming training for 4 weeks; and (iii) sedentary control rats. Myostatin mRNA content was in all cases higher in white than in red muscles. Two bouts of swimming did not alter myostatin expression, whereas swimming training for 4 weeks resulted in a significant reduction of myostatin mRNA contents, significant both in white and red muscles but more pronounced in white muscles. Western blot did not detect any change in the amount of myostatin protein. Immunohistochemistry showed that, in control rats, myostatin was localized in presumptive satellite cells of a few muscle fibres. After training, the number of myostatin-positive spots decreased significantly. Myostatin mRNA content in cardiac muscle was lower than in skeletal muscle and was significantly increased by swimming training. In conclusion, the results obtained showed that intense training caused a decreased expression of myostatin mRNA in white and red skeletal muscles but an increase in cardiac muscle. PMID:16873457

  6. E-box sites and a proximal regulatory region of the muscle creatine kinase gene differentially regulate expression in diverse skeletal muscles and cardiac muscle of transgenic mice.

    PubMed Central

    Shield, M A; Haugen, H S; Clegg, C H; Hauschka, S D

    1996-01-01

    Previous analysis of the muscle creatine kinase (MCK) gene indicated that control elements required for transcription in adult mouse muscle differed from those required in cell culture, suggesting that distinct modes of muscle gene regulation occur in vivo. To examine this further, we measured the activity of MCK transgenes containing E-box and promoter deletions in a variety of striated muscles. Simultaneous mutation of three E boxes in the 1,256-bp MCK 5' region, which abolished transcription in muscle cultures, had strikingly different effects in mice. The mutations abolished transgene expression in cardiac and tongue muscle and caused a reduction in expression in the soleus muscle (a muscle with many slow fibers) but did not affect expression in predominantly fast muscles: quadriceps, abdominals, and extensor digitorum longus. Other regulatory sequences with muscle-type-specific activities were found within the 358-bp 5'-flanking region. This proximal region conferred relatively strong expression in limb and abdominal skeletal muscles but was inactive in cardiac and tongue muscles. However, when the 206-bp 5' enhancer was ligated to the 358-bp region, high levels of tissue-specific expression were restored in all muscle types. These results indicate that E boxes and a proximal regulatory region are differentially required for maximal MCK transgene expression in different striated muscles. The overall results also imply that within skeletal muscles, the steady-state expression of the MCK gene and possibly other muscle genes depends on transcriptional mechanisms that differ between fast and slow fibers as well as between the anatomical and physiological attributes of each specific muscle. PMID:8756664

  7. Cardiac arrest due to a missed diagnosis of Boerhaave's syndrome.

    PubMed

    Davies, Jennifer; Spitzer, David; Phylactou, Maria; Glasser, Martin

    2016-01-01

    A 91-year-old presented with a rare cause of cardiac arrest. He was initially admitted with severe back pain following vomiting and diagnosed with probable aspiration pneumonia. On day 3 of admission, he was discovered in cardiac arrest and cardiopulmonary resuscitation was started. On intubation, a left-sided pneumothorax and subcutaneous emphysema were noted. Needle decompression showed gastric fluid leaking from the cannula. The patient regained a cardiac output, and a subsequent CT scan confirmed a large pneumomediastinum with air tracking to the neck and chest, and bilateral pneumothoraces. A diagnosis of Boerhaave's syndrome was made. The patient was transferred to the intensive care unit but did not survive. This case demonstrates the importance of looking for and treating the rarer reversible causes of cardiac arrest, and of maintaining a high index of suspicion for Boerhaave's syndrome. Despite its rarity, Boerhaave's syndrome is often misdiagnosed on initial presentation, leading to delayed treatment and poor outcomes. PMID:27154984

  8. Open-Loop Control of Oxidative Phosphorylation in Skeletal and Cardiac Muscle Mitochondria by Ca(2.).

    PubMed

    Vinnakota, Kalyan C; Singhal, Abhishek; Van den Bergh, Françoise; Bagher-Oskouei, Masoumeh; Wiseman, Robert W; Beard, Daniel A

    2016-02-23

    In cardiac muscle, mitochondrial ATP synthesis is driven by demand for ATP through feedback from the products of ATP hydrolysis. However, in skeletal muscle at higher workloads there is an apparent contribution of open-loop stimulation of ATP synthesis. Open-loop control is defined as modulation of flux through a biochemical pathway by a moiety, which is not a reactant or a product of the biochemical reactions in the pathway. The role of calcium, which is known to stimulate the activity of mitochondrial dehydrogenases, as an open-loop controller, was investigated in isolated cardiac and skeletal muscle mitochondria. The kinetics of NADH synthesis and respiration, feedback from ATP hydrolysis products, and stimulation by calcium were characterized in isolated mitochondria to test the hypothesis that calcium has a stimulatory role in skeletal muscle mitochondria not apparent in cardiac mitochondria. A range of respiratory states were obtained in cardiac and skeletal muscle mitochondria utilizing physiologically relevant concentrations of pyruvate and malate, and flux of respiration, NAD(P)H fluorescence, and rhodamine 123 fluorescence were measured over a range of extra mitochondrial calcium concentrations. We found that under these conditions calcium stimulates NADH synthesis in skeletal muscle mitochondria but not in cardiac mitochondria. PMID:26910432

  9. Congenital Heart Defects Are Rarely Caused by Mutations in Cardiac and Smooth Muscle Actin Genes

    PubMed Central

    Khodyuchenko, Tatiana; Zlotina, Anna; Pervunina, Tatiana; Zverev, Dmitry; Malashicheva, Anna; Kostareva, Anna

    2015-01-01

    Background. Congenital heart defects (CHDs) often have genetic background due to missense mutations in cardiomyocyte-specific genes. For example, cardiac actin was shown to be involved in pathogenesis of cardiac septum defects and smooth muscle actin in pathogenesis of aortic aneurysm in combination with patent ductus arteriosus (PDA). In the present study, we further searched for mutations in human α-cardiac actin (ACTC1) and smooth muscle α-actin (ACTA2) genes as a possible cause of atrial septum defect type II (ASDII) and PDA. Findings. Total genomic DNA was extracted from peripheral blood of 86 individuals with ASDs and 100 individuals with PDA. Coding exons and flanking intron regions of ACTC1 (NM_005159.4) and ACTA2 (NM_001613) were amplified by PCR with specific primers designed according to the corresponding gene reference sequences. PCR fragments were directly sequenced and analyzed. Sequence analysis of ACTC1 and ACTA2 did not identify any nucleotide changes that altered the coding sense of the genes. In ACTC1 gene, we were able to detect one previously described nucleotide polymorphism (rs2307493) resulting in a synonymous substitution. The frequency of this SNP was similar in the study and control group, thus excluding it from the possible disease-associated variants. Conclusions. Our results confirmed that the mutations in ACTC1 gene are rare (at least <1%) cause of ASDII. Mutations in ACTA2 gene were not detected in patients with PDA, thus being excluded from the list of frequent PDA-associated genetic defects. PMID:25861618

  10. Cardiac function in muscular dystrophy associates with abdominal muscle pathology

    PubMed Central

    Gardner, Brandon B.; Swaggart, Kayleigh A.; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M.

    2015-01-01

    Background The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Methods Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. Findings The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients. PMID:26029630

  11. Permeation through the calcium release channel of cardiac muscle.

    PubMed Central

    Chen, D; Xu, L; Tripathy, A; Meissner, G; Eisenberg, B

    1997-01-01

    Current voltage (I-V) relations were measured from the calcium release channel (CRC) of the sarcoplasmic reticulum of cardiac muscle in 12 KCl solutions, symmetrical and asymmetrical, from 25 mM to 2 M. I-V curves are nearly linear, in the voltage range +/- 150 mV approximately 12kT/e, even in asymmetrical solutions, e.g., 2 M // 100 mM. It is awkward to describe straight lines as sums of exponentials in a wide range of solutions and potentials, and so traditional barrier models have difficulty fitting this data. Diffusion theories with constant fields predict curvilinear I-V relations, and so they are also unsatisfactory. The Poisson and Nernst-Planck equations (PNP) form a diffusion theory with variable fields. They fit the data by using adjustable parameters for the diffusion constant of each ion and for the effective density of fixed (i.e., permanent) charge P(x) along the channel's "filter" (7-A diameter, 10 A long). If P(x) is described by just one parameter, independent of x (i.e., P(x) = P0 = -4.2 M), the fits are satisfactory (RMS error/RMS current = 6.4/67), and the estimates of diffusion coefficients are reasonable D(K) = 1.3 x 10(-6) cm2/s, D(Cl) = 3.9 x 10(-6) cm2/s. The CRC seems to have a small selectivity filter with a very high density of permanent charge. This may be a design principle of channels specialized for large flux. The Appendix derives barrier models, and their prefactor, from diffusion theories (with variable fields) and argues that barrier models are poor descriptions of CRCs in particular and open channels in general. PMID:9284302

  12. Constitutive properties of adult mammalian cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

    1998-01-01

    BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

  13. Hysteresis and the length dependence of calcium sensitivity in chemically skinned rat cardiac muscle.

    PubMed Central

    Harrison, S M; Lamont, C; Miller, D J

    1988-01-01

    1. The relationship between pCa (-log10[Ca2+]) and steady-state isometric tension has been investigated in saponin- or Triton-treated (chemically 'skinned') cardiac muscle of rat. 2. Hysteresis exists in the relationship such that the muscle is less sensitive to Ca2+ during increasing activation (as [Ca2+] is stepped upward) than during reducing activation (as [Ca2+] is stepped downward). 3. The extent of the hysteresis is insensitive to interventions that increase overall calcium sensitivity by chemical means, such as caffeine, carnosine or increased pH. 4. The extent of the hysteresis is sensitive to sarcomere length. The phenomenon is virtually absent above sarcomere lengths of about 2.2-2.3 microns but becomes progressively greater at shorter sarcomere lengths. 5. The effect of sarcomere length on calcium sensitivity is restricted to the upward-going (increasing activation) part of the pCa-tension loop below 2.2 microns. The downward-going (decreasing activation) part of the hysteretic relationship is virtually unaffected by sarcomere length up to 2.2 microns. 6. Significant alterations in sarcomere length do not occur during tension development in the experiments described here: the phenomenon is not attributable to experimental artifacts of this kind. 7. Hysteresis develops sufficiently rapidly to be consistent with a physiological relevance during the normal heart beat. 8. The effects of sarcomere length show that the phenomenon is not due to force per se since, for example, greater peak force produces less hysteresis as sarcomere length is increased towards 2.2 microns. 9. Tonicity increase (by high-molecular-weight dextran), which shrinks the myofilament lattice, increases calcium sensitivity but reduces the effect of sarcomere length on calcium sensitivity. 10. The results suggest that lattice shrinkage is the mechanism which accounts for hysteresis in, and the sarcomere length dependence of, calcium sensitivity in cardiac muscle. Images Fig. 1 Fig. 11

  14. Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised.

    PubMed

    Warskulat, Ulrich; Flögel, Ulrich; Jacoby, Christoph; Hartwig, Hans-Georg; Thewissen, Michael; Merx, Marc W; Molojavyi, Andrej; Heller-Stilb, Birgit; Schrader, Jürgen; Häussinger, Dieter

    2004-03-01

    Taurine is the most abundant free amino acid in heart and skeletal muscle. In the present study, the effects of hereditary taurine deficiency on muscle function were examined in taurine transporter knockout (taut-/-) mice. These mice show an almost complete depletion of heart and skeletal muscle taurine levels. Treadmill experiments demonstrated that total exercise capacity of taut-/- mice was reduced by >80% compared with wild-type controls. The decreased performance of taut-/- mice correlated with increased lactate levels in serum during exercise. Surprisingly, cardiac function of taut-/- mice as assessed by magnetic resonance imaging, echocardiography, and isolated heart studies showed a largely normal phenotype under both control and stimulated conditions. However, analysis of taut-/- skeletal muscle revealed electromyographic abnormalities. (1)H nuclear magnetic resonance spectroscopy of tissue extracts showed that in the heart of taut-/- mice the lack of taurine was compensated by the up-regulation of various organic solutes. In contrast, a deficit of >10 mM in total organic osmolyte concentration was found in skeletal muscle. The present study identifies taurine transport as a crucial factor for the maintenance of skeletal muscle function and total exercise capacity, while cardiac muscle apparently can compensate for the loss of taurine. PMID:14734644

  15. [Postmortem genetic testing in sudden cardiac death due to ion channelopathies].

    PubMed

    Guan, Da-wei; Zhao, Rui

    2010-04-01

    Sudden cardiac death accounts for majority of deaths in human. Evident cardiac lesions that may explain the cause of death can be detected in comprehensive postmortem investigation in most sudden cardiac death. However, no cardiac morphological abnormality is found in a considerable number of cases although the death is highly suspected from cardiac anomaly. With the advances in the modern molecular biology techniques, it has been discovered that many of these sudden deaths are caused by congenital ion channelopathies in myocardial cell, i.e., Brugada syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome, etc. This article presents the molecular genetics, electrocardiographic abnormalities, clinical manifestations, and mechanisms leading to sudden cardiac death with emphasis on the role of postmortem genetic testing in certification of cause of death. It may provide helpful information in investigating sudden cardiac death due to ion channelopathies in medico-legal practice. PMID:20653139

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

    ERIC Educational Resources Information Center

    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…

  17. Fast sodium current in cardiac muscle. A quantitative description.

    PubMed Central

    Ebihara, L; Johnson, E A

    1980-01-01

    The voltage and time-dependence of the tetrodotoxin sensitive, fast sodium current in cardiac muscle is described with the Hodgkin-Huxley formalism using two microelectrode, voltage-clamp data obtained by Ebihara et al. (1980, J. Gen. Physiol., 75:437) from small spherical clusters of tissue-cultured 11-d-old embryonic heart cells. The data chosen from that study for quantitative analysis was obtained at 37 degrees C and in standard tissue-culture medium; it was not smoothed, and the capacitive transient was sufficiently brief to make its removal unnecessary. The sodium current, INa, is considered to be given by the following equation: INa = gNa m3h(V - VNa), where gNa is a constant (23 mS), VNa is the sodium equilibrium potential (29 mV), and m and h are independent, first order, dimensionless variables, which can vary between 0 and 1, as defined by the following differential equations, dm/dt = alpha m(1 - m) - beta mm and dh/dt = alpha h(1 - h) - beta hh, where the rate coefficients, alpha m = [0.32 x (V + 47.13)]/[1 - exp(V + 47.13)] and beta m = 0.08 x exp (-V/11). For potentials more positive than -40 mV, alpha h = 0 and beta h = 1/0.13 (exp [(V + 10.66)/ - 11.1] + 1), and for potentials more negative than -40 mV, alpha h = 0.135 x exp [(-80 - V)/6.8] and beta h = 3.56 x exp (0.079V) + 3.1 x 10(5) exp (0.35V). These functions of potential are similar to those of the squid at 15 degrees C, except that their magnitudes are larger (faster). Using these model equations the membrane current in a membrane patch with and without a series resistance was simulated. For the value of series resistance estimated for the preparation from which the analyzed data were obtained, the effects of series resistance on the shape and magnitude of the inward transient current were found to be minimal. It was concluded that their should be no large errors in the data, even in the absence of complete series resistance compensation. PMID:7260301

  18. Impact of aging on mitochondrial function in cardiac and skeletal muscle.

    PubMed

    Hepple, R T

    2016-09-01

    Both skeletal muscle and cardiac muscle are subject to marked structural and functional impairment with aging and these changes contribute to the reduced capacity for exercise as we age. Since mitochondria are involved in multiple aspects of cellular homeostasis including energetics, reactive oxygen species signaling, and regulation of intrinsic apoptotic pathways, defects in this organelle are frequently implicated in the deterioration of skeletal and cardiac muscle with aging. On this basis, the purpose of this review is to evaluate the evidence that aging causes dysfunction in mitochondria in striated muscle with a view towards drawing conclusions about the potential of these changes to contribute to the deterioration seen in striated muscle with aging. As will be shown, impairment in respiration and reactive oxygen species emission with aging are highly variable between studies and seem to be largely a consequence of physical inactivity. On the other hand, both skeletal and cardiac muscle mitochondria are more susceptible to permeability transition and this seems a likely cause of the increased recruitment of mitochondrial-mediated pathways of apoptosis seen in striated muscle. The review concludes by examining the role of degeneration of mitochondrial DNA versus impaired mitochondrial quality control mechanisms in the accumulation of mitochondria that are sensitized to permeability transition, whereby the latter mechanism is favored as the most likely cause. PMID:27033952

  19. Intracellular diffusion of adenosine phosphates is locally restricted in cardiac muscle.

    PubMed

    Vendelin, Marko; Eimre, Margus; Seppet, Evelin; Peet, Nadezda; Andrienko, Tatiana; Lemba, Maris; Engelbrecht, Jiiri; Seppet, Enn K; Saks, Valdur A

    2004-01-01

    Recent studies have revealed the structural and functional interactions between mitochondria, myofibrils and sarcoplasmic reticulum in cardiac cells. Direct channeling of adenosine phosphates between organelles identified in the experiments indicates that diffusion of adenosine phosphates is limited in cardiac cells due to very specific intracellular structural organization. However, the mode of diffusion restrictions and nature of the intracellular structures in creating the diffusion barriers is still unclear, and, therefore, a subject of active research. The aim of this work is to analyze the possible role of two principally different modes of restriction distribution for adenosine phosphates (a) the uniform diffusion restriction and (b) the localized diffusion limitation in the vicinity of mitochondria, by fitting the experimental data with the mathematical model. The reaction-diffusion model of compartmentalized energy transfer was used to analyze the data obtained from the experiments with the skinned muscle fibers, which described the following processes: mitochondrial respiration rate dependency on exogenous ADP and ATP concentrations; inhibition of endogenous ADP-stimulated respiration by pyruvate kinase (PK) and phosphoenolpyruvate (PEP) system; kinetics of oxygen consumption stabilization after addition of 2 mM MgATP or MgADP; ATPase activity with inhibited mitochondrial respiration; and buildup of MgADP concentration in the medium after addition of MgATP. The analysis revealed that only the second mechanism considered--localization of diffusion restrictions--is able to account for the experimental data. In the case of uniform diffusion restrictions, the model solution was in agreement only with two measurements: the respiration rate as a function of ADP or ATP concentrations and inhibition of respiration by PK + PEP. It was concluded that intracellular diffusion restrictions for adenosine phosphates are not distributed uniformly, but rather are

  20. Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments.

    PubMed Central

    Granzier, H L; Irving, T C

    1995-01-01

    The passive tension-sarcomere length relation of rat cardiac muscle was investigated by studying passive (or not activated) single myocytes and trabeculae. The contribution of collagen, titin, microtubules, and intermediate filaments to tension and stiffness was investigated by measuring (1) the effects of KCl/KI extraction on both trabeculae and single myocytes, (2) the effect of trypsin digestion on single myocytes, and (3) the effect of colchicine on single myocytes. It was found that over the working range of sarcomeres in the heart (lengths approximately 1.9-2.2 microns), collagen and titin are the most important contributors to passive tension with titin dominating at the shorter end of the working range and collagen at longer lengths. Microtubules made a modest contribution to passive tension in some cells, but on average their contribution was not significant. Finally, intermediate filaments contributed about 10% to passive tension of trabeculae at sarcomere lengths from approximately 1.9 to 2.1 microns, and their contribution dropped to only a few percent at longer lengths. At physiological sarcomere lengths of the heart, cardiac titin developed much higher tensions (> 20-fold) than did skeletal muscle titin at comparable lengths. This might be related to the finding that cardiac titin has a molecular mass of 2.5 MDa, 0.3-0.5 MDa smaller than titin of mammalian skeletal muscle, which is predicted to result in a much shorter extensible titin segment in the I-band of cardiac muscle. Passive stress plotted versus the strain of the extensible titin segment showed that the stress-strain relationships are similar in cardiac and skeletal muscle. The difference in passive stress between cardiac and skeletal muscle at the sarcomere level predominantly resulted from much higher strains of the I-segment of cardiac titin at a given sarcomere length. By expressing a smaller titin isoform, without changing the properties of the molecule itself, cardiac muscle is able to

  1. Changes in the cardiac muscle electric activity as a result of Coronary Artery Bypass Graft operation

    NASA Astrophysics Data System (ADS)

    Grajek, Magdalena; Krzyminiewski, Ryszard; Kalawski, Ryszard; Kulczak, Mariusz

    2008-01-01

    Many bioelectric signals have a complex internal structure that can be a rich source of information on the tissue or cell processes. The structure of such signals can be analysed in detail by applying digital methods of signal processing. Therefore, of substantial use in diagnosis of the coronary arterial disease is the method of digital enhancement of increasing signal resolution ECG (NURSE-ECG), permitting detection of temporary changes in the electric potentials in the cardiac muscle in the process of depolarisation. Thanks to the application of NURSE-ECG it has become possible to detect relatively small changes in the electric activity of particular fragments of the cardiac muscle undetectable by the standard ECG method, caused by ischemia, the effect of a drug or infarct. The aim of this study was to identify and analyse changes in the electric activity of the cardiac muscle as a result of the Coronary Artery Bypass Graft (CABG) operation. In this study the method of NURSE-ECG has been applied in order to identify and analyse changes in the electric activity of the cardiac muscle as a result of the CABG operation. In the study performed in cooperation of the Institute of Physics Adam Mickiewicz University and the Strus Hospital, Cardiac Surgery Ward, 37 patients with advanced coronary arterial disease were asked to participate. The patients were examined prior to the operation, on the day after the operation and two months after the operation and a year after the operation. The ECG recordings were subjected to a numerical procedure of resolution enhancement by a NURSE-ECG program to reveal the tentative changes in the electric potential of the cardiac muscle on its depolarisation. Results of the study have shown that the NURSE ECG method can be applied to monitor changes in the electric activity of the cardiac muscle occurring as a result of CABG operation. One the second day after the operation in the majority of patients (70%) a rapid decrease of the total

  2. Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients.

    PubMed

    Dewulf, Joseph P; Barrea, Catherine; Vincent, Marie-Françoise; De Laet, Corinne; Van Coster, Rudy; Seneca, Sara; Marie, Sandrine; Nassogne, Marie-Cécile

    2016-07-01

    Acyl-CoA dehydrogenase 9 (ACAD9) is a mitochondrial protein involved in oxidative phosphorylation complex I biogenesis. This protein also exhibits acyl-CoA dehydrogenase (ACAD) activity. ACAD9-mutated patients have been reported to suffer from primarily heart, muscle, liver, and nervous system disorders. ACAD9 mutation is suspected in cases of elevated lactic acid levels combined with complex I deficiency, and confirmed by ACAD9 gene analysis. At least 18 ACAD9-mutated patients have previously been reported, usually displaying severe cardiac involvement. We retrospectively studied nine additional patients from three unrelated families with a wide spectrum of cardiac involvement between the families as well as the patients from the same families. All patients exhibited elevated lactate levels. Deleterious ACAD9 mutations were identified in all patients except one for whom it was not possible to recover DNA. To our knowledge, this is one of the first reports on isolated mild ventricular hypertrophy due to ACAD9 mutation in a family with moderate symptoms during adolescence. This report also confirms that dilated cardiomyopathy may occur in conjunction with ACAD9 mutation and that some patients may respond clinically to riboflavin treatment. Of note, several patients suffered from patent ductus arteriosus (PDA), with one exhibiting a complex congenital heart defect. It is yet unknown whether these cardiac manifestations were related to ACAD9 mutation. In conclusion, this disorder should be suspected in the presence of lactic acidosis, complex I deficiency, and any cardiac involvement, even mild. PMID:27233227

  3. Production of arrays of cardiac and skeletal muscle myofibers by micropatterning techniques on a soft substrate.

    PubMed

    Cimetta, Elisa; Pizzato, Sara; Bollini, Sveva; Serena, Elena; De Coppi, Paolo; Elvassore, Nicola

    2009-04-01

    Micropatterning and microfabrication techniques have been widely used to pattern cells on surfaces and to have a deeper insight into many processes in cell biology such as cell adhesion and interactions with the surrounding environment. The aim of this study was the development of an easy and versatile technique for the in vitro production of arrays of functional cardiac and skeletal muscle myofibers using micropatterning techniques on soft substrates. Cardiomyocytes were used for the production of oriented cardiac myofibers whereas mouse muscle satellite cells for that of differentiated parallel myotubes. We performed micro-contact printing of extracellular matrix proteins on soft polyacrylamide-based hydrogels photopolymerized onto functionalized glass slides. Our methods proved to be simple, repeatable and effective in obtaining an extremely selective adhesion of both cardiomyocytes and satellite cells onto patterned soft hydrogel surfaces. Cardiomyocytes resulted in aligned cardiac myofibers able to exhibit a synchronous contractile activity after 2 days of culture. We demonstrated for the first time that murine satellite cells, cultured on a soft hydrogel substrate, fuse and form aligned myotubes after 7 days of culture. Immunofluorescence analyses confirmed correct expression of cell phenotype, differentiation markers and sarcomeric organization. These results were obtained in myotubes derived from satellite cells from both wild type and MDX mice which are research models for the study of muscle dystrophy. These arrays of both cardiac and skeletal muscle myofibers could be used as in vitro models for pharmacological screening tests or biological studies at the single fiber level. PMID:18987976

  4. Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring

    PubMed Central

    Beauchamp, Brittany; Thrush, A. Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y.; Patti, Mary-Elizabeth; Harper, Mary-Ellen

    2015-01-01

    Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. PMID:26182362

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

    SciTech Connect

    Josephson, Matthew P.; Sikkink, Laura A.; Penheiter, Alan R.; Burghardt, Thomas P.; Ajtai, Katalin

    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

  6. The tropomyosin binding region of cardiac troponin T modulates crossbridge recruitment dynamics in rat cardiac muscle fibers.

    PubMed

    Gollapudi, Sampath K; Gallon, Clare E; Chandra, Murali

    2013-05-13

    The cardiac muscle comprises dynamically interacting components that use allosteric/cooperative mechanisms to yield unique heart-specific properties. An essential protein in this allosteric/cooperative mechanism is cardiac muscle troponin T (cTnT), the central region (CR) and the T2 region of which differ significantly from those of fast skeletal muscle troponin T (fsTnT). To understand the biological significance of such sequence heterogeneity, we replaced the T1 or T2 domain of rat cTnT (RcT1 or RcT2) with its counterpart from rat fsTnT (RfsT1or RfsT2) to generate RfsT1-RcT2 and RcT1-RfsT2 recombinant proteins. In addition to contractile function measurements, dynamic features of RfsT1-RcT2- and RcT1-RfsT2-reconstituted rat cardiac muscle fibers were captured by fitting the recruitment-distortion model to the force response of small-amplitude (0.5%) muscle length changes. RfsT1-RcT2 fibers showed a 40% decrease in tension and a 44% decrease in ATPase activity, but RcT1-RfsT2 fibers were unaffected. The magnitude of length-mediated increase in crossbridge (XB) recruitment (E0) decreased by ~33% and the speed of XB recruitment (b) increased by ~100% in RfsT1-RcT2 fibers. Our data suggest the following: (1) the CR of cTnT modulates XB recruitment dynamics; (2) the N-terminal end region of cTnT has a synergistic effect on the ability of the CR to modulate XB recruitment dynamics; (3) the T2 region is important for tuning the Ca(2+) regulation of cardiac thin filaments. The combined effects of CR-tropomyosin interactions and the modulating effect of the N-terminal end of cTnT on CR-tropomyosin interactions may lead to the emergence of a unique property that tunes contractile dynamics to heart rates. PMID:23357173

  7. Combined electric field and gap junctions on propagation of action potentials in cardiac muscle and smooth muscle in PSpice simulation.

