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. 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.

  3. Clofibrate, calcium and cardiac muscle.

    PubMed

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

    1982-03-01

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

  4. Cardiac arrhythmia and late-onset muscle weakness caused by a myofibrillar myopathy with unusual histopathological features due to a novel missense mutation in FLNC.

    PubMed

    Avila-Smirnow, D; Gueneau, L; Batonnet-Pichon, S; Delort, F; Bécane, H-M; Claeys, K; Beuvin, M; Goudeau, B; Jais, J-P; Nelson, I; Richard, P; Ben Yaou, R; Romero, N B; Wahbi, K; Mathis, S; Voit, T; Furst, D; van der Ven, P; Gil, R; Vicart, P; Fardeau, M; Bonne, G; Behin, A

    2016-10-01

    Myofibrillar myopathies (MFM) are mostly adult-onset diseases characterized by progressive morphological alterations of the muscle fibers beginning in the Z-disk and the presence of protein aggregates in the sarcoplasm. They are mostly caused by mutations in different genes that encode Z-disk proteins, including DES, CRYAB, LDB3, MYOT, FLNC and BAG3. A large family of French origin, presenting an autosomal dominant pattern, characterized by cardiac arrhythmia associated to late-onset muscle weakness, was evaluated to clarify clinical, morphological and genetic diagnosis. Muscle weakness began during adult life (over 30 years of age), and had a proximal distribution. Histology showed clear signs of a myofibrillar myopathy, but with unusual, large inclusions. Subsequently, genetic testing was performed in MFM genes available for screening at the time of clinical/histological diagnosis, and desmin (DES), αB-crystallin (CRYAB), myotilin (MYOT) and ZASP (LDB3), were excluded. LMNA gene screening found the p.R296C variant which did not co-segregate with the disease. Genome wide scan revealed linkage to 7q.32, containing the FLNC gene. FLNC direct sequencing revealed a heterozygous c.3646T>A p.Tyr1216Asn change, co-segregating with the disease, in a highly conserved amino acid of the protein. Normal filamin C levels were detected by Western-blot analysis in patient muscle biopsies and expression of the mutant protein in NIH3T3 showed filamin C aggregates. This is an original FLNC mutation in a MFM family with an atypical clinical and histopathological presentation, given the presence of significantly focal lesions and prominent sarcoplasmic masses in muscle biopsies and the constant heart involvement preceding significantly the onset of the myopathy. Though a rare etiology, FLNC gene should not be excluded in early-onset arrhythmia, even in the absence of myopathy, which occurs later in the disease course.

  5. The Mechanochemistry of Cardiac Muscle

    PubMed Central

    Pool, Peter E.; Sonnenblick, Edmund H.

    1967-01-01

    The utilization of creatine phosphate (CP) and adenosine triphosphate (ATP) was studied in the iodoacetate (IAA) and nitrogen (N2)-treated cat papillary muscle. Under these conditions the net production of ATP does not occur, and the net utilization of ATP is reflected in a fall in CP concentration. The rate of energy utilization of the IAA-N2-treated cat papillary muscle resting without tension was 0.68 µmole CP/g/min. This rate was increased to 1.07 µmole/g/min when muscles were passively stretched with 2 g of tension. In a series of isometrically contracting muscles CP utilization was found to be proportional to the number of activations and the summated contractile element work. These rates of CP utilization were 0.083 µmole/g/activation and 0.0059 µmole/g-cm of work. The calculated mechanochemical coupling efficiency was 33%. PMID:6034511

  6. 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…

  7. Microwave radiation effects on cardiac muscle cells in vitro

    SciTech Connect

    Galvin, M.J.; Hall, C.A.; McRee, D.I.

    1981-05-01

    Isolated cardiac muscle cells were exposed to microwave radiation in a temperature-controlled waveguide apparatus. Microwave radiation for 90 min at specific absorption rates (SAR) as low as 10 mW/g increases the permeability of cardiac cells to trypan blue. At 100 mW/g the inability of the cells to exclude trypan blue is concurrent with the release of lactic dehydrogenase into the suspending medium. However, when the SAR is decreased to 50 mW/g, trypan blue uptake is still elevated without the concomitant release of lactic dehydrogenase. Transmission electron micrographs of the exposed cells showed cellular damage only at the 100 mW/g exposure level. The microwave-reduced change in membrane permeability was unrelated to a macroscopic heating effect of microwave radiation on the cells, but appeared to be due to some other specific action of microwave radiation on isolated cardiac cells.

  8. Expression of cardiac alpha-actin spares extraocular muscles in skeletal muscle alpha-actin diseases--quantification of striated alpha-actins by MRM-mass spectrometry.

    PubMed

    Ravenscroft, Gianina; Colley, Stephen M J; Walker, Kendall R; Clement, Sophie; Bringans, Scott; Lipscombe, Richard; Fabian, Victoria A; Laing, Nigel G; Nowak, Kristen J

    2008-12-01

    As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle alpha-actin disease is thus probably due to greater levels of cardiac alpha-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle alpha-actin.

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

    PubMed Central

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

    2016-01-01

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

  10. 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.

  11. Model representation of the nonlinear step response in cardiac muscle

    PubMed Central

    Chandra, Murali; Mamidi, Ranganath; Dong, Wenji; Campbell, Kenneth B.

    2010-01-01

    Motivated by the need for an analytical tool that can be used routinely to analyze data collected from isolated, detergent-skinned cardiac muscle fibers, we developed a mathematical model for representing the force response to step changes in muscle length (i.e., quick stretch and release). Our proposed model is reasonably simple, consisting of only five parameters representing: (1) the rate constant by which length change–induced distortion of elastic elements is dissipated; (2) the stiffness of the muscle fiber; (3) the amplitude of length-mediated recruitment of stiffness elements; (4) the rate constant by which this length-mediated recruitment takes place; and (5) the magnitude of the nonlinear interaction term by which distortion of elastic elements affects the number of recruited stiffness elements. Fitting this model to a family of force recordings representing responses to eight amplitudes of step length change (±2.0% baseline muscle length in 0.5% increments) enabled four things: (1) reproduction of all the identifiable features seen in a family of force responses to both positive and negative length changes; (2) close fitting of all records from the whole family of these responses with very little residual error; (3) estimation of all five model parameters with a great degree of certainty; and (4) importantly, ready discrimination between cardiac muscle fibers with different contractile regulatory proteins but showing only subtly different contractile function. We recommend this mathematical model as an analytic tool for routine use in studies of cardiac muscle fiber contractile function. Such model-based analysis gives novel insight to the contractile behavior of cardiac muscle fibers, and it is useful for characterizing the mechanistic effects that alterations of cardiac contractile proteins have on cardiac contractile function. PMID:20660660

  12. Effects of carbon monoxide on cardiac muscle cells in culture

    SciTech Connect

    Nag, A.C.; Chen, K.C.; Cheng, Mei General Motors Research Laboratories, Warren, MI )

    1988-09-01

    Embryonic rat cardiac muscle cells grown in the presence of various tensions of CO (5-95%) without the presence of O{sub 2} survived and exhibited reduced cell growth, which was concentration dependent. When cardiac muscle cells were grown in the presence of a mixture of CO (10-20%) and O{sub 2} (10-20%), the growth rate of these cells was comparable to that of the control cells. Cardiac myocytes continued to beat when exposed to varying tensions of CO, except in the case of 95% CO. The cells exposed to different concentrations of CO contained fewer myofibrils of different stages of differentiation compared with the control and the culture exposed to a mixture of 20% O{sub 2} and 20% CO, with cells that contained abundant, highly differentiated myofibrils. There was no significant difference in the structural organization of mitochondria between the control and the surviving experimental cells. It is evident from the present studies that O{sub 2} is required for the optimum in vitro cellular growth of cardiac muscle. Furthermore, CO in combination with O{sub 2} at a concentration of 10 or 20% can produce optimal growth of cardiac muscle cells in culture. To determine maximum labeling index during the labeling period, cells were continuously labeled with ({sup 3}H)thymidine for 24 h before the termination of cultures.

  13. Skeletal and cardiac muscle pericytes: Functions and therapeutic potential.

    PubMed

    Murray, Iain R; Baily, James E; Chen, William C W; Dar, Ayelet; Gonzalez, Zaniah N; Jensen, Andrew R; Petrigliano, Frank A; Deb, Arjun; Henderson, Neil C

    2017-03-01

    Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.

  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. 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.

  16. 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

  17. A personal historic perspective on the role of chloride in skeletal and cardiac muscle.

    PubMed

    Hutter, Otto F

    2017-03-01

    During the early decades of the last century, skeletal muscle was held to be impermeable to chloride ions. This theory, based on shaky grounds, was famously falsified by Boyle and Conway in 1941. Two decades later and onwards, the larger part of the resting conductance of skeletal muscle was found to be due to chloride ions, sensitive to the chemical environment, and to be time-and-voltage dependent. So, much of the groundwork for the physiological role of chloride ions in skeletal muscle was laid before the game-changing discovery of chloride channels. The early history of the role of chloride in cardiac muscle, and work on the relative permeability to foreign anions of different muscles are also here covered from a personal perspective.

  18. Localisation of AMPK γ subunits in cardiac and skeletal muscles.

    PubMed

    Pinter, Katalin; Grignani, Robert T; Watkins, Hugh; Redwood, Charles

    2013-12-01

    The trimeric protein AMP-activated protein kinase (AMPK) is an important sensor of energetic status and cellular stress, and mutations in genes encoding two of the regulatory γ subunits cause inherited disorders of either cardiac or skeletal muscle. AMPKγ2 mutations cause hypertrophic cardiomyopathy with glycogen deposition and conduction abnormalities; mutations in AMPKγ3 result in increased skeletal muscle glycogen. In order to gain further insight into the roles of the different γ subunits in muscle and into possible disease mechanisms, we localised the γ2 and γ3 subunits, along with the more abundant γ1 subunit, by immunofluorescence in cardiomyocytes and skeletal muscle fibres. The predominant cardiac γ2 variant, γ2-3B, gave a striated pattern in cardiomyocytes, aligning with the Z-disk but with punctate staining similar to T-tubule (L-type Ca(2+) channel) and sarcoplasmic reticulum (SERCA2) markers. In skeletal muscle fibres AMPKγ3 localises to the I band, presenting a uniform staining that flanks the Z-disk, also coinciding with the position of Ca(2+) influx in these muscles. The localisation of γ2-3B- and γ3-containing AMPK suggests that these trimers may have similar functions in the different muscles. AMPK containing γ2-3B was detected in oxidative skeletal muscles which had low expression of γ3, confirming that these two regulatory subunits may be co-ordinately regulated in response to metabolic requirements. Compartmentalisation of AMPK complexes is most likely dependent on the regulatory γ subunit and this differential localisation may direct substrate selection and specify particular functional roles.

  19. Fast optical monitoring of microscopic excitation patterns in cardiac muscle.

    PubMed Central

    Müller, W; Windisch, H; Tritthart, H A

    1989-01-01

    Many vital processes depend on the generation, changes, and conduction of cellular transmembrane potentials. Optical monitoring systems are well suited to detect such cellular electrical activities in networks of excitable cells and also tissues simultaneously at multiple sites. Here, an exceptionally fast array system (16 x 16 photodiodes, up to 4,000,000 samples per second, 12-bit resolution) for imaging voltage-sensitive dye fluorescence, permitted real time measurements of excitation patterns at a microscopic size scale (256 pixels within an area of 1.8-8 mm2), in rat cardiac muscle in vitro. Results emphasize a recent hypothesis for cardiac impulse conduction, based on cardiac structural complexities, that is contradictory to all continuous cable theory models. Images FIGURE 2 PMID:2790142

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

    PubMed

    Clause, Kelly C; Tchao, Jason; Powell, Mary C; Liu, Li J; Huard, Johnny; Keller, Bradley B; Tobita, Kimimasa

    2012-01-01

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

  1. 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

  2. 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

  3. Altered Ca2+ sparks in aging skeletal and cardiac muscle

    PubMed Central

    Weisleder, Noah; Ma, Jianjie

    2008-01-01

    Ca2+ sparks are the fundamental units that comprise Ca2+-induced Ca2+ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca2+ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca2+ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca2+ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca2+ spark activity in aged cardiomyocytes. Ca2+ spark responses reflect the integrated function of the intracellular Ca2+ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca2+ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca2+ spark signaling during aging of striated muscles. PMID:18272434

  4. Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy.

    PubMed Central

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

    1975-01-01

    Degenerated cardiac muscle cells were present in hypertrophied ventricular muscle obtained at operation from 12 (38%) of 32 patients with asymmetric septal hypertrophy (hypertrophic cardiomyopathy) or aortic valvular disease. Degenerated cells demonstrated a wide variety of ultrastructural alterations. Mildly altered cells were normal-sized or hypertrophied and showed focal changes, including preferential loss of thick (myosin) filaments, streaming and clumping of Z band material, and proliferation of the tubules of sarcoplasmic reticulum. Moderately and severely degenerated cells were normal-sized or atrophic and showed additional changes, including extensive myofibrillar lysis and loss of T tubules. The appearance of the most severely degenerated cells usually reflected the cytoplasmic organelle (sarcoplasmic reticulum, glycogen, or mitochondria) which underwent proliferation and filled the myofibril-free areas of these cells. Moderately and severely degenerated cells were present in areas of fibrosis, had thickened basement membranes, and had lost their intercellular connections. These observations suggest that degenerated cardiac muscle cells have poor contractile function and may be responsible for impaired cardiac performance in some patients with chronic ventricular hypertrophy. Images Fig 1 Fig 2 Fig 3 Figs 4-6 Figs 7-8 Fig 9 Fig 10 Fig 11 Figs 12-15 Fig 16 Fig 17 Figs 18-21 Figs 22-23 Fig 24 Fig 25 Fig 26 Fig 27 Figs 28-29 Fig 30 Figs 31-32 Fig 33 PMID:124533

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

    PubMed

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

    2012-11-13

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

  6. 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

  7. A cardiac muscle model relating sarcomere dynamics to calcium kinetics.

    PubMed

    Negroni, J A; Lascano, E C

    1996-05-01

    A muscle model establishing the link between cross-bridge dynamics and intracellular Ca2+ kinetics was assessed by simulation of experiments performed in isolated cardiac muscle. The model is composed by the series arrangement of muscle units formed by inextensible thick and thin filaments in parallel with an elastic element. Attached cross-bridges act as independent force generators whose force is linearly related to the elongation of their elastic structure. Ca2+ kinetics is described by a four-state system of sites on the thin filament associated with troponin C: sites with free troponin C (T), sites with Ca2+ bound to troponin C (TCa); sites with Ca2+ bound to troponin C and attached cross-bridges (TCa*); and sites with troponin C not associated with Ca2+ and attached cross-bridges (T*). The intracellular Ca2+ concentration ([Ca2+]) is controlled solely by the sarcoplasmic reticulum through an inflow function and a saturated outflow pump function. All the simulations were performed using the same set of parameters. The model was able to reproduce the following experiments in cardiac muscle: (a) time course of isometric force (peak force: 46.5 mN/mm2), intracellular [Ca2+] (peak [Ca2+]: 1.5 microM); (b) force-length-[Ca2+] relations; (c) transient response of force to step changes in length; (d) force-velocity relation (maximum velocity: 3 microns/s); (e) the force response to length pulses to estimate the time course of [TCa]; (f) force response to quick releases showing the superactivating and deactivating effects of shortening; (g) stiffness response to sinusoidal length changes; and (h) time course of active state. The good accordance of the simulations with experimental results indicates that the model is an adequate representation of the link between cross-bridge dynamic behaviour and Ca2+ kinetics.

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

    PubMed

    Lewis, Kevin M; Munske, Gerhard R; Byrd, Samuel S; Kang, Jeehoon; Cho, Hyun-Jai; Ríos, Eduardo; Kang, ChulHee

    2016-09-13

    Calsequestrin is glycosylated and phosphorylated during its transit to its final destination in the junctional sarcoplasmic reticulum. To determine the significance and universal profile of these post-translational modifications to mammalian calsequestrin, we characterized, via mass spectrometry, the glycosylation and phosphorylation of skeletal muscle calsequestrin from cattle (B. taurus), lab mice (M. musculus) and lab rats (R. norvegicus) and cardiac muscle calsequestrin from cattle, lab rats and humans. On average, glycosylation of skeletal calsequestrin consisted of two N-acetylglucosamines and one mannose (GlcNAc₂Man₁), while cardiac calsequestrin had five additional mannoses (GlcNAc₂Man₆). Skeletal calsequestrin was not phosphorylated, while the C-terminal tails of cardiac calsequestrin contained between zero to two phosphoryls, indicating that phosphorylation of cardiac calsequestrin may be heterogeneous in vivo. Static light scattering experiments showed that the Ca(2+)-dependent polymerization capabilities of native bovine skeletal calsequestrin are enhanced, relative to the non-glycosylated, recombinant isoform, which our crystallographic studies suggest may be due to glycosylation providing a dynamic "guiderail"-like scaffold for calsequestrin polymerization. Glycosylation likely increases a polymerization/depolymerization response to changing Ca(2+) concentrations, and proper glycosylation, in turn, guarantees both effective Ca(2+) storage/buffering of the sarcoplasmic reticulum and localization of calsequestrin (Casq) at its target site.

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

    PubMed Central

    Lewis, Kevin M.; Munske, Gerhard R.; Byrd, Samuel S.; Kang, Jeehoon; Cho, Hyun-Jai; Ríos, Eduardo; Kang, ChulHee

    2016-01-01

    Calsequestrin is glycosylated and phosphorylated during its transit to its final destination in the junctional sarcoplasmic reticulum. To determine the significance and universal profile of these post-translational modifications to mammalian calsequestrin, we characterized, via mass spectrometry, the glycosylation and phosphorylation of skeletal muscle calsequestrin from cattle (B. taurus), lab mice (M. musculus) and lab rats (R. norvegicus) and cardiac muscle calsequestrin from cattle, lab rats and humans. On average, glycosylation of skeletal calsequestrin consisted of two N-acetylglucosamines and one mannose (GlcNAc2Man1), while cardiac calsequestrin had five additional mannoses (GlcNAc2Man6). Skeletal calsequestrin was not phosphorylated, while the C-terminal tails of cardiac calsequestrin contained between zero to two phosphoryls, indicating that phosphorylation of cardiac calsequestrin may be heterogeneous in vivo. Static light scattering experiments showed that the Ca2+-dependent polymerization capabilities of native bovine skeletal calsequestrin are enhanced, relative to the non-glycosylated, recombinant isoform, which our crystallographic studies suggest may be due to glycosylation providing a dynamic “guiderail”-like scaffold for calsequestrin polymerization. Glycosylation likely increases a polymerization/depolymerization response to changing Ca2+ concentrations, and proper glycosylation, in turn, guarantees both effective Ca2+ storage/buffering of the sarcoplasmic reticulum and localization of calsequestrin (Casq) at its target site. PMID:27649144

  10. Spontaneous tension oscillation in skinned bovine cardiac muscle.

    PubMed

    Fukuda, N; Fujita, H; Fujita, T; Ishiwata, S

    1996-01-01

    Skinned fibres from bovine ventricles exhibited spontaneous tension oscillations when MgADP and inorganic phosphate (Pi) were added to the solution bathing fibres in the relaxed state (ADP-SPOC). A similar type of oscillation was observed at intermediate concentrations of free Ca2+ in the absence of MgADP and Pi (Ca-SPOC). To investigate the correlation between ADP-SPOC and Ca-SPOC, we constructed two-dimensional state diagrams of cardiac muscle using different concentrations of Pi (0-20 mM) and free Ca2+ [pCa=around 5 (+Ca2+), pCa=5.15-6.9 and +EGTA (-Ca2+)], with varying concentrations of MgADP (0-10 mM), with 2 mM MgATP and 2 mM free Mg2+ maintaining ionic strength at 0.15+/-0.01 M, pH 7.0, 25 degrees C. The three-dimensional (pCa-Pi-MgADP) state diagram thus obtained was divided into three regions, i.e. the contraction region in which tension oscillation was undetectable, the spontaneous tension oscillation (SPOC) region and the relaxation region. We found that the regions of ADP-SPOC and Ca-SPOC were continuously connected by a single oscillation region sandwiched between the contraction and relaxation regions. The state diagram, which encompasses physiological conditions, shows that the probability of SPOC is higher in cardiac muscle than in skeletal muscle. From these results, we suggest that, despite distinct ionic conditions, the molecular state of cross-bridges during SPOC is common to both ADP-SPOC and Ca-SPOC.

  11. Uniform sarcomere shortening behavior in isolated cardiac muscle cells

    PubMed Central

    1980-01-01

    We have observed the dynamics of sarcomere shortening and the diffracting action of single, functionally intact, unattached cardiac muscle cells enzymatically isolated from the ventricular tissue of adult rats. Sarcomere length was measured either (a) continuously by a light diffraction method or (b) by direct inspection of the cell's striated image as recorded on videotape or by cinemicroscopy (120--400 frames/s). At physiological levels of added CaCl2 (0.5--2.0 mM), many cells were quiescent (i.e., they did not beat spontaneously) and contracted in response to electrical stimulation (less than or equal to 1.0-ms pulse width). Sarcomere length in the quiescent, unstimulated cells (1.93 +/- 0.10 [SD] micrometers), at peak shortening (1.57 +/- 0.13 micrometers, n = 49), and the maximum velocity of sarcomere shortening and relengthening were comparable to previous observations in intact heart muscle preparations. The dispersion of light diffracted by the cell remained narrow, and individual striations remained distinct and laterally well registered throughout the shortening- relengthening cycle. In contrast, appreciable nonuniformity and internal buckling were seen at sarcomere lengths < 1.8 micrometers when the resting cell, embedded in gelatin, was longitudinally compressed These results indicate (a) that shortening and relengthening is characterized by uniform activation between myofibrils within the cardiac cell and (b) that physiologically significant relengthening forces in living heart muscle originate at the level of the cell rather than in extracellular connections. First-order diffracted light intensity, extremely variable during sarcomere shortening, was always greatest during midrelaxation preceding the onset of a very slow and uniform phase of sarcomere relengthening. PMID:7441197

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

    PubMed

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

    1995-01-01

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

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

    PubMed

    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; Richardson, Russell S

    2014-08-01

    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.

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

    PubMed

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

    2016-05-06

    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.

  15. How Can Death Due to Sudden Cardiac Arrest Be Prevented?

    MedlinePlus

    ... Trials Links Related Topics Arrhythmia Automated External Defibrillator Coronary Heart Disease Heart Failure Long QT Syndrome Send a link ... First Sudden Cardiac Arrest If you have severe coronary heart disease (CHD), you're at increased risk for SCA. ...

  16. The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles.

    PubMed

    Marrelli, Mauro Toledo; Brotto, Marco

    2016-11-02

    Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.

  17. An unusual myopathy: speckled muscle fibers due to enlarged mitochondria.

    PubMed

    Jeffree, Rosalind L; Wills, Edward J; Harper, Clive

    2007-07-01

    We report a 52-year-old woman who presented with a 6-month history of proximal muscle weakness, elevated serum creatine kinase, and myopathic pattern on electromyography (EMG). Histology of the muscle shows a speckled pattern due to clustering of enlarged mitochondria. The pathology resembles that of selenium deficiency. The patient was found to have borderline low serum selenium and also low vitamin D and thyroid-stimulating hormone. The cause of this unusual myopathy is probably multifactorial. This case is important because the unusual pathological picture represents a potentially treatable myopathy. In addition, we hope that publication of the complex clinical and biochemical abnormalities of this case, in conjunction with other case reports, may facilitate future elucidation of muscle mitochondrial function and dysfunction.

  18. Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

    PubMed Central

    Breitbart, Astrid; Auger-Messier, Mannix; Molkentin, Jeffery D.