    PubMed

    Sperelakis, Nicholas

    2003-10-01

    Propagation of action potentials in cardiac muscle and smooth muscle were simulated using the PSpice program. Excitation was transmitted from cell to cell along a strand of 6 cells (cardiac muscle) or 10 cells (smooth muscle) either not connected (control) or connected by low-resistance tunnels (gap-junction connexons). A significant negative cleft potential (V(jv) ) develops in the narrow junctional cleft when the pre-JM fires. V(jc) depolarizes the postjunctional membrane (post-JM) to threshold by a patch-clamp action. With few connecting tunnels, cell-to-cell transmission by the EF mechanism was facilitated. With many tunnels, propagation was dominated by the low-resistance mechanism, and propagation velocity (theta) became very fast and nonphysiological. In conclusion, when the 2 mechanisms for cell-to-cell transfer of excitation were combined, the two mechanisms facilitated each other in a synergistic manner. When there were many connecting tunnels, the tunnel mechanism was dominant. PMID:14661164

  8. A novel site in the muscle creatine kinase enhancer is required for expression in skeletal but not cardiac muscle.

    PubMed

    Fabre-Suver, C; Hauschka, S D

    1996-03-01

    Expression of the muscle creatine kinase (MCK) gene in skeletal and heart muscle is controlled in part by a 5' tissue-specific enhancer. In order to identify new regulatory elements, we designed mutations in a previously untested conserved portion of this enhancer. Transfection analysis of these mutations delineated a new control element, named Trex (Transcriptional regulatory element x), which is required for full transcriptional activity of the MCK enhancer in skeletal but not cardiac muscle cells. Gel mobility shift assays demonstrate that myocyte, myoblast, and fibroblast nuclear extracts but not primary cardiomyocyte nuclear extracts contain a trans-acting factor that binds specifically to Trex. The Trex sequence is similar (7/8 bases) to the TEF-1 consensus DNA-binding site involved in regulating other muscle genes. To determine if TEF-1 interacts with Trex, selected TEF-1 binding sites such as GTIIc and M-CAT and two anti-TEF-1 antisera were used in gel shift assays. These experiments strongly suggest that a factor distinct from TEF-1 binds specifically to Trex. Thus it appears that MCK transcription is regulated in skeletal muscles through a Trex-dependent pathway while Trex is not required for MCK expression in heart. This distinction could account partially for the difference in levels of muscle creatine kinase in these tissues. PMID:8617727

  9. A successful treatment of cardiac tamponade due to an aortic dissection using open-chest massage.

    PubMed

    Keiko, Terasumi; Yanagawa, Youichi; Isoda, Susumu

    2012-05-01

    An 81-year-old woman became unconsciousness after complaining of a backache, and then, an ambulance was called. She was suspected to have an aortic dissection by the emergency medical technicians and was transferred to our department. On arrival, she was in shock. Emergency cardiac ultrasound disclosed good wall motion with cardiac tamponade but no complication of aortic regurgitation. Computed tomography of the trunk revealed a type A aortic dissection with cardiac tamponade. During performance of pericardial drainage, she lapsed into cardiopulmonary arrest. Immediately after sterilization of the patient's upper body with compression of the chest wall, we performed a thoracotomy and dissolved the cardiac tamponade by pericardiotomy and obtained her spontaneous circulation. Fortunately, blood discharge was ceased immediately after controlling her blood pressure aggressively. As she complicated pneumonitis, conservative therapy was performed. Her physical condition gradually improved, and she finally could feed herself and communicate. In cases of acute cardiac tamponade, simple pericardiocentesis often is not effective due to the presence of the clot, and a cardiac tamponade by a Stanford type A aortic dissection is highly possible to complicate cardiac arrest, so emergency physicians should be ready to provide immediate open cardiac massage to treat such patients. PMID:21406318

  10. Cardiac supporting device using artificial rubber muscle: preliminary study to active dynamic cardiomyoplasty.

    PubMed

    Saito, Yoshiaki; Suzuki, Yasuyuki; Goto, Takeshi; Daitoku, Kazuyuki; Minakawa, Masahito; Fukuda, Ikuo

    2015-12-01

    Dynamic cardiomyoplasty is a surgical treatment that utilizes the patient's skeletal muscle to support circulation. To overcome the limitations of autologous skeletal muscles in dynamic cardiomyoplasty, we studied the use of a wrapped-type cardiac supporting device using pneumatic muscles. Four straight rubber muscles (Fluidic Muscle, FESTO, Esslingen, Germany) were used and connected to pressure sensors, solenoid valves, a controller and an air compressor. The driving force was compressed air. A proportional-integral-derivative system was employed to control the device movement. An overflow-type mock circulation system was used to analyze the power and the controllability of this new device. The device worked powerfully with pumped flow against afterload of 88 mmHg, and the beating rate and contraction/dilatation time were properly controlled using simple software. Maximum pressure inside the ventricle and maximum output were 187 mmHg and 546.5 ml/min, respectively, in the setting of 50 beats per minute, a contraction/dilatation ratio of 1:2, a preload of 18 mmHg, and an afterload of 88 mmHg. By changing proportional gain, contraction speed could be modulated. This study showed the efficacy and feasibility of a pneumatic muscle for use in a cardiac supporting device. PMID:26253252

  11. Ca2+-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and cardiac muscle

    PubMed Central

    Murphy, R M; Dutka, T L; Horvath, D; Bell, J R; Delbridge, L M; Lamb, G D

    2013-01-01

    Excessive increases in intracellular [Ca2+] in skeletal muscle fibres cause failure of excitation–contraction coupling by disrupting communication between the dihydropyridine receptors in the transverse tubular system and the Ca2+ release channels (RyRs) in the sarcoplasmic reticulum (SR), but the exact mechanism is unknown. Previous work suggested a possible role of Ca2+-dependent proteolysis in this uncoupling process but found no proteolysis of the dihydropyridine receptors, RyRs or triadin. Junctophilin-1 (JP1; ∼90 kDa) stabilizes close apposition of the transverse tubular system and SR membranes in adult skeletal muscle; its C-terminal end is embedded in the SR and its N-terminal associates with the transverse tubular system membrane. Exposure of skeletal muscle homogenates to precisely set [Ca2+] revealed that JP1 undergoes Ca2+-dependent proteolysis over the physiological [Ca2+] range in tandem with autolytic activation of endogenous μ-calpain. Cleavage of JP1 occurs close to the C-terminal, yielding a ∼75 kDa diffusible fragment and a fixed ∼15 kDa fragment. Depolarization-induced force responses in rat skinned fibres were abolished following 1 min exposure to 40 μm Ca2+, with accompanying loss of full-length JP1. Supraphysiological stimulation of rat skeletal muscle in vitro by repeated tetanic stimulation in 30 mm caffeine also produced marked proteolysis of JP1 (and not RyR1). In dystrophic mdx mice, JP1 proteolysis is seen in limb muscles at 4 and not at 10 weeks of age. Junctophilin-2 in cardiac and skeletal muscle also undergoes Ca2+-dependent proteolysis, and junctophilin-2 levels are reduced following cardiac ischaemia–reperfusion. Junctophilin proteolysis may contribute to skeletal muscle weakness and cardiac dysfunction in a range of circumstances. PMID:23148318

  12. Ca2+-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and cardiac muscle.

    PubMed

    Murphy, R M; Dutka, T L; Horvath, D; Bell, J R; Delbridge, L M; Lamb, G D

    2013-02-01

    Excessive increases in intracellular [Ca(2+)] in skeletal muscle fibres cause failure of excitation-contraction coupling by disrupting communication between the dihydropyridine receptors in the transverse tubular system and the Ca(2+) release channels (RyRs) in the sarcoplasmic reticulum (SR), but the exact mechanism is unknown. Previous work suggested a possible role of Ca(2+)-dependent proteolysis in this uncoupling process but found no proteolysis of the dihydropyridine receptors, RyRs or triadin. Junctophilin-1 (JP1; ∼90 kDa) stabilizes close apposition of the transverse tubular system and SR membranes in adult skeletal muscle; its C-terminal end is embedded in the SR and its N-terminal associates with the transverse tubular system membrane. Exposure of skeletal muscle homogenates to precisely set [Ca(2+)] revealed that JP1 undergoes Ca(2+)-dependent proteolysis over the physiological [Ca(2+)] range in tandem with autolytic activation of endogenous μ-calpain. Cleavage of JP1 occurs close to the C-terminal, yielding a ∼75 kDa diffusible fragment and a fixed ∼15 kDa fragment. Depolarization-induced force responses in rat skinned fibres were abolished following 1 min exposure to 40 μm Ca(2+), with accompanying loss of full-length JP1. Supraphysiological stimulation of rat skeletal muscle in vitro by repeated tetanic stimulation in 30 mm caffeine also produced marked proteolysis of JP1 (and not RyR1). In dystrophic mdx mice, JP1 proteolysis is seen in limb muscles at 4 and not at 10 weeks of age. Junctophilin-2 in cardiac and skeletal muscle also undergoes Ca(2+)-dependent proteolysis, and junctophilin-2 levels are reduced following cardiac ischaemia-reperfusion. Junctophilin proteolysis may contribute to skeletal muscle weakness and cardiac dysfunction in a range of circumstances. PMID:23148318

  13. Amphibian ryanodine receptor isoforms are related to those of mammalian skeletal or cardiac muscle.

    PubMed

    Lai, F A; Liu, Q Y; Xu, L; el-Hashem, A; Kramarcy, N R; Sealock, R; Meissner, G

    1992-08-01

    The ryanodine receptor (RyR)-Ca2+ release channels of frog skeletal muscle have been purified as 30S protein complexes comprised of two high molecular weight polypeptides. The upper and lower bands of the frog doublet comigrated on sodium dodecyl sulfate polyacylamide gels with the mammalian skeletal and cardiac RyR polypeptides, respectively. Immunoblot analysis showed that a polyclonal antiserum to the rat skeletal RyR preferentially cross-reacted with the upper band, whereas monoclonal antibodies to the canine cardiac RyR preferentially cross-reacted with the lower band of the frog receptor doublet. Immunoprecipitation studies indicated the presence of two homooligomer 30S RyR complexes comprised of either the lower or upper polypeptide band of the frog doublet, and immunocytochemical staining revealed their colocalization in frog gastrocnemius muscle. After planar lipid bilayer reconstitution of the 30S frog RyR, single-channel currents were observed that exhibited a Na+ and Ca2+ conductance and pharmacological characteristics similar to those of the mammalian skeletal and cardiac Ca2+ release channels. These results suggest that amphibian skeletal muscle expresses two distinct RyR isoforms that share epitopes in common with the mammalian skeletal or cardiac RyR. PMID:1325114

  14. Allosteric interactions of three muscarine antagonists at bovine tracheal smooth muscle and cardiac M2 receptors.

    PubMed

    Roffel, A F; Elzinga, C R; Meurs, H; Zaagsma, J

    1989-03-01

    The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fast (half life less than 1 min) and was slowed by the cardioselective muscarine antagonists, gallamine, methoctramine and AF-DX 116, concentration dependently. [3H]Dexetimide dissociation from tracheal muscarine receptors was biphasic, with a fast phase (half-life less than 1 min) followed after 4-5 min by a slow phase (half-life = 38.5 min). The fast component, but not the slow component, was slowed by the muscarine antagonists with concentration dependencies very similar to those found in the heart. We conclude from these data that the major population of tracheal smooth muscle muscarine receptors resembles the cardiac M2 type not only with respect to equilibrium binding affinities but also with respect to the secondary, allosteric binding site on the muscarine receptor. The results also imply that the cardiac receptor subtype is much more sensitive to allosteric modulation than the glandular/smooth muscle receptor subtype. PMID:2714370

  15. The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

    PubMed Central

    Ip, H S; Wilson, D B; Heikinheimo, M; Tang, Z; Ting, C N; Simon, M C; Leiden, J M; Parmacek, M S

    1994-01-01

    The unique contractile phenotype of cardiac myocytes is determined by the expression of a set of cardiac muscle-specific genes. By analogy to other mammalian developmental systems, it is likely that the coordinate expression of cardiac genes is controlled by lineage-specific transcription factors that interact with promoter and enhancer elements in the transcriptional regulatory regions of these genes. Although previous reports have identified several cardiac muscle-specific transcriptional elements, relatively little is known about the lineage-specific transcription factors that regulate these elements. In this report, we demonstrate that the slow/cardiac muscle-specific troponin C (cTnC) enhancer contains a specific binding site for the lineage-restricted zinc finger transcription factor GATA-4. This GATA-4-binding site is required for enhancer activity in primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by overexpression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells. In situ hybridization studies demonstrate that GATA-4 and cTnC have overlapping patterns of expression in the hearts of postimplantation mouse embryos and that GATA-4 gene expression precedes cTnC expression. Indirect immunofluorescence reveals GATA-4 expression in cultured cardiac myocytes from neonatal rats. Taken together, these results are consistent with a model in which GATA-4 functions to direct tissue-specific gene expression during mammalian cardiac development. Images PMID:7935467

  16. Targeting of gene expression to skeletal and cardiac muscle of trangenic animals.

    PubMed

    Sands, A T; DeMayo, F; Lei, X; Schwartz, R J

    1991-01-01

    The tissue restricted and developmental potentiation of transcription by chicken alpha-skeletal actin promoter regions fused to the reporter gene chloramphenicol acetyl transferase (CAT) were characterized in transgenic mice. Six of eight expressing transgenic mouse lines containing the chicken alpha-skeletal actin promoter fused to CAT resulted in preferential transgene transcription in skeletal muscle tissue, similar to the endogenous mouse alpha-skeletal actin gene. Two of the eight lines departed from the preferred pattern of skeletal muscle expression with primary expression of the transgene in the heart, a tissue containing primarily cardiac actin isoforms. Developmentally, a transition from embryonic heart to fetal and neonatal skeletal muscle expression was produced by the transgene promoter, a pattern of regulation similar to that of the endogenous alpha-skeletal actin gene. Instances of departure of transgene expression from the endogenous gene implied the existance of higher order muscle gene regulatory mechanisms. PMID:1367249

  17. Different regulatory sequences control creatine kinase-M gene expression in directly injected skeletal and cardiac muscle.

    PubMed Central

    Vincent, C K; Gualberto, A; Patel, C V; Walsh, K

    1993-01-01

    Regulatory sequences of the M isozyme of the creatine kinase (MCK) gene have been extensively mapped in skeletal muscle, but little is known about the sequences that control cardiac-specific expression. The promoter and enhancer sequences required for MCK gene expression were assayed by the direct injection of plasmid DNA constructs into adult rat cardiac and skeletal muscle. A 700-nucleotide fragment containing the enhancer and promoter of the rabbit MCK gene activated the expression of a downstream reporter gene in both muscle tissues. Deletion of the enhancer significantly decreased expression in skeletal muscle but had no detectable effect on expression in cardiac muscle. Further deletions revealed a CArG sequence motif at position -179 within the promoter that was essential for cardiac-specific expression. The CArG element of the MCK promoter bound to the recombinant serum response factor and YY1, transcription factors which control expression from structurally similar elements in the skeletal actin and c-fos promoters. MCK-CArG-binding activities that were similar or identical to serum response factor and YY1 were also detected in extracts from adult cardiac muscle. These data suggest that the MCK gene is controlled by different regulatory programs in adult cardiac and skeletal muscle. Images PMID:8423791

  18. cap alpha. -skeletal and. cap alpha. -cardiac actin genes are coexpressed in adult human skeletal muscle and heart

    SciTech Connect

    Gunning, P.; Ponte, P.; Blau, H.; Kedes, L.

    1983-11-01

    The authors determined the actin isotypes encoded by 30 actin cDNA clones previously isolated from an adult human muscle cDNA library. Using 3' untranslated region probes, derived from ..cap alpha.. skeletal, ..beta..- and ..gamma..-actin cDNAs and from an ..cap alpha..-cardiac actin genomic clone, they showed that 28 of the cDNAs correspond to ..cap alpha..-skeletal actin transcripts. Unexpectedly, however, the remaining two cDNA clones proved to derive from ..cap alpha..-cardiac actin mRNA. Sequence analysis confirmed that the two skeletal muscle ..cap alpha..-cardiac actin cDNAs are derived from transcripts of the cloned ..cap alpha..-cardiac actin gene. Comparison of total actin mRNA levels in adult skeletal muscle and adult heart revealed that the steady-state levels in skeletal muscle are about twofold greater, per microgram of total cellular RNA, than those in heart. Thus, in skeletal muscle and in heart, both of the sarcomeric actin mRNA isotypes are quite abundant transcripts. They conclude that ..cap alpha..-skeletal and ..cap alpha..-cardiac actin genes are coexpressed as an actin pair in human adult striated muscles. Since the smooth-muscle actins (aortic and stomach) and the cytoplasmic actins (..beta.. and ..gamma..) are known to be coexpressed in smooth muscle and nonmuscle cells, respectively, they postulate that coexpression of actin pairs may be a common feature of mammalian actin gene expression in all tissues.

  19. Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells

    PubMed Central

    Swift, Luther M.; Kay, Matthew W.; Lee, Norman H.; Sarvazyan, Narine

    2012-01-01

    Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown. Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction. Methods: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 μg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utilization, oxygen consumption, mitochondrial mass, and Western blot analysis. Results: Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and β-oxidation. The functional outcome was an increase in myocyte fatty acid–substrate utilization, oxygen consumption, mitochondrial mass, PPARα (peroxisome proliferator-activated receptor α) protein expression, and extracellular acidosis. Treatment with a PPARα agonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells. Conclusions: Data suggest that DEHP exposure results in metabolic remodeling of cardiomyocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and posttranscription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid intermediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction. PMID:22672789

  20. [ATRIAL AND BRAIN NATRIURETIC PEPTIDES OF CARDIAC MUSCLE CELLS IN POSTREPERFUSION PERIOD IN RATS].

    PubMed

    Bugrova, M L

    2016-01-01

    Accumulation and release of atrial and brain natriuretic peptides (ANP and BNP) in right atrial cardiac muscle cells has been investigated in rats after 60 minutes and 60 days after the reperfusion start. The total ischemia was simulated by the method of V. G. Korpachev. Immunocytochemical localization of peptides in cardiomyocytes was performed in ultrathin sections using polyclonal antibodies. The intensity of accumulation/excretion of ANP and BNP were analyzed by the method of counting the number of granules (A- and B-types) with immunoreactive labels in 38 x 38 mkm2 visual fields in transmission electron microscope Morgagni 268D (FEI). The results were assessed using Mann-Whitney U-test (p < 0.05). After 60 minutes and 60 days post-reperfusion period, we detected an increase in the synthesis and release of ANP and BNP. The reaction of BNP was more pronounced than ANP. This is due to the fact that ANP is the main hormone of the natriuretic peptide system involved in the regulation of blood pressure in normal conditions, while BNP is the principal regulator of pressure in cardiovascular pathology. PMID:27228659

  1. High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.

    PubMed

    Collet, Marie; Assouline, Zahra; Bonnet, Damien; Rio, Marlène; Iserin, Franck; Sidi, Daniel; Goldenberg, Alice; Lardennois, Caroline; Metodiev, Metodi Dimitrov; Haberberger, Birgit; Haack, Tobias; Munnich, Arnold; Prokisch, Holger; Rötig, Agnès

    2016-08-01

    Acyl-CoA dehydrogenase family, member 9 (ACAD9) mutation is a frequent, usually fatal cause of early-onset cardiac hypertrophy and mitochondrial respiratory chain complex I deficiency in early childhood. We retrospectively studied a series of 20 unrelated children with cardiac hypertrophy and isolated complex I deficiency and identified compound heterozygosity for missense, splice site or frame shift ACAD9 variants in 8/20 patients (40%). Age at onset ranged from neonatal period to 9 years and 5/8 died in infancy. Heart transplantation was possible in 3/8. Two of them survived and one additional patient improved spontaneously. Importantly, the surviving patients later developed delayed-onset neurologic or muscular symptoms, namely cognitive impairment, seizures, muscle weakness and exercise intolerance. Other organ involvement included proximal tubulopathy, renal failure, secondary ovarian failure and optic atrophy. We conclude that ACAD9 mutation is the most frequent cause of cardiac hypertrophy and isolated complex I deficiency. Heart transplantation in children surviving neonatal period should be considered with caution, as delayed-onset muscle and brain involvement of various severity may occur, even if absent prior to transplantation. PMID:26669660

  2. Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

    PubMed

    Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

    2016-09-01

    In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded. PMID:27379608

  3. Severe papillary muscle dysfunction substantiated by atrial pacing during cardiac catheterization.

    PubMed

    Finn, M C; Bower, P J

    1977-05-01

    A patient experienced episodic pulmonary edema accompanying nocturnal angina pectoris. The symptoms were provoked at cardiac catheterization by atrial pacing. Simultaneous onset of chest pain, shortness of breath, and sudden appearance of a large V wave in the pulmonary artery wedge pressure contour confirmed acute mitral valve regurgitation. Rapid reversal of these changes after nitroglycerin administration supported "papillary muscle dysfunction" as the explanation for these hemodynamic changes. PMID:403754

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

    PubMed

    Buchpiguel, C A; Roizemblatt, S; Pastor, E H; Hironaka, F H; Cossermelli, W

    1996-02-01

    To determine the role of scintigraphy in the detection of skeletal and cardiac involvement in dermato- and polymyositis (DM/PM), we studied 30 patients with a confirmed diagnosis of DM/PM (23 females, 7 males; mean age: 35 years). Technetium-99m pyrophosphate (99mTc-PYP) 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, 99mTc-PYP showed 70% and 67Ga 65% accuracy. Abnormal PYP cardiac uptake was observed in 57% of patients, whereas abnormal 67Ga cardiac uptake was seen in only 15%. Electrocardiography was abnormal in 40%, rest gated blood pool study in 23%, and chest X-ray in 13%. In conclusion, both 99mTc-PYP and 67Ga can be useful in the detection of the active phase of muscle disease. However, 99mTc-PYP seems to be more effective than 67Ga in the early diagnosis of cardiac involvement. PMID:8925856

  5. Cardiac Meets Skeletal: What's New in Microfluidic Models for Muscle Tissue Engineering.

    PubMed

    Visone, Roberta; Gilardi, Mara; Marsano, Anna; Rasponi, Marco; Bersini, Simone; Moretti, Matteo

    2016-01-01

    In the last few years microfluidics and microfabrication technique principles have been extensively exploited for biomedical applications. In this framework, organs-on-a-chip represent promising tools to reproduce key features of functional tissue units within microscale culture chambers. These systems offer the possibility to investigate the effects of biochemical, mechanical, and electrical stimulations, which are usually applied to enhance the functionality of the engineered tissues. Since the functionality of muscle tissues relies on the 3D organization and on the perfect coupling between electrochemical stimulation and mechanical contraction, great efforts have been devoted to generate biomimetic skeletal and cardiac systems to allow high-throughput pathophysiological studies and drug screening. This review critically analyzes microfluidic platforms that were designed for skeletal and cardiac muscle tissue engineering. Our aim is to highlight which specific features of the engineered systems promoted a typical reorganization of the engineered construct and to discuss how promising design solutions exploited for skeletal muscle models could be applied to improve cardiac tissue models and vice versa. PMID:27571058

  6. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle.

    PubMed Central

    Wu, J; Johnson, E A; Kootsey, J M

    1996-01-01

    It has been shown that propagation of excitation in cardiac muscle is anisotropic. Compared to propagation at right angles to the long axes of the fibers, propagation along the long axis is faster, the extracellular action potential (AP) is larger in amplitude, and the intracellular AP has a lower maximum rate of depolarization, a larger time constant of the foot, and a lower peak amplitude. These observations are contrary to the predictions of classical one-dimensional (1-D) cable theory and, thus far, no satisfactory theory for them has been reported. As an alternative description of propagation in cardiac muscle, this study provides a quasi-1-D theory that includes a simplified description of the effects of action currents in extracellular space as well as resistive coupling between surface and deeper fibers in cardiac muscle. In terms of classical 1-D theory, this quasi-1-D theory reveals that the anisotropies in the wave form of the AP arise from modifications in the effective membrane ionic current and capacitance. The theory also shows that it is propagation in the longitudinal, not in the transverse direction that deviates from classical 1-D cable theory. Images FIGURE 1 PMID:8913583

  7. The declined phosphorylation of Hsp27 in rat cardiac muscle after simulated microgravity induced by hindlimb unloading

    NASA Astrophysics Data System (ADS)

    Yuan, Ming; Jiang, Shizhong; Li, Zhili; Yuan, Min; Dong, Weijun

    Many studies have shown that simulated microgravity induced by hindlimb unloading can decrease the contractility of rat cardiac muscle however the mechanisms responsible for which remain unclear Actin polymerization which can be regulated by Hsp27 has important role in the transmission of stress force during the contraction of cardiac muscle In this study western blot analysis was used to detect the expression of Hsp27 and phosphorylated Hsp27 FAK and phosphorylated FAK P38 MAPK and phosphorylated P38 MAPK in rat cardiac muscle after 14d hindlimb unloading The results showed that the phosphorylation levels of both Hsp27 and P38 MAPK were declined significantly which may decrease actin polymerization and inhibit the transmission of stress force during the contraction of rat cardiac muscle after hindlimb unloading However the phosphorylation level of FAK was not declined significantly in cardiac muscle The results suggested that the declined phosphorylation level of Hsp27 which may be ascribable to the decline of contractility of rat cardiac muscle after 14d hindlimb unloading may be induced by the declined phosphorylation level of P38 MAPK but not phosphorylation level of FAK

  8. Effect of hypokinesia on contractile function of cardiac muscle

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Trikhpoyeva, A. M.; Gorina, M. S.

    1980-01-01

    Rats were subjected to hypokinesia for two months and the contractile function of isolated papillary muscle was studied. Hypokinesia reduced significantly the isotonic contraction rate which depended on the ATPase activity of the myofibrils; it also reduced the rate and index of relaxation which depended on the functional capacity of the Ca(++) pump of the sarcoplasmic reticulum. The maximum force of isometric contraction determined by the quantity of actomyosin bridges in the myofibrils did not change after hypokinesia. This complex of changes is contrary to that observed in adaptation to exercise when the rate of isotonic contraction and relaxation increases while the force of isometric contraction does not change. The possible mechanism of this stability of the contractile force during adaptation and readaptation of the heart is discussed.

  9. A Cycling Movement Based System for Real-Time Muscle Fatigue and Cardiac Stress Monitoring and Analysis

    PubMed Central

    Chen, Szi-Wen; Liaw, Jiunn-Woei; Chang, Ya-Ju; Chan, Hsiao-Lung; Chiu, Li-Yu

    2015-01-01

    In this study, we defined a new parameter, referred to as the cardiac stress index (CSI), using a nonlinear detrended fluctuation analysis (DFA) of heart rate (HR). Our study aimed to incorporate the CSI into a cycling based fatigue monitoring system developed in our previous work so the muscle fatigue and cardiac stress can be both continuously and quantitatively assessed for subjects undergoing the cycling exercise. By collecting electrocardiogram (ECG) signals, the DFA scaling exponent α was evaluated on the RR time series extracted from a windowed ECG segment. We then obtained the running estimate of α by shifting a one-minute window by a step of 20 seconds so the CSI, defined as the percentage of all the less-than-one α values, can be synchronously updated every 20 seconds. Since the rating of perceived exertion (RPE) scale is considered as a convenient index which is commonly used to monitor subjective perceived exercise intensity, we then related the Borg RPE scale value to the CSI in order to investigate and quantitatively characterize the relationship between exercise-induced fatigue and cardiac stress. Twenty-two young healthy participants were recruited in our study. Each participant was asked to maintain a fixed pedaling speed at a constant load during the cycling exercise. Experimental results showed that a decrease in DFA scaling exponent α or an increase in CSI was observed during the exercise. In addition, the Borg RPE scale and CSI were positively correlated, suggesting that the factors due to cardiac stress might also contribute to fatigue state during physical exercise. Since the CSI can effectively quantify the cardiac stress status during physical exercise, our system may be used in sports medicine, or used by cardiologists who carried out stress tests for monitoring heart condition in patients with heart diseases. PMID:26115515

  10. Skeletal muscle damage and impaired regeneration due to LPL-mediated lipotoxicity

    PubMed Central

    Tamilarasan, K P; Temmel, H; Das, S K; Al Zoughbi, W; Schauer, S; Vesely, P W; Hoefler, G

    2012-01-01

    According to the concept of lipotoxicity, ectopic accumulation of lipids in non-adipose tissue induces pathological changes. The most prominent effects are seen in fatty liver disease, lipid cardiomyopathy, non-insulin-dependent diabetes mellitus, insulin resistance and skeletal muscle myopathy. We used the MCK(m)-hLPL mouse distinguished by skeletal and cardiac muscle-specific human lipoprotein lipase (hLPL) overexpression to investigate effects of lipid overload in skeletal muscle. We were intrigued to find that ectopic lipid accumulation induced proteasomal activity, apoptosis and skeletal muscle damage. In line with these findings we observed reduced Musculus gastrocnemius and Musculus quadriceps mass in transgenic animals, accompanied by severely impaired physical endurance. We suggest that muscle loss was aggravated by impaired muscle regeneration as evidenced by reduced cross-sectional area of regenerating myofibers after cardiotoxin-induced injury in MCK(m)-hLPL mice. Similarly, an almost complete loss of myogenic potential was observed in C2C12 murine myoblasts upon overexpression of LPL. Our findings directly link lipid overload to muscle damage, impaired regeneration and loss of performance. These findings support the concept of lipotoxicity and are a further step to explain pathological effects seen in muscle of obese patients, patients with the metabolic syndrome and patients with cancer-associated cachexia. PMID:22825472

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

    PubMed Central

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

    2013-01-01

    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. PMID:23165765

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

    PubMed

    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

  13. Zebrafish Cardiac Muscle Thick Filaments: Isolation Technique and Three-Dimensional Structure

    PubMed Central

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

    2014-01-01

    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. PMID:24739166

  14. Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle function

    PubMed Central

    Gallagher, Thomas L.; Arribere, Joshua A.; Geurts, Paul A.; Exner, Cameron R. T.; McDonald, Kent L.; Dill, Kariena K.; Marr, Henry L.; Adkar, Shaunak S.; Garnett, Aaron T.; Amacher, Sharon L.; Conboy, John G.

    2012-01-01

    Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos was strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle function. PMID:21925157

  15. Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions.

    PubMed

    Gallagher, Thomas L; Arribere, Joshua A; Geurts, Paul A; Exner, Cameron R T; McDonald, Kent L; Dill, Kariena K; Marr, Henry L; Adkar, Shaunak S; Garnett, Aaron T; Amacher, Sharon L; Conboy, John G

    2011-11-15

    Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos were strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle functions. PMID:21925157

  16. Single bout of running exercise changes LC3-II expression in rat cardiac muscle.

    PubMed

    Ogura, Yuji; Iemitsu, Motoyuki; Naito, Hisashi; Kakigi, Ryo; Kakehashi, Chiaki; Maeda, Seiji; Akema, Tatsuo

    2011-11-01

    Macroautophagy (autophagy) is an intracellular catalytic process. We examined the effect of running exercise, which stimulates cardiac work physiologically, on the expression of microtubule-associated protein 1 light chain 3 (LC3)-II, an indicator of autophagy, as well as some autophagy-related proteins in rat cardiac muscle. The left ventricles were taken from rats immediately (0 h), and at 0.5h, 1h or 3h after a single bout of running exercise on a treadmill for 30 min and also from rats in a rest condition. In these samples, we evaluated the level of LC3-II and p62, and the phosphorylation level of mammalian target of rapamycin (mTOR), Akt and AMP-activated protein kinase alpha (AMPKα) by Western blotting. The exercise produced a biphasic change in LC3-II, with an initial decrease observed immediately after the exercise and a subsequent increase 1h thereafter. LC3-II then returned to the rest level at 3h after the exercise. A negative correlation was found between the LC3-II expression and mTOR phosphorylation, which plays a role in inhibiting autophagy. The exercise increased phosphorylation of AMPKα, which stimulates autophagy via suppression of mTOR phosphorylation, immediately after exercise. The level of p62 and phosphorylated Akt was not altered significantly by the exercise. These results suggest for the first time that a single bout of running exercise induces a biphasic change in autophagy in the cardiac muscle. The exercise-induced change in autophagy might be partially mediated by mTOR in the cardiac muscle. PMID:22005460

  17. Changes of intracellular milieu with fatigue or hypoxia depress contraction of skinned rabbit skeletal and cardiac muscle.

    PubMed Central

    Godt, R E; Nosek, T M

    1989-01-01

    1. Maximal calcium-activated force (Fmax) and calcium sensitivity were markedly decreased in detergent-skinned fibres from skeletal and cardiac muscle by solutions that mimicked the total milieu changes associated with fatigue and hypoxia. Further experiments determined the relative contribution of each of the individual changes in milieu. 2. Both Ca2+ sensitivity and Fmax of skeletal and cardiac fibres were decreased with increased [H+] or inorganic phosphate (Pi). These effects were greater in cardiac muscle. 3. Decreasing MgATP over the range observed with fatigue and hypoxia (6.8-4.7 mM) had no effect on Fmax or Ca2+ sensitivity of either muscle type. 4. Decreasing phosphocreatine (PCr: 15-1 mM) increased Fmax but had little effect on Ca2+ sensitivity in both muscle types. In cardiac fibres, the effect on Fmax could be mimicked by inhibition of endogenous creatine kinase. 5. ADP (0.7 mM) increased Fmax and Ca2+ sensitivity, while AMP (0.06 mM) slightly increased Fmax but had no effect on Ca2+ sensitivity of either skeletal or cardiac fibres. 6. Creatine (25 mM) had no significant effect on either Ca2+ sensitivity or Fmax of skeletal and cardiac muscle fibres. At higher levels (50 mM), however, creatine depressed Fmax and slightly altered Ca2+ sensitivity. 7. Thiophosphorylation of myosin P light chains (phosphorylatable light chains of myosin) in rabbit psoas fibres had no effect on Ca2+ sensitivity, yet slightly but significantly increased Fmax under fatigue conditions. 8. Reducing the affinity for ATP hydrolysis (by adding ADP, AMP and creatine) over the range calculated for fatigue/hypoxia (60-45 kJ/mol) produced the enhancement in Fmax expected from added ADP and AMP in cardiac but not skeletal muscle, indicating that changes in affinity influence Fmax of skeletal muscle. Reducing affinity produced little change in Ca2+ sensitivity of skeletal muscle. In contrast, the change produced in cardiac muscle was greater than that expected from addition of ADP and

  18. Acute regulation of glucose uptake in cardiac muscle of the American eel Anguilla rostrata.

    PubMed

    Rodnick; Bailey; West; Driedzic

    1997-01-01

    We investigated the effects of anoxia and contractile activity on glucose uptake and the intracellular location of hexokinase in cardiac muscle of the American eel Anguilla rostrata. Uptake of 2-deoxyglucose (2-DG) by ventricle strips at 15 °C was increased by 45 % by anoxia and by 85 % by contractile activity over basal conditions. The anoxia- and contraction-induced increase in basal 2-DG uptake was inhibited completely by 25 µmol l-1 cytochalasin B, suggesting that facilitated glucose transporters are involved. Maximal activity of hexokinase in whole homogenates (approximately 10 µmol min-1 g-1 tissue) was 200 times higher than the maximal rate of 2-DG uptake measured in vitro (46 nmol min-1 g-1 tissue). Only 20­25 % of hexokinase activity was localized to the mitochondrial fraction, and this was not altered by perfusion of the hearts with anoxic media. It is therefore unlikely that anoxia-induced stimulation of 2-DG uptake is mediated by intracellular translocation of hexokinase. As in the case of mammalian muscle, glucose 6-phosphate is a potent inhibitor of hexokinase in eel cardiac muscle (IC50=0.44 mmol l-1). In summary, anoxia and contractile activity significantly increase 2-DG uptake in cardiac muscle of American eels, and glucose transport may be rate-limiting for glucose utilization. Increased utilization of glucose during anoxia or contractile activity may involve the recruitment of facilitative glucose transport proteins to the cell surface of myocytes or an increase in the intrinsic activity of glucose transporters already residing at the cell surface. PMID:9344975

  19. Successful extracorporeal life support in sudden cardiac arrest due to coronary anomaly

    PubMed Central

    Park, Jung Wan; Lee, Jae Hyuk; Kim, Ki-Sik; Bang, Duk Won; Hyon, Min-Su; Lee, Min-Ho; Park, Byoung-Won

    2016-01-01

    Extracorporeal life support (ECLS) has recently been reported to have a survival benefit in patients with cardiac arrest. It is now used widely as a lifesaving modality. Here, we describe a case of sudden cardiac arrest (SCA) in a young athlete with an anomalous origin of the right coronary artery from the left coronary sinus. Resuscitation was successful using ECLS before curative bypass surgery. We highlight the efficacy of ECLS for a patient with SCA caused by a rare, unexpected aetiology. In conclusion, ECLS was a lifesaving modality for SCA due to an anomalous coronary artery in this young patient. PMID:27354896

  20. Early detection and efficient therapy of cardiac angiosarcoma due to routine transesophageal echocardiography after cerebrovascular stroke

    PubMed Central

    Vogelgesang, Dirk; Dahm, Johannes B; Großmann, Holm; Hippe, Andre; Hummel, Astrid; Lotze, Christian; Vogelgesang, Silke

    2008-01-01

    Primary malignant cardiac tumors (cardiac angiosarcomas) are exceedingly rare. Since there are initially nonspecific or missing symptoms, these tumors are usually diagnosed only in an advanced, often incurable stage, after the large tumor mass elicits hemodynamic obstructive symptoms. A 59-year-old female presented with symptoms of cerebral ischemia. A computed tomography (CT) scan showed changes suggestive of stroke. Transesophageal echocardiography revealed an inhomogeneous, medium-echogenic, floating mass at the roof of the left atrium near the mouth of the right upper pulmonary vein, indicative of a thrombus. At surgery, a solitary tumor was completely enucleated. Histologically, cardiac angiosarcoma was diagnosed. The patient received adjuvant chemotherapy and was free of symptoms and recurrence of disease at 14 months follow-up. Due to the fortuitous appearance of clinical signs indicative of stroke, cardiac angiosarcoma was diagnosed and effectively treated at an early, nonmetastatic, and therefore potentially curable stage. Although cardiac angiosarcoma is a rare disease, it should be taken into consideration as a potential cause of cerebral embolic disease. PMID:19066013

  1. Simultaneous measurement of cerebral and muscle tissue parameters during cardiac arrest and cardiopulmonary resuscitation

    NASA Astrophysics Data System (ADS)

    Nosrati, Reyhaneh; Ramadeen, Andrew; Hu, Xudong; Woldemichael, Ermias; Kim, Siwook; Dorian, Paul; Toronov, Vladislav

    2015-03-01

    In this series of animal experiments on resuscitation after cardiac arrest we had a unique opportunity to measure hyperspectral near-infrared spectroscopy (hNIRS) parameters directly on the brain dura, or on the brain through the intact pig skull, and simultaneously the muscle hNIRS parameters. Simultaneously the arterial blood pressure and carotid and femoral blood flow were recorded in real time using invasive sensors. We used a novel hyperspectral signalprocessing algorithm to extract time-dependent concentrations of water, hemoglobin, and redox state of cytochrome c oxidase during cardiac arrest and resuscitation. In addition in order to assess the validity of the non-invasive brain measurements the obtained results from the open brain was compared to the results acquired through the skull. The comparison of hNIRS data acquired on brain surface and through the adult pig skull shows that in both cases the hemoglobin and the redox state cytochrome c oxidase changed in similar ways in similar situations and in agreement with blood pressure and flow changes. The comparison of simultaneously measured brain and muscle changes showed expected differences. Overall the results show feasibility of transcranial hNIRS measurements cerebral parameters including the redox state of cytochrome oxidase in human cardiac arrest patients.

  2. Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles.

    PubMed

    Ikezoe, Tome; Mori, Natsuko; Nakamura, Masatoshi; Ichihashi, Noriaki

    2012-01-01

    This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis. PMID:21472438

  3. Application of MicroRNA in Cardiac and Skeletal Muscle Disease Gene Therapy

    PubMed Central

    Huang, Zhan-Peng; Neppl, Ronald L.; Wang, Da-Zhi

    2016-01-01

    MicroRNAs (miRNAs) are a class of small ~22 nt noncoding RNAs. miRNAs regulate gene expression at the posttranscriptional levels by destabilization and degradation of the target mRNA or by translational repression. Numerous studies have demonstrated that miRNAs are essential for normal mammalian development and organ function. Deleterious changes in miRNA expression play an important role in human diseases. We and others have previously reported several muscle-specific miRNAs, including miR-1/206, miR-133, and miR-208. These muscle-specific miRNAs are essential for normal myoblast differentiation and proliferation, and they have also been implicated in various cardiac and skeletal muscular diseases. miRNA-based gene therapies hold great potential for the treatment of cardiac and skeletal muscle disease(s). Herein, we introduce the methods commonly applied to study the biological role of miRNAs, as well as the techniques utilized to manipulate miRNA expression. PMID:21194029

  4. Measurement of transmembrane potential and current in cardiac muscle: a new voltage clamp method.

    PubMed Central

    Goldman, Y; Morad, M

    1977-01-01

    1. A single sucrose gap voltage clamp technique was developed to correct for artifacts of 'leakage' corrent and extracellular resistance making possible improved measurement of membrane current and membrane potential in cardiac muscle. 2. A fourth compartment termed 'guard gap' was added to the sucrose gap. The guard gap is maintained at the same potential as the Reinger pool, so that no extracellular leakage current can flow into the Ringer pool. Comparison of experimental results with the predictions of an idealized cable model indicates that the guard gap is effective in trapping leakage current. 3. The slow charging of membrane capacitance due to extracellular series resistance was accelerated by applying a 'pre-pulse' of the command potential past the final voltage clamp value. 4. A second technique, termed 'chopped current pulse clamp', was used to compensate for the extracellular resistance throughout the voltage clamp step. The applied current was turned on and off at a frequency of 0-5-2 kHz. The membrane potential sampled during the zero current phase was fed back through the clamp loop. 5. With either of these compensation techniques, the voltage and current traces settle to effectively constant values within 2-4 msec after initiation of a hyperpolarizing voltage clamp step from rest. 6. The membrane conductance measured by the prepulse and chopped current-pulse technique are equal and confirm a higher conductance at rest than during the plateau of the action potential. 7. The 'instantaneous' current-voltage relation of the membrane is linear during the plateau of the frog ventricular action potential. PMID:301933

  5. The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

    PubMed Central

    Godfraind, T.; Lesne, M.

    1972-01-01

    1. The uptake of 3H-digitoxin, 3H-ouabain and 3H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect. 2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished. 3. The uptake of inactive doses of dihydro-ouabain was only by a non-saturable mechanism. 4. The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake. 5. The uptake was reduced at 4° C to the clearance of the non-saturable site. 6. ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site. 7. It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides. PMID:4656610

  6. Transgenic Overexpression of LARGE Induces α-Dystroglycan Hyperglycosylation in Skeletal and Cardiac Muscle

    PubMed Central

    Sharp, Paul S.; Liu, Ke; Cirak, Sebahattin; Brown, Susan C.; Wells, Dominic J.; Muntoni, Francesco

    2010-01-01

    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 potential therapies in the

  7. Comparison of heterologously expressed human cardiac and skeletal muscle sodium channels.

    PubMed Central

    Wang, D W; George, A L; Bennett, P B

    1996-01-01

    In this study we have expressed and characterized recombinant cardiac and skeletal muscle sodium channel alpha subunits in tsA-201 cells under identical experimental conditions. Unlike the Xenopus oocyte expression system, in tsA-201 cells (transformed human embryonic kidney) both channels seem to gate rapidly, as in native tissue. In general, hSkM1 gating seemed faster than hH1 both in terms of rate of inactivation and rate of recovery from inactivation as well as time to peak current. The midpoint of the steady-state inactivation curve was approximately 25 mV more negative for hH1 compared with hSkM1. In both isoforms, the steady-state channel availability relationships ("inactivation curves") shifted toward more negative membrane potentials with time. The cardiac isoform showed a minimal shift in the activation curve as a function of time after whole-cell dialysis, whereas hSkM1 showed a continued and marked negative shift in the activation voltage dependence of channel gating. This observation suggests that the mechanism underlying the shift in inactivation voltage dependence may be similar to the one that is causing the shift in the activation voltage dependence in hSkM1 but that this is uncoupled in the cardiac isoform. These results demonstrate the utility and limitations of measuring cardiac and skeletal muscle recombinant Na+ channels in tsA-201 cells. This baseline characterization will be useful for future investigations on channel mutants and pharmacology. PMID:8770201

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

    PubMed Central

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

    2011-01-01

    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-Δ43 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 (∼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 I1,1/I1,0, 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-Δ43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-Δ43. 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.—Muthu, P., Wang, L., Yuan, C.-C., Kazmierczak, K., Huang, W., Hernandez, O. M., Kawai, M., Irving, T. C., Szczesna-Cordary, D. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. PMID:21885653

  9. Laser-patterned stem-cell bridges in a cardiac muscle model for on-chip electrical conductivity analyses

    PubMed Central

    Ma, Zhen; Liu, Qiuying; Liu, Honghai; Yang, Huaxiao; Yun, Julie X.; Eisenberg, Carol; Borg, Thomas K.; Xu, Meifeng; Gao, Bruce Z.

    2012-01-01

    Following myocardial infarction there is an irreversible loss of cardiomyocytes that results in the alteration of electrical propagation in the heart. Restoration of functional electrical properties of the damaged heart muscle is essential to recover from the infarction. While there are a few reports that demonstrate that fibroblasts can form junctions that transmit electrical signals, a potential alternative using the injection of stem cells has emerged as a promising cellular therapy; however, stem-cell electrical conductivity within the cardiac muscle fiber is unknown. In this study, an in vitro cardiac muscle model was established on an MEA-based biochip with multiple cardiomyocytes that mimic cardiac tissue structure. Using a laser beam, stem cells were inserted adjacent to each muscle fiber (cell bridge model) and allowed to form cell-cell contact as determined by the formation of gap junctions. The electrical conductivity of stem cells was assessed and compared with the electrical conductivities of cardiomyocytes and fibroblasts. Results showed that stem cell-myocyte contacts exhibited higher and more stable conduction velocities than myocyte-fibroblast contacts, which indicated that stem cells have higher electrical compatibility with native cardiac muscle fibers than cardiac fibroblasts. PMID:22170399

  10. Changes of contractile responses due to simulated weightlessness in rat soleus muscle

    NASA Astrophysics Data System (ADS)

    Elkhammari, A.; Noireaud, J.; Léoty, C.

    1994-08-01

    Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

  11. Successful use of therapeutic hypothermia after cardiac arrest due to amitriptyline and venlafaxine intoxication.

    PubMed

    Kontio, Terhi; Salo, Ari; Kantola, Teemu; Toivonen, Lauri; Skrifvars, Markus B

    2015-06-01

    The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of depression, but possess significant cardiotoxicity, and are one of the most common medications used in suicide attempts worldwide. TCA poisoning can cause hypotension, seizures, and cardiac conduction disturbances, which can lead to life-threatening arrhythmia. Current guidelines recommend mild therapeutic hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment itself can cause disturbances in cardiac conduction, which could aggravate the effect of TCAs on cardiac conduction. We report the successful use of TH in a 19-year-old woman who was resuscitated from ventricular tachycardia after intentional ingestion of amitriptyline and venlafaxine, a serotonin-norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm was ventricular tachycardia with no detectable pulse. Three defibrillations, magnesium sulfate, and sodium bicarbonate were given and her trachea was intubated, after which return of spontaneous circulation (ROSC) was achieved in 26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of-hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of norepinephrine was initiated for low blood pressure. On arrival at the university hospital, she was unconscious and had dilated pupils. She was tachycardic with a body temperature of 33.5°C. She was transferred to the intensive care unit and TH was maintained with invasive cooling. During the TH treatment, she did not experience any serious cardiac arrhythmia, transthoracic echocardiogram was normal, and the electrocardiogram (ECG) returned to normal. The patient was extubated 45 hours after the cardiac arrest. After the extubation, she was alert and cooperative, but slightly delusional. She was

  12. Differential response of rat cardiac and skeletal muscle glycogen to glucocorticoids.

    PubMed

    Poland, J L; Poland, J W; Honey, R N

    1982-05-01

    Though glucocorticoids were previously implicated in the support of myocardial glycogen supercompensation after exercise, it was unclear why skeletal muscle glycogen did not simultaneously supercompensate since it was also exposed to the exercise-induced glucocorticoid increases. The current study shows that glucocorticoids differentially affect cardiac and skeletal muscle glycogen. Following dexamethasone administration (400 micrograms i.p.) myocardial glycogen peaked at 6 h while glycogen in the soleus, red vastus lateralis, and white vastus lateralis increased more slowly and reached the highest values 17 h postinjection. Concurrently, blood glucose, insulin, and glucagon remained at control levels. Liver glycogen increased within 2 h and continued to rise with a peak value at 17 h. Plasma free fatty acid (FFA) levels increased and remained high throughout the 26-h experimental period. High FFA levels inhibit glycogenolysis and thus could be partially responsible for glucocorticoid-induced glycogen increases. It is postulated that glycogen supercompensation does not readily occur in skeletal muscles after exercise because of the brevity of the corticosterone and FFA increases and the slowness of the skeletal muscle glycogen response to glucocorticoids. PMID:7104851

  13. A computer simulation study of isometric contraction of latissimus dorsi muscle used for cardiac assistance.

    PubMed

    Minoura, T; Mizuhara, H; Tsutsumi, S; Nishimura, K; Ban, T

    1997-01-01

    This study was designed to investigate the feasibility of a skeletal muscle pump employing latissimus dorsi muscle (LDM) for cardiac assistance. We developed and used a 2-dimensional mathematical model for LDM to investigate how the size of pneumatic balloons (30, 38, and 45 ml) and the three different locations (proximal, center, and distal) affect the pressure applied to the balloon by LDM. The computer simulation was performed by coding a visco-elastic and nonlinear 2-dimensional program that employed the finite element method (FEM). The muscle specific parameters of LDM were obtained from animal experiment results. The model is based on Hill's characteristic equation and composed of a contractile component and a passive element. The simulation results indicated that the intermediate and largest sized balloon lead to the highest and the lowest power (volume reduction per unit time interval), respectively. On the other hand, when the balloon is inserted in the distal LDM, the power is lower than in the other two positions, regardless of the balloon size. The above results suggest that the optimal size of the balloon should be selected depending on the muscle specific parameters of the actuator, and that the balloon should be inserted either in the proximal portion or center of the actuator. PMID:9360153

  14. CARDIAC PATHOLOGY EXCEEDS SKELETAL MUSCLE PATHOLOGY IN TWO CASES OF LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2I

    PubMed Central

    Margeta, Marta; Connolly, Anne M.; Winder, Thomas L.; Pestronk, Alan; Moore, Steven A.

    2010-01-01

    Limb-girdle muscular dystrophy type 2I (LGMD-2I) is caused by mutations in fukutin-related protein gene (FKRP) that lead to abnormal glycosylation of α-dystroglycan in skeletal muscle. Heart involvement in LGMD-2I is common, but little is known about underlying cardiac pathology. Here, we describe two patients with LGMD-2I (homozygous FKRP mutation c.826C>A, p.Leu276Ile) who developed severe congestive heart failure requiring cardiac transplantation. The dystrophic pathology and impairment of α-dystroglycan glycosylation were severe in the heart but mild in the skeletal muscle, underscoring the lack of correlation between cardiac and skeletal muscle involvement in some LGMD-2I patients. PMID:19705481

  15. Measurement of calcium release due to inositol trisphosphate receptors in skeletal muscle.

    PubMed

    Casas, Mariana; Altamirano, Francisco; Jaimovich, Enrique

    2012-01-01

    Calcium transients elicited by IP(3) receptors upon electrical stimulation of skeletal muscle cells (slow calcium signals) are often hard to visualize due to their relatively small amplitude compared to the large transient originated from ryanodine receptors associated to excitation-contraction coupling. The study of slow calcium transients, however, is relevant due to their function in regulation of muscle gene expression and in the process of excitation-transcription coupling. Discussed here are the procedures used to record slow calcium signals from both cultured mouse myotubes and from cultured adult skeletal muscle fibers. PMID:22130849

  16. Nitric oxide synthase-dependent "on/off" switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle.

    PubMed

    Amelio, D; Garofalo, F; Wong, W P; Chew, S F; Ip, Y K; Cerra, M C; Tota, B

    2013-08-01

    African lungfishes (Protopterus spp.) are obligate air breathers which enter in a prolonged torpor (aestivation) in association with metabolic depression, and biochemical and morpho-functional readjustments during the dry season. During aestivation, the lungfish heart continues to pump, while the skeletal muscle stops to function but can immediately contract during arousal. Currently, nothing is known regarding the orchestration of the multilevel rearrangements occurring in myotomal and myocardial muscles during aestivation and arousal. Because of its universal role in cardio-circulatory and muscle homeostasis, nitric oxide (NO) could be involved in coordinating these stress-induced adaptations. Western blotting and immunofluorescence microscopy on cardiac and skeletal muscles of Protopterus annectens (freshwater, 6months of aestivation and 6days after arousal) showed that expression, localization and activity of the endothelial-like nitric oxide synthase (eNOS) isoform and its partners Akt and Hsp-90 are tissue-specifically modulated. During aestivation, phospho-eNOS/eNOS and phospho-Akt/Akt ratios increased in the heart but decreased in the skeletal muscle. By contrast, Hsp-90 increased in both muscle types during aestivation. TUNEL assay revealed that increased apoptosis occurred in the skeletal muscle of aestivating lungfish, but the myocardial apoptotic rate of the aestivating lungfish remained unchanged as compared with the freshwater control. Consistent with the preserved cardiac activity during aestivation, the expression of apoptosis repressor (ARC) also remained unchanged in the heart of aestivating and aroused fish as compared with the freshwater control. Contrarily, ARC expression was strongly reduced in the skeletal muscle of aestivating lungfish. On the whole, our data indicate that changes in the eNOS/NO system and cell turnover are implicated in the morpho-functional readjustments occurring in lungfish cardiac and skeletal muscle during the switch

  17. Measurement of high-resolution mechanical contraction of cardiac muscle by induced eddy current.

    PubMed

    Lee, Young-Jae; Lee, Kang-Hwi; Kang, Seung-Jin; Kim, Kyeung-Nam; Khang, Seonah; Koo, Hye Ran; Gi, Sunok; Lee, Joo Hyeon; Lee, Jeong-Whan

    2014-01-01

    There are many types of devices which help to manage a personal health conditions such as heartbeat chest belt, pedometer and smart watch. And the most common device has the relationship with heart rate or ECG data. However, users have to attach some electrode or fasten the belt on the bare skin to measure bio-signal information. Therefore, most of people want more convenient and short-ready-time and no-need to attach electrode. In this paper, we proposed the high-resolution measuring system of mechanical activity of cardiac muscle and thereby measure heartbeat. The principle of the proposed measuring method is that the alternating current generate alternating magnetic field around coil. This primary magnetic field induces eddy current which makes magnetic field against primary coil in the nearby objects. To measure high-resolution changes of the induced secondary magnetic fields, we used digital Phase-locked loop(PLL) circuit which provides more high-resolution traces of frequency changes than the previous studies based on digital frequency counter method. As a result of our preliminary experiment, peak-peak intervals of the proposed method showed high correlation with R-R intervals of clinical ECG signals(r=0.9249). Also, from signal traces of the proposed method, we might make a conjecture that the contraction of atrium or ventricle is reflected by changing conductivity of cardiac muscle which is beating ceaselessly. PMID:25571434

  18. Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: implications for myocardium regeneration.

    PubMed

    Condorelli, G; Borello, U; De Angelis, L; Latronico, M; Sirabella, D; Coletta, M; Galli, R; Balconi, G; Follenzi, A; Frati, G; Cusella De Angelis, M G; Gioglio, L; Amuchastegui, S; Adorini, L; Naldini, L; Vescovi, A; Dejana, E; Cossu, G

    2001-09-11

    The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogeneous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies. PMID:11535818

  19. Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration

    PubMed Central

    Condorelli, G.; Borello, U.; De Angelis, L.; Latronico, M.; Sirabella, D.; Coletta, M.; Galli, R.; Balconi, G.; Follenzi, A.; Frati, G.; Cusella De Angelis, M. G.; Gioglio, L.; Amuchastegui, S.; Adorini, L.; Naldini, L.; Vescovi, A.; Dejana, E.; Cossu, G.

    2001-01-01

    The concept of tissue-restricted differentiation of postnatal stem cells has been challenged by recent evidence showing pluripotency for hematopoietic, mesenchymal, and neural stem cells. Furthermore, rare but well documented examples exist of already differentiated cells in developing mammals that change fate and trans-differentiate into another cell type. Here, we report that endothelial cells, either freshly isolated from embryonic vessels or established as homogenous cells in culture, differentiate into beating cardiomyocytes and express cardiac markers when cocultured with neonatal rat cardiomyocytes or when injected into postischemic adult mouse heart. Human umbilical vein endothelial cells also differentiate into cardiomyocytes under similar experimental conditions and transiently coexpress von Willebrand factor and sarcomeric myosin. In contrast, neural stem cells, which efficiently differentiate into skeletal muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor 2 and bone morphogenetic protein 4, which activate cardiac differentiation in embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate trans-differentiation in coculture, suggesting that different signaling molecules are responsible for cardiac induction during embryogenesis and in successive periods of development. The fact that endothelial cells can generate cardiomyocytes sheds additional light on the plasticity of endothelial cells during development and opens perspectives for cell autologous replacement therapies. PMID:11535818

  20. Regulation of troponin C synthesis in primary culture of chicken cardiac muscle cells.

    PubMed

    Malhotra, S B; Bag, J

    1987-01-01

    Cardiac myocyte cell culture from fourteen day old embryonic chicken heart was prepared. This cultured cell system was used to examine the regulation of troponin C (TnC) synthesis in cardiac muscle. To examine the regulation of TnC polypeptide synthesis, cardiac myocyte cells were pulse labelled with 35S-methionine at different days after plating. The synthesis of TnC was measured by determining the amount of radioactivity incorporated into the TnC polypeptide following separation by two dimensional gel electrophoresis. These measurements showed that TnC synthesis was maximum in 36 to 48 h old cultures and reached its lowest level in 4 day old cultures. This was in contrast to the synthesis of actin and tropomyosin. Synthesis of these polypeptides were lowest in 36 to 48 h old cultures and was maximum in 7 day old cultures. To examine whether the synthesis of TnC polypeptide paralleled the levels of TnC mRNA the sequences homologous to quail slow TnC cDNA clone were measured by hybridisation. The results showed that the decrease in the synthesis of troponin C polypeptide cannot be fully explained by the decrease in the steady state level of troponin C mRNA. The possibility of a role of translational control of troponin C mRNA in this process is discussed. PMID:2890096

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

    SciTech Connect

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    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.