    2011-01-01

    A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future. PMID:21421824

  19. Immobilized Catecholamine and Cocaine Effects on Contractility of Cardiac Muscle

    PubMed Central

    Venter, J. Craig; Ross, John; Dixon, Jack E.; Mayer, Steven E.; Kaplan, Nathan O.

    1973-01-01

    Isoproterenol, norepinephrine, and epinephrine covalently bound to glass beads exert a positive inotropic effect on isometrically contracting papillary muscles from cats. Immobilized isoproterenol maintains increases in force and velocity of contraction for more than 5 hr. 1 μM Cocaine potentiates the action of immobilized norepinephrine, isoproterenol, and epinephrine, but not of isoproterenol in solution. The data presented indicate that the effects of immobilized catecholamines are not due to their coming off the glass. The effects observed with cocaine and immobilized catecholamines are not altered by prior treatment of the muscle with reserpine. These results suggest that the major site of catecholamine action is on receptors located on the extended surface of myocardial cells and a post-junctional site for cocaine potentiation. Images PMID:4515619

  20. Work production and work absorption in muscle strips from vertebrate cardiac and insect flight muscle fibers.

    PubMed

    Maughan, D; Moore, J; Vigoreaux, J; Barnes, B; Mulieri, L A

    1998-01-01

    Stretch activation, which underlies the ability of all striated muscles to do oscillatory work, is a prominent feature of both insect flight and vertebrate cardiac muscle. We have examined and compared work-producing and work-absorbing processes in skinned fibers of Drosophila flight muscle, mouse papillary muscle, and human ventricular strips. Using small amplitude sinusoidal length perturbation analysis, we distinguished viscoelastic properties attributable to crossbridge processes from those attributable to other structures of the sarcomere. Work-producing and work-absorbing processes were identified in Ca(2+)-activated fibers by deconvolving complex stiffness data. An 'active' work-producing process ("B"), attributed to crossbridge action, was identified, as were two work-absorbing processes, one attributable to crossbridge action ("C") and the other primarily to viscoelastic properties of parallel passive structures ("A"). At maximal Ca(2+)-activation (pCa 5, 27 degrees C), maximum net power output (processes A, B and C combined) occurs at a frequency of: 1.3 +/- 0.1 Hz for human, 10.9 +/- 2.2 Hz for mouse, and 226 +/- 9 Hz for fly, comparable to the resting heart rate of the human (1 Hz, 37 degrees C) and mouse (10 Hz, 37 degrees C) and to the wing beat frequency of the fruit fly (200 Hz, 22 degrees C). Process B maximal work production per myosin head is 7-11 x 10(-21) J per perturbation cycle, equivalent to approximately 2 kT of energy. Process C maximal work absorption is about the same magnitude. The equivalence suggests the possibility that a thermal ratchet type mechanism operates during small amplitude length perturbations. We speculate that there may be a survival advantage in having a mechanical energy dissipater (i.e., the C process) at work in muscles if they can be injuriously stretched by the system in which they operate.

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

    PubMed

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

    1978-05-01

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

  2. 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

  3. 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.

  4. Removal of Abnormal Myofilament O-GlcNAcylation Restores Ca2+ Sensitivity in Diabetic Cardiac Muscle

    PubMed Central

    Ma, Junfeng; Slawson, Chad; Zeidan, Quira; Lugo-Fagundo, Nahyr S.; Xu, Mingguo; Shen, Xiaoxu; Gao, Wei Dong; Caceres, Viviane; Chakir, Khalid; DeVine, Lauren; Cole, Robert N.; Marchionni, Luigi; Paolocci, Nazareno; Hart, Gerald W.; Murphy, Anne M.

    2015-01-01

    Contractile dysfunction and increased deposition of O-linked β-N-acetyl-d-glucosamine (O-GlcNAc) in cardiac proteins are a hallmark of the diabetic heart. However, whether and how this posttranslational alteration contributes to lower cardiac function remains unclear. Using a refined β-elimination/Michael addition with tandem mass tags (TMT)–labeling proteomic technique, we show that CpOGA, a bacterial analog of O-GlcNAcase (OGA) that cleaves O-GlcNAc in vivo, removes site-specific O-GlcNAcylation from myofilaments, restoring Ca2+ sensitivity in streptozotocin (STZ) diabetic cardiac muscles. We report that in control rat hearts, O-GlcNAc and O-GlcNAc transferase (OGT) are mainly localized at the Z-line, whereas OGA is at the A-band. Conversely, in diabetic hearts O-GlcNAc levels are increased and OGT and OGA delocalized. Consistent changes were found in human diabetic hearts. STZ diabetic hearts display increased physical interactions of OGA with α-actin, tropomyosin, and myosin light chain 1, along with reduced OGT and increased OGA activities. Our study is the first to reveal that specific removal of O-GlcNAcylation restores myofilament response to Ca2+ in diabetic hearts and that altered O-GlcNAcylation is due to the subcellular redistribution of OGT and OGA rather than to changes in their overall activities. Thus, preventing sarcomeric OGT and OGA displacement represents a new possible strategy for treating diabetic cardiomyopathy. PMID:26109417

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

    PubMed

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

    2014-06-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2016-01-01

    Introduction Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). Conclusion We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery. PMID:27556313

  8. Autophagic Adaptations to Long-term Habitual Exercise in Cardiac Muscle.

    PubMed

    Tam, B T; Pei, X M; Yung, B Y; Yip, S P; Chan, L W; Wong, C S; Siu, P M

    2015-06-01

    Autophagy has been shown to be responsive to physical exercise. However, the effects of prolonged habitual exercise on autophagy in cardiac muscle remain unknown. The present study aimed to examine whether long-term habitual exercise alters the basal autophagic signalling in cardiac muscle. Female Sprague-Dawley rats aged 2 months were randomly assigned to control and exercise groups. Animals in exercise group were kept in cages with free access exercise wheels to perform habitual exercise for 5 months. Animals in the control group were placed in cages without exercise wheels. Ventricular muscle tissues were harvested for analysis after 5 months. Phosphorylation statuses of upstream autophagic regulatory proteins and protein expressions of downstream autophagic facts remained unchanged in the cardiac muscle of exercise animals when compared to control animals. Intriguingly, the protein abundance of microtubule-associated protein-1 light chain -3 II (LC3-II), heat shock protein 72 (HSP72) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly increased in cardiac muscle of exercise rats relative to control rats. 5 months of habitual exercise causes the adaptive increase in LC3-II reserve without altering autophagic flux, which probably contributes to the elevation of cellular autophagic capacity and efficiency of cardiac muscle.

  9. 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.

  10. 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

  11. Effect of muscle length on cross-bridge kinetics in intact cardiac trabeculae at body temperature.

    PubMed

    Milani-Nejad, Nima; Xu, Ying; Davis, Jonathan P; Campbell, Kenneth S; Janssen, Paul M L

    2013-01-01

    Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank-Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (k(tr); which depends on the rate of cross-bridge cycling) in intact trabeculae at body temperature. Using K(+) contractures to induce a tonic level of force, we showed the k(tr) was slower in rabbit muscle (which contains predominantly β myosin) than in rat muscle (which contains predominantly α myosin). Analyses of k(tr) in rat muscle at optimal length (L(opt)) and 90% of optimal length (L(90)) revealed that k(tr) was significantly slower at L(opt) (27.7 ± 3.3 and 27.8 ± 3.0 s(-1) in duplicate analyses) than at L(90) (45.1 ± 7.6 and 47.5 ± 9.2 s(-1)). We therefore show that k(tr) can be measured in intact rat and rabbit cardiac trabeculae, and that the k(tr) decreases when muscles are stretched to their optimal length under near-physiological conditions, indicating that the Frank-Starling mechanism not only increases force but also affects cross-bridge cycling kinetics.

  12. 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

  13. Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles

    PubMed Central

    Qin, Xulei; Riegler, Johannes; Tiburcy, Malte; Zhao, Xin; Chour, Tony; Ndoye, Babacar; Nguyen, Michael; Adams, Jackson; Ameen, Mohamed; Denney, Thomas S.; Yang, Phillip C.; Nguyen, Patricia; Zimmermann, Wolfram H.; Wu, Joseph C.

    2017-01-01

    Background The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance following such treatments are plagued by relatively low detection ability. As the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. Methods and Results Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts one month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, MRI and ultrasound-based strain imaging were performed prior to and four weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac MRI. Although no significant differences were found with global changes in left ventricular ejection fraction (EF) (Control −9.6±1.3% vs. EHM −6.2±1.9%, P=0.17), regional myocardial strain from tagged MRI was able to detect preserved systolic function in EHM-treated animals compared to control (Control 4.4±1.0% vs. EHM 1.0±0.6%, P=0.04). However, ultrasound-based strain failed to detect any significant change (Control 2.1±3.0% vs. EHM 6.3±2.9%, P=0.46). Conclusions This study highlights the feasibility of using cardiac strain from tagged MRI to assess functional changes in rat models due to localized regenerative therapies, which may not be detected by conventional measures of global systolic performance. PMID:27903535

  14. Papillary muscle insertion directly into the anterior mitral leaflet in hypertrophic cardiomyopathy, its identification and cause of outflow obstruction by cardiac magnetic resonance imaging, and its surgical management.

    PubMed

    Rowin, Ethan J; Maron, Barry J; Lesser, John R; Rastegar, Hassan; Maron, Martin S

    2013-06-01

    This case presents an uncommon but important mechanism of muscular left ventricular outflow obstruction in hypertrophic cardiomyopathy due to anomalous and direct papillary muscle insertion into the anterior mitral leaflet, a finding reliably identified clinically by cardiac magnetic resonance imaging. The identification of this left ventricular outflow tract morphology is important before invasive ventricular septal reduction therapy because it dictates a specific surgical strategy. These findings further support the role of cardiac magnetic resonance imaging in the early evaluation of hypertrophic cardiomyopathy patients.

  15. [Fever, asthenia, myalgia and murmur due to cardiac myxoma].

    PubMed

    Giménez Roca, C; Felipe Villalobos, A; Cambra Lasaosa, F J; Prada Martínez, F; Caffarena Calvar, J M; Jou Muñoz, C

    2013-10-01

    Cardiac tumours are rare, especially in children, and most of them are benign. Myxomas are unusual in children, being more common among adults. They are usually located in the left atrium, with 25% appearing in the right. The clinical signs and symptoms depend mainly on where the tumour is located. A feature of these tumours is that they can be accompanied by constitutional symptoms and laboratory abnormalities. Echocardiography is the study of choice, and a prompt resection is required to prevent serious complications. We present a case of a 10 year-old girl diagnosed with right atrial myxoma who presented with a fever, myalgia, asthenia and laboratory abnormalities. Diagnosis was made by echocardiography, and the early surgical resection of the tumour ran smoothly and showed a good postoperative recovery.

  16. 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.

  17. 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…

  18. 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.

  19. Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells.

    PubMed

    Oh, Hidemasa; Chi, Xuan; Bradfute, Steven B; Mishina, Yuji; Pocius, Jennifer; Michael, Lloyd H; Behringer, Richard R; Schwartz, Robert J; Entman, Mark L; Schneider, Michael D

    2004-05-01

    The evidence of cardiomyocyte proliferation in damaged heart implied cardiac regeneration might occur by resident or extra cardiac stem cells. However, the specification and origin of these cells remain unknown. Here, we report using fluorescence-activated cell sorting that cardiac progenitor cells resided in adult heart and colocalized with small capillary vessels, within the stem cell antigen (Sca-1) population expressing high telomerase activity. Notably, hematopoietic stem cells capable of efflux Hoechst 33342, termed side population cells, also were identified within the heart-derived cells. The cardiac progenitor cells (CD45(-)/CD34(-)) express neither cardiac muscle nor endothelial cell markers at an undifferentiated stage. The exposure of 5-azacytidine induced cardiac differentiation, which depends, in part, on Bmpr1a, a type IA receptor for bone morphogenetic protein (BMP). The capability of adult Sca1(+) cells to adopt a cardiac muscle in embryogenesis was substantiated by blastocyst injection, using progenitors from the adult hearts of transgenic mice that harbor a bacterial artificial chromosome expressing GFP via the Nkx-2.5 locus. Intravenously injected progenitors, shortly after ischemic/reperfusion, homed and functionally differentiated 3.5% of total left ventricle in the host myocardium. Differentiation included both fusion-independent and fusion-associated components, proved by the Cre/loxP donor/recipient system. Our studies suggest that endogenous cardiac progenitors reside in the adult heart, regenerate cardiomyocytes functionally, and integrate into the existing heart circuitry.

  20. Fate choice of post-natal mesoderm progenitors: skeletal versus cardiac muscle plasticity.

    PubMed

    Costamagna, Domiziana; Quattrocelli, Mattia; Duelen, Robin; Sahakyan, Vardine; Perini, Ilaria; Palazzolo, Giacomo; Sampaolesi, Maurilio

    2014-02-01

    Regenerative medicine for skeletal and cardiac muscles still constitutes a fascinating and ambitious frontier. In this perspective, understanding the possibilities of intrinsic cell plasticity, present in post-natal muscles, is vital to define and improve novel therapeutic strategies for acute and chronic diseases. In addition, many somatic stem cells are now crossing the boundaries of basic/translational research to enter the first clinical trials. However, it is still an open question whether a lineage switch between skeletal and cardiac adult myogenesis is possible. Therefore, this review focuses on resident somatic stem cells of post-natal skeletal and cardiac muscles and their plastic potential toward the two lineages. Furthermore, examples of myogenic lineage switch in adult stem cells are also reported and discussed.

  1. Occurrence of spontaneous and audiogenic seizures following global brain ischaemia due to cardiac arrest.

    PubMed

    Ułamek-Kozioł, Marzena; Kocki, Janusz; Bogucka-Kocka, Anna; Januszewski, Sławomir; Czuczwar, Stanisław J; Pluta, Ryszard

    2015-01-01

    Transient cardiac arrest due to cardiac vessel bundle occlusion was used to produce a rat model of spontaneous and audiogenic seizures. Among the rats, spontaneous seizures were present in 64%, and audiogenic seizures could be evoked in 86%, during two weeks of survival after cardiac arrest, by exposure to a loud sound produced by rattling keys, beginning one day after the post-ischaemic injury. Data from literature suggested a key role for GABA-ergic system widespread dysfunction especially in the hippocampus in post-cardiac arrest onset of audiogenic seizures. Reduced GABA inhibition in the hippocampus seems responsible for audiogenic seizures following cardiac arrest. In summary it may be considered that the occurrence of audiogenic seizures following cardiac arrest is determined not only by a neuronal loss, especially in the hippocampus, but also by a condition of synapse modification by a regenerative phenomenon. Data from our study clearly indicate that global brain ischaemia due to cardiac arrest may induce the susceptibility to spontaneous and audiogenic seizures, but this effect is transient.

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

    PubMed

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

    2015-01-01

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

  3. Keratose Hydrogels Promote Vascular Smooth Muscle Differentiation from C-kit Positive Human Cardiac Stem Cells.

    PubMed

    Ledford, Benjamin T; Simmons, Jamelle; Chen, Miao; Fan, Huimin; Barron, Catherine; Liu, Zhongmin; Van Dyke, Mark; He, Jia-Qiang

    2017-03-28

    Stem cell-based therapies have demonstrated great potential for the treatment of cardiac diseases, e.g., myocardial infarction; however, low cell viability, low retention/engraftment, and uncontrollable in vivo differentiation after transplantation are still major limitations, which lead low therapeutic efficiency. Biomaterials provide a promising solution to overcome these issues due to their biocompatibility, biodegradability, low/non-immunogenicity, and low/non-cytotoxicity. The present study aims to investigate the impacts of Keratose (KOS) hydrogel biomaterial on cellular viability, proliferation, and differentiation of c-kit+ human cardiac stem cells (hCSCs). Briefly, hCSCs were cultured on both KOS hydrogel-coated dishes and regular tissue culture dishes (Blank control). Cell viability, stemness, proliferation, cellular morphology, and cardiac lineage differentiation were compared between KOS hydrogel and the Blank control at different time points. We found that KOS hydrogel is effective in maintaining hCSCs without any observable toxic effects, although cell size and proliferation rate appeared smaller on the KOS hydrogel compared to the Blank control. To our surprise, KOS hydrogel significantly promoted vascular smooth muscle cell (VSMC) differentiation (~72%), while on the Blank control dishes, most of the hCSCs (~78%) became cardiomyocytes. Further, we also observed "endothelial cell tube-like" microstructures formed by differentiated VSMCs only on KOS hydrogel, suggesting a potential capability of the hCSC-derived VSMCs for in vitro angiogenesis. To the best of our knowledge, this is the first report to discover the preferred differentiation of hCSCs toward VSMCs on KOS hydrogel. The underlying mechanism remains unknown. This innovative methodology may offer a new approach to generate a robust number of VSMCs simply by culturing hCSCs on KOS hydrogel, and the resulting VSMCs may be used in animal studies and clinical trials in

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

    PubMed

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

    2014-04-01

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

  5. 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

  6. 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

  7. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne Muscular Dystrophy

    PubMed Central

    Galindo, Cristi L.; Soslow, Jonathan H.; Brinkmeyer-Langford, Candice L.; Gupte, Manisha; Smith, Holly M.; Sengsayadeth, Seng; Sawyer, Douglas B.; Benson, D. Woodrow; Kornegay, Joe N.; Markham, Larry W.

    2016-01-01

    Background In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. Methods We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ months) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. Results We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. Conclusion These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively. PMID:26672735

  8. Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging

    PubMed Central

    Zhou, Jin; Yun Chong, Shu; Lim, Andrea; Singh, Brijesh K.; Sinha, Rohit A.; Salmon, Adam B.; Yen, Paul M.

    2017-01-01

    Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of ATG3 and ATG12-ATG5. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, PINK1 and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle vs. heart during aging. PMID:28238968

  9. 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

  10. The structure and distribution of satellite cells of cardiac muscles in decapod crustaceans.

    PubMed

    Midsukami, M

    1981-01-01

    The structure and distribution of satellite cells of cardiac muscles were examined in twenty-one species of animals chosen from each tribe within the order Decapoda (Arthropoda, Crustacea). The satellite cells were found in all animals observed. Most of them are morphologically identical with those described in different striated muscles of other species, but some cells have unusual features. The decapod satellite cell occasionally lies right over the region corresponding to the intercalated disc between the apposed cardiac muscle cells. The cell sends cytoplasmic processes into the adjacent muscle cells, enabling the plasma membrane to make close contact with the cleft opening of the intercalated disc, and with the myofibril at the level of the Z-line. Another characteristic feature is the presence of "paired" cells. Such cells are clearly separated from each other over most of the contact area by the respective plasma membranes, which are smooth in appearance and devoid of specialized regions. The significance of the presence of satellite cells in decapod cardiac muscle and its possible role are discussed and compared with those described for other species.

  11. Smyd1b is required for skeletal and cardiac muscle function in zebrafish

    PubMed Central

    Li, Huiqing; Zhong, Yongwang; Wang, Zengfeng; Gao, Jie; Xu, Jin; Chu, Wuying; Zhang, Jianshe; Fang, Shenyun; Du, Shao Jun

    2013-01-01

    Smyd1b is a member of the Smyd family that is specifically expressed in skeletal and cardiac muscles. Smyd1b plays a key role in thick filament assembly during myofibrillogenesis in skeletal muscles of zebrafish embryos. To better characterize Smyd1b function and its mechanism of action in myofibrillogenesis, we analyzed the effects of smyd1b knockdown on myofibrillogenesis in skeletal and cardiac muscles of zebrafish embryos. The results show that knockdown of smyd1b causes significant disruption of myofibril organization in both skeletal and cardiac muscles of zebrafish embryos. Microarray and quantitative reverse transcription-PCR analyses show that knockdown of smyd1b up-regulates heat shock protein 90 (hsp90) and unc45b gene expression. Biochemical analysis reveals that Smyd1b can be coimmunoprecipitated with heat shock protein 90 α-1 and Unc45b, two myosin chaperones expressed in muscle cells. Consistent with its potential function in myosin folding and assembly, knockdown of smyd1b significantly reduces myosin protein accumulation without affecting mRNA expression. This likely results from increased myosin degradation involving unc45b overexpression. Together these data support the idea that Smyd1b may work together with myosin chaperones to control myosin folding, degradation, and assembly into sarcomeres during myofibrillogenesis. PMID:24068325

  12. Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice.

    PubMed

    Ito, Takashi; Oishi, Shohei; Takai, Mika; Kimura, Yasushi; Uozumi, Yoriko; Fujio, Yasushi; Schaffer, Stephen W; Azuma, Junichi

    2010-08-24

    Taurine, a sulfur-containing beta-amino acid, is highly contained in heart and skeletal muscle. Taurine has a variety of biological actions, such as ion movement, calcium handling and cytoprotection in the cardiac and skeletal muscles. Meanwhile, taurine deficiency leads various pathologies, including dilated cardiomyopathy, in cat and fox. However, the essential role of taurine depletion on pathogenesis has not been fully clarified. To address the physiological role of taurine in mammalian tissues, taurine transporter-(TauT-) knockout models were recently generated. TauTKO mice exhibited loss of body weight, abnormal cardiac function and the reduced exercise capacity with tissue taurine depletion. In this chapter, we summarize pathological profile and histological feature of heart and skeletal muscle in TauTKO mice.

  13. Developmental regulation of cation pumps in skeletal and cardiac muscle.

    PubMed

    Dauncey, M J; Harrison, A P

    1996-03-01

    The prenatal and early postnatal periods are critical stages during which long-term development can be affected. For example, retardation of growth during these periods is closely linked to the occurrence of adult degenerative diseases. Appropriate development of muscle is essential for numerous functions, including movement, posture, thermogenesis, breathing and maintenance of the circulation. Defects in normal muscle development could thus impair any of these functions in the neonate and may also have long-term consequences for the health of the individual. Central to normal muscle structure and function is the appropriate development not only of the sarcomeric proteins but also of the sarcolemma, transverse-tubules, sarcoplasmic reticulum and associated membrane-bound ATPases. Long-term regulation of these ATPases is by changes in their concentration, whereas short-term regulation is mediated by alterations in enzyme activity. This review focuses on changes in total concentrations of Na+, K+, and Ca(2+)-ATPases during prenatal and postnatal life, in functionally diverse muscles of mammalian species born at different stages of maturity. Both these cation pumps belong to multigene families and changes in relative abundance of their specific isoforms are also considered because they may have important consequences for contractile performance during distinct stages of development. Finally, potential regulatory mechanisms which alter markedly during normal ontogeny are discussed. These include intrinsic factors such as hormones and contractile activity, extrinsic factors such as nutrition and environmental temperature, and interactions between these variables which are known to be especially important during postnatal development.

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

    PubMed Central

    Santos, Kelli Maria Souza; de Cerqueira Neto, Manoel Luiz; Carvalho, Vitor Oliveira; de Santana Filho, Valter Joviniano; da Silva Junior, Walderi Monteiro; Araújo Filho, Amaro Afrânio; Cerqueira, Telma Cristina Fontes; Cacau, Lucas de Assis Pereira

    2014-01-01

    Introduction Peripheral muscle strength has been little explored in the literature in the context of cardiac rehabilitation. Objective To evaluate the peripheral muscle strength of patients undergoing elective cardiac surgery. Methods This was a longitudinal observational study. The peripheral muscle strength was measured using isometric dynamometry lower limb (knee extensors and flexors) at three different times: preoperatively (M1), the day of discharge (M2) and hospital discharge (M3). Participants received physiotherapy pre and postoperatively during the days of hospitalization during the morning and afternoon. Results Twenty-two patients were evaluated. The values of peripheral muscle strength of knee extensors preoperative found were about 50% lower than those predicted for the healthy population. When comparing muscle strength prior (M1), with the remaining evaluation, found himself in a fall of 29% for the movement of knee extension and 25% for knee flexion in M2 and a decrease of 10% movement for knee extension and 13% for knee flexion in M3 when comparing with M1. Conclusion The values of peripheral muscle strength prior of the study patients were lower than predicted for the healthy population of the same age. After the surgical event this reduction is even more remarkable, being reestablished until the time of discharge, to values close to baseline. PMID:25372909

  15. Wnt signaling balances specification of the cardiac and pharyngeal muscle fields.

    PubMed

    Mandal, Amrita; Holowiecki, Andrew; Song, Yuntao Charlie; Waxman, Joshua S

    2017-02-01

    Canonical Wnt/β-catenin (Wnt) signaling plays multiple conserved roles during fate specification of cardiac progenitors in developing vertebrate embryos. Although lineage analysis in ascidians and mice has indicated there is a close relationship between the cardiac second heart field (SHF) and pharyngeal muscle (PM) progenitors, the signals underlying directional fate decisions of the cells within the cardio-pharyngeal muscle field in vertebrates are not yet understood. Here, we examined the temporal requirements of Wnt signaling in cardiac and PM development. In contrast to a previous report in chicken embryos that suggested Wnt inhibits PM development during somitogenesis, we find that in zebrafish embryos Wnt signaling is sufficient to repress PM development during anterior-posterior patterning. Importantly, the temporal sensitivity of dorso-anterior PMs to increased Wnt signaling largely overlaps with when Wnt signaling promotes specification of the adjacent cardiac progenitors. Furthermore, we find that excess early Wnt signaling can cell autonomously promote expansion of the first heart field (FHF) progenitors at the expense of PM and SHF within the anterior lateral plate mesoderm (ALPM). Our study provides insight into an antagonistic developmental mechanism that balances the sizes of the adjacent cardiac and PM progenitor fields in early vertebrate embryos.

  16. Crosstalk of mesenchymal stem cells and macrophages promotes cardiac muscle repair.

    PubMed

    Wang, Mei; Zhang, Guoru; Wang, Yaling; Liu, Tao; Zhang, Yang; An, Yu; Li, Yongjun

    2015-01-01

    Transplantation of bone-marrow derived mesenchymal stem cells (MSCs) has potential therapeutic effects on cardiac muscle repair. However, the underlying mechanism remains not completely clarified. Here we show that transplantation of MSCs significantly increased local recruitment of macrophages to facilitate cardiac muscle repair. MSCs-induced recovery of cardiac function and attenuation of fibrosis after injury were all abolished by either impaired macrophage infiltration, or by MSCs depletion after macrophage recruitment. However, angiogenesis seemed to be only affected by depletion of macrophages, but not by depletion of MSCs, suggesting that macrophages are responsible for the augmented angiogenesis after MSCs transplantation, while MSCs do not directly contribute to angiogenesis in the functional cardiac repair. Moreover, high level of transforming growth factor β 1 (TGFβ1) was detected in macrophages and high level of BMP7 was detected in MSCs, suggesting that MSCs not only may recruit macrophages to enhance angiogenesis to promote regeneration, but also may secrete BMP7 to contradict the fibrogenic effect of TGFβ1 by macrophages. Our study thus sheds new insight on the interaction of MSCs and macrophages in a functional cardiac repair triggered by MSCs transplantation.

  17. Arrhythmogenic right ventricular cardiomyopathy coincided with the cardiac fibrosis in the inner muscle layer of the left ventricular wall in a boxer dog

    PubMed Central

    YAMADA, Naoaki; KITAMORI, Takashi; KITAMORI, Fumiyo; ISHIGAMI, Kanako; IWANAGA, Koji; ITOU, Taiki; KOBAYASHI, Ryosuke; KUMABE, Shino; DOI, Takuya; SATO, Junko; WAKO, Yumi; TSUCHITANI, Minoru

    2015-01-01

    A 7-year-old female boxer dog died suddenly without any clinical signs. It was suspected that the dog had arrhythmogenic right ventricular cardiomyopathy (ARVC) due to ventricular premature complexes and ventricular tachycardia at 3 years of age. The final diagnosis of ARVC was confirmed by histological characteristics, such as loss of cardiocytes and fibrofatty replacement, occurring in the right and left ventricular walls. In the cardiocytes, non-lipid vacuoles were observed. Cardiac fibrosis and intimal thickening of the small arteries occurred without fatty replacement in the inner muscle layer including the papillary muscles of the left ventricular wall. This paper describes the pathomorphological details of an ARVC case with coincidental cardiac fibrosis in the inner muscle layer of the left ventricular wall. PMID:25959955

  18. Grip force and muscle activity differences due to glove type.

    PubMed

    Kovacs, Kimberly; Splittstoesser, Riley; Maronitis, Anthony; Marras, William S

    2002-01-01

    The purpose of this study was to investigate the effects of different types and sizes of gloves on external grip force and muscle activity. Twenty-one male and seven female volunteers served as subjects. Each subject performed two maximum voluntary grip contractions while wearing each of the 10 glove types. Results indicated significant differences in the effects of different glove types on the peak force, ratio of peak force to normalized flexor muscle EMG activity, and the ratio of peak force to coactivity.

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

    PubMed Central

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

    2015-01-01

    While it is well established that class-I antiarrhythmics block cardiac sodium channels, the mechanism of action of therapeutic levels of these drugs is not well understood. Using a combination of mathematical modeling and in vitro experiments, we studied the failure of activation of action potentials in single ventricular cells and in tissue caused by Na+ channel block. Our computations of block and unblock of sodium channels by a theoretical class-Ib antiarrhythmic agent predict differences in the concentrations required to cause activation failure in single cells as opposed to multicellular preparations. We tested and confirmed these in silico predictions with in vitro experiments on isolated guinea-pig ventricular cells and papillary muscles stimulated at various rates (2–6.67 Hz) and exposed to various concentrations (5 × 10−6 to 500 × 10−6 mol/l) of lidocaine. The most salient result was that whereas large doses (5 × 10−4 mol/l or higher) of lidocaine were required to inhibit action potentials temporarily in single cells, much lower doses (5 × 10−6 mol/l), i.e., therapeutic levels, were sufficient to have the same effect in papillary muscles: a hundredfold difference. Our experimental results and mathematical analysis indicate that the syncytial nature of cardiac tissue explains the effects of clinically relevant doses of Na+ channel blockers. PMID:26342072

  20. Cytoskeletal Basis of Ion Channel Function in Cardiac Muscle

    PubMed Central

    Vatta, Matteo; Faulkner, Georgine

    2009-01-01

    Summary The heart is a force-generating organ that responds to self-generated electrical stimuli from specialized cardiomyocytes. This function is modulated by sympathetic and parasympathetic activity. In order to contract and accommodate the repetitive morphological changes induced by the cardiac cycle, cardiomyocytes depend on their highly evolved and specialized cytoskeletal apparatus. Defects in components of the cytoskeleton, in the long term, affect the ability of the cell to compensate at both functional and structural levels. In addition to the structural remodeling, the myocardium becomes increasingly susceptible to altered electrical activity leading to arrhythmogenesis. The development of arrhythmias secondary to structural remodeling defects has been noted, although the detailed molecular mechanisms are still elusive. Here I will review the current knowledge of the molecular and functional relationships between the cytoskeleton and ion channels and, I will discuss the future impact of new data on molecular cardiology research and clinical practice. PMID:19774097

  1. Fatty Acid Oxidation in Cardiac and Skeletal Muscle Mitochondria is Unaffected by Deletion of CD36

    PubMed Central

    King, Kristen L.; Stanley, William C.; Rosca, Mariana; Kerner, Janos; Hoppel, Charles L.; Febbraio, Maria

    2009-01-01

    Recent studies found that the plasma membrane fatty acid transport protein CD36 also resides in mitochondrial membranes in cardiac and skeletal muscle. Pharmacological studies suggest that CD36 may play an essential role in mitochondrial fatty acid oxidation. We isolated cardiac and skeletal muscle mitochondria from wild type and CD36 knock-out mice. There were no differences between wild type and CD36 knock-out mice in mitochondrial respiration with palmitoyl-CoA, palmitoyl-carnitine or glutamate as substrate. We investigated a potential alternative role for CD36 in mitochondria, ie. the export of fatty acids generated in the matrix. Palmitate export was not different between wild type and CD36 knock out mice. Taken together, CD36 does not appear to play an essential role in mitochondrial uptake of fatty acids or export of fatty acid anions. PMID:17904092

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

    PubMed Central

    Kobirumaki-Shimozawa, Fuyu; Oyama, Kotaro; Serizawa, Takahiro; Mizuno, Akari; Kagemoto, Tatsuya; Shimozawa, Togo; Ishiwata, Shin'ichi; Kurihara, Satoshi; Fukuda, Norio

    2012-01-01

    We here review the use of quantum dots (QDs) for the imaging of sarcomeric movements in cardiac muscle. QDs are fluorescence substances (CdSe) that absorb photons and reemit photons at a different wavelength (depending on the size of the particle); they are efficient in generating long-lasting, narrow symmetric emission profiles, and hence useful in various types of imaging studies. Recently, we developed a novel system in which the length of a particular, single sarcomere in cardiomyocytes can be measured at ~30 nm precision. Moreover, our system enables accurate measurement of sarcomere length in the isolated heart. We propose that QDs are the ideal tool for the study of sarcomere dynamics during excitation-contraction coupling in healthy and diseased cardiac muscle. PMID:22570526

  3. 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

  4. 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

  5. Changes in isoform composition, structure, and functional properties of titin from Mongolian gerbil (Meriones unguiculatus) cardiac muscle after space flight.

    PubMed

    Vikhlyantsev, I M; Okuneva, A D; Shpagina, M D; Shumilina, Yu V; Molochkov, N V; Salmov, N N; Podlubnaya, Z A

    2011-12-01

    Changes in isoform composition, secondary structure, and titin phosphorylation in Mongolian gerbil (Meriones unguiculatus) cardiac muscle were studied after 12-day-long space flight onboard the Russian spacecraft Foton-M3. The effect of titin on the actin-activated myosin ATPase activity at pCa 7.5 and 4.6 was also studied. Almost twofold increase in titin long N2BA isoform content relative to that of short N2B isoform was found on electrophoregrams of cardiac muscle left ventricle of the flight group gerbils. Differences in secondary structure of titin isolated from cardiac muscle of control and flight groups of gerbils were found. An increase in phosphorylation (1.30-1.35-fold) of titin of cardiac muscle of the flight group gerbils was found. A decrease in activating effect of titin of cardiac muscle of the flight group gerbils on actomyosin ATPase activity in vitro was also found. The observed changes are discussed in the context of M. unguiculatus cardiac muscle adaptation to conditions of weightlessness.

  6. 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.

  7. Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse.

    PubMed

    Allen, D L; Harrison, B C; Maass, A; Bell, M L; Byrnes, W C; Leinwand, L A

    2001-05-01

    In this paper, we describe the effects of voluntary cage wheel exercise on mouse cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 6-8 wk; n = 12) [corrected] ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h, and at an average speed of 26.4 m/min. A significant increase in the ratio of heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were significantly increased in the ventricles after 4 wk of voluntary exercise. A significant increase in the percentage of fibers expressing myosin heavy chain (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA) by 2 wk, and a significant decrease in the percentage of fibers expressing IIb MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle showed a greater increase in the percentage of IIa MHC-expressing fibers than did the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for nonexercised). Finally, the number of oxidative fibers as revealed by NADH-tetrazolium reductase histochemical staining was increased in the TA but not the gastrocnemius after 4 wk of voluntary exercise. All results are relative to age-matched mice housed without access to running wheels. Together these data demonstrate that voluntary exercise in mice results in cardiac and skeletal muscle adaptations consistent with endurance exercise.

  8. Contributions of Ca2+-Independent Thin Filament Activation to Cardiac Muscle Function

    PubMed Central

    Aboelkassem, Yasser; Bonilla, Jordan A.; McCabe, Kimberly J.; Campbell, Stuart G.

    2015-01-01

    Although Ca2+ is the principal regulator of contraction in striated muscle, in vitro evidence suggests that some actin-myosin interaction is still possible even in its absence. Whether this Ca2+-independent activation (CIA) occurs under physiological conditions remains unclear, as does its potential impact on the function of intact cardiac muscle. The purpose of this study was to investigate CIA using computational analysis. We added a structurally motivated representation of this phenomenon to an existing myofilament model, which allowed predictions of CIA-dependent muscle behavior. We found that a certain amount of CIA was essential for the model to reproduce reported effects of nonfunctional troponin C on myofilament force generation. Consequently, those data enabled estimation of ΔGCIA, the energy barrier for activating a thin filament regulatory unit in the absence of Ca2+. Using this estimate of ΔGCIA as a point of reference (∼7 kJ mol−1), we examined its impact on various aspects of muscle function through additional simulations. CIA decreased the Hill coefficient of steady-state force while increasing myofilament Ca2+ sensitivity. At the same time, CIA had minimal effect on the rate of force redevelopment after slack/restretch. Simulations of twitch tension show that the presence of CIA increases peak tension while profoundly delaying relaxation. We tested the model’s ability to represent perturbations to the Ca2+ regulatory mechanism by analyzing twitch records measured in transgenic mice expressing a cardiac troponin I mutation (R145G). The effects of the mutation on twitch dynamics were fully reproduced by a single parameter change, namely lowering ΔGCIA by 2.3 kJ mol−1 relative to its wild-type value. Our analyses suggest that CIA is present in cardiac muscle under normal conditions and that its modulation by gene mutations or other factors can alter both systolic and diastolic function. PMID:26588569

  9. 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

  10. Analysis of electric field stimulation of single cardiac muscle cells.

    PubMed Central

    Tung, L; Borderies, J R

    1992-01-01

    Electrical stimulation of cardiac cells by imposed extracellular electric fields results in a transmembrane potential which is highly nonuniform, with one end of the cell depolarized and the other end hyperpolarized along the field direction. To date, the implications of the close proximity of oppositely polarized membranes on excitability have not been explored. In this work we compare the biophysical basis for field stimulation of cells at rest with that for intracellular current injection, using three Luo-Rudy type membrane patches coupled together as a lumped model to represent the cell membrane. Our model shows that cell excitation is a function of the temporal and spatial distribution of ionic currents and transmembrane potential. The extracellular and intracellular forms of stimulation were compared in greater detail for monophasic and symmetric biphasic rectangular pulses, with duration ranging from 0.5 to 10 ms. Strength-duration curves derived for field stimulation show that over a wide range of pulse durations, biphasic waveforms can recruit and activate membrane patches about as effectively as can monophasic waveforms having the same total pulse duration. We find that excitation with biphasic stimulation results from a synergistic, temporal summation of inward currents through the sodium channel in membrane patches at opposite ends of the cell. Furthermore, with both waveform types, a net inward current through the inwardly rectifying potassium channel contributes to initial membrane depolarization. In contrast, models of stimulation by intracellular current injection do not account for the nonuniformity of transmembrane potential and produce substantially different (even contradictory) results for the case of stimulation from rest. PMID:1420884

  11. Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle.

    PubMed Central

    Kolattukudy, P. E.; Quach, T.; Bergese, S.; Breckenridge, S.; Hensley, J.; Altschuld, R.; Gordillo, G.; Klenotic, S.; Orosz, C.; Parker-Thornburg, J.

    1998-01-01

    To explore the possible role of monocyte chemotactic protein (MCP-1) in inflammatory diseases of the heart, we expressed the murine MCP-1(JE) gene under the control of the alpha-cardiac myosin heavy chain promoter to attempt to target MCP-1 expression to the adult heart muscle. The five lines of transgenic mice thus produced showed targeted expression of MCP-1 transcripts and protein in the adult heart muscle and pulmonary vein but not in skeletal muscle. MCP-1 level in the transgenic hearts increased up to 30 to 45 days of age, and leukocyte infiltration into interstitium between cardiomyocytes increased up to 60 to 75 days. The infiltrate was mainly macrophages but not T cells. The presence of MCP-1 in the transgenic hearts did not induce cytokine production indicative of leukocyte activation. Echocardiographic analysis of 1-year-old mice that express MCP-1 in the myocardium and of age-matched controls revealed cardiac hypertrophy and dilation, increases in left ventricular (LV) mass, and systolic and diastolic left ventricular internal diameters. A significant decline in M-mode shortening fraction showed depressed contractile function. Transgenic hearts were 65% heavier, and histological analysis showed moderate myocarditis, edema, and some fibrosis. Thus, MCP-1 expression in the heart muscle may provide a model to investigate myocarditis and cardiomyopathy. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9422528

  12. Cardiac actin is the major actin gene product in skeletal muscle cell differentiation in vitro.

    PubMed Central

    Bains, W; Ponte, P; Blau, H; Kedes, L

    1984-01-01

    We examined the expression of alpha-skeletal, alpha-cardiac, and beta- and gamma-cytoskeletal actin genes in a mouse skeletal muscle cell line (C2C12) during differentiation in vitro. Using isotype-specific cDNA probes, we showed that the alpha-skeletal actin mRNA pool reached only 15% of the level reached in adult skeletal muscle and required several days to attain this peak, which was then stably maintained. However, these cells accumulated a pool of alpha-cardiac actin six times higher than the alpha-skeletal actin mRNA peak within 24 h of the initiation of differentiation. After cells had been cultured for an additional 3 days, this pool declined to 10% of its peak level. In contrast, over 95% of the actin mRNA in adult skeletal muscle coded for alpha-actin. This suggests that C2C12 cells express a pattern of sarcomeric actin genes typical of either muscle development or regeneration and distinct from that seen in mature, adult tissue. Concurrently in the course of differentiation the beta- and gamma-cytoskeletal actin mRNA pools decreased to less than 10% of their levels in proliferating cells. The decreases in beta- and gamma-cytoskeletal actin mRNAs are apparently not coordinately regulated. Images PMID:6493226

  13. 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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  16. The couplonopathies: A comparative approach to a class of diseases of skeletal and cardiac muscle

    PubMed Central

    Figueroa, Lourdes; Manno, Carlo; Kraeva, Natalia; Riazi, Sheila

    2015-01-01

    A novel category of diseases of striated muscle is proposed, the couplonopathies, as those that affect components of the couplon and thereby alter its operation. Couplons are the functional units of intracellular calcium release in excitation–contraction coupling. They comprise dihydropyridine receptors, ryanodine receptors (Ca2+ release channels), and a growing list of ancillary proteins whose alteration may lead to disease. Within a generally similar plan, the couplons of skeletal and cardiac muscle show, in a few places, marked structural divergence associated with critical differences in the mechanisms whereby they fulfill their signaling role. Most important among these are the presence of a mechanical or allosteric communication between voltage sensors and Ca2+ release channels, exclusive to the skeletal couplon, and the smaller capacity of the Ca stores in cardiac muscle, which results in greater swings of store concentration during physiological function. Consideration of these structural and functional differences affords insights into the pathogenesis of several couplonopathies. The exclusive mechanical connection of the skeletal couplon explains differences in pathogenesis between malignant hyperthermia (MH) and catecholaminergic polymorphic ventricular tachycardia (CPVT), conditions most commonly caused by mutations in homologous regions of the skeletal and cardiac Ca2+ release channels. Based on mechanistic considerations applicable to both couplons, we identify the plasmalemma as a site of secondary modifications, typically an increase in store-operated calcium entry, that are relevant in MH pathogenesis. Similar considerations help explain the different consequences that mutations in triadin and calsequestrin have in these two tissues. As more information is gathered on the composition of cardiac and skeletal couplons, this comparative and mechanistic approach to couplonopathies should be useful to understand pathogenesis, clarify diagnosis, and

  17. Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity during exercise in humans.

    PubMed

    Hartwich, Doreen; Dear, William E; Waterfall, Jessica L; Fisher, James P

    2011-12-15

    We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg(-1) at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by -2.6 ± 0.8 and -0.4 ± 0.1 ms mmHg(-1) at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg(-1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans.

  18. Detection of myocardial degeneration with point-of-care cardiac troponin assays and histopathology in lambs with white muscle disease.

    PubMed

    Gunes, Vehbi; Ozcan, Kadir; Citil, Mehmet; Onmaz, Ali C; Erdogan, Hidayet M

    2010-06-01

    The aim of this study was to evaluate the use of human cardiac troponin-I (cTn-I) and cardiac troponin-T (cTn-T) kits for the determination of myocardial degeneration in lambs suffering from white muscle disease (WMD). Cardiac troponin (cTn) analyses and necropsy were performed on 12 lambs with acute WMD. Only cTn analyses were tested in six healthy lambs. cTn-I and cTn-T tests were positive for all lambs with WMD, but negative in healthy lambs. Necropsy revealed that the cardiac and skeletal muscles of lambs with WMD had chalky white lesions, which appeared as necrosis and calcification in histopathology. The histopathological findings of the heart muscle and increased cTn in lambs with WMD suggested that marked myocardial degeneration may be detected by point-of-care cTn assays in lambs.

  19. Pulmonary Arterial Capacitance Predicts Cardiac Events in Pulmonary Hypertension Due to Left Heart Disease

    PubMed Central

    Sugimoto, Koichi; Yoshihisa, Akiomi; Nakazato, Kazuhiko; Jin, Yuichiro; Suzuki, Satoshi; Yokokawa, Tetsuro; Misaka, Tomofumi; Yamaki, Takayoshi; Kunii, Hiroyuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

    2016-01-01

    Background Although pulmonary hypertension due to left heart disease (LHD-PH) accounts for the largest proportion of pulmonary hypertension, few reports on the epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial capacitance (PAC) has attracted attention as a possible factor of right ventricular afterload along with pulmonary vascular resistance. We therefore investigated the clinical significance of PAC in LHD-PH. Methods The subject consisted of 252 LHD-PH patients (145 men, mean age 63.4 ± 14.7 years) diagnosed by right heart catheterization. PAC was estimated by the ratio between stroke volume and pulmonary arterial pulse pressure. Patients were classified into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the 2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the 4th quartile 3.61 to 12.14 ml/mmHg). The end-points were defined as rehospitalization due to worsening heart failure and/or cardiac death. The Cox proportional hazard regression model was used to determine what variables were associated with cardiac events. Results The patients in the 1st quartile had the lowest cardiac index and stroke volume index, and the highest mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four patients experienced cardiac events during the follow-up period (median 943 days). The event-free rate of the 1st quartile was significantly lower than that of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1% [4th quartile], P < 0.001). The Cox hazard analysis revealed that PAC was significantly associated with cardiac events (HR 0.556, 95% CI 0.424–0.730, P < 0.001). Conclusion PAC is useful in the prediction of cardiac event risk in LHD-PH patients. PMID:27875533

  20. 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.

  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. The mode of inotropic action of ciguatoxin on guinea-pig cardiac muscle.

    PubMed Central

    Seino, A.; Kobayashi, M.; Momose, K.; Yasumoto, T.; Ohizumi, Y.

    1988-01-01

    1. Ciguatoxin (CTX) caused a dose-dependent increase in the contractile force of the guinea-pig isolated left atria at concentrations ranging from 0.1 to 10 ng ml-1 with the ED50 value of 0.5 ng ml-1. 2. In the atria, tetrodotoxin (5 x 10(-7) M) inhibited markedly the inotropic action of CTX. The inotropic effect of CTX at low concentrations was abolished by practolol (10(-5) M) and reserpine (2 mg kg-1 daily, for 3 days), whereas that of CTX at high concentrations was partially inhibited by both drugs. 3. In single atrial cells, CTX (3 ng ml-1) produced a marked increase in the amplitude of longitudinal contractions. 4. CTX (3 ng ml-1) caused marked prolongation in the falling phase of action potentials of atrial strips without affecting the maximum rate of rise of action potentials and membrane resting potentials. The effect of CTX on action potentials was abolished by tetrodotoxin (10(-6) M). 5. The whole-cell patch-clamp experiments on myocytes revealed that CTX (20 ng ml-1) shifted the current-voltage curve of Na inward currents by 40 mV in the negative direction. CTX caused a small sustained Na inward current even at resting membrane potentials. 6. These results suggest that the inotropic action of lower concentrations of CTX is primarily due to an indirect action via noradrenaline release, whereas that of higher concentrations is caused not only by an indirect action but also by a direct action on voltage-dependent Na channels of cardiac muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3207997

  3. "Dropped-head" syndrome due to isolated myositis of neck extensor muscles: MRI findings.