  2. A muscle powered cardiac assist device for right ventricular support: total assist or partial assist?

    PubMed

    Sakakibara, N; Watanabe, G; Misaki, T; Mukai, A; Tsubota, M; Takemura, H; Ohtake, Y; Iwa, T

    1990-01-01

    A muscle powered cardiac assist device (MCAD) for right ventricular support requires optimized diastolic filling to obtain full stroke and acceptable fluid dynamics. A valved and spring-assembled skeletal muscle ventricle (SMV) was designed as a prototype MCAD, regardless of fluid dynamics. The present study addresses the optimal bypass method for right ventricular support, and predicts the future design for an implantable MCAD. Latissimus dorsi muscle (LDM) of 11 dogs were conditioned electrically for a one year maximum, and transformed into fatigue-resistant muscles (Type I fibers). Superior and inferior vena cavae were anastomosed using one arm of a Y-shaped vascular graft, as an inflow conduit, and the outflow conduit was placed on the main pulmonary artery. SMV was wrapped with transformed LDM and the bypass method was varied by SVC and/or IVC ligation. SMV demonstrated sufficient right ventricular support on total bypass (70% compared with control output), and the maximum pump off-to-on flow ratio (200%) was obtained. Maximum SMV power output was 0.27 X 10(6) erg, which was equivalent to that of canine right ventricle. Right atrial-to-pulmonary artery bypass was also constructed by using SMV in another 14 dogs, and also showed that total bypass was preferable for optimal SMV diastolic filling. In conclusion, specific requirements for a future MCAD include a subsystem assembly such as a spring, magnet, or alternative auxiliary muscle pump assembly for MCAD filling, and total bypass with optimized fluid dynamics and anatomic fitting. PMID:2252702

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

    PubMed

    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. PMID:26679609

  4. 32-Channel System to Measure the Electrophysiological Properties of Bioengineered Cardiac Muscle.

    PubMed

    Salazar, Betsy H; Reddy, Anilkumar K; Zewei Tao; Madala, Sridhar; Birla, Ravi K

    2015-06-01

    The purpose of this study was to develop, assess, and validate a custom 32-channel system to analyze the electrical properties of 3-D artificial heart muscle (3D-AHM). In this study, neonatal rat cardiac cells were cultured in a fibrin gel to drive the formation of 3D-AHM. Once the tissues were fully formed, the customized electrocardiogram (EKG) sensing system was used to obtain the different electrophysiological characteristics of the muscle constructs. Additionally, this system was used to evaluate the electrical properties of native rat hearts, for comparison to the fabricated tissues and native values found in the literature. Histological evaluation showed extensive cellularization and cardiac tissue formation. EKG data analysis yielded time delays between the signals ranging from 0 to 7 ms. Optical maps exhibited slight trends in impulse propagation throughout the fabricated tissue. Conduction velocities were calculated longitudinally at 277.81 cm/s, transversely at 300.79 cm/s, and diagonally at 285.68 cm/s for 3D-AHM. The QRS complex exhibited an R-wave amplitude of 438.42 ± 36.96 μV and an average duration of 317.5 ± 16.5 ms for the tissue constructs. The data collected in this study provide a clearer picture about the intrinsic properties of the 3D-AHM while proving our system's efficacy for EKG data procurement. To achieve a viable and permanent solution, the bioengineered heart muscle must physiologically resemble native heart tissue as well as mimic its electrical properties for proper contractile function. This study allows us to monitor such properties and assess the necessary changes that will improve construct development and function. PMID:25667345

  5. Motor imagery muscle contraction strength influences spinal motor neuron excitability and cardiac sympathetic nerve activity

    PubMed Central

    Bunno, Yoshibumi; Suzuki, Toshiaki; Iwatsuki, Hiroyasu

    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 sensor of a pinch meter for 5 min. [Results] The F-waves and LF/HF ratio during motor imagery at 50% MVC were significantly increased compared with those at rest, whereas those during motor imagery at 10% MVC were not significantly different from those at rest. The relative values of the F/M amplitude ratio during motor imagery at 50% MVC were significantly higher than those at 10% MVC. The relative values of persistence and the LF/HF ratio during motor imagery were similar during motor imagery at the two muscle contraction strengths. [Conclusion] Motor imagery can increase the spinal motor neuron excitability and cardiac sympathetic nerve activity. Motor imagery at 50% MVC may be more effective than motor imagery at 10% MVC. PMID:26834354

  6. Three-dimensional organization of troponin on cardiac muscle thin filaments in the relaxed state.

    PubMed

    Yang, Shixin; Barbu-Tudoran, Lucian; Orzechowski, Marek; Craig, Roger; Trinick, John; White, Howard; Lehman, William

    2014-02-18

    Muscle contraction is regulated by troponin-tropomyosin, which blocks and unblocks myosin binding sites on actin. To elucidate this regulatory mechanism, the three-dimensional organization of troponin and tropomyosin on the thin filament must be determined. Although tropomyosin is well defined in electron microscopy helical reconstructions of thin filaments, troponin density is mostly lost. Here, we determined troponin organization on native relaxed cardiac muscle thin filaments by applying single particle reconstruction procedures to negatively stained specimens. Multiple reference models led to the same final structure, indicating absence of model bias in the procedure. The new reconstructions clearly showed F-actin, tropomyosin, and troponin densities. At the 25 Å resolution achieved, troponin was considerably better defined than in previous reconstructions. The troponin density closely resembled the shape of troponin crystallographic structures, facilitating detailed interpretation of the electron microscopy density map. The orientation of troponin-T and the troponin core domain established troponin polarity. Density attributable to the troponin-I mobile regulatory domain was positioned where it could hold tropomyosin in its blocking position on actin, thus suggesting the underlying structural basis of thin filament regulation. Our previous understanding of thin filament regulation had been limited to known movements of tropomyosin that sterically block and unblock myosin binding sites on actin. We now show how troponin, the Ca(2+) sensor, may control these movements, ultimately determining whether muscle contracts or relaxes. PMID:24559988

  7. Cardiac arrest during radical nephrectomy due to a mass in the right ventricular outflow tract.

    PubMed

    Kim, Hee Young; Baek, Seung-Hoon; Yoon, Ji Uk; Lee, Dong Hoon; Byeon, Gyeong-Jo; Ahn, Ji Hye

    2016-09-01

    We report cardiac arrest due to obstruction of the right ventricular outflow tract (RVOT) caused by an RVOT mass that was not identified preoperatively. A 62-year-old woman with renal cell carcinoma (RCC) experienced deteriorating hypotension and bradycardia during radical nephrectomy. Hemodynamic stability was maintained on extracorporeal membrane oxygenation, and after surgery, she was transferred to the intensive care unit. On postoperative day 3, transthoracic echocardiography showed an intracardiac mass obstructing the RVOT, which caused severe functional pulmonary stenosis and moderate resting pulmonary hypertension. Despite maintaining extracorporeal membrane oxygenation, the patient died of cardiac arrest. Our findings suggest that it may be necessary to perform additional tests if RCC has invaded the renal vein and inferior vena cava or if a patient with RCC has abnormal cardiovascular symptoms without definite etiology for exclusion of cardiac metastasis or tumor thrombus. In addition, intraoperative transesophageal echocardiography might be the procedure of choice for the evaluation of these conditions because other diagnostic tests are difficult to perform during surgery. In conclusion, for patients with acute hemodynamic instability for whom other possible causes have been excluded, we recommend that anesthesiologists use transesophageal echocardiography to detect outflow tract obstruction or pulmonary thromboembolism and perform anesthetic management. PMID:27555152

  8. Muscle-Specific Splicing of a Heterologous Exon Mediated by a Single Muscle-Specific Splicing Enhancer from the Cardiac Troponin T Gene

    PubMed Central

    Cooper, Thomas A.

    1998-01-01

    The chicken cardiac troponin T (cTNT) gene contains a single 30-nucleotide alternative exon that is included in embryonic striated muscle and skipped in the adult. Transient-transfection analysis of cTNT minigenes in muscle and fibroblast cell cultures previously identified four muscle-specific splicing enhancers (MSEs) that promote exon inclusion specifically in embryonic striated muscle cultures. Three MSEs located in the intron downstream from the alternative exon were sufficient for muscle-specific exon inclusion. In the present study, the boundaries of these MSEs were defined by scanning mutagenesis, allowing analysis of individual elements in gain-of-function experiments. Concatamers of MSE2 were necessary and sufficient to promote muscle-specific inclusion of a heterologous exon, indicating that it is a target for muscle-specific regulation. Sequences present in MSE2 are also found in MSE4, suggesting that these two MSEs act in a similar manner. MSE3 appears to be different from MSE2 and MSE4 yet is able to functionally replace both of these elements, demonstrating functional redundancy of elements that are likely to bind different factors. MSE2 and MSE4 each contain a novel sequence motif that is found adjacent to a number of alternative exons that undergo regulated splicing in striated muscle, suggesting a common role for this element in muscle-specific regulation. PMID:9671461

  9. Autophagic Signaling and Proteolytic Enzyme Activity in Cardiac and Skeletal Muscle of Spontaneously Hypertensive Rats following Chronic Aerobic Exercise

    PubMed Central

    McMillan, Elliott M.; Paré, Marie-France; Baechler, Brittany L.; Graham, Drew A.; Rush, James W. E.; Quadrilatero, Joe

    2015-01-01

    Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG) of hypertensive rats had higher (p<0.05) caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05) ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05) Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05) Beclin-1 and ATG7 protein, as well as decreased (p<0.05) caspase-3, calpain, and cathepsin activity. Left ventricle (LV) of hypertensive rats had reduced (p<0.05) AMPKα and LC3II protein, as well as elevated (p<0.05) p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05) proteasome activity but reduced (p<0.05) caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats. PMID:25799101

  10. MALADAPTIVE SKELETAL MUSCLE METABOLISM PRECEDES MALADAPTIVE CHANGES IN CARDIAC METABOLISM AND FUNCTION WITH "WESTERN" DIET IN THE WISTAR RAT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity and diabetes are associated with increased fatty acid availability in excess of fatty acid oxidation capacity, which is implicated in the pathogenesis of skeletal muscle insulin resistance and cardiac contractile dysfunction. We tested the hypothesis that a "western" diet induces maladaptati...

  11. Skeletal muscle Na,K-pump concentration in children and its relationship to cardiac glycoside distribution.

    PubMed

    Kjeldsen, K; Grøn, P

    1989-08-01

    Skeletal muscle Na,K-pump (cardiac glycoside receptor) concentration was quantified in 18 0- to 8-year-old human subjects by vanadate facilitated [3H]ouabain binding to intact vastus lateralis samples obtained at autopsy. No age-dependent change in [3H]ouabain binding site concentration was observed. Mean value +/- S.E.M. was 268 +/- 17 pmol/g wet wt. (n = 18), range 182 to 433 pmol/g wet wt. At the age of 1 day, 3.5 month and 8 years and 8 months, unspecific uptake and retention of [3H]ouabain was 1.6, 1.4 and 1.5% of the total uptake and retention; release of specifically bound [3H]ouabain during the washout procedure took place with T 1/2 of 97, 90 and 73 hr; and apparent affinity constants for [3H]ouabain binding (KD) was 1.3 x 10(-8), 0.9 x 10(-8) and 1.2 x 10(-8) mol/l. [3H]Ouabain binding site concentrations and kinetics were in agreement with values from adults except that in children apparent affinity constant (KD) was 1.7 times the value in adults. The observation of no age-dependent changes in human skeletal muscle Na,K-adenosine triphosphatase concentration was at variance with the observations of such changes in animals. The total number of Na,K-pumps in the pool of skeletal muscles increased from 10 to 50 times that in the heart from birth to old age. The skeletal muscle pool of Na,K-pumps seems to constitute a distribution volume of importance during digitalization in children as well as adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2547946

  12. Measuring the mechanical efficiency of a working cardiac muscle sample at body temperature using a flow-through calorimeter.

    PubMed

    Taberner, Andrew J; Johnston, Callum M; Pham, Toan; June-Chiew Han; Ruddy, Bryan P; Loiselle, Denis S; Nielsen, Poul M F

    2015-08-01

    We have developed a new `work-loop calorimeter' that is capable of measuring, simultaneously, the work-done and heat production of isolated cardiac muscle samples at body temperature. Through the innovative use of thermoelectric modules as temperature sensors, the development of a low-noise fluid-flow system, and implementation of precise temperature control, the heat resolution of this device is 10 nW, an improvement by a factor of ten over previous designs. These advances have allowed us to conduct the first flow-through measurements of work output and heat dissipation from cardiac tissue at body temperature. The mechanical efficiency is found to vary with peak stress, and reaches a peak value of approximately 15 %, a figure similar to that observed in cardiac muscle at lower temperatures. PMID:26738140

  13. Functional coupling with cardiac muscle promotes maturation of hPSC-derived sympathetic neurons

    PubMed Central

    Oh, Yohan; Cho, Gun-Sik; Li, Zhe; Hong, Ingie; Zhu, Renjun; Kim, Min-Jeong; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang

    2016-01-01

    Summary Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B:eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties, and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX:eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish. PMID:27320040

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

    NASA Astrophysics Data System (ADS)

    Reed, Jason; Hsueh, Carlin; Mishra, Bud; Gimzewski, James K.

    2008-09-01

    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.

  15. The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction

    PubMed Central

    Kazmierczak, Katarzyna; Xu, Yuanyuan; Jones, Michelle; Guzman, Georgianna; Hernandez, Olga M.; Kerrick, W. Glenn L.; Szczesna-Cordary, Danuta

    2011-01-01

    Summary To study the regulation of cardiac muscle contraction by the myosin essential light chain (ELC) and the physiological significance of its N-terminal extension, we generated transgenic (Tg) mice partially replacing the endogenous mouse ventricular ELC with either the human ventricular ELC wild type (Tg-WT) or its 43 amino acid N-terminal truncation mutant (Tg-Δ43) in the murine hearts. The mutant protein is similar in sequence to the short ELC variant present in skeletal muscle and the ELC protein distribution in Tg-Δ43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Δ43 mice demonstrate reduced force per cross-sectional area of muscle, which is likely caused by a reduced number of force generating myosin cross-bridges and/or by decreased force per cross-bridge. As the mice grow older, the contractile force per cross-sectional area further decreases in Tg-Δ43 mice and the mutant hearts develop a phenotype of non-pathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Δ43 mice also exhibits reduced myosin content. Our results suggest that the role of the N-terminal ELC extension is to maintain the integrity of myosin and to modulate force generation by decreasing myosin neck region compliance and promoting strong cross-bridge formation and/or by enhancing myosin attachment to actin. PMID:19361417

  16. Early Treatment with Lisinopril and Spironolactone Preserves Cardiac and Skeletal Muscle in Duchenne Muscular Dystrophy Mice

    PubMed Central

    Rafael-Fortney, Jill A.; Chimanji, Neeraj S.; Schill, Kevin E.; Martin, Christopher D.; Murray, Jason D.; Ganguly, Ranjit; Stangland, Jenna E.; Tran, Tam; Xu, Ying; Canan, Benjamin D.; Mays, Tessily A.; Delfín, Dawn A.; Janssen, Paul M.L.; Raman, Subha V.

    2011-01-01

    Background Nearly-universal cardiomyopathy in Duchenne muscular dystrophy (DMD) contributes to heart failure and death. As DMD patients show myocardial fibrosis well before functional impairment, we postulated that earlier treatment using drugs with anti-fibrotic effect may be beneficial. Methods and Results Three groups of 10 utrn+/−;mdx or “het” mice with skeletal myopathy and cardiomyopathy that closely mimics clinical DMD were studied. One het group received spironolactone and lisinopril starting at 8 weeks-of-life (het-treated-8), a second received the same starting at 4 weeks-of-life (het-treated-4), and the third het group was untreated. At 20 weeks, all mice had normal EFs though circumferential strain rate was abnormal (−0.21±0.08) in untreated hets. This improved to −0.40±0.07 in het-treated-8 mice (p=0.003), and further improved to −0.56±0.10 in het-treated-4 mice (p=0.014 for het-treated-4 vs. het-treated-8). Treated mice showed less cardiomyocyte damage, with a 44% reduction in intra-cardiomyocyte serum IgG localization in het-treated-8 mice (p<0.0001), and further 53% reduction in het-treated-4 mice (p=0.0003 vs. het-treated-8); matrix metalloproteinases were similarly reduced. Cardiac, limb and diaphragm function by ex vivo muscle testing remained at 80% of normal with early treatment compared to a decline to 40% of normal skeletal muscle function without treatment. Conclusions These findings offer clinically-available medications with proven anti-fibrotic effect as a new therapeutic strategy in DMD. Early initiation greatly attenuated myocardial disease and, for the first time with these drugs, improved skeletal myopathy. Thus, early initiation of such agents warrants further clinical evaluation to maintain ambulatory, respiratory and cardiac function for DMD and related myopathies. PMID:21768542

  17. The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis.

    PubMed

    Tunwell, R E; Wickenden, C; Bertrand, B M; Shevchenko, V I; Walsh, M B; Allen, P D; Lai, F A

    1996-09-01

    Rapid Ca2+ efflux from intracellular stores during cardiac muscle excitation-contraction coupling is mediated by the ryanodine-sensitive calcium-release channel, a large homotetrameric complex present in the sarcoplasmic reticulum. We report here the identification, primary structure and topological analysis of the ryanodine receptor-calcium release channel from human cardiac muscle (hRyR-2). Consistent with sedimentation and immunoblotting studies on the hRyR-2 protein, sequence analysis of ten overlapping cDNA clones reveals an open reading frame of 14901 nucleotides encoding a protein of 4967 amino acid residues with a predicted molecular mass of 564 569 Da for hRyR-2. In-frame insertions corresponding to eight and ten amino acid residues were found in two of the ten cDNAs isolated, suggesting that novel, alternatively spliced transcripts of the hRyR-2 gene might exist. Six hydrophobic stretches, which are present within the hRyR-2 C-terminal 500 amino acids and are conserved in all RyR sequences, may be involved in forming the transmembrane domain that constitutes the Ca(2+)-conducting pathway, in agreement with competitive ELISA studies with a RyR-2-specific antibody. Sequence alignment of hRyR-2 with other RyR isoforms indicates a high level of overall identity within the RyR family, with the exception of two important regions that exhibit substantial variability. Phylogenetic analysis suggests that the RyR-2 isoform diverged from a single ancestral gene before the RyR-1 and RyR-3 isoforms to form a distinct branch of the RyR family tree. PMID:8809036

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

    SciTech Connect

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

    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.

  19. Concise Review: Skeletal Muscle Stem Cells and Cardiac Lineage: Potential for Heart Repair

    PubMed Central

    Hassan, Narmeen; Tchao, Jason

    2014-01-01

    Valuable and ample resources have been spent over the last two decades in pursuit of interventional strategies to treat the unmet demand of heart failure patients to restore myocardial structure and function. At present, it is clear that full restoration of myocardial structure and function is outside our reach from both clinical and basic research studies, but it may be achievable with a combination of ongoing research, creativity, and perseverance. Since the 1990s, skeletal myoblasts have been extensively investigated for cardiac cell therapy of congestive heart failure. Whereas the Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial revealed that transplanted skeletal myoblasts did not integrate into the host myocardium and also did not transdifferentiate into cardiomyocytes despite some beneficial effects on recipient myocardial function, recent studies suggest that skeletal muscle-derived stem cells have the ability to adopt a cardiomyocyte phenotype in vitro and in vivo. This brief review endeavors to summarize the importance of skeletal muscle stem cells and how they can play a key role to surpass current results in the future and enhance the efficacious implementation of regenerative cell therapy for heart failure. PMID:24371329

  20. Muscle-specific vascular endothelial growth factor deletion induces muscle capillary rarefaction creating muscle insulin resistance.

    PubMed

    Bonner, Jeffrey S; Lantier, Louise; Hasenour, Clinton M; James, Freyja D; Bracy, Deanna P; Wasserman, David H

    2013-02-01

    Muscle insulin resistance is associated with a reduction in vascular endothelial growth factor (VEGF) action and muscle capillary density. We tested the hypothesis that muscle capillary rarefaction critically contributes to the etiology of muscle insulin resistance in chow-fed mice with skeletal and cardiac muscle VEGF deletion (mVEGF(-/-)) and wild-type littermates (mVEGF(+/+)) on a C57BL/6 background. The mVEGF(-/-) mice had an ~60% and ~50% decrease in capillaries in skeletal and cardiac muscle, respectively. The mVEGF(-/-) mice had augmented fasting glucose turnover. Insulin-stimulated whole-body glucose disappearance was blunted in mVEGF(-/-) mice. The reduced peripheral glucose utilization during insulin stimulation was due to diminished in vivo cardiac and skeletal muscle insulin action and signaling. The decreased insulin-stimulated muscle glucose uptake was independent of defects in insulin action at the myocyte, suggesting that the impairment in insulin-stimulated muscle glucose uptake was due to poor muscle perfusion. The deletion of VEGF in cardiac muscle did not affect cardiac output. These studies emphasize the importance for novel therapeutic approaches that target the vasculature in the treatment of insulin-resistant muscle. PMID:23002035

  1. Effects of high-fat mixed-lipid diet and exercise on the antioxidant system in skeletal and cardiac muscles of rats with colon carcinoma.

    PubMed

    Perse, Martina; Injac, Rade; Strukelj, Borut; Cerar, Anton

    2009-01-01

    Epidemiological and experimental studies suggest that eating habits and a sedentary lifestyle play a critical role in the incidence of colon carcinoma. In order to investigate the effects of high-fat mixed-lipid (HFML) diet in conjunction with long-term swimming, the antioxidant capacity of skeletal and cardiac muscles were observed in rats with 1,2-dimethylhydrazine (DMH)-induced colon carcinoma. Male Wistar rats were randomly divided into one control group and four cancer groups: sedentary and swimming groups fed low fat corn oil diet and sedentary and swimming groups, fed a HFML diet. After 6 months of swimming, rats were sacrificed and the blood, cardiac and soleus muscle were taken for analysis. Serum cholesterol, triglyceride and glucose concentrations were measured and the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase as well as levels of malondialdehyde and glutathione were determined. The results showed that endurance swimming prevented lipid peroxidation in the soleus muscle of HFML diet rats due to elevated activities of antioxidant enzymes. On the other hand, increased lipid peroxidation in the hearts of all cancer groups indicated that DMH-induced colon carcinoma impaired the antioxidant status of the heart. This failure in heart tissue indicated that enhanced antioxidant capacity after regular physical activity is not sufficient to offset oxidative stress caused by DMH-induced colon carcinoma. PMID:19904015

  2. Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets.

    PubMed

    Yamazaki, Aiko; Yashiro, Masateru; Mii, Sumiyuki; Aki, Ryoichi; Hamada, Yuko; Arakawa, Nobuko; Kawahara, Katsumasa; Hoffman, Robert M; Amoh, Yasuyuki

    2016-03-01

    Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the follicle. Previous studies have shown that HAP stem cells can differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. HAP stem cells effected nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. The differentiation potential to cardiac muscle cells was greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol. In the present study, we observed that isoproterenol directs HAP stem cells to differentiate to cardiac muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. These results demonstrate that HAP stem cells have great potential to form beating cardiac muscle cells in tissue sheets. PMID:27104748

  3. The costs of a suburban paramedic program in reducing deaths due to cardiac arrest.

    PubMed

    Urban, N; Bergner, L; Eisenberg, M S

    1981-04-01

    The marginal costs per averted death of a suburban paramedic program are estimated to be approximately $42,000, when program costs are attributed entirely to cardiac arrest cases due to underlying heart disease, and indirect costs attributable to episode-related hospitalization are included, It is suggested that at $42,000 per cardiac arrest death averted the program is cost-beneficial by two criteria. First, it compares favorably with an estimate obtained from the literature of the value to the average individual of saving the life of a myocardial infarction patient. Second, the people of King County passed a cost-commensurate Paramedic Program Property Tax Levy in 1979, revealing their willingness to support the program. Results of the study should be generalized in accordance with the facts that in King County 1) the population density averages approximately 1,300 per square mile; 2) a basic emergency medical system ensures a 4-minute average response time to initiation of cardiopulmonary resuscitation; 3) a citizen-training program in cardiopulmonary resuscitation further reduces average time to initiation of basic life support; and 4) the paramedic program is designed to ensure a 10-minute average time to definitive care. PMID:6785539

  4. Artificial aortic valve dysfunction due to pannus and thrombus – different methods of cardiac surgical management

    PubMed Central

    Marcinkiewicz, Anna; Kośmider, Anna; Walczak, Andrzej; Zwoliński, Radosław; Jaszewski, Ryszard

    2015-01-01

    Introduction Approximately 60 000 prosthetic valves are implanted annually in the USA. The risk of prosthesis dysfunction ranges from 0.1% to 4% per year. Prosthesis valve dysfunction is usually caused by a thrombus obstructing the prosthetic discs. However, 10% of prosthetic valves are dysfunctional due to pannus formation, and 12% of prostheses are damaged by both fibrinous and thrombotic components. The authors present two patients with dysfunctional aortic prostheses who were referred for cardiac surgery. Different surgical solutions were used in the treatment of each case. Case study 1 The first patient was a 71-year-old woman whose medical history included arterial hypertension, stable coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and hypercholesterolemia; she had previously undergone left-sided mastectomy and radiotherapy. The patient was admitted to the Cardiac Surgery Department due to aortic prosthesis dysfunction. Transthoracic echocardiography revealed complete obstruction of one disc and a severe reduction in the mobility of the second. The mean transvalvular gradient was very high. During the operation, pannus covering the discs’ surface was found. A biological aortic prosthesis was reimplanted without complications. Case study 2 The second patient was an 87-year-old woman with arterial hypertension, persistent atrial fibrillation, and COPD, whose past medical history included gastric ulcer disease and ischemic stroke. As in the case of the first patient, she was admitted due to valvular prosthesis dysfunction. Preoperative transthoracic echocardiography revealed an obstruction of the posterior prosthetic disc and significant aortic regurgitation. Transesophageal echocardiography and fluoroscopy confirmed the prosthetic dysfunction. During the operation, a thrombus growing around a minor pannus was found. The thrombus and pannus were removed, and normal functionality of the prosthetic valve was restored

  5. Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle

    PubMed Central

    Burgoyne, Thomas; Morris, Edward P.; Luther, Pradeep K.

    2015-01-01

    The Z-band in vertebrate striated muscle crosslinks actin filaments of opposite polarity from adjoining sarcomeres and transmits tension along myofibrils during muscular contraction. It is also the location of a number of proteins involved in signalling and myofibrillogenesis; mutations in these proteins lead to myopathies. Understanding the high-resolution structure of the Z-band will help us understand its role in muscle contraction and the role of these proteins in the function of muscle. The appearance of the Z-band in transverse-section electron micrographs typically resembles a small-square lattice or a basketweave appearance. In longitudinal sections, the Z-band width varies more with muscle type than species: slow skeletal and cardiac muscles have wider Z-bands than fast skeletal muscles. As the Z-band is periodic, Fourier methods have previously been used for three-dimensional structural analysis. To cope with variations in the periodic structure of the Z-band, we have used subtomogram averaging of tomograms of rat cardiac muscle in which subtomograms are extracted and compared and similar ones are averaged. We show that the Z-band comprises four to six layers of links, presumably α-actinin, linking antiparallel overlapping ends of the actin filaments from the adjoining sarcomeres. The reconstruction shows that the terminal 5–7 nm of the actin filaments within the Z-band is devoid of any α-actinin links and is likely to be the location of capping protein CapZ. PMID:26362007

  6. Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle.

    PubMed

    Burgoyne, Thomas; Morris, Edward P; Luther, Pradeep K

    2015-11-01

    The Z-band in vertebrate striated muscle crosslinks actin filaments of opposite polarity from adjoining sarcomeres and transmits tension along myofibrils during muscular contraction. It is also the location of a number of proteins involved in signalling and myofibrillogenesis; mutations in these proteins lead to myopathies. Understanding the high-resolution structure of the Z-band will help us understand its role in muscle contraction and the role of these proteins in the function of muscle. The appearance of the Z-band in transverse-section electron micrographs typically resembles a small-square lattice or a basketweave appearance. In longitudinal sections, the Z-band width varies more with muscle type than species: slow skeletal and cardiac muscles have wider Z-bands than fast skeletal muscles. As the Z-band is periodic, Fourier methods have previously been used for three-dimensional structural analysis. To cope with variations in the periodic structure of the Z-band, we have used subtomogram averaging of tomograms of rat cardiac muscle in which subtomograms are extracted and compared and similar ones are averaged. We show that the Z-band comprises four to six layers of links, presumably α-actinin, linking antiparallel overlapping ends of the actin filaments from the adjoining sarcomeres. The reconstruction shows that the terminal 5-7nm of the actin filaments within the Z-band is devoid of any α-actinin links and is likely to be the location of capping protein CapZ. PMID:26362007

  7. Characterization of the zebrafish cx36.7 gene promoter: Its regulation of cardiac-specific expression and skeletal muscle-specific repression.

    PubMed

    Miyagi, Hisako; Nag, Kakon; Sultana, Naznin; Munakata, Keijiro; Hirose, Shigehisa; Nakamura, Nobuhiro

    2016-02-15

    Zebrafish connexin 36.7 (cx36.7/ecx) has been identified as a key molecule in the early stages of heart development in this species. A defect in cx36.7 causes severe heart malformation due to the downregulation of nkx2.5 expression, a result which resembles congenital heart disease in humans. It has been shown that cx36.7 is expressed specifically in early developing heart cardiomyocytes. However, the regulatory mechanism for the cardiac-restricted expression of cx36.7 remains to be elucidated. In this study we isolated the 5'-flanking promoter region of the cx36.7 gene and characterized its promoter activity in zebrafish embryos. Deletion analysis showed that a 316-bp upstream region is essential for cardiac-restricted expression. This region contains four GATA elements, the proximal two of which are responsible for promoter activation in the embryonic heart and serve as binding sites for gata4. When gata4, gata5 and gata6 were simultaneously knocked down, the promoter activity was significantly decreased. Moreover, the deletion of the region between -316 and -133bp led to EGFP expression in the embryonic trunk muscle. The distal two GATA and A/T-rich elements in this region act as repressors of promoter activity in skeletal muscle. These results suggest that cx36.7 expression is directed by cardiac promoter activation via the two proximal GATA elements as well as by skeletal muscle-specific promoter repression via the two distal GATA elements. PMID:26692140

  8. Fulminant mediastinitis due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: atypical presentation and spreading following cardiac surgery†

    PubMed Central

    Valenzuela, Horacio; Carrascal, Yolanda; Maroto, Laura; Arce, Nuria

    2013-01-01

    Mediastinitis due to Klebsiella pneumoniae, related to thoracic wall contamination after cardiac surgery, has rarely been described. We aim to report a case of fulminant mediastinitis due to extended-spectrum beta-lactamase-producing K. pneumoniae, secondary to a disseminated concomitant pulmonary infection. The patient remained pauci-symptomatic until clinical manifestations of sepsis acutely appeared. PMID:23416348

  9. Physical Exercise Regulates p53 Activity Targeting SCO2 and Increases Mitochondrial COX Biogenesis in Cardiac Muscle with Age

    PubMed Central

    Qi, Zhengtang; He, Jie; Su, Yuhui; He, Qiang; Liu, Jingxia; Yu, Lu; Al-Attas, Omar; Hussain, Tajamul; Ding, Shuzhe; Ji, Liu; Qian, Min

    2011-01-01

    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. PMID:21750704

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

    PubMed

    Qi, Zhengtang; He, Jie; Su, Yuhui; He, Qiang; Liu, Jingxia; Yu, Lu; Al-Attas, Omar; Hussain, Tajamul; Ding, Shuzhe; Ji, Liu; Qian, Min

    2011-01-01

    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. PMID:21750704

  11. Carnitine Palmitoyltransferase-1b (CPT1b) Deficiency Aggravates Pressure-Overload-Induced Cardiac Hypertrophy due to Lipotoxicity

    PubMed Central

    He, Lan; Kim, Teayoun; Long, Qinqiang; Liu, Jian; Wang, Peiyong; Zhou, Yiqun; Ding, Yishu; Prasain, Jeevan; Wood, Philip A.; Yang, Qinglin

    2012-01-01

    Background Carnitine palmitoyltransferase 1(CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT-1 activity by specific CPT-1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby posting concerns on the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 in order to evaluate it as a safe and effective therapeutic approach. Methods and Results Heterozygous CPT1b knockout mice (CPT1b+/−) were subjected to transverse aorta constriction (TAC)-induced pressure-overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by two weeks of transverse aorta constriction (TAC), CPT1b+/− mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b+/− mice exhibited exacerbated cardiac hypertrophy and remodeling compared with that in wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b+/− than in controlled mice. Moreover, the CPT1b+/− heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocytes apoptosis. Conclusions We conclude that CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be applied in the clinical use of CPT-1 inhibitors. PMID:22932257

  12. Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons.

    PubMed

    Oh, Yohan; Cho, Gun-Sik; Li, Zhe; Hong, Ingie; Zhu, Renjun; Kim, Min-Jeong; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang

    2016-07-01

    Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but it has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show that they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B::eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX2B::eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish. PMID:27320040

  13. Relaxin protects cardiac muscle cells from hypoxia/reoxygenation injury: involvement of the Notch-1 pathway.

    PubMed

    Boccalini, Giulia; Sassoli, Chiara; Formigli, Lucia; Bani, Daniele; Nistri, Silvia

    2015-01-01

    In animal models, the cardiotropic hormone relaxin has been shown to protect the heart against ischemia and reperfusion-induced damage, acting by multiple mechanisms that primarily involve the coronary vessels. This in vitro study evaluates whether relaxin also has a direct protective action on cardiac muscle cells. H9c2 rat cardiomyoblasts and primary mouse cardiomyocytes were subjected to hypoxia and reoxygenation. In some experiments, relaxin was added preventatively before hypoxia; in others, at reoxygenation. To elucidate its mechanisms of action, we focused on Notch-1, which is involved in heart pre- and postconditioning to ischemia. Inactivated RLX was used as negative control. Relaxin (17 nmol/L, EC50 4.7 nmol/L), added 24 h before hypoxia or at reoxygenation, protected against cardiomyocyte injury. In fact, relaxin significantly increased cell viability (assayed by trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), decreased apoptosis (assayed by TUNEL and bax/bcl-2 ratio), and reduced nitroxidative damage (assayed by nitrotyrosine expression and 8-hydroxy-deoxyguanosine levels). These effects were partly attributable to the ability of relaxin to upregulate Notch-1 signaling; indeed, blockade of Notch-1 activation with the specific inhibitor DAPT reduced relaxin-induced cardioprotection during hypoxia and reoxygenation. This study adds new mechanistic insights on the cardioprotective role of relaxin on ischemic and oxidative damage. PMID:25342127

  14. High resolution measurement of striation patterns and sarcomere motions in cardiac muscle cells.

    PubMed Central

    Krueger, J W; Denton, A

    1992-01-01

    We describe an extension of the method of Myers et al. (1982) to measure with high precision the uniformity of contractile motions that occur between sarcomeres in the isolated cardiac muscle cell (guinea pig and rat). The image of the striations, observed with modulation contrast microscopy, was detected by a linear array of photodiodes. Sarcomere length was measured greater than 500/s from the frequency of the array's video signal at two selectable regions of the cell. A precision test grating demonstrated that method resolves known differences in the spacing between two contiguous striations to +/- 0.01 micron and that the effects of image translation and microscopic resolution are minor. The distribution of striation spacing appears to be discrete in isolated segments of the cell, and patches of fairly uniform length can be identified that are laterally contiguous. When electrically triggered, contraction is synchronous and the sarcomeres shorten and relengthen smoothly. The contrast between the striations is transiently enhanced during relengthening, an indication that the contracting cell can not be treated as a simple grating. Pauses that occur during late in relengthening (and transient contractile alternans) are characterized by very synchronized activity. These forms of irregular contractile behavior are not explained by desynchronization of a mechanism of release of intracellular calcium. A companion article describes application of the technique to study the nonuniform motions that occur between sarcomeres. Images FIGURE 1 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:1540686

  15. Ultrastructure of the cysts of Sarcocystis grueneri from cardiac muscle of reindeer (Rangifer tarandus tarandus).

    PubMed

    Gjerde, B

    1985-01-01

    Cysts of Sarcocystis grueneri from cardiac muscle of reindeer (Rangifer tarandus) in Norway were examined by transmission electron microscopy. The limiting unit membrane of the cyst proper formed regularly spaced invaginations into the cyst at numerous sites coinciding with interruptions in the underlying osmiophilic layer. The primary cyst wall formed numerous strip-like, sinuous protrusions, which were 30-40 nm thick, 150-300 nm wide and up to 4.5 microns long, and were running in parallel with the surface of the cyst. Generally the protrusions were arranged in several closely spaced layers compressed against the cyst. The nature and arrangement of the protrusions render them undetectable by light microscopy. Cyst ground substance divided the interior of the cyst into compartments containing typical sarcosporidian metrocytes and cystozoites. The cysts of S. grueneri from reindeer were ultrastructurally similar to cysts reported from red deer, roe deer and moose by other workers. The possibility that these cervids are hosts for a common Sarcocystis species is discussed. PMID:3922150

  16. Acute cardiac tamponade due to spontaneous bleeding in a child with haemophilia A.

    PubMed

    Goz, Mustafa; Hazar, Abdussemet; Mordeniz, Cengiz; Kocarslan, Aydemir; Demirkol, Abbas Heval; Koc, Ahmet

    2010-08-01

    In severe haemophilia A, patients, start from the first years of life, with spontaneous bleeding and require transfusion. However, cardiac tamponade due to spontaneous pericardial bleeding is rare. An 11-year-old boy receiving haemophilia A treatment was referred to the Department of Paediatric Haematology with pneumonia, fever, dyspnoea, and palpitation. In his PA chest radiograph, pneumonic infiltration in the right lung and enlargement in the pericardial area were found. On his echocardiograph, pericardial effusion reaching 3.9 cm and other findings of tamponade were detected. APTT was outside the measurable range. It was deranged to > 120 seconds. The patient received 1000 U of factor VIII intravenously. A pericardial window was made via left anterior mini thoracotomy due to fluid drained. In his control echocardiograph taken after one month, no pathology was found. At 50th day, the patient showed left pleural serohaemorrhagic effusion, which was treated with tube thoracostomy. In haemophilia A patients, either pericardiocentesis or subxiphoid pericardial drainage or pericardial window creation via thoracotomy may be applied, depending on the primary pathology. In paediatric cases, pericardial window creation via mini thoracotomy can be an alternative treatment of choice considering complications such as recurring bleeding and effusion during pericardiocentesis. PMID:20726209

  17. Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Machado, C R; Camargos, E R; Teixeira, M M

    2001-05-01

    The ability of toxins to activate the cardiovascular system plays an important role in the morbidity and lethality of the Tityus serrulatus scorpion envenoming. Most of the actions of the scorpion toxins are indirect and due to the release of adrenergic and cholinergic neurotransmitters. Accordingly, treatment following envenoming is targeted towards inhibition of adrenergic and cholinergic receptors. Here, we have sought evidence for a direct action of T. serrulatus venom on the isolated rat heart (Langendorff's method). We show that the bradycardia induced by T. serrulatus venom was completely blocked by atropine, a muscarinic receptor antagonist. Similarly, the increase in heart rate that follows the venom-induced bradycardia was totally inhibited by a beta(1)-adrenoceptor antagonist or by chemical sympathetic denervation with 6-hydroxydopamine. In contrast to these findings, the venom-induced increase in contractile force was not modified by beta(1)-adrenoceptor blockade or by chemical sympathetic denervation. The results clearly demonstrate that the chronotropic effects of T. serrulatus are dependent on neurotransmitter release, but the inotropic effects are not. The neurotransmitter-independent increase in contractility seems to be a direct action of the venom on cardiomyocytes. We suggest that this direct effect on cardiac fibers may play a role in the development of cardiac arrhythmias and contractility defects following envenoming with T. serrulatus scorpion. PMID:11072050

  18. Pax3 and Tbx5 specify whether PDGFRα+ cells assume skeletal or cardiac muscle fate in differentiating ES cells

    PubMed Central

    Magli, Alessandro; Schnettler, Erin; Swanson, Scott A; Borges, Luciene; Hoffman, Kirsta; Stewart, Ron; Thomson, James A; Keirstead, Susan A.; Perlingeiro, Rita C. R.

    2014-01-01

    Embryonic stem (ES) cells represent an ideal model to study how lineage decisions are established during embryonic development. Using a doxycycline-inducible mouse ES cell line, we have previously shown that expression of the transcriptional activator Pax3 in early mesodermal cells leads to the robust generation of paraxial mesoderm progenitors that ultimately differentiate into skeletal muscle precursors. Here we show that the ability of this transcription factor to induce the skeletal myogenic cell fate occurs at the expenses of the cardiac lineage. Our results show that the PDGFRα+FLK1− sub-fraction represents the main population affected by Pax3, through down-regulation of several transcripts encoding for proteins involved in cardiac development. We demonstrate that although Nkx2-5, Tbx5 and Gata4 negatively affect Pax3 skeletal myogenic activity, the cardiac potential of embryoid body (EB)-derived cultures is restored solely by forced expression of Tbx5. Taking advantage of this model, we employed an unbiased genome wide approach to identify genes whose expression is rescued by Tbx5, and which could represent important regulators of cardiac development. These findings elucidate mechanisms regulating the commitment of mesodermal cells in the early embryo and identify the Tbx5 cardiac transcriptome. PMID:24677751

  19. Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

    SciTech Connect

    McGrew, S.G.; Inui, Makoto; Chadwick, C.C.; Boucek, R.J. Jr.; Jung, C.Y.; Fleischer, S. )

    1989-02-07

    The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar.

  20. REGULATION OF CARDIAC AND SKELETAL MUSCLE PROTEIN SYNTHESIS BY INDIVIDUAL BRANCHED-CHAIN AMINO ACIDS IN NEONATAL PIGS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal muscle grows at a very rapid rate in the neonatal pig, due in part to an enhanced sensitivity of protein synthesis to the postprandial rise in amino acids. An increase in leucine alone stimulates protein synthesis in skeletal muscle of the neonatal pig; however, the effect of isoleucine and...

  1. Regulation of intracellular pH in cardiac muscle during cell shrinkage and swelling in anisosmolar solutions.

    PubMed

    Whalley, D W; Hemsworth, P D; Rasmussen, H H

    1994-02-01

    The effect on intracellular pH (pHi) of exposure to solutions of progressively increasing osmolarity from 418 to 620 mosM and to hyposmolar solutions (240 mosM) was examined in guinea pig ventricular muscle using ion-selective microelectrodes. Exposure of tissue to 418 mosM Tyrode solution (100 mM sucrose added) produced an intracellular alkalosis of approximately 0.1 U, whereas exposure to 620 mosM solution (300 mM sucrose added) caused an intracellular acidosis of approximately 0.1 U. The maximal rate of recovery of pHi from acidosis induced by an NH4Cl prepulse increased progressively as extracellular osmolarity was raised from 310 to 620 mosM. This suggests that the acidosis observed at steady state in 620 mosM solution is not due to inhibition of the Na(+)-H+ exchanger. In the presence of 10 microM ryanodine, exposure to 620 mosM solution produced a sustained intracellular alkalosis. We suggest that the decrease in pHi during exposure to 620 mosM solution is due, at least in part, to the acidifying influence of Ca2+ release from the sarcoplasmic reticulum. This decrease in pHi is expected to contribute to the negative inotrop reported in studies of cardiac contractility in markedly hyperosmolar solutions. There was no change in pHi when tissue was exposed to hyposmolar solution. However, the maximal rate of recovery of pHi from acidosis was slower in hyposmolar than in isosmolar solution, despite a concomitant decrease in the intracellular buffer capacity. This suggests that osmotic cell swelling results in inhibition of the sarcolemmal Na(+)-H+ exchanger. PMID:8141367

  2. Impact of detubulation on force and kinetics of cardiac muscle contraction.

    PubMed

    Ferrantini, Cecilia; Coppini, Raffaele; Sacconi, Leonardo; Tosi, Benedetta; Zhang, Mei Luo; Wang, Guo Liang; de Vries, Ewout; Hoppenbrouwers, Ernst; Pavone, Francesco; Cerbai, Elisabetta; Tesi, Chiara; Poggesi, Corrado; ter Keurs, Henk E D J

    2014-06-01

    Action potential-driven Ca(2+) currents from the transverse tubules (t-tubules) trigger synchronous Ca(2+) release from the sarcoplasmic reticulum of cardiomyocytes. Loss of t-tubules has been reported in cardiac diseases, including heart failure, but the effect of uncoupling t-tubules from the sarcolemma on cardiac muscle mechanics remains largely unknown. We dissected intact rat right ventricular trabeculae and compared force, sarcomere length, and intracellular Ca(2+) in control trabeculae with trabeculae in which the t-tubules were uncoupled from the plasma membrane by formamide-induced osmotic shock (detubulation). We verified disconnection of a consistent fraction of t-tubules from the sarcolemma by two-photon fluorescence imaging of FM4-64-labeled membranes and by the absence of tubular action potential, which was recorded by random access multiphoton microscopy in combination with a voltage-sensitive dye (Di-4-AN(F)EPPTEA). Detubulation reduced the amplitude and prolonged the duration of Ca(2+) transients, leading to slower kinetics of force generation and relaxation and reduced twitch tension (1 Hz, 30°C, 1.5 mM [Ca(2+)]o). No mechanical changes were observed in rat left atrial trabeculae after formamide shock, consistent with the lack of t-tubules in rodent atrial myocytes. Detubulation diminished the rate-dependent increase of Ca(2+)-transient amplitude and twitch force. However, maximal twitch tension at high [Ca(2+)]o or in post-rest potentiated beats was unaffected, although contraction kinetics were slower. The ryanodine receptor (RyR)2 Ca-sensitizing agent caffeine (200 µM), which increases the velocity of transverse Ca(2+) release propagation in detubulated cardiomyocytes, rescued the depressed contractile force and the slower twitch kinetics of detubulated trabeculae, with negligible effects in controls. We conclude that partial loss of t-tubules leads to myocardial contractile abnormalities that can be rescued by enhancing and accelerating the

  3. Diastolic scattered light fluctuation, resting force and twitch force in mammalian cardiac muscle

    PubMed Central

    Lakatta, E. G.; Lappé, D. L.

    1981-01-01

    1. When coherent light was passed through isolated isometric cardiac muscles during the diastolic or resting period, intensity fluctuations were observed in the scattered field. The frequency of these intensity fluctuations (f½) varied with many experimental interventions known to enhance Ca2+ flux into the cell. 2. In rat muscles stimulated at low frequencies (0.1 ± 2.0 min-1) stepwise increases (0.4-10 mm) of [Ca2+] in the bathing fluid ([Ca2+]e), or addition of ouabain (10-6-6 × 10-4 m) to the perfusate caused stepwise increases in f½. These were paralleled by increments in resting force (RF) such that the changes in f½ and RF were highly correlated. Substitution of K+ for Na+ in the perfusate resulted in parallel transients in RF and f½. 3. In contrast to the rat, most cat muscles stimulated at low frequencies in the steady state exhibited neither diastolic intensity fluctuations nor Ca2+-dependent changes in RF in [Ca2+]e of 10 mm or less; when [Ca2+]e was increased to 12-32 mm, however, steady-state Ca2+-dependent f½ and RF were observed. In a given [Ca2+]e reduction of [Na+]e increased f½. In the transient state following cessation of regular stimulation at more rapid rates (12-96 min-1) intensity fluctuations were present in all [Ca2+]e and decayed with time (seconds to minutes); the f½ and time course of the decay of the fluctuations were determined by the rate of prior stimulation and [Ca2+]e. 4. Maximum potentiation of twitch force in response to the above inotropic interventions was associated with an optimal level of f½ which was similar in both species; when higher levels of f½ were produced by more intense inotropic intervention, twitch force declined. Over the range of inotropic intervention up to and including that at which maximum twitch potentiation occurred, the increase in diastolic f½ predicted the extent of twitch potentiation with a high degree of accuracy (r > 0.97) both in the transient and steady states. 5. In contrast to the

  4. Calsequestrin and the calcium release channel of skeletal and cardiac muscle.

    PubMed

    Beard, N A; Laver, D R; Dulhunty, A F

    2004-05-01

    Calsequestrin is by far the most abundant Ca(2+)-binding protein in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. It allows the Ca2+ required for contraction to be stored at total concentrations of up to 20mM, while the free Ca2+ concentration remains at approximately 1mM. This storage capacity confers upon muscle the ability to contract frequently with minimal run-down in tension. Calsequestrin is highly acidic, containing up to 50 Ca(2+)-binding sites, which are formed simply by clustering of two or more acidic residues. The Kd for Ca2+ binding is between 1 and 100 microM, depending on the isoform, species and the presence of other cations. Calsequestrin monomers have a molecular mass of approximately 40 kDa and contain approximately 400 residues. The monomer contains three domains each with a compact alpha-helical/beta-sheet thioredoxin fold which is stable in the presence of Ca2+. The protein polymerises when Ca2+ concentrations approach 1mM. The polymer is anchored at one end to ryanodine receptor (RyR) Ca2+ release channels either via the intrinsic membrane proteins triadin and junctin or by binding directly to the RyR. It is becoming clear that calsequestrin has several functions in the lumen of the SR in addition to its well-recognised role as a Ca2+ buffer. Firstly, it is a luminal regulator of RyR activity. When triadin and junctin are present, calsequestrin maximally inhibits the Ca2+ release channel when the free Ca2+ concentration in the SR lumen is 1mM. The inhibition is relieved when the Ca2+ concentration alters, either because of small changes in the conformation of calsequestrin or its dissociation from the junctional face membrane. These changes in calsequestrin's association with the RyR amplify the direct effects of luminal Ca2+ concentration on RyR activity. In addition, calsequestrin activates purified RyRs lacking triadin and junctin. Further roles for calsequestrin are indicated by the kinase activity of the protein, its

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25643692

  6. Titin-based modulation of active tension and interfilament lattice spacing in skinned rat cardiac muscle.

    PubMed

    Fukuda, Norio; Wu, Yiming; Farman, Gerrie; Irving, Thomas C; Granzier, Henk

    2005-02-01

    The effect of titin-based passive tension on Ca2+ sensitivity of active tension and interfilament lattice spacing was studied in skinned rat ventricular trabeculae by measuring the sarcomere length (SL)-dependent change in Ca2+ sensitivity and performing small angle X-ray diffraction studies. To vary passive tension, preparations were treated with trypsin at a low concentration (0.31 mug/ml) for a short period (13 min) at 20 degrees C, that resulted in approximately 40% degradation of the I-band region of titin, with a minimal effect on A-band titin. We found that the effect of trypsin on titin-based passive tension was significantly more pronounced immediately after stretch than at steady state, 30 min after stretch (i.e., trypsin has a greater effect on viscosity than on elasticity of passive cardiac muscle). Ca2+ sensitivity was decreased by trypsin treatment at SL 2.25 microm, but not at SL 1.9 microm, resulting in marked attenuation of the SL-dependent increase in Ca2+ sensitivity. The SL-dependent change in Ca2+ sensitivity was significantly correlated with titin-based passive tension. Small-angle X-ray diffraction experiments revealed that the lattice spacing expands after trypsin treatment, especially at SL 2.25 microm, providing an inverse linear relationship between the lattice spacing and Ca2+ sensitivity. These results support the view that titin-based passive tension promotes actomyosin interaction and that the mechanism includes interfilament lattice spacing modulation. PMID:15688246

  7. Effects of anisosmotic stress on cardiac muscle cell length, diameter, area, and sarcomere length

    NASA Technical Reports Server (NTRS)

    Tanaka, R.; Barnes, M. A.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    The purpose of this study was to examine the effects of anisosmotic stress on adult mammalian cardiac muscle cell (cardiocyte) size. Cardiocyte size and sarcomere length were measured in cardiocytes isolated from 10 normal rats and 10 normal cats. Superfusate osmolarity was decreased from 300 +/- 6 to 130 +/- 5 mosM and increased to 630 +/- 8 mosM. Cardiocyte size and sarcomere length increased progressively when osmolarity was decreased, and there were no significant differences between cat and rat cardiocytes with respect to percent change in cardiocyte area or diameter; however, there were significant differences in cardiocyte length (2.8 +/- 0.3% in cat vs. 6.1 +/- 0.3% in rat, P < 0.05) and sarcomere length (3.3 +/- 0.3% in cat vs. 6.1 +/- 0.3% in rat, P < 0.05). To determine whether these species-dependent differences in length were related to diastolic interaction of the contractile elements or differences in relative passive stiffness, cardiocytes were subjected to the osmolarity gradient 1) during treatment with 7 mM 2,3-butanedione monoxime (BDM), which inhibits cross-bridge interaction, or 2) after pretreatment with 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (EGTA), a bivalent Ca2+ chelator. Treatment with EGTA or BDM abolished the differences between cat and rat cardiocytes. Species-dependent differences therefore appeared to be related to the degree of diastolic cross-bridge association and not differences in relative passive stiffness. In conclusion, the osmolarity vs. cell size relation is useful in assessing the cardiocyte response to anisosmotic stress and may in future studies be useful in assessing changes in relative passive cardiocyte stiffness produced by pathological processes.

  8. Repression of the cardiac myosin light chain‐2 gene in skeletal muscle requires site‐specific association of antithetic regulator, Nished, and HDACs

    PubMed Central

    Mathew, Sumy; Galatioto, Josephine; Mascareno, Eduardo

    2008-01-01

    Abstract The transcriptional activation mechanisms that regulate tissue‐specific expression of cardiac muscle genes have been extensively investigated, but little is known of the regulatory events involved in repression of cardiac‐specific genes in non‐cardiac cells. We have previously reported that Nished, a ubiquitous transcription factor, interacts with a positive sequence element, the Intron Regulatory Element (IRE) as well as a negatively acting element, the Cardiac‐Specific Sequence (CSS), in myosin light chain‐2 (MLC2v) gene to promote activation and repression of the gene in cardiac and skeletal muscle cells respectively. Here, we show that the negative regulation of cardiac MLC2v gene in skeletal muscle cells is mediated via the interaction of Nished with histone deacetylase (HDAC) co‐repressor. Treatment of cells with the HDAC inhibitor, Trichostatin A (TSA), alleviates the repressor activity of Nished in a dose‐dependent manner. Co‐transfection studies in primary muscle cells in culture and in Nished expressing stable skeletal muscle cell line demonstrate that Nished down‐regulates the cardiac MLC2 gene expression when its association is restricted to CSS alone. Chromatin immunoprecipitation data suggest that the CSS‐mediated repression of cardiac MLC2v gene in skeletal muscle cells excludes the participation of the positive element IRE despite the presence of an identical Nished binding site. Taken together, it appears that the negative control of MLC2v transcription is based on a dual mode of regulations, one that affords inaccessibility of IRE to Nished and second that promotes the formation of the transcription repression complex at the inhibitory CSS site to silence the cardiac gene in skeletal muscle cell. PMID:19604314

  9. A case of cerebral embolism due to cardiac myxoma presenting with multiple cerebral microaneurysms detected on first MRI scans.

    PubMed

    Sato, Takahiro; Saji, Naoki; Kobayashi, Kazuto; Shibazaki, Kensaku; Kimura, Kazumi

    2016-03-01

    A 64-year-old man developed right arm weakness and dysarthria, and was admitted to our hospital. Diffusion-weighted magnetic resonance imaging of the brain showed a high intensity area in the frontal lobe. T2*-weighted images showed multiple spotty low intensity lesions in bilateral cerebral hemispheres, mimicking cerebral microbleeds. Cerebral angiography showed multiple aneurysms in the anterior, middle, posterior cerebral arteries and cerebellar arteries. Transthoracic echocardiography revealed a floating structure in the left atrial chamber, indicating cardiac myxoma. We diagnosed cardioembolic ischemic stroke due to left atrial myxoma. Cardiac surgery for excision of a left atrial myxoma was performed on the 3rd hospital day. Multiple aneurysms should be taken into account for differential diagnosis in patients with cardiac myxoma and with atypical spotty low intensity on T2*-weighted images. PMID:26797485

  10. Dynamics of cross-bridge cycling, ATP hydrolysis, force generation, and deformation in cardiac muscle.

    PubMed

    Tewari, Shivendra G; Bugenhagen, Scott M; Palmer, Bradley M; Beard, Daniel A

    2016-07-01

    Despite extensive study over the past six decades the coupling of chemical reaction and mechanical processes in muscle dynamics is not well understood. We lack a theoretical description of how chemical processes (metabolite binding, ATP hydrolysis) influence and are influenced by mechanical processes (deformation and force generation). To address this need, a mathematical model of the muscle cross-bridge (XB) cycle based on Huxley's sliding filament theory is developed that explicitly accounts for the chemical transformation events and the influence of strain on state transitions. The model is identified based on elastic and viscous moduli data from mouse and rat myocardial strips over a range of perturbation frequencies, and MgATP and inorganic phosphate (Pi) concentrations. Simulations of the identified model reproduce the observed effects of MgATP and MgADP on the rate of force development. Furthermore, simulations reveal that the rate of force re-development measured in slack-restretch experiments is not directly proportional to the rate of XB cycling. For these experiments, the model predicts that the observed increase in the rate of force generation with increased Pi concentration is due to inhibition of cycle turnover by Pi. Finally, the model captures the observed phenomena of force yielding suggesting that it is a result of rapid detachment of stretched attached myosin heads. PMID:25681584

  11. Cooperative cross-bridge activation of thin filaments contributes to the Frank-Starling mechanism in cardiac muscle.

    PubMed

    Smith, L; Tainter, C; Regnier, M; Martyn, D A

    2009-05-01

    Myosin cross-bridges play an important role in the regulation of thin-filament activation in cardiac muscle. To test the hypothesis that sarcomere length (SL) modulation of thin-filament activation by strong-binding cross-bridges underlies the Frank-Starling mechanism, we inhibited force and strong cross-bridge binding to intermediate levels with sodium vanadate (Vi). Force and stiffness varied proportionately with [Ca(2+)] and [Vi]. Increasing [Vi] (decreased force) reduced the pCa(50) of force-[Ca(2+)] relations at 2.3 and 2.0 microm SL, with little effect on slope (n(H)). When maximum force was inhibited to approximately 40%, the effects of SL on force were diminished at lower [Ca(2+)], whereas at higher [Ca(2+)] (pCa < 5.6) the relative influence of SL on force increased. In contrast, force inhibition to approximately 20% significantly reduced the sensitivity of force-[Ca(2+)] relations to changes in both SL and myofilament lattice spacing. Strong cross-bridge binding cooperatively induced changes in cardiac troponin C structure, as measured by dichroism of 5' iodoacetamido-tetramethylrhodamine-labeled cardiac troponin C. This apparent cooperativity was reduced at shorter SL. These data emphasize that SL and/or myofilament lattice spacing modulation of the cross-bridge component of cardiac thin-filament activation contributes to the Frank-Starling mechanism. PMID:19413974

  12. Nandrolone decanoate negatively reverses the beneficial effects of exercise on cardiac muscle via sarcolemmal, but not mitochondrial KATP channel.