    PubMed

    Gaeta, Michele; Mazziotti, Silvio; Toscano, Antonio; Rodolico, Carmelo; Mazzeo, Anna; Blandino, Alfredo

    2006-02-01

    MRI findings of a patient with dropped-head syndrome due to focal myositis of the neck extensor muscles are presented. MRI showed oedematous changes and marked enhancement of the neck extensor muscles. After therapy MRI demonstrated disappearance of the abnormal findings.

  4. Modeling of Cardiac Muscle Thin Films: Pre-stretch, Passive and Active Behavior

    PubMed Central

    Shim, Jongmin; Grosberg, Anna; Nawroth, Janna C.; Parker, Kevin Kit; Bertoldi, Katia

    2012-01-01

    Recent progress in tissue engineering has made it possible to build contractile bio-hybrid materials that undergo conformational changes by growing a layer of cardiac muscle on elastic polymeric membranes. Further development of such muscular thin films for building actuators and powering devices requires exploring several design parameters, which include the alignment of the cardiac myocytes and the thickness/Young’s modulus of elastomeric film. To more efficiently explore these design parameters, we propose a 3-D phenomenological constitutive model, which accounts for both the passive deformation including pre-stretch and the active behavior of the cardiomyocytes. The proposed 3-D constitutive model is implemented within a finite element framework, and can be used to improve the current design of bio-hybrid thin films and help developing bio-hybrid constructs capable of complex conformational changes. PMID:22236531

  5. 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.

  6. Sudden Cardiac Death of a Body Packer Due to Cocaine Cardiotoxicity

    PubMed Central

    Pramanik, Parthasarathi; Vidua, Raghvendra Kumar

    2016-01-01

    This article presents a case of sudden cardiac death due to the effects of cocaine concealed in the body of a male drug smuggler in his 40s, a so-called body packer. A total of 57 body packets filled with cocaine powder were discovered in his body cavities. The detailed autopsy examination, including histopathology and toxicology findings, is discussed with the aim of describing the mechanism of cocaine intoxication in the body packer and an analysis of cocaine-induced cardiotoxicity and sudden death. PMID:27932899

  7. Segregation of cardiac and skeletal muscle-specific regulatory elements of the beta-myosin heavy chain gene.

    PubMed Central

    Rindt, H; Knotts, S; Robbins, J

    1995-01-01

    The beta-myosin heavy chain (beta-MyHC) gene is expressed in cardiac and slow skeletal muscles. To examine the regulatory sequences that are required for the gene's expression in the two compartments in vivo, we analyzed the expression pattern of a transgene consisting of the beta-MyHC gene 5' upstream region linked to the chloramphenicol acetyltransferase reporter gene. By using 5600 bp of 5' upstream region, the transgene was expressed at high levels in the slow skeletal muscles. Decreased levels of thyroid hormone led to the up-regulation of the transgene in both cardiac and skeletal muscles, mimicking the behavior of the endogenous beta-MyHC gene. After deleting the distal 5000 bp, the level of reporter gene expression was strongly reduced. However, decreased levels of thyroid hormone led to an 80-fold skeletal muscle-specific increase in transgene expression, even upon the ablation of a conserved cis-regulatory element termed MCAT, which under normal (euthyroid) conditions abolishes muscle-specific expression. In contrast, cardiac-specific induction was not detected with the deletion construct. These observations indicate that the cardiac and skeletal muscle regulatory elements can be functionally segregated on the beta-MyHC gene promoter. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7878016

  8. Segregation of cardiac and skeletal muscle-specific regulatory elements of the beta-myosin heavy chain gene.

    PubMed

    Rindt, H; Knotts, S; Robbins, J

    1995-02-28

    The beta-myosin heavy chain (beta-MyHC) gene is expressed in cardiac and slow skeletal muscles. To examine the regulatory sequences that are required for the gene's expression in the two compartments in vivo, we analyzed the expression pattern of a transgene consisting of the beta-MyHC gene 5' upstream region linked to the chloramphenicol acetyltransferase reporter gene. By using 5600 bp of 5' upstream region, the transgene was expressed at high levels in the slow skeletal muscles. Decreased levels of thyroid hormone led to the up-regulation of the transgene in both cardiac and skeletal muscles, mimicking the behavior of the endogenous beta-MyHC gene. After deleting the distal 5000 bp, the level of reporter gene expression was strongly reduced. However, decreased levels of thyroid hormone led to an 80-fold skeletal muscle-specific increase in transgene expression, even upon the ablation of a conserved cis-regulatory element termed MCAT, which under normal (euthyroid) conditions abolishes muscle-specific expression. In contrast, cardiac-specific induction was not detected with the deletion construct. These observations indicate that the cardiac and skeletal muscle regulatory elements can be functionally segregated on the beta-MyHC gene promoter.

  9. HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte.

    PubMed

    Claycomb, W C; Lanson, N A; Stallworth, B S; Egeland, D B; Delcarpio, J B; Bahinski, A; Izzo, N J

    1998-03-17

    We have derived a cardiac muscle cell line, designated HL-1, from the AT-1 mouse atrial cardiomyocyte tumor lineage. HL-1 cells can be serially passaged, yet they maintain the ability to contract and retain differentiated cardiac morphological, biochemical, and electrophysiological properties. Ultrastructural characteristics typical of embryonic atrial cardiac muscle cells were found consistently in the cultured HL-1 cells. Reverse transcriptase-PCR-based analyses confirmed a pattern of gene expression similar to that of adult atrial myocytes, including expression of alpha-cardiac myosin heavy chain, alpha-cardiac actin, and connexin43. They also express the gene for atrial natriuretic factor. Immunohistochemical staining of the HL-1 cells indicated that the distribution of the cardiac-specific markers desmin, sarcomeric myosin, and atrial natriuretic factor was similar to that of cultured atrial cardiomyocytes. A delayed rectifier potassium current (IKr) was the most prominent outward current in HL-1 cells. The activating currents displayed inward rectification and deactivating current tails were voltage-dependent, saturated at >+20 mV, and were highly sensitive to dofetilide (IC50 of 46.9 nM). Specific binding of [3H]dofetilide was saturable and fit a one-site binding isotherm with a Kd of 140 +/- 60 nM and a Bmax of 118 fmol per 10(5) cells. HL-1 cells represent a cardiac myocyte cell line that can be repeatedly passaged and yet maintain a cardiac-specific phenotype.

  10. Sternal fractures and delayed cardiac tamponade due to a severe blunt chest trauma.

    PubMed

    Liang, Huai-min; Chen, Qiu-lin; Zhang, Er-yong; Hu, Jia

    2016-04-01

    Sternal fractures caused by blunt chest trauma are associated with an increased incidence of cardiac injury. Reports of the incidence of cardiac injury associated with sternal fracture range from 18% to 62%. Delayed cardiac tamponade is a rare phenomenon that appears days or weeks after injury. Moreover, after nonpenetrating chest trauma, cardiac tamponade is very rare and occurs in less than 1 of 1000. This case describes a patient who had delayed cardiac tamponade 17 days after a severe blunt chest trauma.

  11. Myosin types and fiber types in cardiac muscle. I. Ventricular myocardium

    PubMed Central

    1981-01-01

    Antisera against bovine atrial myosin were raised in rabbits, purified by affinity chromatography, and absorbed with insolubilized ventricular myosin. Specific anti-bovine atrial myosin (anti-bAm) antibodies reacted selectively with atrial myosin heavy chains, as determined by enzyme immunoassay combined with SDS-gel electrophoresis. In direct and indirect immunofluorescence assay, anti-bAm was found to stain all atrial muscle fibers and a minor proportion of ventricular muscle fibers in the right ventricle of the bovine heart. In contrast, almost all muscle fibers in the left ventricle were unreactive. Purkinje fibers showed variable reactivity. In the rabbit heart, all atrial muscle fibers were stained by anti-bAm, whereas ventricular fibers showed a variable response in both the right and left ventricle, with a tendency for reactive fibers to be more numerous in the right ventricle and in subepicardial regions. Diversification of fiber types with respect to anti-bAm reactivity was found to occur during late stages of postnatal development in the rabbit heart and to be influenced by thyroid hormone. All ventricular muscle fibers became strongly reactive after thyroxine treatment, whereas they became unreactive or poorly reactive after propylthiouracil treatment. These findings are consistent with the existence of different ventricular isomyosins whose relative proportions can vary according to the thyroid state. Variations in ventricular isomyosin composition can account for the changes in myosin Ca2+-activated ATPase activity previously observed in cardiac muscle from hyper- and hypothyroid animals and may be responsible for the changes in the velocity of contraction of ventricular myocardium that occur under these conditions. The differential distribution of ventricular isomyosins in the normal heart suggests that fiber types with different contractile properties may coexist in the ventricular myocardium. PMID:7009623

  12. Massive palmitoylation-dependent endocytosis during reoxygenation of anoxic cardiac muscle

    PubMed Central

    Lin, Mei-Jung; Fine, Michael; Lu, Jui-Yun; Hofmann, Sandra L; Frazier, Gary; Hilgemann, Donald W

    2013-01-01

    In fibroblasts, large Ca transients activate massive endocytosis (MEND) that involves membrane protein palmitoylation subsequent to mitochondrial permeability transition pore (PTP) openings. Here, we characterize this pathway in cardiac muscle. Myocytes with increased expression of the acyl transferase, DHHC5, have decreased Na/K pump activity. In DHHC5-deficient myocytes, Na/K pump activity and surface area/volume ratios are increased, the palmitoylated regulatory protein, phospholemman (PLM), and the cardiac Na/Ca exchanger (NCX1) show greater surface membrane localization, and MEND is inhibited in four protocols. Both electrical and optical methods demonstrate that PTP-dependent MEND occurs during reoxygenation of anoxic hearts. Post-anoxia MEND is ablated in DHHC5-deficient hearts, inhibited by cyclosporine A (CsA) and adenosine, promoted by staurosporine (STS), reduced in hearts lacking PLM, and correlates with impaired post-anoxia contractile function. Thus, the MEND pathway appears to be deleterious in severe oxidative stress but may constitutively contribute to cardiac sarcolemma turnover in dependence on metabolic stress. DOI: http://dx.doi.org/10.7554/eLife.01295.001 PMID:24282237

  13. Glutaredoxin-2 Is Required to Control Oxidative Phosphorylation in Cardiac Muscle by Mediating Deglutathionylation Reactions*

    PubMed Central

    Mailloux, Ryan J.; Xuan, Jian Ying; McBride, Skye; Maharsy, Wael; Thorn, Stephanie; Holterman, Chet E.; Kennedy, Christopher R. J.; Rippstein, Peter; deKemp, Robert; da Silva, Jean; Nemer, Mona; Lou, Marjorie; Harper, Mary-Ellen

    2014-01-01

    Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2−/−) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered by restoring the redox environment to that favoring the deglutathionylated states of proteins. Grx2−/− hearts also developed left ventricular hypertrophy and fibrosis, and mice became hypertensive. Mitochondrial energetics from Grx2 heterozygotes (Grx2+/−) were also dysfunctional, and hearts were hypertrophic. Intriguingly, Grx2+/− mice were far less hypertensive than Grx2−/− mice. Thus, Grx2 plays a vital role in modulating mitochondrial metabolism in cardiac muscle, and Grx2 deficiency leads to pathology. As mitochondrial ATP production was restored by the addition of reductants, these findings may be relevant to novel redox-related therapies in cardiac disease. PMID:24727547

  14. Hypoxia Enhances Differentiation of Hair Follicle-Associated-Pluripotent (HAP) Stem Cells to Cardiac-Muscle Cells.

    PubMed

    Shirai, Kyoumi; Hamada, Yuko; Arakawa, Nobuko; Yamazaki, Aiko; Tohgi, Natsuko; Aki, Ryoichi; Mii, Sumiyuki; Hoffman, Robert M; Amoh, Yasuyuki

    2017-03-01

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair-follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and nestin-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We recently 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. In the present study, we report that, under hypoxic conditions, HAP stem cells differentiated to troponin-positive cardiac-muscle cells at a higher rate that under normoxic conditions. Hypoxia did not influence the differentiation to other cell types. For future use of HAP stem cells for cardiac muscle regeneration, hypoxia should enhance the rate of differentiation thereby providing patients more opportunities to use their own HAP stem cells which are easily accessible, for this purpose. J. Cell. Biochem. 118: 554-558, 2017. © 2016 Wiley Periodicals, Inc.

  15. 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

  16. Aberrant muscle syndrome: hypertrophy of the hand and arm due to aberrant muscles with or without hypertrophy of the muscles.

    PubMed

    Ogino, Toshihiko; Satake, Hiroshi; Takahara, Masatoshi; Kikuchi, Noriaki; Watanabe, Tadayosi; Iba, Kousuke; Ishii, Seiichi

    2010-06-01

    Five patients were reported in our congenital anomaly registry who had six hands in total with muscular hyperplasia, aberrant muscles, ulnar drift of the fingers in the metacarpophalangeal (MP) joints, flexion contractures of the MP joints, and enlargement of the metacarpal spaces. Thirty patients with unilateral involvement of this condition have been reported previously. We reviewed these cases and found that the condition varied in severity and that it was reported using different names. However, this condition seems different from true macrodactyly and multiple camptodactyly, including windblown hand, and seems to be an isolated entity of congenital upper limb anomaly. The authors recommend 'aberrant muscle syndrome' or 'accessory muscle syndrome' as a diagnostic name, because this seems to be the most common pathological finding in this condition.

  17. 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.

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

    PubMed

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

    2015-10-01

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

  19. Spontaneous baroreflex control of cardiac output during dynamic exercise, muscle metaboreflex activation, and heart failure.

    PubMed

    Ichinose, Masashi; Sala-Mercado, Javier A; O'Leary, Donal S; Hammond, Robert L; Coutsos, Matthew; Ichinose, Tomoko; Pallante, Marco; Iellamo, Ferdinando

    2008-03-01

    We have previously shown that spontaneous baroreflex-induced changes in heart rate (HR) do not always translate into changes in cardiac output (CO) at rest. We have also shown that heart failure (HF) decreases this linkage between changes in HR and CO. Whether dynamic exercise and muscle metaboreflex activation (via imposed reductions in hindlimb blood flow) further alter this translation in normal and HF conditions is unknown. We examined these questions using conscious, chronically instrumented dogs before and after pacing-induced HF during mild and moderate dynamic exercise with and without muscle metaboreflex activation. We measured left ventricular systolic pressure (LVSP), CO, and HR and analyzed the spontaneous HR-LVSP and CO-LVSP relationships. In normal animals, mild exercise significantly decreased HR-LVSP (-3.08 +/- 0.5 vs. -5.14 +/- 0.6 beats.min(-1).mmHg(-1); P < 0.05) and CO-LVSP (-134.74 +/- 24.5 vs. -208.6 +/- 22.2 ml.min(-1).mmHg(-1); P < 0.05). Moderate exercise further decreased both and, in addition, significantly reduced HR-CO translation (25.9 +/- 2.8% vs. 52.3 +/- 4.2%; P < 0.05). Muscle metaboreflex activation at both workloads decreased HR-LVSP, whereas it had no significant effect on CO-LVSP and the HR-CO translation. HF significantly decreased HR-LVSP, CO-LVSP, and the HR-CO translation in all situations. We conclude that spontaneous baroreflex HR responses do not always cause changes in CO during exercise. Moreover, muscle metaboreflex activation during mild and moderate dynamic exercise reduces this coupling. In addition, in HF the HR-CO translation also significantly decreases during both workloads and decreases even further with muscle metaboreflex activation.

  20. 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.

  1. Acute Liver Failure Due to Budd-Chiari Syndrome in the Setting of Cardiac Synovial Sarcoma.

    PubMed

    Stine, Jonathan G; Newton, Kelly; Vinayak, Ajeet G

    2015-04-01

    Primary malignant tumors of the heart, specifically cardiac sarcomas, are rare and mainly diagnosed at autopsy. Acute Budd-Chiari syndrome is a recognized cause of acute liver failure and has been associated with several rare cardiac tumors: atrial myxoma, caval rhabdomyosarcoma, and primary cardiac adenocarcinoma. We present the first case of a fatal, highly differentiated cardiac synovial sarcoma that presented as acute liver failure from Budd-Chiari syndrome.

  2. Evaluation of Skeletal and Cardiac Muscle Function after Chronic Administration of Thymosin β-4 in the Dystrophin Deficient Mouse

    PubMed Central

    Spurney, Christopher F.; Cha, Hee-Jae; Sali, Arpana; Pandey, Gouri S.; Pistilli, Emidio; Guerron, Alfredo D.; Gordish-Dressman, Heather; Hoffman, Eric P.; Nagaraju, Kanneboyina

    2010-01-01

    Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tβ4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ) and mdx mice, 8–10 weeks old, were treated with 150 µg of Tβ4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tβ4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tβ4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tβ4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tβ4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy. PMID:20126456

  3. Simulation of steady state and transient cardiac muscle response experiments with a Huxley-based contraction model.

    PubMed

    Negroni, Jorge A; Lascano, Elena C

    2008-08-01

    A cardiac muscle model is presented with the purpose of representing a wide range of mechanical experiments at constant and transient Ca(2+) concentration. Modifications of a previous model were: weak and power attached crossbridge states, a troponin system involving three consecutive regulatory troponin-tropomyosin units acting together in Ca(2+) kinetics and detachment constants depending on crossbridge length. This model improved cooperativity (Hill coefficient close to 4) and the force-velocity relationship, and incorporated the representation of the four phases of muscle response to length and force steps, isotonic shortening and isosarcometric contractions, preserving previous satisfactory results. Moreover, experimentally reported effects, such as length dependence on Ca(2+) affinity, the decreased cooperativity at higher Ca(2+) concentrations, temperature effects on the stiffness-frequency relationship and the isometric internal shortening due to series elasticity, were obtained. In conclusion, the model is more comprehensive than a previous version because it is able to represent a wider variety of steady state experiments, the mechanical variables in twitches can be adequately related to intracellular Ca(2+), and all the simulations were performed with the same set of parameters.

  4. 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

    2015-11-06

    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.

  5. Sarcomere mechanics in uniform and nonuniform cardiac muscle: a link between pump function and arrhythmias.

    PubMed

    Ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

    2008-03-01

    Starling's law and the end-systolic pressure-volume relationship (ESPVR) reflect the effect of sarcomere length (SL) on the development of stress (sigma) and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to that of skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL -[Ca2+](free) relationships (sigma-SL-Ca relationships) at submaximal [Ca2+] in intact and skinned trabeculae were similar, although the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-Ca relationship by using a kinetic model assuming that the rates of Tn-C Ca2+ binding and/or cross-bridge (XB) cycling are determined by either the SL, [Ca2+], or sigma. We analyzed the correlation between the model results and steady-state sigma measurements at varied SL at [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that the dominant feedback mechanism is SL-, sigma-, or [Ca2+]-dependent, and that the feedback mechanism regulates Tn-C Ca2+ affinity, XB kinetics, or the unitary XB force. The analysis strongly suggests that the feedback of the number of strong XBs to cardiac Tn-C Ca2+ affinity is the dominant mechanism regulating XB recruitment. Using this concept in a model of twitch-sigma accurately reproduced the sigma-SL-Ca relationship and the time courses of twitch sigma and the intracellular [Ca2+]i. The foregoing concept has equally important repercussions for the nonuniformly contracting heart, in which arrhythmogenic Ca2+ waves arise from weakened areas in the cardiac muscle. These Ca2+ waves can reversibly be induced with nonuniform excitation-contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating

  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.

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

    PubMed

    Bunno, Yoshibumi; Suzuki, Toshiaki; Iwatsuki, Hiroyasu

    2015-12-01

    [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.

  8. Quantitative model for Schädler's isometric oscillations in insect flight and cardiac muscle.

    PubMed

    Smith, D A

    1991-10-01

    Schädler and colleagues (1969, 1971) and Steiger (1977a) have found that tetanized insect fibrillar and cardiac muscles exhibit damped isometric oscillations in tension following a quick stretch. This behaviour cannot be explained by the conventional sliding filament model at full activation, or by including stretch activation in the obvious way. However, it is predicted by a sliding filament model which allows these muscles to be further activated by an increase in thin-filament tension even at high calcium levels (above 10(-5) M), providing the strength gamma of strain-activation coupling exceeds a critical value. Calculations from a comprehensive model of the actin-myosin contraction cycle suggest that this can be achieved if the phosphate release and head rotation steps are both regulated by calcium and thin-filament tension. The model also predicts a delayed tension rise following a quick release for subcritical values of gamma. Current knowledge of sarcomere structure and regulation of contractility in striated muscle indicates that this strain-activation mechanism alone cannot account for all stretch-activation phenomena, although many can be predicted if the regulatory filament is allowed to carry passive tension.

  9. Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism.

    PubMed

    Logan, Jill K; Pantle, Hardin; Huiras, Paul; Bessman, Edward; Bright, Leah

    2014-07-01

    When a previously healthy adult experiences atraumatic cardiac arrest, providers must quickly identify the etiology and implement potentially lifesaving interventions such as advanced cardiac life support. A subset of these patients develop cardiac arrest or periarrest due to pulmonary embolism (PE). For these patients, an early, presumptive diagnosis of PE is critical in this patient population because administration of thrombolytic therapy may significantly improve outcomes. This article reviews thrombolysis as a potential treatment option for patients in cardiac arrest or periarrest due to presumed PE, identifies features associated with a high incidence of PE, evaluates thrombolytic agents, and systemically reviews trials evaluating thrombolytics in cardiac arrest or periarrest. Despite potentially improved outcomes with thrombolytic therapy, this intervention is not without risks. Patients exposed to thrombolytics may experience major bleeding events, with the most devastating complication usually being intracranial hemorrhage. To optimize the risk-benefit ratio of thrombolytics for treatment of cardiac arrest due to PE, the clinician must correctly identify patients with a high likelihood of PE and must also select an appropriate thrombolytic agent and dosing protocol.

  10. Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

    PubMed Central

    2010-01-01

    The regulation of myocardial contraction and relaxation kinetics is currently incompletely understood. When the amplitude of contraction is increased via the Frank-Starling mechanism, the kinetics of the contraction slow down, but when the amplitude of contraction is increased with either an increase in heart rate or via β-adrenergic stimulation, the kinetics speed up. It is also unknown how physiological mechanisms affect the kinetics of contraction versus those of relaxation. We investigated contraction-relaxation coupling in isolated trabeculae from the mouse and rat and stimulated them to contract at various temperatures, frequencies, preloads, and in the absence and presence of β-adrenergic stimulation. In each muscle at least 16 different conditions were assessed, and the correlation coefficient of the speed of contraction and relaxation was very close (generally >0.98). Moreover, in all but one of the analyzed murine strains, the ratio of the minimum rate of the derivative of force development (dF/dt) over maximum dF/dt was not significantly different. Only in trabeculae isolated from myosin-binding protein-C mutant mice was this ratio significantly lower (0.61 ± 0.07 vs. 0.84 ± 0.02 in 11 other strains of mice). Within each strain, this ratio was unaffected by modulation of length, frequency, or β-adrenergic stimulation. Rat trabeculae showed identical results; the balance between kinetics of contraction and relaxation was generally constant (0.85 ± 0.04). Because of the great variety in underlying excitation-contraction coupling in the assessed strains, we concluded that contraction-relation coupling is a property residing in the cardiac sarcomere. PMID:20656885

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

    PubMed

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

    2013-12-01

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

  12. 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

  13. Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

    PubMed

    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.