    PubMed

    Bayat, Gholamreza; Javan, Mohammad; Safari, Fatemeh; Khalili, Azadeh; Shokri, Saeed; Goudarzvand, Mahdi; Salimi, Mehdi; Hajizadeh, Sohrab

    2016-03-01

    ATP-sensitive potassium channels are supposed to have a substantial role in improvement of cardiac performance. This study was performed to evaluate whether nandrolone decanoate (ND) and (or) exercise training could affect the expression of cardiac KATP channel subunits. Thirty-five male albino Wistar rats were randomly divided into 5 groups, including sedentary control (SC), sedentary vehicle (SV), sedentary ND (SND), exercise control (EC), and exercise and ND (E+ND). Exercise training was performed on a treadmill 5 times per week. ND was injected (10 mg/kg/week, i.m.) to the rats in the SND and E+ND groups. Following cardiac isolation, the expression of both sarcolemmal and mitochondrial subunits of KATP channel was measured using Western blot method. The expression of sarcolemmal, but not mitochondrial, subunits of KATP channel (Kir6.2 and SUR2) of EC group was significantly higher compared with SC group while ND administration (SND group) did not show any change in their expression. In the E+ND group, ND administration led to decrease of the over-expression of sarcolemmal Kir6.2 and SUR2 which was previously induced by exercise. There was no significant association between the mitochondrial expression of either Kir6.2 or SUR2 proteins and administration of ND or exercise. Supra-physiological dosage of ND negatively reverses the effects of exercise on the cardiac muscle expression of sarcolemmal, but not mitochondrial, KATP channel subunits. PMID:26909616

  13. Cardiac conduction system

    MedlinePlus Videos and Cool Tools

    ... cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. The main components ... the cardiac conduction system’s electrical activity in the heart.

  14. Nanostructured, highly aligned poly(hydroxy butyrate) electrospun fibers for differentiation of skeletal and cardiac muscle cells.

    PubMed

    Ricotti, Leonardo; Polini, Alessandro; Genchi, Giada G; Ciofani, Gianni; Iandolo, Donata; Mattoli, Virgilio; Menciassi, Arianna; Dario, Paolo; Pisignano, Dario

    2011-01-01

    The influence of novel nanostructured anisotropically electrospun poly(hydroxy butyrate) matrices on skeletal and cardiac muscle-like cell proliferation and differentiation was investigated, in comparison with isotropic and no-topographically cues-provided substrates. After the matrix characterization, in terms of surface SEM imaging and mechanical properties, cell differentiation on the different substrates was evaluated. Myogenin and F-actin staining at several differentiation time-points suggested that aligned nanofibers promote differentiation of both cell types. Moreover, quantitative parameters for each cell line are provided to clarify which aspects of the differentiation process are influenced by the different matrix topographies. PMID:22255117

  15. Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged Mdx mice.

    PubMed

    Bostick, Brian; Yue, Yongping; Long, Chun; Marschalk, Nate; Fine, Deborah M; Chen, Jing; Duan, Dongsheng

    2009-02-01

    Duchenne muscular dystrophy (DMD) affects both skeletal and cardiac muscle. It is currently unclear whether the strategies developed for skeletal muscle can ameliorate cardiomyopathy. Synthetic mini-/micro-dystrophin genes have yielded impressive skeletal muscle protection in animal models. The 6-kb DeltaH2-R19 minigene is particularly promising because it completely restores skeletal muscle force to wild-type levels. Here, we examined whether expressing this minigene in the heart, but not skeletal muscle, could normalize cardiac function in the mdx model of DMD cardiomyopathy. Transgenic mdx mice were generated to express the DeltaH2-R19 minigene under the control of the alpha-myosin heavy-chain promoter. Heart structure and function were examined in adult and very old mice. The DeltaH2-R19 minigene enhanced cardiomyocyte sarcolemmal strength and prevented myocardial fibrosis. It also restored the dobutamine response and enhanced treadmill performance. Surprisingly, heart-restricted DeltaH2-R19 minigene expression did not completely normalize electrocardiogram and hemodynamic abnormalities. Overall, systolic function and ejection fraction were restored to normal levels but stroke volume and cardiac output remained suboptimal. Our results demonstrate that the skeletal muscle-proven DeltaH2-R19 minigene can correct cardiac histopathology but cannot fully normalize heart function. Novel strategies must be developed to completely restore heart function in DMD. PMID:19066599

  16. Skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    NASA Technical Reports Server (NTRS)

    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

  18. Activation Kinetics of Skinned Cardiac Muscle by Laser Photolysis of Nitrophenyl-EGTA

    PubMed Central

    Martin, Hunter; Bell, Marcus G.; Ellis-Davies, Graham C. R.; Barsotti, Robert J.

    2004-01-01

    The kinetics of Ca2+-induced contractions of chemically skinned guinea pig trabeculae was studied using laser photolysis of NP-EGTA. The amount of free Ca2+ released was altered by varying the output from a frequency-doubled ruby laser focused on the trabeculae, while maintaining constant total [NP-EGTA] and [Ca2+]. The time courses of the rise in stiffness and tension were biexponential at 23°C, pH 7.1, and 200 mM ionic strength. At full activation (pCa < 5.0), the rates of the rapid phase of the stiffness and tension rise were 56 ± 7 s−1 (n = 7) and 48 ± 6 s−1 (n = 11) while the amplitudes were 21 ± 2 and 23 ± 3%, respectively. These rates had similar dependencies on final [Ca2+] achieved by photolysis: 43 and 50 s−1 per pCa unit, respectively, over a range of [Ca2+] producing from 15% to 90% of maximal isometric tension. At all [Ca2+], the rise in stiffness initially was faster than that of tension. The maximal rates for the slower components of the rise in stiffness and tension were 4.1 ± 0.8 and 6.2 ± 1.0 s−1. The rate of this slower phase exhibited significantly less Ca2+ sensitivity, 1 and 4 s−1 per pCa unit for stiffness and tension, respectively. These data, along with previous studies indicating that the force-generating step in the cross-bridge cycle of cardiac muscle is marginally sensitive to [Ca2+], suggest a mechanism of regulation in which Ca2+ controls the attachment step in the cross-bridge cycle via a rapid equilibrium with the thin filament activation state. Myosin kinetics sets the time course for the rise in stiffness and force generation with the biexponential nature of the mechanical responses to steps in [Ca2+] arising from a shift to slower cross-bridge kinetics as the number of strongly bound cross-bridges increases. PMID:14747333

  19. Dysautonomia Due to Reduced Cholinergic Neurotransmission Causes Cardiac Remodeling and Heart Failure ▿ ‡

    PubMed Central

    Lara, Aline; Damasceno, Denis D.; Pires, Rita; Gros, Robert; Gomes, Enéas R.; Gavioli, Mariana; Lima, Ricardo F.; Guimarães, Diogo; Lima, Patricia; Bueno, Carlos Roberto; Vasconcelos, Anilton; Roman-Campos, Danilo; Menezes, Cristiane A. S.; Sirvente, Raquel A.; Salemi, Vera M.; Mady, Charles; Caron, Marc G.; Ferreira, Anderson J.; Brum, Patricia C.; Resende, Rodrigo R.; Cruz, Jader S.; Gomez, Marcus Vinicius; Prado, Vania F.; de Almeida, Alvair P.; Prado, Marco A. M.; Guatimosim, Silvia

    2010-01-01

    Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction. PMID:20123977

  20. Effects of ACE2 deficiency on physical performance and physiological adaptations of cardiac and skeletal muscle to exercise.

    PubMed

    Motta-Santos, Daisy; Dos Santos, Robson Augusto Souza; Oliveira, Marilene; Qadri, Fatimunnisa; Poglitsch, Marko; Mosienko, Valentina; Kappes Becker, Lenice; Campagnole-Santos, Maria Jose; M Penninger, Joseph; Alenina, Natalia; Bader, Michael

    2016-07-01

    The renin-angiotensin system (RAS) is related to physiological adaptations induced by exercise. Angiotensin-converting enzyme (ACE) 2 is a major regulator of the RAS in tissues, as it metabolizes angiotensin (Ang) II to Ang-(1-7). The aim of this study was to determine the effects of ACE2 deficiency on physical performance and physiological adaptations induced by voluntary running. Physical performance, body composition and plasma angiotensin levels, as well as tissue morphology and gene expression of RAS components in the left ventricle (LV) and skeletal muscle (gastrocnemius), were evaluated in ACE2-deficient (ACE2(-/y)) and wild-type (ACE2(+/y)) mice after 6 weeks of voluntary wheel running. ACE2(-/y) mice run less than ACE2(+/y) mice (19±4.7 vs. 26±12.6 revolutions per day × 100, P<0.01). The ACE2(+/y) group presented a lower fat mass (15±1.1%) and higher muscle mass (76.6±1.6%) after 6 weeks of voluntary running compared with the sedentary control group (fat mass: 18.3±2.1%; muscle mass: 72.7±2.2). However, no change in body composition was observed in ACE2(-/y) mice after exercise. Heart and skeletal muscle hypertrophy was observed only in trained ACE2(+/y) mice. Besides a small decrease in Ang I in ACE2(-/y) mice, plasma levels of angiotensin peptides remained unchanged by exercise or ACE2 deficiency. In the LV of trained animals, AT2 gene expression was higher in ACE2(+/y) compared with ACE2(-/y) mice. ACE2 deficiency leads to an increase in AT1 gene expression in skeletal muscle. ACE expression in soleus was increased in all exercised groups. ACE2 deficiency affects physical performance and impairs cardiac and skeletal muscle adaptations to exercise. PMID:27053009

  1. Recurrent proptotic diplopia due to congestive expansion of cavernous haemangioma with relapsing right-sided cardiac failure

    PubMed Central

    O'Mahony, D.; O'Neill, E.

    1999-01-01

    A 75-year-old man with a recent history of pulmonary embolism, presented with collapse followed by a gran mal seizure and right-sided non-pulsatile proptosis. On recovery, he had diplopia on lateral and upward gaze and signs of congestive cardiac failure. Further pulmonary embolism was proven by lung scintigraphy. Computed tomography of his orbits confirmed a contrast-enhancing space-occupying lesion of the medial wall of the right orbit, with no intracranial abnormality. The patient was investigated for metastatic tumour as a possible cause of the space-occupying lesion and the unprovoked thromboembolic event, but no evidence of malignancy was found. The orbital lesion was not biopsied because of the risk of bleeding from anticoagulation. Three weeks later, the patient re-presented with recurrent cardiac failure, proptosis, and diplopia. A transorbital ultrasound confirmed an encapsulated, well-defined vascular lesion, with typical appearances and Doppler flow characteristics of a cavernous haemangioma. Diuretic therapy abolished the proptosis and diplopia in tandem with relief of the cardiac failure. This is the first description of recurrent proptosis with diplopia due to recurrent congestive expansion of an orbital cavernous haemangioma.


Keywords: haemangioma; proptosis; diplopia; cardiac failure PMID:10621902

  2. Internal jugular vein cannulation complications and elimination of the muscular triangle of the neck due to aberrant infrahyoid muscles.

    PubMed

    Raikos, Athanasios; Agnihotri, Ashwin; Yousif, Saif; Kordali, Panagiota; Saberi, Minu; Brand-Saberi, Beate

    2014-01-01

    We report on a rare case of anatomical variations of the infrahyoid muscles with prominent clinical significance. The aberrant anatomy was on the right side of the neck and involved the omohyoid and sternohyoid muscles. The superior belly of the omohyoid was duplicated in width due to an aberrant belly anteriorly and merged with fibers of the inferior belly inferiorly and the sternohyoid muscle medially. An additional aberrant muscle slip extended between the inferior third of the sternohyoid muscle and united with the inferior belly of the omohyoid. The intermediate tendon between the two bellies of the omohyoid was absent, whereas the so-called muscular triangle of the neck was diminished. Due to the arrangement and fusion of myofibers the muscle could be termed as omo-sternohyoid muscle. A profound hematoma was noted in the aberrant muscle at the area overlying the internal jugular vein indicating difficulty in obtaining jugular venous access for catheter placement. Clinicians and surgeons should be aware of muscular anatomic variations when intervening in the lateral neck area as the classical anatomical landmarks might be misinterpreted and confuse. PMID:25329135

  3. Orientation of the N- and C-terminal lobes of the myosin regulatory light chain in cardiac muscle.

    PubMed

    Kampourakis, Thomas; Sun, Yin-Biao; Irving, Malcolm

    2015-01-20

    The orientations of the N- and C-terminal lobes of the cardiac isoform of the myosin regulatory light chain (cRLC) in the fully dephosphorylated state in ventricular trabeculae from rat heart were determined using polarized fluorescence from bifunctional sulforhodamine probes. cRLC mutants with one of eight pairs of surface-accessible cysteines were expressed, labeled with bifunctional sulforhodamine, and exchanged into demembranated trabeculae to replace some of the native cRLC. Polarized fluorescence data from the probes in each lobe were combined with RLC crystal structures to calculate the lobe orientation distribution with respect to the filament axis. The orientation distribution of the N-lobe had three distinct peaks (N1-N3) at similar angles in relaxation, isometric contraction, and rigor. The orientation distribution of the C-lobe had four peaks (C1-C4) in relaxation and isometric contraction, but only two of these (C2 and C4) remained in rigor. The N3 and C4 orientations are close to those of the corresponding RLC lobes in myosin head fragments bound to isolated actin filaments in the absence of ATP (in rigor), but also close to those of the pair of heads folded back against the filament surface in isolated thick filaments in the so-called J-motif conformation. The N1 and C1 orientations are close to those expected for actin-bound myosin heads with their light chain domains in a pre-powerstroke conformation. The N2 and C3 orientations have not been observed previously. The results show that the average change in orientation of the RLC region of the myosin heads on activation of cardiac muscle is small; the RLC regions of most heads remain in the same conformation as in relaxation. This suggests that the orientation of the dephosphorylated RLC region of myosin heads in cardiac muscle is primarily determined by an interaction with the thick filament surface. PMID:25606679

  4. Early cardiac tamponade due to tension pneumopericardium after bilateral lung transplantation.

    PubMed

    Lasocki, Sigismond; Castier, Yves; Geffroy, Arnaud; Mal, Hervé; Brugière, Olivier; Lesèche, Guy; Montravers, Philippe

    2007-10-01

    We report the case of a 42-year-old woman who developed severe hemodynamic instability with marked arterial pulsed pressure variation in the early course of bilateral lung transplantation. The diagnosis of tension pneumopericardium was made on Day 2 post-operatively based on chest X-ray and echocardiography. Transoesophageal echocardiography revealed both a cardiac tamponade and a right-to-left shunt via a patent foramen ovale. The treatment and mechanisms of these two rare complications are discussed. PMID:17919630

  5. Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.

    PubMed

    Kennedy, Hannah; Haack, Tobias B; Hartill, Verity; Mataković, Lavinija; Baumgartner, E Regula; Potter, Howard; Mackay, Richard; Alston, Charlotte L; O'Sullivan, Siobhan; McFarland, Robert; Connolly, Grainne; Gannon, Caroline; King, Richard; Mead, Scott; Crozier, Ian; Chan, Wandy; Florkowski, Chris M; Sage, Martin; Höfken, Thomas; Alhaddad, Bader; Kremer, Laura S; Kopajtich, Robert; Feichtinger, René G; Sperl, Wolfgang; Rodenburg, Richard J; Minet, Jean Claude; Dobbie, Angus; Strom, Tim M; Meitinger, Thomas; George, Peter M; Johnson, Colin A; Taylor, Robert W; Prokisch, Holger; Doudney, Kit; Mayr, Johannes A

    2016-09-01

    We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosphatase was significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized. PMID:27523597

  6. Combined analyses of creatine kinase MB, cardiac troponin I and myoglobin in pericardial and cerebrospinal fluids to investigate myocardial and skeletal muscle injury in medicolegal autopsy cases.

    PubMed

    Wang, Qi; Michiue, Tomomi; Ishikawa, Takaki; Zhu, Bao-Li; Maeda, Hitoshi

    2011-09-01

    Creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and myoglobin (Mb) are biochemical markers of myocardial injury; however, Mb is more abundant in skeletal muscles. The present study involved analysis of these markers in pericardial and cerebrospinal fluids (PCF and CSF) from serial medicolegal autopsy cases (n=295, within 48h) to examine their efficacy in determining the cause of death. Although these markers showed a slight postmortem time-dependent elevation, except for CK-MB in CSF, the distribution depended on the cause of death. Mb levels in PCF and CSF were higher in fatal hyperthermia (heat stroke) and methamphetamine abuse, and CK-MB in both fluids was also higher in the latter. In psychotropic drug intoxication, CK-MB, cTnI and Mb were higher in PCF, but only cTnI was elevated in CSF. In electrocution and cerebrovascular disease, each marker was higher in PCF and also relatively high in CSF. PCF cTnI level was higher in acute pulmonary embolism without significant elevation of any other markers, whereas CSF CK-MB was higher in acute blunt brain injury death and methamphetamine abuse. In most cases of delayed brain injury death, hypothermia (cold exposure) and pneumonia, these markers were low or intermediate in both PCF and CSF; however, sudden cardiac death, asphyxiation and fire fatality cases showed few characteristic findings. These observations suggest that combined analyses of these markers in postmortem PCF and CSF, in addition to blood samples, are helpful for evaluating the severity of myocardial and/or skeletal muscle damage in death processes, in particular for investigating deaths due to hyperthermia, hypothermia, electrocution and intoxication. PMID:21683643

  7. Evidence of an association between cardiac-locomotor synchronization and lower leg muscle blood perfusion during walking

    PubMed Central

    Takeuchi, Shinta; Nishida, Yusuke; Mizushima, Takashi

    2015-01-01

    [Purpose] The purpose of this study was to investigate whether the occurrence of cardiac-locomotor synchronization (CLS) improves lower leg muscle blood perfusion during walking. [Subjects and Methods] Eleven healthy men were studied while performing two treadmill protocols. The CLS protocol involved subjects walking at the frequency of their heart rate (HR) to induce CLS. The free protocol (reference) involved subjects walking at a self-selected cadence. The treadmill load was identical in the two protocols. Electrocardiographic signals for HR, foot switch signals for step rate and near-infrared spectroscopy (NIRS) signals for total haemoglobin (total Hb) in the lower leg muscles were measured continuously for 10 min after HR reached a steady state. [Results] The mean HR and mean step rate did not differ between the CLS and free protocols. However, total Hb was significantly higher in the CLS protocol than in the free protocol. The rate of increase in total Hb positively correlated with the strength of CLS. [Conclusion] These results suggest that the occurrence of CLS enhances lower leg muscle blood perfusion by increasing the strength of CLS during walking. PMID:26180328

  8. Isotonic contractile impairment due to genetic CLC-1 chloride channel deficiency in myotonic mouse diaphragm muscle.

    PubMed

    van Lunteren, Erik; Pollarine, Jennifer; Moyer, Michelle

    2007-07-01

    The hallmark of genetic CLC-1 chloride channel deficiency in myotonic humans, goats and mice is delayed muscle relaxation resulting from persistent electrical discharges. In addition to the ion channel defect, muscles from myotonic humans and mice also have major changes in fibre type and myosin isoform composition, but the extent to which this affects isometric contractions remains controversial. Many muscles, including the diaphragm, shorten considerably during normal activities, but shortening contractions have never been assessed in myotonic muscle. The present study tested the hypothesis that CLC-1 deficiency leads to an impairment of muscle isotonic contractile performance. This was tested in vitro on diaphragm muscle from SWR/J-Clcn1(adr-mto)/J myotonic mice. The CLC-1-deficient muscle demonstrated delayed relaxation, as expected. During the contractile phase, there were significant reductions in power and work across a number of stimulation frequencies and loads in CLC-1-deficient compared with normal muscle, the magnitude of which in many instances exceeded 50%. Reductions in shortening and velocity of shortening occurred, and were more pronounced when calculated as a function of absolute than relative load. However, the maximal unloaded shortening velocity calculated from Hill's equation was not altered significantly. The impaired isotonic contractile performance of CLC-1-deficient muscle persisted during fatigue-inducing stimulation. These data indicate that genetic CLC-1 chloride channel deficiency in mice not only produces myotonia but also substantially worsens the isotonic contractile performance of diaphragm muscle. PMID:17483199

  9. Vortex shedding as a precursor of turbulent electrical activity in cardiac muscle.

    PubMed Central

    Cabo, C; Pertsov, A M; Davidenko, J M; Baxter, W T; Gray, R A; Jalife, J

    1996-01-01

    In cardiac tissue, during partial blockade of the membrane sodium channels, or at high frequencies of excitation, inexcitable obstacles with sharp edges may destabilize the propagation of electrical excitation waves, causing the formation of self-sustained vortices and turbulent cardiac electrical activity. The formation of such vortices, which visually resembles vortex shedding in hydrodynamic turbulent flows, was observed in sheep epicardial tissue using voltage-sensitive dyes in combination with video-imaging techniques. Vortex shedding is a potential mechanism leading to the spontaneous initiation of uncontrolled high-frequency excitation of the heart. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 7 PMID:8785270

  10. Inappropriate shocks delivered by implantable cardiac defibrillators during oversensing of activity of diaphagmatic muscle

    PubMed Central

    Babuty, D; Fauchier, L; Cosnay, P

    1999-01-01

    Two cases are reported (both men, one 72 and one 54 years old) of inappropriate shocks delivered by an implantable cardiac defibrillator (ICD) device, which oversensed the myopotentials induced by deep breathing and Valsalva manoeuvre. No damage to leads was associated with the oversensing of myopotentials. The mechanism of the inappropriate shocks was determined using real time electrograms. Modification of the duration of ventricular detection and decrease in sensitivity made it possible to avoid the oversensing of myopotentials and to deliver ICD treatment.

 Keywords: implantable cardiac defibrillator;  inappropriate shocks;  myopotentials PMID:10220554

  11. Theiler's murine encephalomyelitis virus-induced cardiac and skeletal muscle disease.

    PubMed Central

    Gómez, R M; Rinehart, J E; Wollmann, R; Roos, R P

    1996-01-01

    The DA strain of Theiler's murine encephalomyelitis virus, a member of the cardiovirus genus of picornaviruses, induces a restricted and persistent infection associated with a demyelinating process following intracerebral inoculation of mice; both virus infection and the immune response are believed to contribute to the late white matter disease. We now report that intraperitoneal inoculation with DA produces an acute myositis that progresses to a chronic inflammatory muscle disease in CD-1 mice as well as several inbred mouse strains. Some mouse strains also develop central nervous system white matter disease and a focal myocarditis. Infectious virus in skeletal muscle falls to undetectable levels 3 weeks postinoculation (p.i.), although viral genome persists for at least 12 weeks p.i., the longest period of observation. Severe combined immunodeficient animals have evidence of muscle pathology as long as 5 weeks p.i., suggesting that DA virus is capable of inducing chronic muscle disease in the absence of an immune response. The presence in immunocompetent mice, however, of prominent muscle inflammation in the absence of infectious virus suggests that the immune system also contributes to the pathology. T lymphocytes are the predominant cell type infiltrating the skeletal muscle during the chronic disease. This murine model may further our understanding of virus-induced chronic myositis and help to clarify the pathogenesis of human inflammatory myopathies. PMID:8971022

  12. Healthy older humans exhibit augmented carotid-cardiac baroreflex sensitivity with aspirin during muscle mechanoreflex and metaboreflex activation.

    PubMed

    Drew, Rachel C; Blaha, Cheryl A; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2015-10-01

    Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 ± 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P < 0.05) but did not affect 6-keto-PGF1α. After aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 ± 0.03 vs. -0.14 ± 0.02 and operating point gain: -0.11 ± 0.03 vs. -0.04 ± 0.01 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively, P < 0.05). In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control. PMID:26371168

  13. An investigation of fatigue phenomenon in the upper limb muscle due to short duration pulses in an FES system

    NASA Astrophysics Data System (ADS)

    Naeem, Jannatul; Wong Azman, Amelia; Khan, Sheroz; Mohd Mustafah, Yasir

    2013-12-01

    Functional Electrical Stimulation (FES) is a method of artificially stimulating muscles or nerves in order to result in contraction or relaxation of muscles. Many studies have shown that FES system has helped patients to live a better lives especially those who are suffering from physical mobility. Unfortunately, one of the main limitations of an FES system besides of its high cost is largely due to muscle fatigue. Muscle fatigue will affect the training duration which could delay patients' recovery rate. In this paper, we analyzed the occurrence of this fatigue phenomenon in terms of stimulator parameters such as amplitude, frequency, pulse width and pulse shape. The objective of this investigation is to identify other key features of the FES system parameters in order to prolong the training duration among patients. The experiment has been done on a healthy person for the duration of one minute and later the muscles response will be observed. Resultant muscle response is recorded as force using force resistive sensor. The experimental results show muscles will get fatigue at a different rate as the frequency increases. The experiment also shows that the duty cycle is reciprocal to the resultant force.

  14. Sexual Dimorphism in the Alterations of Cardiac Muscle Mitochondrial Bioenergetics Associated to the Ageing Process.

    PubMed

    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. PMID:24682352

  15. [An autopsy case of progressive generalized muscle atrophy over 14 years due to post-polio syndrome].

    PubMed

    Oki, Ryosuke; Uchino, Akiko; Izumi, Yuishin; Ogawa, Hirohisa; Murayama, Shigeo; Kaji, Ryuji

    2016-01-01

    We report the case of a 72-year-old man who had contracted acute paralytic poliomyelitis in his childhood. Thereafter, he had suffered from paresis involving the left lower limb, with no relapse or progression of the disease. He began noticing slowly progressive muscle weakness and atrophy in the upper and lower extremities in his 60s. At the age of 72, muscle weakness developed rapidly, and he demonstrated dyspnea on exertion and dysphagia. He died after about 14 years from the onset of muscle weakness symptoms. Autopsy findings demonstrated motoneuron loss and glial scars not only in the plaque-like lesions in the anterior horns, which were sequelae of old poliomyelitis, but also throughout the spine. No Bunina bodies, TDP-43, and ubiquitin inclusions were found. Post-polio syndrome is rarely fatal due to rapid progressive dyspnea and dysphagia. Thus, the pathological findings in the patient are considered to be related to the development of muscle weakness. PMID:26616485

  16. [Cardiac Angiosarcoma with Acute Myocardial Infarction due to Tumor Embolism;Report of a Case].

    PubMed

    Date, Yusuke; Miyazu, Katsuyuki; Ikeda, Masahiro

    2016-09-01

    We report the case of a 28-year-old man with a rare angiosarcoma complicated by acute myocardial infarction secondary to tumor embolism. He was transported to our emergency unit because of sudden onset of chest pain. The echocardiography showed a 42×60 mm mass in the left ventricle, and the coronary angiography showed embolic occlusion of the proximal left anterior descending and circumflex arteries. Emergent surgical removal of the mass was attempted under cardiopulmonary bypass, concomitant with double coronary artery bypass grafting and mitral valve replacement with a mechanical prosthesis. However, complete tumor excision was impossible. The postoperative pathological examination revealed undifferentiated angiosarcoma. Twenty days after the operation, the patient suffered acute cerebral hemorrhage from a metastatic tumor in the brain. He died at 37 days after the initial cardiac surgery. PMID:27586319

  17. Calcium Alternans is Due to an Order-Disorder Phase Transition in Cardiac Cells

    NASA Astrophysics Data System (ADS)

    Alvarez-Lacalle, Enrique; Echebarria, Blas; Spalding, Jon; Shiferaw, Yohannes

    2015-03-01

    Electromechanical alternans is a beat-to-beat alternation in the strength of contraction of a cardiac cell, which can be caused by an instability of calcium cycling. Using a distributed model of subcellular calcium we show that alternans occurs via an order-disorder phase transition which exhibits critical slowing down and a diverging correlation length. We apply finite size scaling along with a mapping to a stochastic coupled map model, to show that this transition in two dimensions is characterized by critical exponents consistent with the Ising universality class. These findings highlight the important role of cooperativity in biological cells, and suggest novel approaches to investigate the onset of the alternans instability in the heart.