  14. NK4 Antagonizes Tbx1/10 to Promote Cardiac versus Pharyngeal Muscle Fate in the Ascidian Second Heart Field

    PubMed Central

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

    2013-01-01

    The heart and head muscles share common developmental origins and genetic underpinnings in vertebrates, including humans. Parts of the heart and cranio-facial musculature derive from common mesodermal progenitors that express NKX2-5, ISL1, and TBX1. This ontogenetic kinship is dramatically reflected in the DiGeorge/Cardio-Velo-Facial syndrome (DGS/CVFS), where mutations of TBX1 cause malformations in the pharyngeal apparatus and cardiac outflow tract. Cardiac progenitors of the first heart field (FHF) do not require TBX1 and segregate precociously from common progenitors of the second heart field (SHF) and pharyngeal muscles. However, the cellular and molecular mechanisms that govern heart versus pharyngeal muscle specification within this lineage remain elusive. Here, we harness the simplicity of the ascidian larva to show that, following asymmetric cell division of common progenitors, NK4/NKX2-5 promotes GATAa/GATA4/5/6 expression and cardiac specification in the second heart precursors by antagonizing Tbx1/10-mediated inhibition of GATAa and activation of Collier/Olf/EBF (COE), the determinant of atrial siphon muscle (ASM) specification. Our results uncover essential regulatory connections between the conserved cardio-pharyngeal factor Tbx1/10 and muscle determinant COE, as well as a mutual antagonism between NK4 and Tbx1/10 activities upstream of GATAa and COE. The latter cross-antagonism underlies a fundamental heart versus pharyngeal muscle fate choice that occurs in a conserved lineage of cardio-pharyngeal progenitors. We propose that this basic ontogenetic motif underlies cardiac and pharyngeal muscle development and evolution in chordates. PMID:24311985

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

    PubMed

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

    2013-05-01

    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.

  16. 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.

  17. 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.

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

    PubMed

    Pinali, Christian; Kitmitto, Ashraf

    2014-11-01

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

  19. Activity of Cecropia lyratiloba extract on contractility of cardiac and smooth muscles in Wistar rats.

    PubMed

    Ramos Almeida, Roberta; Montani Raimundo, Juliana; Rodrigues Oliveira, Rodrigo; Coelho Kaplan, Maria Auxiliadora; Gattass, Cerli Rocah; Sudo, Roberto Takashi; Zapata-Sudo, Gisele

    2006-01-01

    1. Brazilian forests show high diversity of medicinal plants and several are used in folk medicine for the treatment of hypertension and asthma. The aim of the present study was to investigate the effects of a methanol extract (ME) of Cecropia lyratiloba and its flavonoid fraction (FF) on the contractility of cardiac, vascular and tracheal smooth muscles. 2. Twitches of rat papillary muscles were obtained with electrical stimulation and were recorded before and after exposure to increasing concentrations of ME and FF. 3. Cardiac depression was induced by FF. At 500 microg/mL FF, the amplitude of twitches was reduced to 56.7 +/- 5.1% of control values (P < 0.05). 4. The contractile response to a single concentration of adrenaline (10 micromol/L) was measured before and after exposure to ME and FF in rat aorta rings with intact endothelium. Both ME and FF inhibited adrenaline-induced contractions of the aorta in a concentration-dependent manner. Adrenaline-induced contractions were reduced to 46.4 +/- 9.9 and 34.2 +/- 6.9% (P < 0.05) of control in the presence of 500 microg/mL ME and FF, respectively. 5. The flavonoids isolated from FF, namely isoorientin and a mixture of orientin and isovitexin, were also tested in the aorta. These flavonoid do not seem to be responsible for the vasorelaxant effects of ME and FF. 6. No changes were observed in acetylcholine-precontracted trachea when exposed to ME or FF. 7. Endothelium-dependent vasodilation induced by FF is likely to be mediated by the release of nitric oxide because vascular relaxation was abolished in the presence of N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. 8. In conclusion, vascular relaxation induced by ME and FF could explain the traditional use of the extract of C. lyratiloba for treatment of arterial hypertension.

  20. Effects of pH on spontaneous tension oscillation in skinned bovine cardiac muscle.

    PubMed

    Fukuda, N; Ishiwata, S

    1999-07-01

    Skinned cardiac muscle preparations exhibit spontaneous tension oscillations (spontaneous oscillatory contractions; SPOCs) in the absence of Ca2+, and in the presence of MgATP, MgADP and inorganic phosphate (Pi; ADP-SPOC). Similar oscillations occur in the presence of sub-micromolar concentrations of Ca2+ under normal activating conditions without MgADP and Pi (Ca-SPOC). In the study presented here, we investigated the effects of pH on both types of SPOC in skinned bovine cardiac ventricular muscle. First, a decrease in pH increased the MgADP concentration required to induce the half-maximal isometric tension that is obtained in the absence of Ca2+ and in the presence of MgATP (ADP-contraction). The inhibitory effect of Pi on ADP-contractions was not affected by pH. Second, ADP-SPOCs occurred upon the addition of Pi to the solution that resulted in ADP-contraction, and the relative amplitude and the period of the tension oscillation in the presence of 2 mM MgATP, 10 mM MgADP and 10 mM Pi were unchanged under all pH conditions examined (6.6, 7.0, 7.4). On the contrary, the relative amplitude and the period of the Ca-SPOCs were markedly diminished at pH 6.6. Finally, we constructed state diagrams showing the effects of pH on SPOC conditions. The state diagram shows that SPOCs occur less frequently under acidic conditions than at neutral pH. We suggest that the intermediate state of crossbridges that is required for SPOCs is more difficult to attain at a low pH.

  1. 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

  2. Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression.

    PubMed

    Witting, Nanna; Duno, Morten; Petri, Helle; Krag, Thomas; Bundgaard, Henning; Kober, Lars; Vissing, John

    2013-08-01

    Since the initial description in 2010 of anoctamin 5 deficiency as a cause of muscular dystrophy, a handful of papers have described this disease in cases of mixed populations. We report the first large regional study and present data on new aspects of prevalence, muscular and cardiac phenotypic characteristics, and muscle protein expression. All patients in our neuromuscular unit with genetically unclassified, recessive limb girdle muscular dystrophy (LGMD2), Miyoshi-type distal myopathy (MMD) or persistent asymptomatic hyperCK-emia (PACK) were assessed for mutations in the ANO5 gene. Genetically confirmed patients were evaluated with muscular and cardiopulmonary examination. Among 40 unclassified patients (28 LGMD2, 5 MMD, 7 PACK), 20 were homozygous or compound heterozygous for ANO5 mutations, (13 LGMD2, 5 MMD, 2 PACK). Prevalence of ANO5 deficiency in Denmark was estimated at 1:100.000 and ANO5 mutations caused 11 % of our total cohort of LGMD2 cases making it the second most common LGMD2 etiology in Denmark. Eight patients complained of dysphagia and 3 dated symptoms of onset in childhood. Cardiac examinations revealed increased frequency of premature ventricular contractions. Four novel putative pathogenic mutations were discovered. Total prevalence and distribution of phenotypes of ANO5 disease in a representative regional cohort are described for the first time. A high prevalence of ANO5 deficiency was found among patients with unclassified LGMD2 (46 %) and MMD (100 %). The high incidence of reported dysphagia is a new phenotypic feature not previously reported, and cardiac investigations revealed that ANO5-patients may have an increased risk of ventricular arrhythmia.

  3. Pluripotent stem cell derivation and differentiation toward cardiac muscle: novel techniques and advances in patent literature.

    PubMed

    Quattrocelli, Mattia; Thorrez, Lieven; Sampaolesi, Maurilio

    2013-04-01

    Pluripotent stem cells hold unprecedented potential for regenerative medicine, disease modeling and drug screening. Embryonic stem cells (ESCs), standard model for pluripotency studies, have been recently flanked by induced pluripotent stem cells (iPSCs). iPSCs are obtained from somatic cells via epigenetic and transcriptional reprogramming, overcoming ESC-related ethical issues and enabling the possibility of donor-matching pluripotent cell lines. Since the European Court of Justice banned patents involving embryo disaggregation to generate human ESCs, iPSCs can now fuel the willingness of European companies to invest in treatments based on stem cells. Moreover, iPSCs share many unique features of ESCs, such as unlimited self-renewal potential and broad differentiation capability, even though iPSCs seem more susceptible to genomic instability and display epigenetic biases as compared to ESCs. Both ESCs and iPSCs have been intensely investigated for cardiomyocyte production and cardiac muscle regeneration, both in human and animal models. In vitro and in vivo studies are continuously expanding and refining this field via genetic manipulation and cell conditioning, trying to achieve standard and reproducible products, eligible for clinical and biopharmaceutical scopes. This review focuses on the recently growing body of patents, concerning technical advances in production, expansion and cardiac differentiation of ESCs and iPSCs.

  4. Rat muscle opacity decrease due to the osmosis of a simple mixture

    NASA Astrophysics Data System (ADS)

    Oliveira, Luís; Lage, Armindo; Pais Clemente, M.; Tuchin, Valery V.

    2010-09-01

    It is known that the fibrous structure of muscle causes light scattering. This phenomenon occurs due to the refractive index discontinuities located between muscle fibers and interstitial fluid. To study the possibility of reducing light scattering inside muscle, we consider its spectral transmittance evolution during an immersion treatment with an optical clearing solution containing ethanol, glycerol, and distilled water. Our methodology consists of registering spectral transmittance of muscle samples while immersed in that solution. With the spectral data collected, we represent the transmittance evolution for some wavelengths during the treatment applied. Additionally, we study the variations that the treatment has caused on the samples regarding tissue refractive index and mass. By analyzing microscopic photographs of tissue cross section, we can also verify changes in the internal arrangement of muscle fibers caused by the immersion treatment. Due to a mathematical model that we develop, we can explain the variations observed in the studied parameters and estimate the amount of optical clearing agent that has diffused into the tissue samples during the immersion treatment. At the end of the study, we observe and explain the improvement in tissue spectral transmittance, which is approximately 65% after 20 min.

  5. Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish.

    PubMed

    Fujii, Tomoaki; Tsunesumi, Shin-ichiro; Yamaguchi, Kiyoshi; Watanabe, Sumiko; Furukawa, Yoichi

    2011-01-01

    Modifications of histone tails are involved in the regulation of a wide range of biological processes including cell cycle, cell survival, cell division, and cell differentiation. Among the modifications, histone methylation plays a critical role in cardiac and skeletal muscle differentiation. In our earlier studies, we found that SMYD3 has methyltransferase activity to histone H3 lysine 4, and that its up-regulation is involved in the tumorigenesis of human colon, liver, and breast. To clarify the role of Smyd3 in development, we have studied its expression patterns in zebrafish embryos and the effect of its suppression on development using Smyd3-specific antisense morpholino-oligonucleotides. We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle.

  6. Effects of hypertonic perfusion on the ultrastructure of frog cardiac muscle.

    PubMed

    Hatae, J; Kawata, H

    1978-11-01

    The ultrastructural changes induced by hypertonic perfusion were investigated using the ventricular muscle of the bullfrog. It was demonstrated that the fixative tonicity critically affects the ultrastructure. Effects of sucrose-, NaCl- and urea-hypertonicities were investigated and compared. In both sucrose- and NaCl-hypertonic media, although the cardiac muscle strongly shrank and the extracellular spaces markedly increased according to increasing tonicity the width of the intercalated disc cleft remained unchanged and the cleft was never separated even in 3 times hypertonicity. The sucrose-hypertonicity made the feature of the fine structure extremely obscure and the electron densities in both the Z-line and the intercalated disc region markedly decreased. When both the perfusate and fixative were made hypertonic by urea, which is known to easily penetrate the cell membrane, a shrinkage of the myocardial cells was observed but to a lesser extent as compared with sucrose or NaCl. The striation pattern was disordered in this condition though the intercalated discs were never affected.

  7. 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

  8. Impact of transglutaminase on the textural, physicochemical, and structural properties of chicken skeletal, smooth, and cardiac muscles.

    PubMed

    Ahhmed, Abdulatef M; Nasu, Tetsuo; Muguruma, Michio

    2009-12-01

    This study examined the effects of microbial transglutaminase (MTG; 3.1mg/ml) on chicken skeletal, smooth, and cardiac muscles; the meat containing the different muscle types was shaped into sausages and treated at 40°C and/or 78°C for 30min. Although the three muscle types were obtained from the same bird, the effects of MTG addition were not uniform. All the muscle types showed a significant increase in the breaking strength (P<0.01), but skeletal muscle exhibited the maximum increase. All samples showed a decrease in the fluorescence intensity and a significant reduction in the concentration of proteins that were extracted in a high ionic strength solution (P<0.05). Scanning electron microscopy images and histological studies revealed that different muscle types had different physical structures and frameworks after MTG treatment, which is a reflection of the differences in the reaction specificity of MTG with different muscle proteins. Histological studies revealed that the reactions of MTG with meat proteins are both exogenous and endogenous. Cooking loss data suggested that MTG did not have any negative effect on water retention during cooking. MTG appears to be a functional and contributive substance since the results suggest that MTG can function on all muscle types that are mechanically processed for different industrial applications. MTG aggregates muscle proteins in different ways that improve their organoleptic properties such as texture, appearance, and water retention.

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

    PubMed

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

    1998-07-01

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

  10. Magnetic resonance diagnosis of tarsal tunnel syndrome due to flexor digitorum accessorius longus and peroneocalcaneus internus muscles.

    PubMed

    Duran-Stanton, Amelia M; Bui-Mansfield, Liem T

    2010-01-01

    Anomalous muscles of the ankle are common. Although they are often asymptomatic, they can sometimes cause tarsal tunnel syndrome. We report a case of tarsal tunnel syndrome due to flexor digitorum accessorius longus and peroneocalcaneus internus muscles diagnosed on magnetic resonance imaging. Recognition of the most common accessory muscles of the ankle on magnetic resonance imaging and tarsal tunnel syndrome are also reviewed.

  11. 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

    2016-01-01

    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.

  12. Emerging Cardiac Imaging Modalities for the Early Detection of Cardiotoxicity due to Anticancer Therapies.

    PubMed

    López-Fernández, Teresa; Thavendiranathan, Paaladinesh

    2017-02-08

    The undeniable advances in the field of oncology have finally led to a decrease in overall cancer-related mortality. However, this population of long-term cancer survivors is now facing a shift toward a substantial increase in cardiovascular morbidity and mortality. Because the development of overt cardiotoxicity can be associated with poor outcomes, preclinical identification of cardiac toxicity is important. This will promote early instauration of treatments to prevent overt heart dysfunction and allow oncologists to continue cancer therapy in an uninterrupted manner. Surveillance strategies for the early detection of cardiac injury include cardiac imaging and biomarkers during treatment. In this review, we outline existing cardiac imaging modalities to detect myocardial changes in patients undergoing cancer treatment and in survivors, and their strengths and limitations.

  13. A 3-D cardiac muscle construct for exploring adult marrow stem cell based myocardial regeneration.

    PubMed

    Valarmathi, Mani T; Goodwin, Richard L; Fuseler, John W; Davis, Jeffrey M; Yost, Michael J; Potts, Jay D

    2010-04-01

    Adult bone marrow stromal cells (BMSCs) are capable of differentiating into cardiomyocyte-like cells in vitro and contribute to myocardial regeneration in vivo. Consequently, BMSCs may potentially play a vital role in cardiac repair and regeneration. However, this concept has been limited by inadequate and inconsistent differentiation of BMSCs into cardiomyocytes along with poor survival and integration of neo-cardiomyocytes after implantation into ischemic myocardium. In order to overcome these barriers and to explore adult stem cell based myocardial regeneration, we have developed an in vitro model of three-dimensional (3-D) cardiac muscle using rat ventricular embryonic cardiomyocytes (ECMs) and BMSCs. When ECMs and BMSCs were seeded sequentially onto a 3-D tubular scaffold engineered from topographically aligned type I collagen-fibers and cultured in basal medium for 7, 14, 21, or 28 days, the maturation and co-differentiation into a cardiomyocyte lineage was observed. Phenotypic induction was characterized at morphological, immunological, biochemical and molecular levels. The observed expression of transcripts coding for cardiomyocyte phenotypic markers and the immunolocalization of cardiomyogenic lineage-associated proteins revealed typical expression patterns of neo-cardiomyogenesis. At the biochemical level differentiating cells exhibited appropriate metabolic activity and at the ultrastructural level myofibrillar and sarcomeric organization were indicative of an immature phenotype. Our 3-D co-culture system sustains the ECMs in vitro continuum of differentiation process and simultaneously induces the maturation and differentiation of BMSCs into cardiomyocyte-like cells. Thus, this novel 3-D co-culture system provides a useful in vitro model to investigate the functional role and interplay of developing ECMs and BMSCs during cardiomyogenic differentiation.

  14. Dihydropyridine-sensitive calcium channels in cardiac and skeletal muscle membranes: studies with antibodies against the. cap alpha. subunits

    SciTech Connect

    Takahashi, M.; Catterall, W.A.

    1987-08-25

    Polyclonal antibodies (PAC-2) against the purified skeletal muscle calcium channel were prepared and shown to be directed against ..cap alpha.. subunits of this protein by immunoblotting and immunoprecipitation. These polypeptides have an apparent molecular weight of 162,000 without reduction of disulfide bonds. Under conditions where the functional properties of the purified skeletal muscle calcium channel are retained, ..beta.. subunits (M/sub r/ 50,000) and lambda subunits (M/sub r/ 33,000) are coprecipitated, demonstrating specific noncovalent association of these three polypeptides in the purified skeletal muscle channel. PAC-2 immunoprecipitated cardiac calcium channels labeled with (/sup 3/H)isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5-(methoxycarbonyl)pyridine-3-carboxylate ((/sup 3/H)PN200-110) at a 3-fold higher concentration than skeletal muscle channels. Preincubation with cardiac calcium channels blocked only 49% of the immunoreactivity of PAC-2 toward skeletal muscle channels, indicating that these two proteins have both homologous and distinct epitopes. The immunoreactive component of the cardiac calcium channel was identified by immunoprecipitation and polyacrylamide gel electrophoresis as a polypeptide with an apparent molecular weight of 170,000 before reduction of disulfide bonds and 141,000 after reduction, in close analogy with the properties of the ..cap alpha../sub 2/ subunits of the skeletal muscle channel. The calcium channels were radiolabeled with /sup 32/P and /sup 125/I. It is concluded that these two calcium channels have a homologous, but distinct, ..cap alpha.. subunit as a major polypeptide component.

  15. Fulminating gas-forming psoas muscle abscess due to Klebsiella pneumoniae following a deep neck infection.

    PubMed

    Jang, T N; Juang, G D; Fung, C P

    1997-02-01

    Psoas muscle abscess due to Klebsiella pneumoniae infection is rare. We report a 55-year-old diabetic man who presented with progressive back pain of 1 month's duration. The patient had undergone surgical drainage for a deep neck infection with K. pneumoniae 43 days previously. On the present admission, physical examination revealed tenderness over the anterior upper aspect of both thighs, and computed tomography showed pneumoretroperitoneum dissecting the bilateral iliopsoas muscles. Parenteral administration of antibiotics was started immediately. Due to the patient's poor health status, we opted for repeated computed tomographic and sonographic-guided percutaneous drainage rather than surgical drainage. Blood and pus cultures revealed only K. pneumoniae. The patient recovered without significant sequelae. This report stresses the risk of metastatic infections caused by K. pneumoniae, especially in diabetic patients. Our experience suggests that repeated percutaneous drainage is feasible in cases of severe iliopsoas abscess, especially when risks associated with surgery are high.

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

    PubMed

    Watanabe, Nobuhiro; Hotta, Harumi

    2016-01-01

    Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm(2)) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: -56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = -0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: -9 to +3 bpm, p < 0.0001) but not the vagus nerve (range: -75 to +30 bpm, p = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = -0.62, p = 0.0066). These

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

    PubMed Central

    Watanabe, Nobuhiro; Hotta, Harumi

    2017-01-01

    Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm2) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: −56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = −0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: −9 to +3 bpm, p < 0.0001) but not the vagus nerve (range: −75 to +30 bpm, p = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = −0.62, p = 0

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

    PubMed

    Malecot, C O; Katzung, B G

    1987-04-01

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

  19. AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism

    PubMed Central

    Sung, Miranda M.; Zordoky, Beshay N.; Bujak, Adam L.; Lally, James S.V.; Fung, David; Young, Martin E.; Horman, Sandrine; Miller, Edward J.; Light, Peter E.; Kemp, Bruce E.; Steinberg, Gregory R.; Dyck, Jason R.B.

    2015-01-01

    Aims AMP-activated protein kinase (AMPK) is thought to be a central player in regulating myocardial metabolism and its activation has been shown to inhibit cardiac hypertrophy. Recently, mice with muscle-specific deletion of AMPK β1/β2 subunits (AMPKβ1β2-deficient mice, β1β2M-KO) have been generated and possess <10% of normal AMPK activity in muscle. However, how/if dramatic AMPK deficiency alters cardiac metabolism, function, or morphology has not been investigated. Therefore, the aim of this study was to determine whether a significant loss of AMPK activity alters cardiac function, metabolism, and hypertrophy, and whether this may play a role in the pathogenesis of heart failure. Methods and results β1β2M-KO mice exhibit an approximate 25% reduction in systolic and diastolic function compared with wild-type (WT) littermates. Despite the well-documented role of AMPK in controlling myocardial energy metabolism, there was no difference in basal glucose and fatty acid oxidation rates between β1β2M-KO and WT mice. However, there was reduced AMPK-mediated phosphorylation of troponin I in β1β2M-KO and reduced ventricular cell shortening in the presence of low Ca2+, which may explain the impaired cardiac function in these mice. Interestingly, β1β2M-KO mice did not display any signs of compensatory cardiac hypertrophy, which could be attributed to impaired activation of p38 MAPK. Conclusions β1β2M-KO mice display evidence of dilated cardiomyopathy. This is the first mouse model of AMPK deficiency that demonstrates cardiac dysfunction in the absence of pathological stress and provides insights into the role of AMPK in regulating myocardial function, metabolism, hypertrophy, and the progression to heart failure. PMID:26023060

  20. Regulation of energy consumption in cardiac muscle: analysis of isometric contractions.

    PubMed

    Landesberg, A; Sideman, S

    1999-03-01

    The well-known linear relationship between oxygen consumption and force-length area or the force-time integral is analyzed here for isometric contractions. The analysis, which is based on a biochemical model that couples calcium kinetics with cross-bridge cycling, indicates that the change in the number of force-generating cross bridges with the change in the sarcomere length depends on the force generated by the cross bridges. This positive-feedback phenomenon is consistent with our reported cooperativity mechanism, whereby the affinity of the troponin for calcium and, hence, cross-bridge recruitment depends on the number of force-generating cross bridges. Moreover, it is demonstrated that a model that does not include a feedback mechanism cannot describe the dependence of energy consumption on the loading conditions. The cooperativity mechanism, which has been shown to determine the force-length relationship and the related Frank-Starling law, is shown here to provide the basis for the regulation of energy consumption in the cardiac muscle.