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

    SciTech Connect

    Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.; Ertel, P.J.; Bemis, K.G.; Robertson, D.W. )

    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.

  19. Cardiac and aortic structural alterations due to surgically-induced menopause associated with renovascular hypertension in rats.

    PubMed

    Mendonça, Leonardo de Souza; Fernandes-Santos, Caroline; Mandarim-de-Lacerda, Carlos Alberto

    2007-08-01

    Menopause and hypertension independently alter cardiovascular remodelling, but little is known about their effect on left ventricular and aortic wall remodelling. Eight-weeks-old Wistar rats were divided into four groups of six animals each: Sham group, OVX group (ovariectomized rats), 2K1C (two-kidneys, one-clip rats) and OVX + 2K1C group and kept until 19 weeks. Blood pressure (BP) increased 12% in OVX group, 35% in 2K1C and OVX + 2K1C groups compared with sham group. Vaginal cytology showed Sham and 2K1C rats cycling normally, whereas OVX and OVX + 2K1C rats were persistently in dioestrus or proestrus. At euthanasia, left ventricle (LV) and thoracic aorta were removed and analysed (immunohistochemistry and stereology). LV mass/tibia length ratio and cross-sectional area of cardiomyocytes increased in all groups except Sham. The intramyocardial vascularization reduced 30% in comparison with Sham group, with no difference among OVX, 2K1C and OVX + 2K1C groups. The cardiac interstitium increased more than 45% in both 2K1C and OVX + 2K1C groups compared with Sham, but there was no significant difference between Sham and OVX groups. Nuclei number of LV cardiomyocyte diminished in OVX group, followed by 2K1C group and OVX + 2K1C group, with no difference between the 2K1C and the OVX + 2K1C groups. There was positive immunostaining for angiotensin II AT1 receptor in smooth muscle cell layer of aortic tunica media in all groups. These results show that both ovariectomy and renovascular hypertension enhance BP as a single stimulus and therefore produce adverse cardiac remodelling. However, renovascular hypertension exerts a far greater influence than surgically-induced menopause in this parameter. PMID:17696911

  20. Types of muscle tissue (image)

    MedlinePlus

    The 3 types of muscle tissue are cardiac, smooth, and skeletal. Cardiac muscle cells are located in the walls of the heart, appear striated, and are under involuntary control. Smooth muscle fibers are located in walls of hollow ...

  1. Changes in Tibiofemoral Forces due to Variations in Muscle Activity during Walking

    PubMed Central

    DeMers, Matthew S.; Pal, Saikat; Delp, Scott L.

    2015-01-01

    Muscles induce large forces in the tibiofemoral joint during walking and thereby influence the health of tissues like articular cartilage and menisci. It is possible to walk with a wide variety of muscle coordination patterns, but the effect of varied muscle coordination on tibiofemoral contact forces remains unclear. The goal of this study was to determine the effect of varied muscle coordination on tibiofemoral contact forces. We developed a musculoskeletal model of a subject walking with an instrumented knee implant. Using an optimization framework, we calculated the tibiofemoral forces resulting from muscle coordination that reproduced the subject’s walking dynamics. We performed a large set of optimizations in which we systematically varied the coordination of muscles to determine the influence on tibiofemoral force. Model-predicted tibiofemoral forces arising with minimum muscle activation matched in vivo forces measured during early stance, but were greater than in vivo forces during late stance. Peak tibiofemoral forces during late stance could be reduced by increasing the activation of the gluteus medius, uniarticular hip flexors, and soleus, and by decreasing the activation of the gastrocnemius and rectus femoris. These results suggest that retraining of muscle coordination could substantially reduce tibiofemoral forces during late stance. PMID:24615885

  2. Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders

    PubMed Central

    Saini-Chohan, Harjot K.; Mitchell, Ryan W.; Vaz, Frédéric M.; Zelinski, Teresa; Hatch, Grant M.

    2012-01-01

    As the specific composition of lipids is essential for the maintenance of membrane integrity, enzyme function, ion channels, and membrane receptors, an alteration in lipid composition or metabolism may be one of the crucial changes occurring during skeletal and cardiac myopathies. Although the inheritance (autosomal dominant, autosomal recessive, and X-linked traits) and underlying/defining mutations causing these myopathies are known, the contribution of lipid homeostasis in the progression of these diseases needs to be established. The purpose of this review is to present the current knowledge relating to lipid changes in inherited skeletal muscle disorders, such as Duchenne/Becker muscular dystrophy, myotonic muscular dystrophy, limb-girdle myopathic dystrophies, desminopathies, rostrocaudal muscular dystrophy, and Dunnigan-type familial lipodystrophy. The lipid modifications in familial hypertrophic and dilated cardiomyopathies, as well as Barth syndrome and several other cardiac disorders associated with abnormal lipid storage, are discussed. Information on lipid alterations occurring in these myopathies will aid in the design of improved methods of screening and therapy in children and young adults with or without a family history of genetic diseases. PMID:22065858

  3. Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

    PubMed Central

    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

  4. Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

    PubMed Central

    Mansfield, Catherine; West, Tim G.; Curtin, Nancy A.; Ferenczi, Michael A.

    2012-01-01

    The contractile performance of the heart is linked to the energy that is available to it. Yet, the heart needs to respond quickly to changing demands. During diastole, the heart fills with blood and the heart chambers expand. Upon activation, contraction of cardiac muscle expels blood into the circulation. Early in systole, parts of the left ventricle are being stretched by incoming blood, before contraction causes shrinking of the ventricle. We explore here the effect of stretch of contracting permeabilized cardiac trabeculae of the rat on the rate of inorganic phosphate (Pi) release resulting from ATP hydrolysis, using a fluorescent sensor for Pi with millisecond time resolution. Stretch immediately reduces the rate of Pi release, an effect observed both at full calcium activation (32 μmol/liter of Ca2+), and at a physiological activation level of 1 μmol/liter of Ca2+. The results suggest that stretch redistributes the actomyosin cross-bridges toward their Pi-containing state. The redistribution means that a greater fraction of cross-bridges will be poised to rapidly produce a force-generating transition and movement, compared with cross-bridges that have not been subjected to stretch. At the same time stretch modifies the Pi balance in the cytoplasm, which may act as a cytoplasmic signal for energy turnover. PMID:22692210

  5. Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model.

    PubMed

    Landesberg, A; Sideman, S

    1994-08-01

    This study describes the regulation of mechanical activity in the intact cardiac muscle, the effects of the free calcium transients and the mechanical constraints, and emphasizes the central role of the troponin complex in regulating muscle activity. A "loose coupling" between calcium binding to troponin and cross-bridge cycling is stipulated, allowing the existence of cross bridges in the strong conformation without having bound calcium on the neighboring troponin. The model includes two feedback mechanisms: 1) a positive feedback, or cooperativity, in which the cycling cross bridges affect the affinity of troponin for calcium, and 2) a negative mechanical feedback, where the filament-sliding velocity affects cross-bridge cycling. The model simulates the reported experimental force-length and force-velocity relationships at different levels of activation. The dependence of the shortening velocity on calcium concentration, sarcomere length, internal load, and rate of cross-bridge cycling is described analytically in agreement with reported data. Furthermore, the model provides an analytic solution for Hill's equation of the force-velocity relationship and for the phenomena of unloaded shortening velocity and force deficit. The model-calculated changes in free calcium in various mechanical conditions are in good agreement with the available experimental results. PMID:8067434

  6. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks

    PubMed Central

    Camcıoğlu, Burcu; Boşnak-Güçlü, Meral; Karadallı, Müşerrefe Nur; Akı, Şahika Zeynep; Türköz-Sucak, Gülsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS. PMID:26060589

  7. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks.

    PubMed

    Camcıoğlu, Burcu; Boşnak-Güçlü, Meral; Karadallı, Müşerrefe Nur; Akı, Şahika Zeynep; Türköz-Sucak, Gülsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS. PMID:26060589

  8. Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses

    PubMed Central

    Huebsch, Nathaniel; Loskill, Peter; Deveshwar, Nikhil; Spencer, C. Ian; Judge, Luke M.; Mandegar, Mohammad A.; B. Fox, Cade; Mohamed, Tamer M.A.; Ma, Zhen; Mathur, Anurag; Sheehan, Alice M.; Truong, Annie; Saxton, Mike; Yoo, Jennie; Srivastava, Deepak; Desai, Tejal A.; So, Po-Lin; Healy, Kevin E.; Conklin, Bruce R.

    2016-01-01

    Tissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements. Here we describe an approach that combines features of EHM and cardiospheres: Micro-Heart Muscle (μHM) arrays, in which elongated muscle fibers are formed in an easily fabricated template, with as few as 2,000 iPS-CM per individual tissue. Within μHM, iPS-CM exhibit uniaxial contractility and alignment, robust sarcomere assembly, and reduced variability and hypersensitivity in drug responsiveness, compared to monolayers with the same cellular composition. μHM mounted onto standard force measurement apparatus exhibited a robust Frank-Starling response to external stretch, and a dose-dependent inotropic response to the β-adrenergic agonist isoproterenol. Based on the ease of fabrication, the potential for mass production and the small number of cells required to form μHM, this system provides a potentially powerful tool to study cardiomyocyte maturation, disease and cardiotoxicology in vitro. PMID:27095412

  9. Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses.

    PubMed

    Huebsch, Nathaniel; Loskill, Peter; Deveshwar, Nikhil; Spencer, C Ian; Judge, Luke M; Mandegar, Mohammad A; B Fox, Cade; Mohamed, Tamer M A; Ma, Zhen; Mathur, Anurag; Sheehan, Alice M; Truong, Annie; Saxton, Mike; Yoo, Jennie; Srivastava, Deepak; Desai, Tejal A; So, Po-Lin; Healy, Kevin E; Conklin, Bruce R

    2016-01-01

    Tissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements. Here we describe an approach that combines features of EHM and cardiospheres: Micro-Heart Muscle (μHM) arrays, in which elongated muscle fibers are formed in an easily fabricated template, with as few as 2,000 iPS-CM per individual tissue. Within μHM, iPS-CM exhibit uniaxial contractility and alignment, robust sarcomere assembly, and reduced variability and hypersensitivity in drug responsiveness, compared to monolayers with the same cellular composition. μHM mounted onto standard force measurement apparatus exhibited a robust Frank-Starling response to external stretch, and a dose-dependent inotropic response to the β-adrenergic agonist isoproterenol. Based on the ease of fabrication, the potential for mass production and the small number of cells required to form μHM, this system provides a potentially powerful tool to study cardiomyocyte maturation, disease and cardiotoxicology in vitro. PMID:27095412

  10. Influence of menstrual cycle phase on muscle metaboreflex control of cardiac baroreflex sensitivity, heart rate and blood pressure in humans.

    PubMed

    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. PMID:22613743

  11. Relationship between adductor pollicis muscle thickness and subjective global assessment in a cardiac intensive care unit

    PubMed Central

    Karst, Fernanda Pickrodt; Vieira, Renata Monteiro; Barbiero, Sandra

    2015-01-01

    Objective To verify the relationship between the adductor pollicis muscle thickness test and the subjective global assessment and to correlate it with other anthropometric methods. Methods This observational cross-sectional study was conducted in the intensive care unit of a cardiology hospital in the state of Rio Grande do Sul, Brazil. The hospitalized patients underwent subjective global assessment and adductor pollicis muscle thickness tests on both hands, along with measurement of the right calf circumference. Laboratory parameters, length of stay, vital signs and electronic medical record data and tests were all collected. Results The study population included 83 patients, of whom 62% were men. The average age was 68.6 ± 12.5 years. The most common reason for hospitalization was acute myocardial infarction (34.9%), and the most common pathology was systolic blood pressure (63.9%), followed by diabetes mellitus (28.9%). According to subjective global assessment classifications, 62.7% of patients presented no nutritional risk, 20.5% were moderately malnourished and 16.9% were severely malnourished. Women had a higher nutritional risk, according to both the subjective global assessment and the adductor pollicis muscle thickness test, the cutoff for which was < 6.5mm (54.8%; p = 0.001). The pathology presenting the greatest nutritional risk was congestive heart failure (p = 0.001). Evaluation of the receiver operating characteristic (ROC) curve between adductor pollicis muscle thickness and subjective global assessment showed the accuracy of the former, with an area of 0.822. Conclusion Adductor pollicis muscle thickness proved to be a good method for evaluating nutritional risk. PMID:26761475

  12. Distinct gene expression patterns in skeletal and cardiac muscle are dependent on common regulatory sequences in the MLC1/3 locus.

    PubMed Central

    McGrew, M J; Bogdanova, N; Hasegawa, K; Hughes, S H; Kitsis, R N; Rosenthal, N

    1996-01-01

    The myosin light-chain 1/3 locus (MLC1/3) is regulated by two promoters and a downstream enhancer element which produce two protein isoforms in fast skeletal muscle at distinct stages of mouse embryogenesis. We have analyzed the expression of transcripts from the internal MLC3 promoter and determined that it is also expressed in the atria of the heart. Expression from the MLC3 promoter in these striated muscle lineages is differentially regulated during development. In transgenic mice, the MLC3 promoter is responsible for cardiac-specific reporter gene expression while the downstream enhancer augments expression in skeletal muscle. Examination of the methylation status of endogenous and transgenic promoter and enhancer elements indicates that the internal promoter is not regulated in a manner similar to that of the MLC1 promoter or the downstream enhancer. A GATA protein consensus sequence in the proximal MLC3 promoter but not the MLC1 promoter binds with high affinity to GATA-4, a cardiac muscle- and gut-specific transcription factor. Mutation of either the MEF2 or GATA motifs in the MLC3 promoter attenuates its activity in both heart and skeletal muscles, demonstrating that MLC3 expression in these two diverse muscle types is dependent on common regulatory elements. PMID:8754853

  13. Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration.

    PubMed

    Shrestha, Uttam M; Seo, Youngho; Botvinick, Elias H; Gullberg, Grant T

    2015-11-01

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images. PMID:26450115

  14. Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

    SciTech Connect

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

    2015-10-09

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. We find these results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.

  15. Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

    DOE PAGESBeta

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

    2015-10-09

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variationmore » of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. We find these results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.« less

  16. Image Reconstruction in Higher Dimensions: Myocardial Perfusion Imaging of Tracer Dynamics with Cardiac Motion Due to Deformation and Respiration

    PubMed Central

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

    2015-01-01

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases due to redistribution of the counts over the cardiac-respiratory gates. However, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images. PMID:26450115

  17. Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

    NASA Astrophysics Data System (ADS)

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

    2015-11-01

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.

  18. Effects of nutritional supplementation with l-arginine on repair of injuries due to muscle strain: experimental study on rats☆

    PubMed Central

    Couto, Lauren Izabel Medeiros; Wuicik, William Luiz; Kuhn, Ivan; Capriotti, Juan Rodolfo Vilela; Repka, João Carlos

    2015-01-01

    Objective To evaluate the influence of oral supplementation with arginine on regeneration of injuries due to straining of the anterior tibial muscle of rats. Methods Twenty-four Wistar rats of weight 492.5 ± 50.45 g were used. Injuries were induced through straining the anterior tibial muscles. The rats were separated into three groups of eight rats each. In the untreated group (UTG), after induction of injuries, the rats were observed for 24 h. In the simulation group (SG) and the arginine group (AG) respectively, the rats received isotonic saline solution and arginine solution via direct gavage, over a seven-day period. At the end of the period, blood samples were collected for serum evaluations of creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and C-reactive protein (CRP). The right and left anterior tibial muscles were resected for histopathological evaluations on the muscle injuries, investigating edema, hemorrhage and disorganization or morphometric alteration of the muscle fibers. The tissue repair was investigated in terms of proliferation of adipose tissue, angiogenesis and collagen fibers. The ANOVA and Student's t methods were used and p ≤ 0.05 was taken to be statistically significant. Results In the serum evaluations, the AG showed lower CK assay values and higher AST values. In the histopathological evaluation, the UTG presented edema and hemorrhage compatible with injuries due to strain; the SG presented edema and hemorrhage with proliferation of adipose tissue and collagen fibers; and the AG presented not only the findings of the SG but also, especially, intense angiogenesis. Conclusion Oral supplementation with arginine did not cause any significant metabolic alterations that would contraindicate its use and it induced angiogenesis during the repair of muscles injured due to strain. PMID:26401505

  19. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system.

    PubMed Central

    Balligand, J L; Kelly, R A; Marsden, P A; Smith, T W; Michel, T

    1993-01-01

    Nitric oxide (NO) synthesized from L-arginine is a ubiquitous intracellular chemical messenger and is involved in signal transduction in diverse mammalian cells, including vascular endothelium and neuronal tissues. The role of the NO-signaling pathway in the direct modulation of cardiac function is less well characterized. In this report, the effects of inhibitors of NO synthase (NOS) were examined in isolated neonatal and adult rat ventricular myocytes exposed to either muscarinic or adrenergic agonists. Carbachol (10 microM) caused a 91% inhibition of the spontaneous beating rate of cultured neonatal rat cardiac myocytes. N omega-monomethyl-L-arginine, an L-arginine analog that inhibits NOS, and methylene blue, an inhibitor of NO, blocked the negative chronotropic effect of carbachol but had no effect on the basal beating rate of these cells. The inhibition by N omega-monomethyl-L-arginine of the negative chronotropic effect of carbachol was reversed by adding excess L-arginine. The negative chronotropic effect of carbachol was also mimicked by analogs of cGMP, a second messenger implicated in mediating the action of NO in other cell types. Production of NO could be detected directly in carbachol-stimulated neonatal myocytes by using a reporter cell bioassay. The regulation of adrenergic responsiveness by the NO signaling system was also documented in studies of adult cardiac myocyte contractility. The NOS inhibitor N omega-nitro-L-arginine significantly increased the inotropic effect of the beta-adrenergic agonist isoproterenol on electrically stimulated adult rat ventricular myocytes, whereas this inhibitor had no effect on basal contractility. Inhibition of NO production by N omega-monomethyl-L-arginine in these cells, as measured by reporter cell bioassay, was also reversible with excess L-arginine. Thus, the physiologic response of isolated neonatal and adult ventricular myocytes to both muscarinic cholinergic and beta-adrenergic stimulation is mediated, at

  20. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells.

    PubMed

    Chen, Qi; Zhang, Hui; Liu, Yang; Adams, Susanne; Eilken, Hanna; Stehling, Martin; Corada, Monica; Dejana, Elisabetta; Zhou, Bin; Adams, Ralf H

    2016-01-01

    Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity. The developmental sources of these cells and molecular mechanisms controlling their progenitors in the heart are only partially understood. Here we show that endocardial endothelial cells are progenitors of pericytes and vascular smooth muscle cells in the murine embryonic heart. Endocardial cells undergo endothelial-mesenchymal transition and convert into primitive mesenchymal progenitors expressing the platelet-derived growth factor receptors, PDGFRα and PDGFRβ. These progenitors migrate into the myocardium, differentiate and assemble the wall of coronary vessels, which requires canonical Wnt signalling involving Frizzled4, β-catenin and endothelial cell-derived Wnt ligands. Our findings identify a novel and unexpected population of progenitors for coronary mural cells with potential relevance for heart function and disease conditions. PMID:27516371

  1. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells

    PubMed Central

    Chen, Qi; Zhang, Hui; Liu, Yang; Adams, Susanne; Eilken, Hanna; Stehling, Martin; Corada, Monica; Dejana, Elisabetta; Zhou, Bin; Adams, Ralf H.

    2016-01-01

    Mural cells of the vessel wall, namely pericytes and vascular smooth muscle cells, are essential for vascular integrity. The developmental sources of these cells and molecular mechanisms controlling their progenitors in the heart are only partially understood. Here we show that endocardial endothelial cells are progenitors of pericytes and vascular smooth muscle cells in the murine embryonic heart. Endocardial cells undergo endothelial–mesenchymal transition and convert into primitive mesenchymal progenitors expressing the platelet-derived growth factor receptors, PDGFRα and PDGFRβ. These progenitors migrate into the myocardium, differentiate and assemble the wall of coronary vessels, which requires canonical Wnt signalling involving Frizzled4, β-catenin and endothelial cell-derived Wnt ligands. Our findings identify a novel and unexpected population of progenitors for coronary mural cells with potential relevance for heart function and disease conditions. PMID:27516371

  2. Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans.

    PubMed

    Drew, Rachel C; Muller, Matthew D; Blaha, Cheryl A; Mast, Jessica L; Herr, Michael D; Stocker, Sean D; Sinoway, Lawrence I

    2013-10-15

    Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% (P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; -0.71 ± 0.14 vs. -0.37 ± 0.08 and GOP; -0.69 ± 0.13 vs. -0.35 ± 0.12 beats·min(-1)·mmHg(-1) for aspirin and placebo, respectively; P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors. PMID:23970529

  3. The cardiac muscle duplex as a method to study myocardial heterogeneity

    PubMed Central

    Solovyova, O.; Katsnelson, L.B.; Konovalov, P.V.; Kursanov, A.G.; Vikulova, N.A.; Kohl, P.; Markhasin, V.S.

    2014-01-01

    This paper reviews the development and application of paired muscle preparations, called duplex, for the investigation of mechanisms and consequences of intra-myocardial electro-mechanical heterogeneity. We illustrate the utility of the underlying combined experimental and computational approach for conceptual development and integration of basic science insight with clinically relevant settings, using previously published and new data. Directions for further study are identified. PMID:25106702

  4. Cardiac myofibroblasts express alpha smooth muscle actin during right ventricular pressure overload in the rabbit.

    PubMed Central

    Leslie, K. O.; Taatjes, D. J.; Schwarz, J.; vonTurkovich, M.; Low, R. B.

    1991-01-01

    A number of changes occur in contractile proteins and mechanical performance of the heart within 2 weeks of right ventricular pressure overload in 8- to 12-week-old rabbits. These changes are accompanied by increases in collagen concentration and the ratio of type I to type III collagen. The purpose of the present study was to evaluate the evolution of these connective tissue changes morphologically and to characterize the interstitial cells that might be responsible. The myocardium is infiltrated by mononuclear inflammatory cells 2 days after banding, accompanied by focal myocyte necrosis. By 7 days, the inflammatory infiltrates subside and the damaged myocytes seen at 2 days are replaced by new collagen and a population of spindle-shaped cells, with ultrastructural features of myofibroblasts. A significant proportion of these cells contain alpha smooth muscle actin by immunohistochemical analysis. At 14 days, there is a large increase in stainable collagen with complex remodeling and reduplication of the collagen fiber network of the interstitium. Alpha smooth muscle actin-containing myofibroblasts persist, but their immunoreactivity appears reduced compared with day 7. The authors hypothesize that the interstitial fibroblasts that acquire smooth-muscle-like features in this model play a critical role in the heart's response to severe and sudden mechanical stress and are at least partly responsible for the changes in connective tissue that occur as a result of pressure overload in this model. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1853934

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

    PubMed

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

    2013-04-01

    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 CHO(M2) 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 heart slices were highly variable and only 10% of murine cardiomyocytes expressed muscarinic receptors. M2 receptors were evenly distributed across individual cells and their density in freshly isolated embryonic cardiomyocytes was ~1μm(-2), increasing at birth (to ~3μm(-2)) and decreasing back to ~1μm(-2) after birth. M2 receptors were primarily monomeric but formed reversible dimers. They diffused freely at the plasma membrane, moving approximately 4-times faster in heart slices than in cultured cardiomyocytes. Knowledge of receptor density and mobility has allowed receptor collision rate to be modeled by Monte Carlo simulations. Our estimated encounter rate of 5-10 collisions per second, may explain the latency between acetylcholine application and GIRK channel opening. PMID:23357106

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

    PubMed Central

    Nenasheva, Tatiana A.; Neary, Marianne; Mashanov, Gregory I.; 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 heart slices were highly variable and only 10% of murine cardiomyocytes expressed muscarinic receptors. M2 receptors were evenly distributed across individual cells and their density in freshly isolated embryonic cardiomyocytes was ~ 1 μm− 2, increasing at birth (to ~ 3 μm− 2) and decreasing back to ~ 1 μm− 2 after birth. M2 receptors were primarily monomeric but formed reversible dimers. They diffused freely at the plasma membrane, moving approximately 4-times faster in heart slices than in cultured cardiomyocytes. Knowledge of receptor density and mobility has allowed receptor collision rate to be modeled by Monte Carlo simulations. Our estimated encounter rate of 5–10 collisions per second, may explain the latency between acetylcholine application and GIRK channel opening. PMID:23357106

  7. Irreversible muscle damage in bodybuilding due to long-term intramuscular oil injection.

    PubMed

    Banke, I J; Prodinger, P M; Waldt, S; Weirich, G; Holzapfel, B M; Gradinger, R; Rechl, H

    2012-10-01

    Intramuscular oil injections generating slowly degrading oil-based depots represent a controversial subject in bodybuilding and fitness. However they seem to be commonly reported in a large number of non-medical reports, movies and application protocols for 'site-injections'. Surprisingly the impact of long-term (ab)use on the musculature as well as potential side-effects compromising health and sports ability are lacking in the medical literature. We present the case of a 40 year old male semi-professional bodybuilder with systemic infection and painful reddened swellings of the right upper arm forcing him to discontinue weightlifting. Over the last 8 years he daily self-injected sterilized sesame seed oil at numerous intramuscular locations for the purpose of massive muscle building. Whole body MRI showed more than 100 intramuscular rather than subcutaneous oil cysts and loss of normal muscle anatomy. 2-step septic surgery of the right upper arm revealed pus-filled cystic scar tissue with the near-complete absence of normal muscle. MRI 1 year later revealed the absence of relevant muscle regeneration. Persistent pain and inability to perform normal weight training were evident for at least 3 years post-surgery. This alarming finding indicating irreversible muscle mutilation may hopefully discourage people interested in bodybuilding and fitness from oil-injections. The impact of such chronic tissue stress on other diseases like malignancy remains to be determined. PMID:22592548

  8. Role of sarcomere mechanics and Ca2+ overload in Ca2+ waves and arrhythmias in rat cardiac muscle.

    PubMed

    ter Keurs, Henk E D J; Wakayama, Yuji; Sugai, Yoshinao; Price, Guy; Kagaya, Yutaka; Boyden, Penelope A; Miura, Masahito; Stuyvers, Bruno D M

    2006-10-01

    Ca(2+) release from the sarcoplasmic reticulum (SR) depends on the sarcoplasmic reticulum (SR) Ca(2+) load and the cytosolic Ca(2+) level. Arrhythmogenic Ca(2+) waves underlying triggered propagated contractions arise from Ca(2+) overloaded regions near damaged areas in the cardiac muscle. Ca(2+) waves can also be induced in undamaged muscle, in regions with nonuniform excitation-contraction (EC) coupling by the cycle of stretch and release in the border zone between the damaged and intact regions. We hypothesize that rapid shortening of sarcomeres in the border zone during relaxation causes Ca(2+) release from troponin C (TnC) on thin filaments and initiates Ca(2+) waves. Elimination of this shortening will inhibit the initiation of Ca(2+) waves, while SR Ca(2+) overload will enhance the waves. Force, sarcomere length (SL), and [Ca(2+)](i) were measured and muscle length was controlled. A small jet of Hepes solution with an extracellular [Ca(2+)] 10 mM (HC), or HC containing BDM, was used to weaken a 300 mum long muscle segment. Trains of electrical stimuli were used to induce Ca(2+) waves. The effects of small exponential stretches on triggered propagatory contraction (TPC) amplitude and propagation velocity of Ca(2+) waves (V(prop)) were studied. Sarcomere shortening was uniform prior to activation. HC induced spontaneous diastolic sarcomere contractions in the jet region and attenuated twitch sarcomere shortening; HC+ butanedione monoxime (BDM) caused stretch only in the jet region. Stimulus trains induced Ca(2+) waves, which started inside the HC jet region during twitch relaxation. Ca(2+) waves started in the border zone of the BDM jet. The initial local [Ca(2+)](i) rise of the waves by HC was twice that by BDM. The waves propagated at a V(prop) of 2.0 +/- 0.2 mm/sec. Arrhythmias occurred frequently in trabeculae following exposure to the HC jet. Stretch early during relaxation, which reduced sarcomere shortening in the weakened regions, substantially

  9. Animal models of cardiac cachexia.

    PubMed

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993

  10. Reorganised anticipatory postural adjustments due to experimental lower extremity muscle pain.

    PubMed

    Shiozawa, Shinichiro; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    2013-12-01

    Automated movements adjusting postural control may be hampered during musculoskeletal pain leaving a risk of incomplete control of balance. This study investigated the effect of experimental muscle pain on anticipatory postural adjustments by reaction task movements. While standing, nine healthy males performed two reaction time tasks (shoulder flexion of dominant side and bilateral heel lift) before, during and after experimental muscle pain. On two different days experimental pain was induced in the m. vastus medialis (VM) or the m. tibialis anterior (TA) of the dominant side by injections of hypertonic saline (1ml, 5.8%). Isotonic saline (1ml, 0.9%) was used as control injection. Electromyography (EMG) was recorded from 13 muscles. EMG onset, EMG amplitude, and kinematic parameters (shoulder and ankle joint) were extracted. During shoulder flexion and VM pain the onset of the ipsilateral biceps femoris was significantly faster than baseline and post injection sessions. During heels lift in the VM and TA pain conditions the onset of the contralateral TA was significantly faster than baseline and post injection sessions in bilateral side. VM pain significantly reduced m. quadriceps femoris activity and TA pain significantly reduced ipsilateral VM activity and TA activity during bilateral heel lift. The EMG reaction time was delayed in bilateral soleus muscles during heels lift with VM and TA pain. The faster onset of postural muscle activity during anticipatory postural adjustments may suggest a compensatory function to maintain postural control whereas the reduced postural muscle activity during APAs may indicate a pain adaptation strategy to avoid secondary damage. PMID:24071550

  11. Diet-induced Lethality Due to Deletion of the Hdac3 Gene in Heart and Skeletal Muscle*♦

    PubMed Central

    Sun, Zheng; Singh, Nikhil; Mullican, Shannon E.; Everett, Logan J.; Li, Li; Yuan, Lijun; Liu, Xi; Epstein, Jonathan A.; Lazar, Mitchell A.