  1. The regulation of the calcium conductance of cardiac muscle by adrenaline.

    PubMed Central

    Reuter, H; Scholz, H

    1977-01-01

    1. The effect of adrenaline on the Ca-dependent slow inward current, Is, of mammalian cardiac muscle has been investigated by the voltage-clamp method. The mechanism of the increase in the conductance, gs, was analysed on the basis of a kinetic scheme (Hodgkin & Huxley, 1952) applicable to this system. 2. The rate constants alphad and betad, of activation of gs were not influenced by adrenaline, although the limiting conductance, gs, was greatly increased. 3. Reduction of [Ca]o from 1-8 to 0-2 mM decreased the amplitude of inward tail currents when gs was fully activated; however, the relative decrease of the current amplitude was the same with and without adrenaline. The reversal potential, ER, of Is was not changed by the drug. This indicates that the catecholamine has no influence on the selectivity of these conductance channels. 4. An increase in the number of functional conductance channels by adrenaline is discussed as a possible mechanism for the increase in Gs. PMID:839456

  2. Ryanodine modification of cardiac muscle responses to potassium-free solutions. Evidence for inhibition of sarcoplasmic reticulum calcium release

    PubMed Central

    1983-01-01

    To test whether ryanodine blocks the release of calcium from the sarcoplasmic reticulum in cardiac muscle, we examined its effects on the aftercontractions and transient depolarizations or transient inward currents developed by guinea pig papillary muscles and voltage-clamped calf cardiac Purkinje fibers in potassium-free solutions. Ryanodine (0.1-1.0 microM) abolished or prevented aftercontractions and transient depolarizations by the papillary muscles without affecting any of the other sequelae of potassium removal. In the presence of 4.7 mM potassium and at a stimulation rate of 1 Hz, ryanodine had only a small variable effect on papillary muscle force development and action potential characteristics. In calf Purkinje fibers, ryanodine (1 nM-1 microM) completely blocked the aftercontractions and transient inward currents without altering the steady state current-voltage relationship. Ryanodine also abolished the twitch in potassium-free solutions, but it enhanced the tonic force during depolarizing voltage- clamp steps. This latter effect was dependent on the combination of ryanodine and potassium-free solutions. The slow inward current was not blocked by 1 microM ryanodine, but ryanodine did appear to abolish an outward current that remained in the presence of 0.5 mM 4- aminopyridine. Our observations are consistent with the hypothesis that ryanodine, by inhibiting the release of calcium from the sarcoplasmic reticulum, prevents the oscillations in intracellular calcium that activate the transient inward currents and aftercontractions associated with calcium overload states. PMID:6631403

  3. Effects of muscle potential depression and muscle stimulation caused by different insulation coating configurations on cardiac pacemakers.

    PubMed

    Yajima, Toshimi; Yamada, Kenichi; Okubo, Naoko; Nitta, Takashi; Ochi, Masami; Shimizu, Kazuo

    2005-01-01

    Insulation coating was added to the external pacemaker surface to prevent unnecessary electric current leakage to the periphery because the pulse generator body is used as an anode in unipolar pacing. However, a model without insulation coating has recently been used, so we studied the effects on muscle potential inhibition and muscle stimulation of pacemakers in unipolar pacing with different parts of the pacemaker body coated with insulation. Case comparisons were made for the following models: insulated except for the center of one side (33, group C), insulated except for the peripheral zone (10, group E), and noncoated models (11, group N). The muscle detection threshold voltage, muscle detection threshold pulse duration, muscle potential sensing threshold (MP), and lead resistance were measured. A comparison was made of the amount of energy (En) needed to reach the muscle stimulation threshold. For MP values, there was no significant statistical difference between group C and E, whereas a significant difference was present between group C and N and between group E and N. For En values, there was a significant difference between group C and E and between group C and N, but there was no significant difference between group E and N. The muscle potential sensing threshold dose not have a change in group E and much muscle stimulation energy is needed. The muscle potential sensing threshold was low in group N, requiring much muscle stimulation energy. Based on these results, it is usually not necessary to coat the pacemaker with insulation for unipolar pacing.

  4. Cardiac failure due to a giant desmoid tumour of the posterior mediastinum.

    PubMed

    Bouchikh, Mohammed; Arame, Alex; Riquet, Marc; Le Pimpec-Barthes, Françoise

    2013-12-01

    We report a rare case of a giant desmoid tumour responsible for cardiac and respiratory failure. Complete removal was decided upon, despite an initial failure in another centre because of symptom severity. In such cases, wide local resection remains the best therapeutic approach, but the risk of local recurrence is high. Literature review confirms the exceptional presentation and the benefit of aggressive surgery.

  5. Implantable Cardiac Defibrillator Pocket Infection Due to a Previously Undescribed Cupriavidus Species▿

    PubMed Central

    Christensen, Joshua B.; Vitko, Nicholas P.; Voskuil, Martin I.; Castillo-Mancilla, Jose R.

    2010-01-01

    The genus Cupriavidus consists of Gram-negative, nonfermenting bacteria most of which are environmental organisms, though some species have been associated with human disease. We report the recovery and identification of an isolate that represents a previously undescribed species of Cupriavidus from an implantable cardiac defibrillator pocket infection. PMID:20427695

  6. 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.

  7. 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

  8. Effects of ONO-1101, a novel beta-antagonist, on action potential and membrane currents in cardiac muscle.

    PubMed

    Muraki, K; Nakagawa, H; Nagano, N; Henmi, S; Kawasumi, H; Nakanishi, T; Imaizumi, K; Tokuno, T; Atsuki, K; Imaizumi, Y; Watanabe, M

    1996-08-01

    Direct effects of ONO-1101 ¿(-)-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-3-[4-[(S) -2-hydroxy-3-(2-morpholino carbonylamino)ethylamino] propoxy]phenylpropionate monohydrochloride), a novel beta-antagonist, on action potential parameters and membrane currents, and its beta adrenoceptor antagonism were examined in cardiac muscle. Action potential-parameters in papillary muscle of reserpinized animals and membrane currents recorded from single myocytes obtained from guinea pig and rabbit hearts were not affected by 1 to 100 microM ONO-1101. On the other hand, ONO-1101 markedly inhibited the potentiation of Ca current by isoproterenol in single cardiac myocytes of the guinea pig. The concentration-response relationship of Ca current for isoproterenol was shifted to the right. This effect resembled that of esmolol, which is also a beta adrenoceptor antagonist. A Schild plot analysis revealed the slope and pA2 value of each antagonist (ONO-1101, 0.94, 8.0; and esmolol, 0.98, 7.3, respectively) and demonstrated that ONO-1101 is about 5 times more potent than esmolol as a beta-antagonist. Two other effects of isoproterenol: 1) potentiation of delayed rectifier K current and 2) activation of chloride current, were also inhibited by ONO-1101. The time required for 50% removal of beta-antagonism of ONO-1101 and esmolol after the washout was estimated as 4 and 6 min, respectively, in depolarized papillary muscle. These results suggest that ONO-1101 is a potent beta-antagonist whose effects were removed quickly by washout. When applied at what is thought to be a clinical dosage, ONO-1101 had no direct effects on action potential-parameters and membrane currents in cardiac muscle. These characteristics of ONO-1101 suggest that this agent may be effective in clinical use.

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

    PubMed

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

    2015-04-15

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

  10. 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.

  11. 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.

  12. The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle.

    PubMed

    Bodnár, Mandy; Schlichthörl, Günter; Daut, Jürgen

    2015-05-01

    We studied the potassium current flowing through TREK-1 channels in rat cardiac ventricular myocytes. We separated the TREK-1 current from other current components by blocking most other channels with a blocker cocktail. We tried to inhibit the TREK-1 current by activating protein kinase A (PKA) with a mixture of forskolin and isobutyl-methylxanthine (IBMX). Activation of PKA blocked an outwardly rectifying current component at membrane potentials positive to -40 mV. At 37 °C, application of forskolin plus IBMX reduced the steady-state outward current measured at positive voltages by about 52 %. Application of the potassium channel blockers quinidine or tetrahexylammonium also reduced the steady-state outward current by about 50 %. Taken together, our results suggest that the increase in temperature from 22 to 37 °C increased the TREK-1 current by a factor of at least 5 and that the average density of the TREK-1 current in rat cardiomyocytes at 37 °C is about 1.5 pA/pF at +30 mV. The contribution of TREK-1 to the action potential was assessed by using a dynamic patch clamp technique. After subtraction of simulated TREK-1 currents, action potential duration at 50 or 90 % repolarisation was increased by about 12 %, indicating that TREK-1 may be functionally important in rat ventricular muscle. During sympathetic stimulation, inhibition of TREK-1 channels via PKA is expected to prolong the action potential primarily in subendocardial myocytes; this may decrease the transmural dispersion of repolarisation and thus may serve to prevent the occurrence of arrhythmias.

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

    PubMed

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

    2015-05-01

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

  14. Impaired contractile function due to decreased cardiac myosin binding protein C content in the sarcomere

    PubMed Central

    Cheng, Y.; Wan, X.; McElfresh, T. A.; Chen, X.; Gresham, K. S.; Rosenbaum, D. S.; Chandler, M. P.

    2013-01-01

    Mutations in cardiac myosin binding protein C (MyBP-C) are a common cause of familial hypertrophic cardiomyopathy (FHC). The majority of MyBP-C mutations are expected to reduce MyBP-C expression; however, the consequences of MyBP-C deficiency on the regulation of myofilament function, Ca2+ homeostasis, and in vivo cardiac function are unknown. To elucidate the effects of decreased MyBP-C expression on cardiac function, we employed MyBP-C heterozygous null (MyBP-C+/−) mice presenting decreases in MyBP-C expression (32%) similar to those of FHC patients carrying MyBP-C mutations. The levels of MyBP-C phosphorylation were reduced 53% in MyBP-C+/− hearts compared with wild-type hearts. Skinned myocardium isolated from MyBP-C+/− hearts displayed decreased cross-bridge stiffness at half-maximal Ca2+ activations, increased steady-state force generation, and accelerated rates of cross-bridge recruitment at low Ca2+ activations (<15% and <25% of maximum, respectively). Protein kinase A treatment abolished basal differences in rates of cross-bridge recruitment between MyBP-C+/− and wild-type myocardium. Intact ventricular myocytes from MyBP-C+/− hearts displayed abnormal sarcomere shortening but unchanged Ca2+ transient kinetics. Despite a lack of left ventricular hypertrophy, MyBP-C+/− hearts exhibited elevated end-diastolic pressure and decreased peak rate of LV pressure rise, which was normalized following dobutamine infusion. Furthermore, electrocardiogram recordings in conscious MyBP-C+/− mice revealed prolonged QRS and QT intervals, which are known risk factors for cardiac arrhythmia. Collectively, our data show that reduced MyBP-C expression and phosphorylation in the sarcomere result in myofilament dysfunction, contributing to contractile dysfunction that precedes compensatory adaptations in Ca2+ handling, and chamber remodeling. Perturbations in mechanical and electrical activity in MyBP-C+/− mice could increase their susceptibility to cardiac

  15. Is skeletal muscle luxury perfusion the main hemodynamic effect of high-dose insulin in cardiac surgery?

    PubMed

    Lindholm, L; Nilsson, B; Kirnö, K; Sellgren, J; Nilsson, F; Jeppsson, A

    2000-08-01

    Insulin, in combination with glucose and potassium (GIK), can be used in heart surgery to improve hemodynamic performance. This study evaluates the role of skeletal muscle vasodilation in hemodynamic effects of high-dose GIK therapy early after coronary surgery. Thirty-three male patients undergoing coronary artery bypass grafting were included in a prospective, randomized and controlled study. Eleven patients received infusions of mixed amino acids (11.4 g) and insulin solution (225 IU insulin, glucose with the glucose clamp technique, and potassium), 11 patients received infusions of mixed amino acids (11.4 g) and 11 patients served as control subjects. During combined insulin and amino acid infusion, cardiac output increased by 13+/-3% (+0.6+/-0.2 L x min(-1)) and systemic vascular resistance decreased by 24+/-3% (-320+/-46 dyn x s x cm(-5)). The changes differed from those in the control group (CO: -0.2+/-0.1 L x min(-1), p < 0.05; SVR: +136+/-42 dyn x s x cm(-5), p < 0.05). Changes in skeletal muscle perfusion and leg vascular resistance did not differ significantly among the groups. At most, changes in leg blood flow could explain 40% of the changes in cardiac output. Skeletal muscle luxury perfusion is not the main hemodynamic effect of high-dose insulin in the early postoperative period after coronary surgery.

  16. Fast lidocaine block of cardiac and skeletal muscle sodium channels: one site with two routes of access.

    PubMed Central

    Zamponi, G W; Doyle, D D; French, R J

    1993-01-01

    We have studied the block by lidocaine and its quaternary derivative, QX-314, of single, batrachotoxin (BTX)-activated cardiac and skeletal muscle sodium channels incorporated into planar lipid bilayers. Lidocaine and QX-314, applied to the intracellular side, appear to induce incompletely resolved, rapid transitions between the open and the blocked state of BTX-activated sodium channels from both heart and skeletal muscle. We used amplitude distribution analysis (Yellen, G. 1984. J. Gen. Physiol. 84:157-186.) to estimate the rate constants for block and unblock. Block by lidocaine and QX-314 from the cytoplasmic side exhibits rate constants with similar voltage dependence. The blocking rate increases with depolarization, and the unblocking rate increases with hyperpolarization. Fast lidocaine block was virtually identical for sodium channels from skeletal (rat, sheep) and cardiac (beef, sheep) muscle. Lidocaine block from the extracellular side occurred at similar concentrations. However, for externally applied lidocaine, the blocking rate was voltage-independent, and was proportional to concentration of the uncharged, rather than the charged, form of the drug. In contrast, unblocking rates for internally and externally applied lidocaine were identical in magnitude and voltage dependence. Our kinetic data suggest that lidocaine, coming from the acqueous phase on the cytoplasmic side in the charged form, associates and dissociates freely with the fast block effector site, whereas external lidocaine, in the uncharged form, approaches the same site via a direct, hydrophobic path. PMID:8396459

  17. 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

    2009-05-06

    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.

  18. Cooperative Cross-Bridge Activation of Thin Filaments Contributes to the Frank-Starling Mechanism in Cardiac Muscle

    PubMed Central

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

    2009-01-01

    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 [Ca2+] and [Vi]. Increasing [Vi] (decreased force) reduced the pCa50 of force-[Ca2+] relations at 2.3 and 2.0 μm SL, with little effect on slope (nH). When maximum force was inhibited to ∼40%, the effects of SL on force were diminished at lower [Ca2+], whereas at higher [Ca2+] (pCa < 5.6) the relative influence of SL on force increased. In contrast, force inhibition to ∼20% significantly reduced the sensitivity of force-[Ca2+] 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

  19. Modifications of muscle synergies and spinal maps due to absence of visual feedback in patients with unilateral vestibular disease.

    PubMed

    Monaco, V; Martelli, D; Nacci, A; Fattori, B; Berrettini, S; Micera, S

    2012-01-01

    The present study aimed at describing the modifications of muscle synergies and spinal activity due to the absence of visual feedback, in patients affected by unilateral vestibular disease. Patients were tested both during unperturbed quite stance and walking while the activity of 7 bilateral muscles, from the leg to the trunk, were recorded for the estimation of muscle synergies and spinal activity. Results showed that during locomotion the absence of visual feedback did not significantly modify either the principal roles underlying muscle activity (i.e., synergies) or the spinal bursts. Conversely, during the upright stance, the absence of visual feedback involved a significant coupling of ankle dorsi- and plantar-flexor muscle groups with a consequent shift of the motoneuronal (MN) activity toward most caudal segments. Results revealed that the muscle synergies are able to document an increased activity of sensory-motor afferences leading a more intense role of the forward based mechanism underlying balance control in vestibular patients.

  20. Phosphofructo-1-Kinase Deficiency Leads to a Severe Cardiac and Hematological Disorder in Addition to Skeletal Muscle Glycogenosis

    PubMed Central

    García, Miguel; Pujol, Anna; Ruzo, Albert; Riu, Efrén; Ruberte, Jesús; Arbós, Anna; Serafín, Anna; Albella, Beatriz; Felíu, Juan Emilio; Bosch, Fátima

    2009-01-01

    Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm−/−). Here, we show that Pfkm−/− mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm−/− mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm−/− mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm−/− mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies. PMID:19696889

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

    PubMed

    Swiderski, R E; Solursh, M

    1990-07-01

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

  2. Chronic Alcohol Intoxication Is Not Accompanied by an Increase in Calpain Proteolytic Activity in Cardiac Muscle of Rats.

    PubMed

    Gritsyna, Yu V; Salmov, N N; Bobylev, A G; Fadeeva, I S; Fesenko, N I; Sadikova, D G; Kukushkin, N I; Podlubnaya, Z A; Vikhlyantsev, I M

    2017-02-01

    Enzymatic activity of Ca2+-dependent calpain proteases as well as the content and gene expression of μ-calpain (activated by micromolar calcium ion concentrations), calpastatin (inhibitor of calpains), and titin (substrate for calpains) were investigated in cardiac muscles of rats subjected to chronic alcoholization for 3 and 6 months. There was no increase in the "heart weight/body weight" parameter indicating development of heart hypertrophy in the alcoholized rats, while a decreasing trend was observed for this parameter in the rats after 6-month modeling of alcoholic cardiomyopathy, which indicated development of atrophic changes in the myocardium. Fluorometric measurements conducted using the Calpain Activity Assay Kit did not reveal any changes in total calpain activity in protein extracts of cardiac muscles of the rats alcoholized for 3 and 6 months. Western blot analysis did not show reliable changes in the contents of μ-calpain and calpastatin, and SDS-PAGE did not reveal any decrease in the titin content in the myocardium of rats after the chronic alcohol intoxication. Autolysis of μ-calpain was also not verified, which could indicate that proteolytic activity of this enzyme in myocardium of chronically alcoholized rats is not enhanced. Using Pro-Q Diamond staining, changes in phosphorylation level of titin were not detected in cardiac muscle of rats after chronic alcoholization during three and six months. A decrease in µ-calpain and calpastatin mRNA content (~1.3-fold, p ≤ 0.01 and ~1.9-fold, p ≤ 0.01, respectively) in the myocardium of rats alcoholized for 3 months and decrease in calpastatin mRNA (~1.4-fold, p ≤ 0.01) in animals alcoholized for 6 months was demonstrated using real-time PCR. These results indicate negative effect of chronic alcohol intoxication on expression of the abovementioned genes.

  3. Molecular defects in cardiac myofibrillar proteins due to thyroid hormone imbalance and diabetes.

    PubMed

    Machackova, Jarmila; Barta, Judit; Dhalla, Naranjan S

    2005-12-01

    The heart very often becomes a victim of endocrine abnormalities such as thyroid hormone imbalance and insulin deficiency, which are manifested in a broad spectrum of cardiac dysfunction from mildly compromised function to severe heart failure. These functional changes in the heart are largely independent of alterations in the coronary arteries and instead reside at the level of cardiomyocytes. The status of cardiac function reflects the net of underlying subcellular modifications induced by an increase or decrease in thyroid hormone and insulin plasma levels. Changes in the contractile and regulatory proteins constitute molecular and structural alterations in myofibrillar assembly, called myofibrillar remodeling. These alterations may be adaptive or maladaptive with respect to the functional and metabolic demands on the heart as a consequence of the altered endocrine status in the body. There is a substantial body of information to indicate alterations in myofibrillar proteins including actin, myosin, tropomyosin, troponin, titin, desmin, and myosin-binding protein C in conditions such as hyperthyroidism, hypothyroidism, and diabetes. The present article is focussed on discussion how myofibrillar proteins are altered in response to thyroid hormone imbalance and lack of insulin or its responsiveness, and how their structural and functional changes explain the contractile defects in the heart.

  4. Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency.

    PubMed

    Lee, Eun-Jeong; De Winter, Josine M; Buck, Danielle; Jasper, Jeffrey R; Malik, Fady I; Labeit, Siegfried; Ottenheijm, Coen A; Granzier, Henk

    2013-01-01

    The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT) and nebulin deficient (NEB KO) mice. Nebulin is a sarcomeric protein that when absent (NEB KO mouse) or present at low levels (nemaline myopathy (NM) patients with NEB mutations) causes muscle weakness. We studied the effect of fast skeletal troponin activation on WT muscle and tested whether it might be a therapeutic mechanism to increase muscle strength in nebulin deficient muscle. We measured tension-pCa relations with and without added CK-2066260. Maximal active tension in NEB KO tibialis cranialis fibers in the absence of CK-2066260 was ∼60% less than in WT fibers, consistent with earlier work. CK-2066260 shifted the tension-calcium relationship leftwards, with the largest relative increase (up to 8-fold) at low to intermediate calcium levels. This was a general effect that was present in both WT and NEB KO fiber bundles. At pCa levels above ∼6.0 (i.e., calcium concentrations <1 µM), CK-2066260 increased tension of NEB KO fibers to beyond that of WT fibers. Crossbridge cycling kinetics were studied by measuring k(tr) (rate constant of force redevelopment following a rapid shortening/restretch). CK-2066260 greatly increased k(tr) at submaximal activation levels in both WT and NEB KO fiber bundles. We also studied the sarcomere length (SL) dependence of the CK-2066260 effect (SL 2.1 µm and 2.6 µm) and found that in the NEB KO fibers, CK-2066260 had a larger effect on calcium sensitivity at the long SL. We conclude that fast skeletal muscle troponin activation increases force at submaximal activation in both wildtype and NEB KO fiber bundles and, importantly, that this troponin activation is a potential therapeutic mechanism for increasing force in NM and other skeletal muscle diseases with loss of muscle strength.

  5. 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

  6. Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

    PubMed Central

    Gasser, R N; Vaughan-Jones, R D

    1990-01-01

    1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. Ion-selective microelectrodes recorded potassium (Ks+) and pH (pHs) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in Ks+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min). 2. The sulphonylurea compounds, glibenclamide (200 microM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of Ks+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas. 3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 microM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic Ks+ accumulation is not fuelled by the background K+ current [iK1] which was shown, as expected, to be Ba2+ sensitive). 5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pHo in the absence of DOG) lengthened rather than shortened the AP. 6. The

  7. Mechanisms of force inhibition by halothane and isoflurane in intact rat cardiac muscle

    PubMed Central

    Hanley, Peter J; Loiselle, Denis S

    1998-01-01

    did not restore peak force. Moreover, halothane (1 %) and isoflurane (1.6 %) each reduced maximal Ca2+-activated force (attained using ryanodine tetani and a high external [Ca2+]) by around 15 %. We conclude that the negative inotropic actions of halothane and isoflurane on intact cardiac muscle reflect both reduced availability of Ca2+ and decreased responsiveness of the contractile system to Ca2+. The inhibitory action of the volatile anaesthetics on mitochondrial function does not contribute significantly to the negative inotropy but may lead to changes in cellular autofluorescence and misinterpretation of fluorescent Ca2+ indicator signals. PMID:9481684

  8. The Neuromuscular Transform of the Lobster Cardiac System Explains the Opposing Effects of a Neuromodulator on Muscle Output

    PubMed Central

    Williams, Alex H.; Calkins, Andrew; O'Leary, Timothy; Symonds, Renee; Marder, Eve

    2013-01-01

    Motor neuron activity is transformed into muscle movement through a cascade of complex molecular and biomechanical events. This nonlinear mapping of neural inputs to motor behaviors is called the neuromuscular transform (NMT). We examined the NMT in the cardiac system of the lobster Homarus americanus by stimulating a cardiac motor nerve with rhythmic bursts of action potentials and measuring muscle movements in response to different stimulation patterns. The NMT was similar across preparations, which suggested that it could be used to predict muscle movement from spontaneous neural activity in the intact heart. We assessed this possibility across semi-intact heart preparations in two separate analyses. First, we performed a linear regression analysis across 122 preparations in physiological saline to predict muscle movements from neural activity. Under these conditions, the NMT was predictive of contraction duty cycle but was unable to predict contraction amplitude, likely as a result of uncontrolled interanimal variability. Second, we assessed the ability of the NMT to predict changes in motor output induced by the neuropeptide C-type allatostatin. Wiwatpanit et al. (2012) showed that bath application of C-type allatostatin produced either increases or decreases in the amplitude of the lobster heart contractions. We show that an important component of these preparation-dependent effects can arise from quantifiable differences in the basal state of each preparation and the nonlinear form of the NMT. These results illustrate how properly characterizing the relationships between neural activity and measurable physiological outputs can provide insight into seemingly idiosyncratic effects of neuromodulators across individuals. PMID:24133260

  9. Bradycardia during Transradial Cardiac Catheterization due to Catheter Manipulation: Resolved by Catheter Removal

    PubMed Central

    Kumar, Vishesh; Stys, Adam

    2017-01-01

    Purpose. To report the resolution of bradycardia encountered during transradial cardiac catheterization through the catheter pullback technique in two cases. Case Report. A 62-year-old male and an 81-year-old male underwent coronary angiogram to evaluate for coronary artery disease and as a result of positive stress test, respectively. Upon engagement of the FL 3.5 catheter into the ascending aorta through the transradial approach, the first case developed bradycardia with a heart rate of 39 beats per minute. The second case developed profound bradycardia with a heart rate of 25 beats per minute upon insertion of the 5 Fr FL 3.5 catheter near the right brachiocephalic trunk through the right radial access. Conclusion. Bradycardia can be subsided by removal of the catheter during catheter manipulation in patients undergoing transradial coronary angiogram if there is a suspicion of excessive stretching of aortic arch receptors and/or carotid sinus receptors. PMID:28348915

  10. Small Fractions of Muscular Dystrophy Embryonic Stem Cells Yield Severe Cardiac and Skeletal Muscle Defects in Adult Mouse Chimeras.