    2011-01-01

    Many human diseases result from the influence of the nutritional environment on gene expression. The environment interacts with the genome by altering the epigenome, including covalent modification of nucleosomal histones. Here, we report a novel and dramatic influence of diet on the phenotype and survival of mice in which histone deacetylase 3 (Hdac3) is deleted postnatally in heart and skeletal muscle. Although embryonic deletion of myocardial Hdac3 causes major cardiomyopathy that reduces survival, we found that excision of Hdac3 in heart and muscle later in development leads to a much milder phenotype and does not reduce survival when mice are fed normal chow. Remarkably, upon switching to a high fat diet, the mice begin to die within weeks and display signs of severe hypertrophic cardiomyopathy and heart failure. Down-regulation of myocardial mitochondrial bioenergetic genes, specifically those involved in lipid metabolism, precedes the full development of cardiomyopathy, suggesting that HDAC3 is important in maintaining proper mitochondrial function. These data suggest that loss of the epigenomic modifier HDAC3 causes dietary lethality by compromising the ability of cardiac mitochondria to respond to changes of nutritional environment. In addition, this study provides a mouse model for diet-inducible heart failure. PMID:21808063

  12. Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation

    PubMed Central

    Mamidi, Ranganath; Gresham, Kenneth S.; Stelzer, Julian E.

    2014-01-01

    Enhanced cardiac contractile function with increased sarcomere length (SL) is, in part, mediated by a decrease in the radial distance between myosin heads and actin. The radial disposition of myosin heads relative to actin is modulated by cardiac myosin binding protein-C (cMyBP-C), suggesting that cMyBP-C contributes to the length-dependent activation (LDA) in the myocardium. However, the precise roles of cMyBP-C in modulating cardiac LDA are unclear. To determine the impact of cMyBP-C on LDA, we measured isometric force, myofilament Ca2+-sensitivity (pCa50) and length-dependent changes in kinetic parameters of cross-bridge (XB) relaxation (krel), and recruitment (kdf) due to rapid stretch, as well as the rate of force redevelopment (ktr) in response to a large slack-restretch maneuver in skinned ventricular multicellular preparations isolated from the hearts of wild-type (WT) and cMyBP-C knockout (KO) mice, at SL's 1.9 μm or 2.1 μm. Our results show that maximal force was not significantly different between KO and WT preparations but length-dependent increase in pCa50 was attenuated in the KO preparations. pCa50 was not significantly different between WT and KO preparations at long SL (5.82 ± 0.02 in WT vs. 5.87 ± 0.02 in KO), whereas pCa50 was significantly different between WT and KO preparations at short SL (5.71 ± 0.02 in WT vs. 5.80 ± 0.01 in KO; p < 0.05). The ktr, measured at half-maximal Ca2+-activation, was significantly accelerated at short SL in WT preparations (8.74 ± 0.56 s−1 at 1.9 μm vs. 5.71 ± 0.40 s−1 at 2.1 μm, p < 0.05). Furthermore, krel and kdf were accelerated by 32% and 50%, respectively at short SL in WT preparations. In contrast, ktr was not altered by changes in SL in KO preparations (8.03 ± 0.54 s−1 at 1.9 μm vs. 8.90 ± 0.37 s−1 at 2.1 μm). Similarly, KO preparations did not exhibit length-dependent changes in krel and kdf. Collectively, our data implicate cMyBP-C as an important regulator of LDA via its impact on

  13. [Time costs cardiac muscle tissue--prehospital therapy of acute myocardial infarct--a case report].

    PubMed

    Eschenburg, G; Pappert, D; Ohlmeier, H

    2003-01-01

    Symptoms of an acute myocardial infarction are a common reason for calling the emergency physician. Pre-hospital mortality caused by cardiac infarction is constantly high. The main potential for decreasing infarction mortality lies in the pre-hospital period. The problems and prospects of treatment in the early period are described in the case of a 73-year-old patient with an acute anterior infarction. The diagnostic and therapeutic approach is shown and discussed in this concrete case, taking into consideration the guidelines for diagnostics and therapy of acute myocardial infarction in the pre-hospital period of the German Society for Cardiology. A particular focus is the management of pre-hospital thrombolysis, the preconditions, realization and risks of which are described. In this context, the experience and competence of the emergency physician is prerequisite for the exact diagnosis and therapy. Furthermore, the importance of a smooth transition from pre-hospital therapy to intensive care is emphasized. PMID:12666508

  14. Cardiac Electrophysiological Alterations in Heart/Muscle-Specific Manganese-Superoxide Dismutase-Deficient Mice: Prevention by a Dietary Antioxidant Polyphenol

    PubMed Central

    Matsumoto, Akio; Tagashira, Motoyuki; Kanda, Tomomasa; Nakaya, Haruaki

    2014-01-01

    Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2−/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2−/− mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2−/− mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2−/− LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K+ current (IK1) was decreased in the LV cells of H/M-Sod2−/− mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2−/− mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density of IK1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances. PMID:24772433

  15. Task Failure during Exercise to Exhaustion in Normoxia and Hypoxia Is Due to Reduced Muscle Activation Caused by Central Mechanisms While Muscle Metaboreflex Does Not Limit Performance

    PubMed Central

    Torres-Peralta, Rafael; Morales-Alamo, David; González-Izal, Miriam; Losa-Reyna, José; Pérez-Suárez, Ismael; Izquierdo, Mikel; Calbet, José A. L.

    2016-01-01

    To determine whether task failure during incremental exercise to exhaustion (IE) is principally due to reduced neural drive and increased metaboreflex activation eleven men (22 ± 2 years) performed a 10 s control isokinetic sprint (IS; 80 rpm) after a short warm-up. This was immediately followed by an IE in normoxia (Nx, PIO2:143 mmHg) and hypoxia (Hyp, PIO2:73 mmHg) in random order, separated by a 120 min resting period. At exhaustion, the circulation of both legs was occluded instantaneously (300 mmHg) during 10 or 60 s to impede recovery and increase metaboreflex activation. This was immediately followed by an IS with open circulation. Electromyographic recordings were obtained from the vastus medialis and lateralis. Muscle biopsies and blood gases were obtained in separate experiments. During the last 10 s of the IE, pulmonary ventilation, VO2, power output and muscle activation were lower in hypoxia than in normoxia, while pedaling rate was similar. Compared to the control sprint, performance (IS-Wpeak) was reduced to a greater extent after the IE-Nx (11% lower P < 0.05) than IE-Hyp. The root mean square (EMGRMS) was reduced by 38 and 27% during IS performed after IE-Nx and IE-Hyp, respectively (Nx vs. Hyp: P < 0.05). Post-ischemia IS-EMGRMS values were higher than during the last 10 s of IE. Sprint exercise mean (IS-MPF) and median (IS-MdPF) power frequencies, and burst duration, were more reduced after IE-Nx than IE-Hyp (P < 0.05). Despite increased muscle lactate accumulation, acidification, and metaboreflex activation from 10 to 60 s of ischemia, IS-Wmean (+23%) and burst duration (+10%) increased, while IS-EMGRMS decreased (−24%, P < 0.05), with IS-MPF and IS-MdPF remaining unchanged. In conclusion, close to task failure, muscle activation is lower in hypoxia than in normoxia. Task failure is predominantly caused by central mechanisms, which recover to great extent within 1 min even when the legs remain ischemic. There is dissociation between the

  16. Double muscling in cattle due to mutations in the myostatin gene

    PubMed Central

    McPherron, Alexandra C.; Lee, Se-Jin

    1997-01-01

    Myostatin (GDF-8) is a member of the transforming growth factor β superfamily of secreted growth and differentiation factors that is essential for proper regulation of skeletal muscle mass in mice. Here we report the myostatin sequences of nine other vertebrate species and the identification of mutations in the coding sequence of bovine myostatin in two breeds of double-muscled cattle, Belgian Blue and Piedmontese, which are known to have an increase in muscle mass relative to conventional cattle. The Belgian Blue myostatin sequence contains an 11-nucleotide deletion in the third exon which causes a frameshift that eliminates virtually all of the mature, active region of the molecule. The Piedmontese myostatin sequence contains a missense mutation in exon 3, resulting in a substitution of tyrosine for an invariant cysteine in the mature region of the protein. The similarity in phenotypes of double-muscled cattle and myostatin null mice suggests that myostatin performs the same biological function in these two species and is a potentially useful target for genetic manipulation in other farm animals. PMID:9356471

  17. Solubilization and characterization of a ouabain-sensitive protein from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM-JSR) in cat cardiac muscle.

    PubMed

    Fujino, S; Satoh, K; Bando, T; Kurokawa, T; Nakai, T; Takashima, K; Fujino, M

    1989-05-15

    A new glycoprotein of 31,500 dalton, which has a high affinity for ouabain, and is independent of (Na+-K+)-ATPase, was solubilized from transverse tubule membrane and junctional sarcoplasmic reticulum complexes (TTM-JSR) of cat cardiac muscle. This protein could be extracted only in small amounts from sarcolemma-plasma membrane (SLM-PL) fragments, suggesting that it indeed originates from the TTM-JSR. PMID:2721638

  18. Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function.

    PubMed

    Ermolova, N V; Martinez, L; Vetrone, S A; Jordan, M C; Roos, K P; Sweeney, H L; Spencer, M J

    2014-07-01

    Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease caused by mutations in the gene encoding dystrophin (DYS). Tumor necrosis factor (TNF) has been implicated in the pathogenesis since short-term treatment of mdx mice with TNF blocking drugs proved beneficial; however, it is not clear whether long-term treatment will also improve long-term outcomes of fibrosis and cardiac health. In this investigation, short and long-term dosing studies were carried out using the TNF blocking drug Remicade and a variety of outcome measures were assessed. Here we show no demonstrable benefit to muscle strength or morphology with 10mg/kg or 20mg/kg Remicade; however, 3mg/kg produced positive strength benefits. Remicade treatment correlated with reductions in myostatin mRNA in the heart, and concomitant reductions in cardiac and skeletal fibrosis. Surprisingly, although Remicade treated mdx hearts were less fibrotic, reductions in LV mass and ejection fraction were also observed, and these changes coincided with reductions in AKT phosphorylation on threonine 308. Thus, TNF blockade benefits mdx skeletal muscle strength and fibrosis, but negatively impacts AKT activation, leading to deleterious changes to dystrophic heart function. These studies uncover a previously unknown relationship between TNF blockade and alteration of muscle growth signaling pathways. PMID:24844454

  19. Reduced ability to release adenosine by diabetic rat cardiac fibroblasts due to altered expression of nucleoside transporters

    PubMed Central

    Podgorska, Marzena; Kocbuch, Katarzyna; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2006-01-01

    Adenosine produced by cardiac cells is known to attenuate the proliferation of cardiac fibroblasts (CFs), inhibit collagen synthesis, and protect the myocardium against ischaemic and reperfusion injury. Diabetic patients' hearts exhibit ventricular hypertrophy and demonstrate reduced tolerance to hypoxia or ischaemia. In this study, we characterize the effects of glucose and insulin on processes that determine the release of adenosine from CFs. We showed that during ATP depletion, rat CFs cultured in the absence of insulin release significantly less adenosine compared to cells grown in the presence of insulin. Moreover, under both conditions the quantity of released adenosine depends on glucose concentration. We demonstrate that this is due to altered expression of nucleoside transporters. High glucose (25 mm) induced 85% decrease in nucleoside transporter ENT1 mRNA levels. Decrease of the insulin level below 10−11m resulted in over 3-fold increase in the nucleoside transporter CNT2 mRNA content. Measurements of adenosine transport in CFs cultured in the presence of 5 mm glucose and 10 nm insulin showed that the bidirectional equilibrative adenosine transport accounted for 70% of the overall adenosine uptake. However, cells grown in the presence of high glucose (25 mm) demonstrated 65% decrease of the bidirectional equilibrative adenosine transport. Experiments on CFs cultured in the absence of insulin showed that the unidirectional Na+-dependent adenosine uptake rose in these cells more than 4-fold. These results indicate that the development of diabetes may result in an increased uptake of interstitial adenosine by CFs, and reduction of the ability of these cells to release adenosine during ATP deprivation. PMID:16873415

  20. Isolation and characterization of a Streptococcus pyogenes protein that binds to basal laminae of human cardiac muscle.

    PubMed Central

    Winters, B D; Ramasubbu, N; Stinson, M W

    1993-01-01

    A 9-kDa glycosaminoglycan-binding protein (GAG-BP) was isolated from Streptococcus pyogenes and purified to homogeneity by affinity chromatography on heparin-agarose. The protein selectively bound to the basal laminae of human cardiac muscle and had an apparent dissociation constant of 2.5 x 10(-7) M. Chemical analyses indicated that the GAG-BP was rich in alanine, lysine, and arginine (pI 9.5) and devoid of tyrosine, methionine, histidine, and half-cystine. There were no detectable carbohydrate or phosphate substituents. The amino acid sequence of the N terminus of GAG-BP showed homology with those of histone-like DNA-binding proteins of several other bacteria. Circular dichroism spectroscopy indicated that the protein was made up of 50% beta-sheet and 50% beta-turn and random coil in aqueous solution; however, when the protein complexed with heparin, it adopted a more ordered structure containing 25% alpha-helix, 50% beta-sheet, and 25% beta-turn and random coil. The GAG-BP cross-reacted serologically with a component of similar size in extracts of other group A streptococci and was present in the culture medium during late logarithmic growth. Images PMID:8335359

  1. Bispyridinium non-oximes: An evaluation of cardiac effects in isolated hearts and smooth muscle relaxing effects in jejunum.

    PubMed

    Neumaier, Katharina; Worek, Franz; Thiermann, Horst; Wille, Timo

    2016-09-01

    Bispyridinium non-oximes seem to be promising candidates for the generic treatment of nerve agent poisoning as they interact with nicotinic and muscarinic acetylcholine receptors. The lead compound MB327 showed therapeutic effectiveness in vitro and in vivo but was toxic at higher doses. In the present study, the effect of various bispyridinium non-oximes on isolated heart and small intestine function was investigated. Bispyridinium non-oximes and oximes were tested in at least seven different concentrations in rat jejunum preparations pre-treated with carbachol. All bispyridinium non-oximes showed classical dose response curves with MB327 being the most effective (EC50=6.6μM) and MB782 being slightly less effective (EC50=10.4μM). Neither the bispyridinium non-oximes nor the oximes showed cardiotoxic effects in the isolated Langendorff heart. The tested bispyridinum compounds showed no direct cardiac effect but had variable smooth muscle relaxing effects. Further in vivo studies are required to get more insight into potential toxic mechanisms of these promising nerve agent antidotes. PMID:27184650

  2. Isoforms of α-Actinin from Cardiac, Smooth, and Skeletal Muscle Form Polar Arrays of Actin Filaments

    PubMed Central

    Taylor, Kenneth A.; Taylor, Dianne W.; Schachat, Fred

    2000-01-01

    We have used a positively charged lipid monolayer to form two-dimensional bundles of F-actin cross-linked by α-actinin to investigate the relative orientation of the actin filaments within them. This method prevents growth of the bundles perpendicular to the monolayer plane, thereby facilitating interpretation of the electron micrographs. Using α-actinin isoforms isolated from the three types of vertebrate muscle, i.e., cardiac, skeletal, and smooth, we have observed almost exclusively cross-linking between polar arrays of filaments, i.e., actin filaments with their plus ends oriented in the same direction. One type of bundle can be classified as an Archimedian spiral consisting of a single actin filament that spirals inward as the filament grows and the bundle is formed. These spirals have a consistent hand and grow to a limiting internal diameter of 0.4–0.7 μm, where the filaments appear to break and spiral formation ceases. These results, using isoforms usually characterized as cross-linkers of bipolar actin filament bundles, suggest that α-actinin is capable of cross-linking actin filaments in any orientation. Formation of specifically bipolar or polar filament arrays cross-linked by α-actinin may require additional factors that either determine the filament orientation or restrict the cross-linking capabilities of α-actinin. PMID:10791977

  3. Center of Pressure Displacement of Standing Posture during Rapid Movements Is Reorganised Due to Experimental Lower Extremity Muscle Pain

    PubMed Central

    Shiozawa, Shinichiro; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    2015-01-01

    Background Postural control during rapid movements may be impaired due to musculoskeletal pain. The purpose of this study was to investigate the effect of experimental knee-related muscle pain on the center of pressure (CoP) displacement in a reaction time task condition. Methods Nine healthy males performed two reaction time tasks (dominant side shoulder flexion and bilateral heel lift) before, during, and after experimental pain induced in the dominant side vastus medialis or the tibialis anterior muscles by hypertonic saline injections. The CoP displacement was extracted from the ipsilateral and contralateral side by two force plates and the net CoP displacement was calculated. Results Compared with non-painful sessions, tibialis anterior muscle pain during the peak and peak-to-peak displacement for the CoP during anticipatory postural adjustments (APAs) of the shoulder task reduced the peak-to-peak displacement of the net CoP in the medial-lateral direction (P<0.05). Tibialis anterior and vastus medialis muscle pain during shoulder flexion task reduced the anterior-posterior peak-to-peak displacement in the ipsilateral side (P<0.05). Conclusions The central nervous system in healthy individuals was sufficiently robust in maintaining the APA characteristics during pain, although the displacement of net and ipsilateral CoP in the medial-lateral and anterior-posterior directions during unilateral fast shoulder movement was altered. PMID:26680777

  4. Cardiac conduction system

    MedlinePlus Videos and Cool Tools

    ... signals to the heart muscle causing it to contract. The main components of the cardiac conduction system ... the sequence by causing the atrial muscles to contract. From there, the signal travels to the AV ...

  5. Phosphorylation of myosin regulatory light chain controls myosin head conformation in cardiac muscle.

    PubMed

    Kampourakis, Thomas; Irving, Malcolm

    2015-08-01

    The effect of phosphorylation on the conformation of the regulatory light chain (cRLC) region of myosin in ventricular trabeculae from rat heart was determined by polarized fluorescence from thiophosphorylated cRLCs labelled with bifunctional sulforhodamine (BSR). Less than 5% of cRLCs were endogenously phosphorylated in this preparation, and similarly low values of basal cRLC phosphorylation were measured in fresh intact ventricle from both rat and mouse hearts. BSR-labelled cRLCs were thiophosphorylated by a recombinant fragment of human cardiac myosin light chain kinase, which was shown to phosphorylate cRLCs specifically at serine 15 in a calcium- and calmodulin-dependent manner, both in vitro and in situ. The BSR-cRLCs were exchanged into demembranated trabeculae, and polarized fluorescence intensities measured for each BSR-cRLC in relaxation, active isometric contraction and rigor were combined with RLC crystal structures to calculate the orientation distribution of the C-lobe of the cRLC in each state. Only two of the four C-lobe orientation populations seen during relaxation and active isometric contraction in the unphosphorylated state were present after cRLC phosphorylation. Thus cRLC phosphorylation alters the equilibrium between defined conformations of the cRLC regions of the myosin heads, rather than simply disordering the heads as assumed previously. cRLC phosphorylation also changes the orientation of the cRLC C-lobe in rigor conditions, showing that the orientation of this part of the myosin head is determined by its interaction with the thick filament even when the head is strongly bound to actin. These results suggest that cRLC phosphorylation controls the contractility of the heart by modulating the interaction of the cRLC region of the myosin heads with the thick filament backbone. PMID:26057075

  6. Phosphorylation of myosin regulatory light chain controls myosin head conformation in cardiac muscle

    PubMed Central

    Kampourakis, Thomas; Irving, Malcolm

    2015-01-01

    The effect of phosphorylation on the conformation of the regulatory light chain (cRLC) region of myosin in ventricular trabeculae from rat heart was determined by polarized fluorescence from thiophosphorylated cRLCs labelled with bifunctional sulforhodamine (BSR). Less than 5% of cRLCs were endogenously phosphorylated in this preparation, and similarly low values of basal cRLC phosphorylation were measured in fresh intact ventricle from both rat and mouse hearts. BSR-labelled cRLCs were thiophosphorylated by a recombinant fragment of human cardiac myosin light chain kinase, which was shown to phosphorylate cRLCs specifically at serine 15 in a calcium- and calmodulin-dependent manner, both in vitro and in situ. The BSR-cRLCs were exchanged into demembranated trabeculae, and polarized fluorescence intensities measured for each BSR-cRLC in relaxation, active isometric contraction and rigor were combined with RLC crystal structures to calculate the orientation distribution of the C-lobe of the cRLC in each state. Only two of the four C-lobe orientation populations seen during relaxation and active isometric contraction in the unphosphorylated state were present after cRLC phosphorylation. Thus cRLC phosphorylation alters the equilibrium between defined conformations of the cRLC regions of the myosin heads, rather than simply disordering the heads as assumed previously. cRLC phosphorylation also changes the orientation of the cRLC C-lobe in rigor conditions, showing that the orientation of this part of the myosin head is determined by its interaction with the thick filament even when the head is strongly bound to actin. These results suggest that cRLC phosphorylation controls the contractility of the heart by modulating the interaction of the cRLC region of the myosin heads with the thick filament backbone. PMID:26057075

  7. Distinct functions of the laminin β LN domain and collagen IV during cardiac extracellular matrix formation and stabilization of alary muscle attachments revealed by EMS mutagenesis in Drosophila

    PubMed Central

    2014-01-01

    Background The Drosophila heart (dorsal vessel) is a relatively simple tubular organ that serves as a model for several aspects of cardiogenesis. Cardiac morphogenesis, proper heart function and stability require structural components whose identity and ways of assembly are only partially understood. Structural components are also needed to connect the myocardial tube with neighboring cells such as pericardial cells and specialized muscle fibers, the so-called alary muscles. Results Using an EMS mutagenesis screen for cardiac and muscular abnormalities in Drosophila embryos we obtained multiple mutants for two genetically interacting complementation groups that showed similar alary muscle and pericardial cell detachment phenotypes. The molecular lesions underlying these defects were identified as domain-specific point mutations in LamininB1 and Cg25C, encoding the extracellular matrix (ECM) components laminin β and collagen IV α1, respectively. Of particular interest within the LamininB1 group are certain hypomorphic mutants that feature prominent defects in cardiac morphogenesis and cardiac ECM layer formation, but in contrast to amorphic mutants, only mild defects in other tissues. All of these alleles carry clustered missense mutations in the laminin LN domain. The identified Cg25C mutants display weaker and largely temperature-sensitive phenotypes that result from glycine substitutions in different Gly-X-Y repeats of the triple helix-forming domain. While initial basement membrane assembly is not abolished in Cg25C mutants, incorporation of perlecan is impaired and intracellular accumulation of perlecan as well as the collagen IV α2 chain is detected during late embryogenesis. Conclusions Assembly of the cardiac ECM depends primarily on laminin, whereas collagen IV is needed for stabilization. Our data underscore the importance of a correctly assembled ECM particularly for the development of cardiac tissues and their lateral connections. The mutational

  8. Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles.

    PubMed

    Sugo, Tsukasa; Terada, Michiko; Oikawa, Tatsuo; Miyata, Kenichi; Nishimura, Satoshi; Kenjo, Eriya; Ogasawara-Shimizu, Mari; Makita, Yukimasa; Imaichi, Sachiko; Murata, Shumpei; Otake, Kentaro; Kikuchi, Kuniko; Teratani, Mika; Masuda, Yasushi; Kamei, Takayuki; Takagahara, Shuichi; Ikeda, Shota; Ohtaki, Tetsuya; Matsumoto, Hirokazu

    2016-09-10

    Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment. This conjugate showed durable gene-silencing in the heart and skeletal muscle for one month after intravenous administration in normal mice. In particular, 1μg siRNA conjugate showed significant gene-silencing in the gastrocnemius when injected intramuscularly. In a mouse model of peripheral artery disease, the treatment with myostatin-targeting siRNA conjugate by intramuscular injection resulted in significant silencing of myostatin and hypertrophy of the gastrocnemius, which was translated into the recovery of running performance. These data demonstrate the utility of antibody conjugation for siRNA delivery and the therapeutic potential for muscular diseases. PMID:27369865

  9. Effect of exercise training and anabolic androgenic steroids on hemodynamics, glycogen content, angiogenesis and apoptosis of cardiac muscle in adult male rats

    PubMed Central

    Hassan, Asmaa F.; Kamal, Manal M.

    2013-01-01

    Objectives To investigate the effects of exercise training and anabolic androgenic steroids (AAS) on hemodynamics, glycogen content, angiogenesis, apoptosis and histology of cardiac muscle. Methods Forty rats were divided into 4 groups; control, steroid, exercise-trained and exercise-trained plus steroid groups. The exercise-trained and trained plus steroid groups, after one week of water adaptation, were exercised by jumping into water for 5 weeks. The steroid and trained plus steroid groups received nandrolone decanoate, for 5 weeks. Systolic blood pressure and heart rate (HR) were monitored weekly. Heart weight/body weight ratio (HW/BW ratio) were determined. Serum testosterone, vascular endothelial growth factor (VEGF), cardiac caspase-3 activity and glycogen content were measured. Results Compared with control, the steroid group had significantly higher blood pressure, HR, sympathetic nerve activity, testosterone level, HW/BW and cardiac caspase-3 activity. Histological examination revealed apoptotic changes and hypertrophy of cardiomyocytes. In exercise-trained group, cardiac glycogen, VEGF and testosterone levels were significantly higher while HR was significantly lower than control. HW/BW was more than control confirmed by hypertrophy of cardiomyocytes with angiogenesis on histological examination. Trained plus steroid group, had no change in HR, with higher blood pressure and HW/BW than control, cardiac glycogen and serum VEGF were higher than control but lower than exercise-trained group. Histological examination showed hypertrophy of cardiomyoctes with mild angiogenesis rather than apoptosis. Conclusion When exercise is augmented with AAS, exercise-associated cardiac benefits may not be fully gained with potential cardiac risk from AAS if used alone or combined with exercise. PMID:23559905

  10. Selective control of fibroblast proliferation and its effect on cardiac muscle differentiation in vitro.

    PubMed

    Clark, W A

    1976-09-01

    The stability of the differentiated state of cardiac myocytes in vitro was examined under culture conditions which selectively stimulated or inhibited proliferation of fibroblasts. Regulation of fibroblast proliferation in cultures of myocardial cells from 8-day embryonic chicks was achieved by adjustment of the glutamine (Gln) concentration in the culture medium (Ham's F-12 medium containing 2 x amino acids and 5% fetal calf serum). Myocardial cells, when plated at 80 cells/mm2 in Gln- medium, maintained a stable density of approximately 40% of the plating density for more than 30 days. When Gln was added to the medium (292 micrograms/ml) fibroblast proliferation was stimulated, and by 5-6 days after this addition cell densities had increased to confluency. The selective action of glutamine on fibroblast proliferation was determined by labeling cultures with tritiated thymidine ([3H]TdR) and scoring its incorporation into myocytes and fibroblasts by radioautography. After 2 weeks in Gln- medium, the mitotic index was 0.3% and the [3H]TdR-labeling index (1.5-hr pulse) was 6.4%. In addition, the proportion of myocytes in the population was constant at 64.2% for at least 30 days in vitro, and contractile activity was observed for up to 6 months. After 5 days of Gln replacement, the cells exhibited a labeling index of 25%, the proportion of myocytes decreased to less than 10% and contractile activity was rarely observed. Although the [3H]TdR-labeling index of fibroblasts and myocytes was nearly identical in Gln- medium, the addition of Gln produced a fivefold stimulation in the fibroblast labeling index, but did not affect myocyte proliferation or DNA synthesis. A unique phenomenon of myocyte congregation was observed only in Gln- medium which resulted in the formation of myocyte colonies from which fibroblasts were largely absent. It is suggested that this process with the resultant establishment of a functional electrical syncytium plays a significant role in the