    PubMed

    Gonzalez, J Patrick; Kyrychenko, Sergii; Kyrychenko, Viktoriia; Schneider, Joel S; Granier, Celine J; Himelman, Eric; Lahey, Kevin C; Zhao, Qingshi; Yehia, Ghassan; Tao, Yuan-Xiang; Bhaumik, Mantu; Shirokova, Natalia; Fraidenraich, Diego

    2017-03-01

    Duchenne muscular dystrophy (DMD) is characterized by the loss of the protein dystrophin, leading to muscle fragility, progressive weakening, and susceptibility to mechanical stress. Although dystrophin-negative mdx mouse models have classically been used to study DMD, phenotypes appear mild compared to patients. As a result, characterization of muscle pathology, especially in the heart, has proven difficult. We report that injection of mdx embryonic stem cells (ESCs) into Wild Type blastocysts produces adult mouse chimeras with severe DMD phenotypes in the heart and skeletal muscle. Inflammation, regeneration and fibrosis are observed at the whole organ level, both in dystrophin-negative and dystrophin-positive portions of the chimeric tissues. Skeletal and cardiac muscle function are also decreased to mdx levels. In contrast to mdx heterozygous carriers, which show no significant phenotypes, these effects are even observed in chimeras with low levels of mdx ESC incorporation (10%-30%). Chimeric mice lack typical compensatory utrophin upregulation, and show pathological remodeling of Connexin-43. In addition, dystrophin-negative and dystrophin-positive isolated cardiomyocytes show augmented calcium response to mechanical stress, similar to mdx cells. These global effects highlight a novel role of mdx ESCs in triggering muscular dystrophy even when only low amounts are present. Stem Cells 2017;35:597-610.

  11. The influence of priming exercise on oxygen uptake, cardiac output, and muscle oxygenation kinetics during very heavy-intensity exercise in 9- to 13-yr-old boys.

    PubMed

    Barker, Alan R; Jones, Andrew M; Armstrong, Neil

    2010-08-01

    The present study examined the effect of priming exercise on O(2) uptake (Vo(2)) kinetics during subsequent very heavy exercise in eight 9- to 13-yr-old boys. We hypothesised that priming exercise would 1) elevate muscle O(2) delivery prior to the subsequent bout of very heavy exercise, 2) have no effect on the phase II Vo(2) tau, 3) elevate the phase II Vo(2) total amplitude, and 4) reduce the magnitude of the Vo(2) slow component. Each participant completed repeat 6-min bouts of very heavy-intensity cycling exercise separated by 6 min of light pedaling. During the tests Vo(2), muscle oxygenation (near infrared spectroscopy), and cardiac output (Q) (thoracic impedance) were determined. Priming exercise increased baseline muscle oxygenation and elevated Q at baseline and throughout the second exercise bout. The phase II Vo(2) tau was not altered by priming exercise (bout 1: 22 + or - 7 s vs. bout 2: 20 + or - 4 s; P = 0.30). However, the time constant describing the entire Vo(2) response from start to end of exercise was accelerated (bout 1: 43 + or - 8 s vs. bout 2: 36 + or - 5 s; P = 0.002) due to an increased total phase II Vo(2) amplitude (bout 1: 1.73 + or - 0.33 l/min vs. bout 2: 1.80 + or - 0.59 l/min; P = 0.002) and a reduced Vo(2) slow component amplitude (bout 1: 0.18 + or - 0.08 l/min vs. bout 2: 0.12 + or - 0.09 l/min; P = 0.048). These results suggest that phase II Vo(2) kinetics in young boys is principally limited by intrinsic muscle metabolic factors, whereas the Vo(2) total phase II and slow component amplitudes may be O(2) delivery sensitive.

  12. Status spasticus and psoas muscle edema due to anti-GAD antibody associated stiff-man syndrome.

    PubMed

    Maramattom, Boby Varkey

    2015-08-01

    Severe muscle rigidity and spasms are uncommon causes of Intensive Care Unit (ICU) admissions. Stiff-man syndrome (SMS) is a rare disorder characterized by continuous muscle spasms, axial muscle rigidity, "tin soldier gait," and continuous motor unit activity on electromyography. There are three clinical variants of SMS; stiff-limb syndrome, classical SMS, and paraneoplastic encephalomyelitis with rigidity and myoclonus. Three types of antibodies have been associated with SMS; however, anti-glutamic acid decarboxylase (GAD) antibodies are the most frequent and are seen in the idiopathic type of SMS. The spasms of SMS can be very disabling and severe enough to cause muscle ruptures and skeletal fractures. We present a case of anti-GAD positive SMS with "status spasticus" causing bilateral psoas myoedema and rhabdomyolysis due to repeated axial muscle jerking in a 64-year-old man and discuss the differential diagnosis of a "jerking patient in the ICU."

  13. Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias.

    PubMed

    ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Zhang, Mei Luo; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

    2008-01-01

    Starling's Law and the well-known end-systolic pressure-volume relationship (ESPVR) of the left ventricle reflect the effect of sarcomere length (SL) on stress (sigma) development and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL-[Ca2+]free relationships (sigma-SL-CaR) at submaximal [Ca2+] in intact and skinned trabeculae were similar, albeit that the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-CaR using a kinetic model where we assumed that the rates of Ca2+ binding by Troponin-C (Tn-C) and/or cross-bridge (XB) cycling are determined by SL, [Ca2+] or stress. We analyzed the correlation between the model results and steady state stress measurements at varied SL and [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that: (i) the dominant feedback mechanism is SL, stress or [Ca2+]-dependent; and (ii) the feedback mechanism regulates: Tn-C-Ca2+ affinity, XB kinetics or, unitary XB-force. The analysis strongly suggests that feedback of the number of strong XBs to cardiac Tn-C-Ca2+ affinity is the dominant mechanism that regulates XB recruitment. Application of this concept in a mathematical model of twitch-stress accurately reproduced the sigma-SL-CaR and the time course of twitch-stress as well as the time course of intracellular [Ca2+]i. Modeling of the response of the cardiac twitch to rapid stress changes using the above feedback model uniquely predicted the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. The above concept has important repercussions for the non-uniformly contracting heart in which arrhythmogenic Ca2+ waves arise from weakened areas in cardiac

  14. Combined administration of 5-HT2 and thromboxane A2 antagonists: effects on platelet aggregation and isolated cardiac muscle

    PubMed Central

    Shaw, Linda A; Batey, Andrew J; Coker, Susan J

    1997-01-01

    doses of each antagonist alone. Only the combination of ICI 170,809 (0.3 mg kg−1) and ICI 192,605 (0.3 mg kg−1 min−1) reduced the response to U46619 plus 5-HT plus collagen (7.6±1.4 Ω versus 15.0±0.5 Ω in controls). In rat isolated ventricular muscle preparations, ICI 170,809 increased the effective refractory period; e.g. from 39±4 to 86±18 ms, 10 min after adding 30 μM to left papillary muscles. ICI 192,605 did not increase the effective refractory period itself and did not alter the ability of ICI 170,809 to prolong the effective refractory period. In the presence of 100 μM ICI 192,605, ICI 170,809 (30 μM) increased the effective refractory period from 38±7 to 100±30 ms. These results indicate that the previously observed antiarrhythmic activity of combined administration of the higher doses of ICI 170,809 and ICI 192,605 is unlikely to be due to direct effects on cardiac muscle but could be a consequence of reduced platelet aggregation. PMID:9222543

  15. Senile Cardiac Calcification Syndrome: A Rare Case of Extensive Calcification of Left Ventricular Papillary Muscle

    PubMed Central

    Kim, Eun Jin; Song, Bong Gun; Sohn, Hyung Rae; Hong, Su-Min; Park, Dong Won; Heo, Seung Hye; Kim, Kye Yeon; Cho, Wook-Hyun; Choi, Suk-Koo

    2011-01-01

    Extensive papillary muscle calcification is uncommon and only scarce literature about causes and the clinical significance is available, whereas small calcific deposits are common findings in elderly people and are located most commonly at the apex. Papillary muscle calcification has been associated with coronary artery disease, dilated cardiomyopathy, mitral valve disease, hypercalcemia, and increased calcium phosphate product in end stage renal disease. We reported a rare case of extensive calcification of anterolateral papillary muscle diagnosed by echocardiography and multidetector computed tomography.

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

    PubMed

    Sivashanmugam, Preethi; Mullainadhan, Vigneswari; Karundevi, Balasubramanian

    2017-03-25

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

  17. Effect of epinephrine and lidocaine therapy on outcome after cardiac arrest due to ventricular fibrillation.

    PubMed

    Weaver, W D; Fahrenbruch, C E; Johnson, D D; Hallstrom, A P; Cobb, L A; Copass, M K

    1990-12-01

    One hundred ninety-nine patients with out-of-hospital cardiac arrest persisted in ventricular fibrillation after the first defibrillation attempt and were then randomly assigned to receive either epinephrine or lidocaine before the next two shocks. The resulting electrocardiographic rhythms and outcomes for each group of patients were compared for each group and also compared with results during the prior 2 years, a period when similar patients primarily received sodium bicarbonate as initial adjunctive therapy. Asystole occurred after defibrillation with threefold frequency after repeated injection of lidocaine (15 of 59, 25%) compared with patients treated with epinephrine (four of 55, 7%) (p less than 0.02). There was no difference in the proportion of patients resuscitated after treatment with either lidocaine or epinephrine (51 of 106, 48% vs. 50 of 93, 54%) and in the proportion surviving (18, 19% vs. 21, 20%), respectively. Resuscitation (64% vs. 50%, p less than 0.005) but not survival rates (24% vs. 20%) were higher during the prior 2-year period in which initial adjunctive drug treatment for persistent ventricular fibrillation primarily consisted of a continuous infusion of sodium bicarbonate. The negative effect of lidocaine or epinephrine treatment was explained in part by their influence on delaying subsequent defibrillation attempts. Survival rates were highest (30%) in a subset of patients who received no drug therapy between shocks. We conclude that currently recommended doses of epinephrine and lidocaine are not useful for improving outcome in patients who persist in ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Recurrent aborted sudden cardiac death with seizures and rhabdomyolysis due to bulimia-induced hypokalemia: report of one case.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia

    2014-06-01

    Recurrent vomiting due to bulimia associated with abuse of furosemide and laxatives causing severe hypokalemia may result in recurrent aborted sudden cardiac death (SCD) and seizures. We report a 25-year-old female with a history of bulimia associated with abuse of furosemide and laxatives since the age of 15 years, migraine since puberty, renal abscesses at age 20 y, and rhabdomyolysis of unknown cause at age 24 y. She experienced aborted SCD due to severe hypokalemia with symptomatic seizures at 21 and 25 years of age. Bulimia patients additionally taking laxatives or furosemide are at particular risk of SCD and rhabdomyolysis and require periodic determination of electrolytes, potassium substitution, and adequate psychiatric therapy and surveillance.

  19. 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...

  20. 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

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

    DOE PAGES

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; ...

    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

  2. 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.

  3. Effects of Mg2+ on Ca2+ handling by the sarcoplasmic reticulum in skinned skeletal and cardiac muscle fibres.

    PubMed

    Kabbara, A A; Stephenson, D G

    1994-10-01

    The influence of myoplasmic Mg2+ (0.05-10 mM) on Ca2+ accumulation (net Ca2+ flux) and Ca2+ uptake (pump-driven Ca2+ influx) by the intact sarcoplasmic reticulum (SR) was studied in skinned fibres from the toad iliofibularis muscle (twitch portion), rat extensor digitorum longus (EDL) muscle (fast twitch), rat soleus muscle (slow twitch) and rat cardiac trabeculae. Ca2+ accumulation was optimal between 1 and 3 mM Mg2+ in toad fibres and reached a plateau between 1 and 10 mM Mg2+ in the rat EDL fibres and between 3 and 10 mM Mg2+ in the rat cardiac fibres. In soleus fibres, optimal Ca2+ accumulation occurred at 10 mM Mg2+. The same trend was obtained with all preparations at 0.3 and 1 microM Ca2+. Experiments with 2,5-di-(tert-butyl)-1,4-benzohydroquinone, a specific inhibitor of the Ca2+ pump, revealed a marked Ca2+ efflux from the SR of toad iliofibularis fibres in the presence of 0.2 microM Ca2+ and 1 mM Mg2+. Further experiments indicated that the SR Ca2+ leak could be blocked by 10 microM ruthenium red without affecting the SR Ca2+ pump and this allowed separation between SR Ca2+ uptake and SR Ca2+ accumulation. At 0.3 microM Ca2+, Ca2+ uptake was optimal with 1 mM Mg2+ in the toad iliofibularis and rat EDL fibres and between 1 and 10 mM Mg2+ in the rat soleus and trabeculae preparations. At higher [Ca2+] (1 microM), Ca2+ uptake was optimal with 1 mM Mg2+ in the iliofibularis fibres and between 1 and 3 mM Mg2+ in the EDL fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Inhibition of a signaling pathway in cardiac muscle cells by active mitogen-activated protein kinase kinase.

    PubMed Central

    Thorburn, J; Carlson, M; Mansour, S J; Chien, K R; Ahn, N G; Thorburn, A

    1995-01-01

    Signaling via the Ras pathway involves sequential activation of Ras, Raf-1, mitogen-activated protein kinase kinase (MKK), and the extracellular signal-regulated (ERK) group of mitogen-activated protein (MAP) kinases. Expression from the c-Fos, atrial natriuretic factor (ANF), and myosin light chain-2 (MLC-2) promoters during phenylephrine-induced cardiac muscle cell hypertrophy requires activation of this pathway. Furthermore, constitutively active Ras or Raf-1 can mimic the action of phenylephrine in inducing expression from these promoters. In this study, we tested whether constitutively active MKK, the molecule immediately downstream of Raf, was sufficient to induce expression. Expression of constitutively active MKK induce ERK2 kinase activity and caused expression from the c-Fos promoter, but did not significantly activate expression of reporter genes under the control of either the ANF or MLC-2 promoters. Expression of CL100, a phosphatase that inactivates ERKs, prevented expression from all of the promoters. Taken together, these data suggest that ERK activation is required for expression from the Fos, ANF, and MLC-2 promoters but MKK and ERK activation is sufficient for expression only from the Fos promoter. Constitutively active MKK synergized with phenylephrine to increase expression from a c-Fos- or an AP1-driven reporter. However, active MKK inhibited phenylephrine- and Raf-1-induced expression from the ANF and MLC-2 promoters. A DNA sequence in the MLC-2 promoter that is a target for inhibition by active MKK, but not CL100, was mapped to a previously characterized DNA element (HF1) that is responsible for cardiac specificity. Thus, activation of cardiac gene expression during phenylephrine-induced hypertrophy requires ERK activation but constitutive activation by MKK can inhibit expression by targeting a DNA element that controls the cardiac specificity of gene expression. PMID:8589450

  5. The effects of progressive hypoxia and re-oxygenation on cardiac function, white muscle perfusion and haemoglobin saturation in anaesthetised snapper (Pagrus auratus).

    PubMed

    Janssen, G J A; Jerrett, A R; Black, S E; Forster, M E

    2010-04-01

    The effects of progressive hypoxia and re-oxygenation on cardiac function, white muscle perfusion and haemoglobin saturation were investigated in anaesthetised snapper (Pagrus auratus). White muscle perfusion and haemoglobin saturation were recorded in real time using fibre optic methodology. A marked fall in heart rate (HR) was evoked when the water bath dissolved oxygen (DO) concentration decreased below 1.5 mg L(-1). This bradycardia deepened over the subsequent 20 min of progressive hypoxia and noticeable arrhythmias occurred, suggesting that hypoxia had direct and severe effects on the cardiac myocytes. Perfusion to the white muscle decreased below a DO concentration of 3 mg L(-1), and oxyhaemoglobin concentration decreased once the DO fell below ca. 2 mg L(-1). During re-oxygenation, heart rate and white muscle perfusion increased as the DO concentration exceeded 1.9 +/- 0.1 mg L(-1), whereas haemoglobin saturation increased once the external DO concentration reached 2.9 mg L(-1). These changes occurred in anaesthetised fish, in which sensory function must be impaired, if not abolished. As white muscle perfusion both fell and increased prior to changes in white muscle oxyhaemoglobin saturation, a local hypoxia is more likely to be the consequence than the cause of the reduced blood delivery, and changes upstream from the tail vasculature must be responsible. HR and tissue haemoglobin concentrations did increase simultaneously on re-oxygenation suggesting an increased cardiac output as the cause.

  6. Polymeric scaffold aided stem cell therapeutics for cardiac muscle repair and regeneration.

    PubMed

    Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2013-09-01

    The constantly expanding repository of novel polymers and stem cells has opened up new vistas in the field of cardiac tissue engineering. Successful regeneration of the complex cardiac tissue mainly centres on the appropriate scaffold material with topographical features that mimic the native environment. The integration of stem cells on these scaffolds is expected to enhance the regeneration potential. This review elaborates on the interplay of these vital factors in achieving the functional cardiac tissue. The recent advances in polymers, nanocomposites, and stem cells from different sources are highlighted. Special emphasis is laid on the clinical trials involving stem cells and the state-of-the-art materials to obtain a balanced perspective on the translational potential of this strategy.

  7. Cardiac tamponade due to low-volume effusive constrictive pericarditis in a patient with uncontrolled type II autoimmune polyglandular syndrome.

    PubMed

    Palmer, William C; Kurklinsky, Andrew; Lane, Gary; Ussavarungsi, Kamonpun; Blackshear, Joseph L

    2014-03-01

    Type II autoimmune polyglandular syndrome (APS), a relatively common endocrine disorder, includes primary adrenal insufficiency coupled with type 1 diabetes mellitus and/or autoimmune primary hypothyroidism. Autoimmune serositis, an associated disease, may present as symptomatic pericardial effusion. We present a case of a 54-year old male with APS who developed pericarditis leading to cardiac tamponade with a subacute loculated effusion. After urgent pericardiocentesis intrapericardial pressure dropped to 0, while central venous pressures remain elevated, consistent with acute effusive constrictive pericarditis. Contrast computerized tomography confirmed increased pericardial contrast enhancement. The patient recovered after prolonged inotropic support and glucocorticoid administration. He re-accumulated the effusion 16 days later, requiring repeat pericardiocentesis. Effusive-constrictive pericarditis, an uncommon pericardial syndrome, is characterized by simultaneous pericardial inflammation and tamponade. Prior cases of APS associated with cardiac tamponade despite low volumes of effusion have been reported, albeit without good demonstration of hemodynamic findings. We report a case of APS with recurrent pericardial effusion due to pericarditis and marked hypotension with comprehensive clinical and hemodynamic assessment. These patients may require aggressive support with pericardiocentesis, inotropes, and hormone replacement therapy. They should be followed closely for recurrent tamponade.

  8. Aborted Sudden Cardiac Death in a Female Patient Presenting with Takotsubo-Like Cardiomyopathy due to Epicardial Coronary Vasospasm

    PubMed Central

    Eisele, Tom; Nunninger, Peter; Münz, Benedikt

    2017-01-01

    Takotsubo cardiomyopathy is characterized by apical ballooning of the left ventricle (LV) in the absence of relevant coronary artery stenosis, which typically occurs in elderly women after emotional stress. Catecholamine cardiotoxicity, metabolic disturbance, and coronary microvascular impairment have previously been proposed as underlying pathophysiologic mechanisms of takotsubo cardiomyopathy, whereas myocardial stunning resulting from epicardial coronary artery vasospasm is not generally accepted as a cause of takotsubo cardiomyopathy. The prognosis of takotsubo cardiomyopathy is generally more favourable compared to myocardial infarction; however, severe complications such as rupture of the LV and life-threatening arrhythmias may occur. Herein, we describe a case of an 84-year-old female, who presented with aborted sudden cardiac death due to ventricular fibrillation. Echocardiography suggested LV apical ballooning with severely impaired LV-function, so that takotsubo cardiomyopathy was suspected. However, coronary angiography revealed epicardial spasm of the left anterior ascending, which resolved after intracoronary injection of 0.2 mg nitroglycerine. Cardiac magnetic resonance exhibited subendocardial late enhancement and echocardiography showed normalization of LV dysfunction during follow-up. The patient was put on conservative treatment with nitrates and calcium inhibitors and ICD implantation were deferred.

  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. 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.

  11. Energetics of Na(+)-Ca(2+) exchange in resting cardiac muscle.

    PubMed Central

    Ponce-Hornos, J E; Philipson, K D; Bonazzola, P; Langer, G A

    1999-01-01

    The energetic effect of extracellular Na(+) removal and readmission (in a nominally Ca(2+)-free perfusate) in Langendorff-perfused ventricles of transgenic mice (TM), which overexpress the sarcolemmal Na(+)-Ca(2+) exchanger; normal mice (NM); young (7-12 days old) rats (YR); and older (13-20 days old) rats (OR) was studied. In all heart muscles, extracellular Na(+) removal induced an increase in heat production (H(1)). Na(+) readmission further increased heat production to a peak value (H(2)) followed by a decrease toward initial values. These effects were more marked in the YR and TM as compared with the OR and NM groups, respectively. Caffeine (1 mM), ryanodine (0.2 microM), and verapamil (1 microM) decreased H(1) and H(2) in both rat groups. EGTA (1 mM) decreased H(1) and H(2) in the YR but not in the OR group. Thapsigargin (1 microM) decreased H(1) and H(2) in all four hearts preparations. A possible interpretation is that Na(+)-Ca(2+) exchange acts as an energy-saving mechanism to prevent Ca(2+) accumulation at the junctional sarcoplasmic reticulum zone (JSR) and thus prevents further release of Ca(2+). Extracellular Na(+) removal lead to Ca(2+) accumulation in the JSR inducing further SR-Ca(2+) release and increased energy release. Na(+) readmission removes the accumulated Ca(2+) at the JSR (cleft) zone by exchanging Ca(2+) with Na(+) producing a transitory increase in energy release due to Na(+)-K pump activation. PMID:10585954

  12. Sites and modes of action of proctolin and the FLP F2 on lobster cardiac muscle.

    PubMed

    Wilkens, J L; Shinozaki, T; Yazawa, T; ter Keurs, H E D J

    2005-02-01

    At the threshold concentration (1-10 pmol l(-1)), the neuropeptide hormones proctolin (PR) and the FLRFamide-like peptide (FLP) F(2) cause an increase in amplitude of electrically evoked contractions (each contraction is a brief tetanus) of lobster heart ostial muscle. At higher concentrations each peptide also induces an increase in tonus (contracture). The PR-induced contracture and augmentation of tetani are proportional to increases in [Ca2+]i. The rate of onset and recovery of peptide-induced effects on both tetani and contracture appeared to reduced by Ca2+ storage by the sarcoplasmic reticulum (SR). Enhanced tetani following a contracture may be due to enhanced voltage-gated Ca2+ current and sarcoplasmic reticular (SR) Ca2+ loading. The SR Ca2+ loading appears to be specific for PR and F2, since glutamic-acid-induced contractures are not followed by increased tetani. The prolonged elevation of [Ca2+]i during contracture causes a right-ward shift in the force-pCa curve indicating a decrease in myofibrillar sensitivity to Ca2+. Blocking voltage-gated Ca2+ channels with Cd2+, nifedipine or verapamil, while reducing tetani, does not prevent peptide-induced contracture and enhanced tetani. Opening SR Ca2+ channels and depleting SR Ca2+ with either caffeine or ryanodine blocked tetani but permitted accelerated peptide-induced contractures. We conclude that PR and F2 at low concentration enhance voltage-dependent Ca2+ induced Ca2+ release from the SR, while higher hormone levels directly gate Ca2+ entry across the sarcolemma.

  13. 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.

  14. Effect of Isoflurane on Myocardial Energetic and Oxidative Stress in Cardiac Muscle from Zucker Diabetic Fatty Rat

    PubMed Central

    Shen, Xiaoxu; Bhatt, Niraj; Xu, Jianhong; Meng, Tao; Aon, Miguel A.; O’Rourke, Brian; Berkowitz, Dan E.; Cortassa, Sonia

    2014-01-01

    The effect of inhalational anesthetics on myocardial contraction and energetics in type 2 diabetes mellitus is unknown. We investigated the effect of isoflurane (ISO) on force and intracellular Ca2+ transient (iCa), myocardial oxygen consumption (MVo2), and energetics/redox behavior in trabecular muscles from Zucker diabetic fatty (ZDF) rats. At baseline, force and corresponding iCa were lower in ZDF trabeculae than in controls. ISO decreased force in both groups in a dose-dependent manner. ISO did not affect iCa amplitude in controls, but ISO > 1.5% significantly reduced iCa amplitude in ZDF trabeculae. ISO-induced force depression fully recovered as a result of increased iCa when external Ca2+ was raised in controls. However, both force and iCa remained low in ZDF muscle at elevated external Ca2+. In controls, force, iCa, and MVo2 increased when stimulation frequency was increased from 0.5 to 1.5 Hz. ZDF muscles, however, exhibited blunted responses in force and iCa and decreased MVo2. Oxidative stress levels were unchanged in control muscles but increased significantly in ZDF muscles after exposure to ISO. Finally, the depressive effect of ISO was prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) in ZDF muscles. These findings suggest that ISO dose-dependently attenuates force in control and ZDF muscles with differential effect on iCa. The mechanism of force depression by ISO in controls is mainly decreased myofilament Ca2+ sensitivity, whereas in ZDF muscles the ISO-induced decrease in contraction is due to worsening oxidative stress, which inhibits iCa and force development. PMID:24431470

  15. 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.

  16. 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

  17. Giant Purulent Pericarditis with Cardiac Tamponade Due to Streptococcus intermedius Rapidly Progressing to Constriction.

    PubMed

    Tigen, Elif T; Sari, Ibrahim; Ak, Koray; Sert, Sena; Tigen, Kursat; Korten, Volkan

    2015-08-01

    Purulent pericardial effusion, although rare, is a life-threatening condition usually produced by the extension of a nearby bacterial infection locus or by blood dissemination in the immune-suppressed subjects or in the course of cardiothoracic surgery. Because clinical features of purulent pericardial effusion are often nonspecific, it can cause delay in diagnosis. Therefore, a high index of suspicion is required for timely diagnosis and management. Herein, we describe a case of giant purulent pericardial effusion due to Streptococcus intermedius with the history of bronchiectasis and pneumonia, which was successfully treated with pericardiocentesis via parasternal approach, appropriate antibiotics, and pericardiectomy.

  18. Lanthanum Probe Studies of Cellular Pathophysiology Induced by Hypoxia in Isolated Cardiac Muscle

    PubMed Central

    Burton, Karen P.; Hagler, Herbert K.; Templeton, Gordon H.; Willerson, James T.; Buja, L. Maximilian

    1977-01-01

    This study was undertaken to evaluate directly the relationship between evolution of irreversible myocardial injury induced by hypoxia in an isolated papillary muscle preparation and the development of pathophysiological alterations related to severely impaired membrane function. An ionic lanthanum probe technique was employed as a cytochemical marker to monitor the progression of cellular injury, and data from this cytologic technique were correlated with ultrastructure and measurements of contractile parameters in a total of 67 muscles subjected to control conditions or to graded intervals of hypoxia with or without reoxygenation. Marked depression of developed tension and rate of tension development occurred after 30 min of hypoxia. Contractile function showed significant recovery with reoxygenation after 1 h and 15 min of hypoxia but remained depressed when reoxygenation was provided after 2 or 3 h of hypoxia. Examination by transmission and analytical electron microscopy (energy dispersive X-ray microanalysis) revealed lanthanum deposition only in extracellular regions of control muscles and muscles subjected to 30 min of hypoxia. After hypoxic intervals of over 1 h, abnormal intracytoplasmic and intramitochondrial localization of lanthanum were detected. After 1 h and 15 min of hypoxia, abnormal intracellular lanthanum accumulation was associated with only minimal ultrastructural evidence of injury; muscle provided reoxygenation after 1 h and 15 min of hypoxia showed improved ultrastructure and did not exhibit intracellular lanthanum deposits upon exposure to lanthanum during the reoxygenation period. After 2 to 3 h of hypoxia, abnormal intracellular lanthanum accumulation was associated with ultrastructural evidence of severe muscle injury which persisted after reoxygenation. Thus, the data support the conclusion that cellular and membrane alterations responsible for abnormal intracellular lanthanum deposition precede the development of irreversible injury

  19. 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.

  20. Stretch of contracting cardiac muscle abruptly decreases the rate of phosphate release at high and low calcium.

    PubMed

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

    2012-07-27

    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 (P(i)) release resulting from ATP hydrolysis, using a fluorescent sensor for P(i) with millisecond time resolution. Stretch immediately reduces the rate of P(i) release, an effect observed both at full calcium activation (32 μmol/liter of Ca(2+)), and at a physiological activation level of 1 μmol/liter of Ca(2+). The results suggest that stretch redistributes the actomyosin cross-bridges toward their P(i)-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 P(i) balance in the cytoplasm, which may act as a cytoplasmic signal for energy turnover.

  1. Development of metabolic enzyme activity in locomotor and cardiac muscles of the migratory barnacle goose.

    PubMed

    Bishop, C M; Butler, P J; Egginton, S; el Haj, A J; Gabrielsen, G W

    1995-07-01

    Preflight development of the goslings was typified by rapid increases in the mitochondrial enzymes of the semimembranosus and heart ventricular muscles resulting in near-adult values by 3 wk of age. In contrast, aerobic capacity of the pectoralis muscle initially developed slowly but showed a rapid increase between 5 and 7 wk of age, in preparation for becoming airborne. Activities of glycolytic enzymes in the pectoralis muscle showed similar patterns of development as those found for the aerobic enzymes, except for hexokinase, which was low at all ages, indicating an adaptation for catabolism of both intracellular glycogen and plasma fatty acids in preference to plasma glucose. Muscle mass specific activity of citrate synthase in the pectoralis increased by only 33% from goslings during the first few days of flight, compared with premigratory geese. Activities of anaerobic glycolytic enzymes in the ventricles were low, but values for hexokinase, which is involved in the phosphorylation of plasma glucose, developed rapidly. Values for lactate dehydrogenase were also high, reflecting the capacity of the heart to catabolize plasma lactate. Substrate flux supplied by carnitine palmitoyltransferase and oxoglutarate dehydrogenase (OGD), in the pectoralis muscles of the premigratory geese, appears to have the smallest excess capacities to meet the requirements of sustained aerobic flight. The average maximum oxygen uptake for premigratory geese during flight, as indicated by values for OGD, is calculated to be 484 ml O2/min (or 208 ml O2.min-1.kg-1).

  2. Kindlin-2 interacts with α-actinin-2 and β1 integrin to maintain the integrity of the Z-disc in cardiac muscles.

    PubMed

    Qi, Lihua; Yu, Yu; Chi, Xiaochun; Xu, Weizhi; Lu, Danyu; Song, Yao; Zhang, Youyi; Zhang, Hongquan

    2015-07-22

    Kindlin-2, as an integrin-interacting protein, was known to be required for the maintenance of cardiac structure and function in zebrafish. However, the mechanism remains unclear. We found that Kindlin-2 interacts and colocalizes with α-actinin-2 at the Z-disc of mouse cardiac muscles and there Kindlin-2 also interacts with β1 integrin. Knockdown of Kindlin-2 influences the association of β1 integrin with α-actinin-2 and disrupts the structure of the Z-disc and leads to cardiac dysfunction. Our data indicated that Kindlin-2 is a novel α-actinin-2-interacting protein and plays an important role in the regulation of cardiac structure and function.

  3. 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

  4. Biochemical and biomolecular aspects of oxidative stress due to acute and severe hypoxia in human muscle tissue.

    PubMed

    Corbucci, G G; Sessego, R; Velluti, C; Salvi, M

    1995-01-01

    Mitochondrial oxidative stress was investigated in severe and acute hypoxia and in reperfusion applied to human muscle tissues. The biochemical and biomolecular relationship between the response of the respiratory-chain enzymic complexes and the metabolism of specific hypoxia stress proteins (HSP) suggest an adaptive mechanism which antagonizes the oxidative damage due to acute and severe tissue hypoxia.

  5. Recurrent rhabdomyolysis due to muscle β-enolase deficiency: very rare or underestimated?

    PubMed

    Musumeci, Olimpia; Brady, Stefen; Rodolico, Carmelo; Ciranni, Annamaria; Montagnese, Federica; Aguennouz, M'hammed; Kirk, Richard; Allen, Elizabeth; Godfrey, Richard; Romeo, Sara; Murphy, Elaine; Rahman, Shamima; Quinlivan, Ros; Toscano, Antonio

    2014-12-01

    Muscle β-enolase deficiency is a very rare inherited metabolic myopathy caused by an enzymatic defect of distal glycolysis. So far, the condition has been described in only one patient with mutations in ENO3 in a compound heterozygous state who presented with exercise intolerance, post-exercise myalgia and mild hyperCKemia but no pigmenturia. We describe two men, one Italian and one Turkish, with consanguineous parents, who complained of several episodes of intense myalgia, cramps, generalized muscle tenderness and dark urine. No other family members reported similar symptoms. In both cases, there was a very mild rise in lactate during a forearm exercise test. Muscle biopsy showed minimal changes with no lipid or glycogen accumulation. Biochemical studies on muscle tissue demonstrated a marked reduction of muscle β-enolase activity (20 and 10% of residual activity, respectively). Molecular genetic analysis of ENO3 gene revealed two novel homozygous missense mutations, (p.Asn151Ser and p.Glu187Lys). Both mutations segregated as expected in the two families. Although quite rare, muscle β-enolase deficiency should be considered in the differential diagnosis of patients presenting with recurrent rhabdomyolysis. It may present also with a more severe phenotype than previously thought.

  6. 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

  7. 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

  8. Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation*

    PubMed Central

    Cattin, Marie-Elodie; Wang, Jessica; Weldrick, Jonathan J.; Roeske, Cassandra L.; Mak, Esther; Thorn, Stephanie L.; DaSilva, Jean N.; Wang, Yibin; Lusis, Aldon J.; Burgon, Patrick G.

    2015-01-01

    Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (muscle enriched A-type lamin-interacting protein), a unique protein of unknown function, is required for proper cardiac adaptation. Mlip−/− mice exhibited normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of Akt/mTOR pathways. Cardiac-specific MLIP overexpression led to an inhibition of Akt/mTOR, providing evidence of a direct impact of MLIP on these key signaling pathways. Mlip−/− hearts showed an impaired capacity to adapt to stress (isoproterenol-induced hypertrophy), likely because of deregulated Akt/mTOR activity. Genome-wide association studies showed a genetic association between Mlip and early response to cardiac stress, supporting the role of MLIP in cardiac adaptation. Together, these results revealed that MLIP is required for normal myocardial adaptation to stress through integrated regulation of the Akt/mTOR pathways. PMID:26359501

  9. 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

  10. Distinct association between the antagonistic jaw muscle activity levels and cardiac activity during chewing and NREM sleep in the freely moving guinea pigs.

    PubMed

    Kato, Takafumi; Masuda, Yuji; Miyano, Keiji; Higashiyama, Makoto; Yano, Hiroyuki; Haque, Tahsinul; Sato, Fumihiko; Yoshida, Atsushi

    2015-04-10

    The aim of this study was to investigate the changes of the association between cardiac activity and the electromyographic (EMG) level of the antagonistic jaw muscles during chewing and NREM sleep in guinea pigs after systemic clonidine injections. Ten animals were prepared for chronic experiments to monitor sleep, cardiac activity and EMG activity of jaw-closing masseter (MAS) and jaw-opening anterior belly of digastric (ADG) muscles. The recordings were made for ten hours with the injections of saline or clonidine (10 μg/kg, i.p.). Integrated EMG activity of the two muscles and mean heart rate (mHR) were calculated for every 10-s epoch. During the two hours after clonidine injection, the duration of REM sleep and mHR were significantly reduced. During chewing, the high EMG activity level of the two muscles and the activity ratio between the two muscles were not modified although mHR was decreased. During NREM sleep, after clonidine injection, the low EMG activity level at baseline was further decreased by 20-30% in parallel to a decrease of mHR although the heterogeneity of the activity ratio remained unaltered. The results suggest that the maintenance of the activity level for the antagonistic jaw muscles are regulated by the distinct physiological mechanisms reflecting the behavioral states during conscious chewing and unconscious NREM sleep.

  11. Acute decrease in the stiffness of resting muscle belly due to static stretching.

    PubMed

    Taniguchi, K; Shinohara, M; Nozaki, S; Katayose, M

    2015-02-01

    The purpose of the study was to examine the acute effect of static stretching exercise on the resting stiffness of gastrocnemius muscle belly. Ten healthy young adults performed standing wall stretching in dorsiflexion for 1 min at a time and repeated five times. Before and after stretching, the shear modulus was measured in medial and lateral heads of the resting gastrocnemius muscle with ultrasound shear-wave elastography. After the stretching, dorsiflexion range of motion (ROM) of the ankle joint increased (P < 0.01) by 3.9° and returned in 20 min. Immediately after stretching, shear modulus decreased (P < 0.01) by 14%, compared with before stretching across muscle heads. The decrease in shear modulus returned in 20 min after stretching. In the comparison group of 10 additional subjects, the standing intervention without stretching had no influence on these measures. There was a negative correlation between dorsiflexion ROM and shear modulus in either head before and after stretching. The results demonstrate the transient decreases in the stiffness of the resting gastrocnemius muscle belly and indicate that joint flexibility is greater in individuals with lower resting stiffness of the muscle belly.

  12. 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.

  13. Changes in EMG activity in the upper trapezius muscle due to local vibration exposure.

    PubMed

    Aström, Charlotte; Lindkvist, Markus; Burström, Lage; Sundelin, Gunnevi; Karlsson, J Stefan

    2009-06-01

    Exposure to vibration is suggested as a risk factor for developing neck and shoulder disorders in working life. Mechanical vibration applied to a muscle belly or a tendon can elicit a reflex muscle contraction, also called tonic vibration reflex, but the mechanisms behind how vibration could cause musculoskeletal disorders has not yet been described. One suggestion has been that the vibration causes muscular fatigue. This study investigates whether vibration exposure changes the development of muscular fatigue in the trapezius muscle. Thirty-seven volunteers (men and women) performed a sub-maximal isometric shoulder elevation for 3 min. This was repeated four times, two times with induced vibration and two times without. Muscle activity was measured before and after each 3-min period to look at changes in the electromyography parameters. The result showed a significantly smaller mean frequency decrease when performing the shoulder elevation with vibration (-2.51 Hz) compared to without vibration (-4.04 Hz). There was also a slightly higher increase in the root mean square when exposed to vibration (5.7% of maximal voluntary contraction) compared to without (3.8% of maximal voluntary contraction); however, this was not statistically significant. The results of the present study indicate that short-time exposure to vibration has no negative acute effects on the fatiguing of upper trapezius muscle.

  14. Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with Cystic Fibrosis

    PubMed Central

    Neubauer, Henning; Wirth, Clemens; Ruf, Katharina; Hebestreit, Helge; Beer, Meinrad

    2012-01-01

    Cystic fibrosis (CF) is one of the most common inherited diseases and is caused by mutations in the CFTR gene. Although the pulmonary and gastrointestinal manifestations of the disease remain in the focus of treatment, recent studies have shown expression of the CFTR gene product in skeletal muscle cells and observed altered intramuscular Ca2+ release dynamics in CFTR-deficient animal models. Physical exercise is beneficial for maintaining fitness and well-being in CF patients and constitutes one aspect of modern multimodal treatment, which has considerably increased life span and reduced morbidity. We report on a case of acute muscle trauma resulting from excessive dumbbell exercise in a young adult with cystic fibrosis and describe clinical, laboratory and imaging characteristics of acute exercise-induced muscle injury. PMID:22606534

  15. 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

  16. Cross-bridge movement in rat cardiac muscle as a function of calcium concentration.

    PubMed Central

    Matsubara, I; Maughan, D W; Saeki, Y; Yagi, N

    1989-01-01

    1. By applying the X-ray diffraction method to chemically skinned papillary muscles of the rat, the transfer of myosin heads from the thick to the thin filaments was studied as a function of Ca2+ concentration. 2. No significant transfer of the heads occurred when the Ca2+ concentration was below the threshold of contraction (pCa 6.2). 3. During the maximum isometric contraction at pCa 4.4, 80% of the myosin heads were transferred to the thin filament. 4. When the muscle was activated isometrically at low Ca2+ concentrations (pCa 6.2-5.8), where the average tension was less than 20% of the maximum, a disproportionately large number of myosin heads were transferred to the thin filament. 5. It was concluded that a significant fraction of the heads transferred at the low Ca2+ concentrations does not produce tension. PMID:2621610

  17. 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

  18. 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

  19. High Expression of Nuclear Factor 90 (NF90) Leads to Mitochondrial Degradation in Skeletal and Cardiac Muscles

    PubMed Central

    Kakinuma, Yoshihiko; Kai, Shoko; Yagyu, Ken-ichi; Todaka, Hiroshi; Chi, Eunsup; Okada, Shoshiro; Ujihara, Takako; Morisawa, Keiko; Ono, Masafumi; Sugiyama, Yasunori; Ishida, Waka; Fukushima, Atsuki; Tsuda, Masayuki; Agata, Yasutoshi; Taniguchi, Taketoshi

    2012-01-01

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

  20. Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness.

    PubMed

    Lee, Soah; Serpooshan, Vahid; Tong, Xinming; Venkatraman, Sneha; Lee, Meelim; Lee, Jaecheol; Chirikian, Orlando; Wu, Joseph C; Wu, Sean M; Yang, Fan

    2017-03-30

    Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1.25 × 10(8)/mL) with tunable stiffness and degradation. In comparison to the cells in high stiffness (16 kPa)/slow degrading hydrogels, hiPSC-CMs in low stiffness (2 kPa)/fast degrading and intermediate stiffness (9 kPa)/intermediate degrading hydrogels exhibit increased intercellular network formation, α-actinin and connexin-43 expression, and contraction velocity. Only the 9 kPa microtissues exhibit organized sarcomeric structure and significantly increased contractile stress. This demonstrates that muscle-mimicking stiffness together with robust cellular interconnection contributes to enhancement in sarcomeric organization and contractile function of the engineered cardiac tissue. This study highlights the importance of intercellular connectivity, physiologically-relevant cell density, and matrix stiffness to best support 3D cardiac tissue engineering.

  1. The new compound, LASSBio 294, increases the contractility of intact and saponin-skinned cardiac muscle from Wistar rats.

    PubMed

    Sudo, R T; Zapata-Sudo, G; Barreiro, E J

    2001-10-01

    1. A new compound designated as LASSBio 294 (L-294), 3,4-methylenedioxybenzoyl-2-thienylhydrazone, was synthesized as an alternative therapeutic for cardiac dysfunction. 2. L-294 increased in a dose-dependent manner the spontaneous contractions of isolated hearts from Wistar rats with maximal effect (128.0+/-0.7% of control) observed at 25 microM. 3. The positive inotropic effect of L-294 was also observed in electrically stimulated cardiac tissues from Wistar rats. The maximal increment of twitches, at 200 microM, was 163.1+/-18.4% for atrial, 153.5+/-28.5% for papillary and 201.5+/-18.5% for ventricular muscles. 4. In saponin skinned ventricular cells: (a) L-294 present in the period of sarcoplasmic reticulum (SR) loading with Ca(2+) shifted the dose and caffeine-induced contracture curve; (b) L-294 (100 microM) increased 40% the Ca(2+) uptake into SR; (c) L-294 did not significantly alter the sensitivity of contractile proteins to Ca(2+) in SR-disrupted skinned ventricular cells. 5. Retrograde perfusion of the isolated heart from Wistar rats with L-294 (100 microM) did not cause any significant change in rhythm, heart rate (control, 220+/-14.7 b.p.m.; 246+/-24.6 b.p.m. for L-294), PR interval (control, 66.0+/-2.4 ms; 64.0+/-2.3 ms for L-294) or QRS duration (control, 28.8+/-3.4 ms; 32.0+/-2.0 ms for L-294). 6. These results suggest a novel mechanism for a positive cardioinotropic effect through an interaction with the Ca(2+) uptake/release process of the SR. The effect of L-294 could be explained by a pronounced increased accumulation of Ca(2+) into the SR.

  2. Physiologic Basis and Pathophysiologic Implications of the Diastolic Properties of the Cardiac Muscle

    PubMed Central

    Ferreira-Martins, João; Leite-Moreira, Adelino F.

    2010-01-01

    Although systole was for long considered the core of cardiac function, hemodynamic performance is evenly dependent on appropriate systolic and diastolic functions. The recognition that isolated diastolic dysfunction is the major culprit for approximately fifty percent of all heart failure cases imposes a deeper understanding of its underlying mechanisms so that better diagnostic and therapeutic strategies can be designed. Risk factors leading to diastolic dysfunction affect myocardial relaxation and/or its material properties by disrupting the homeostasis of cardiomyocytes as well as their relation with surrounding matrix and vascular structures. As a consequence, slower ventricular relaxation and higher myocardial stiffness may result in higher ventricular filling pressures and in the risk of hemodynamic decompensation. Thus, determining the mechanisms of diastolic function and their implications in the pathophysiology of heart failure with normal ejection fraction has become a prominent field in basic and clinical research. PMID:20625419

  3. 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

  4. 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

  5. Exacerbated cardiac fibrosis induced by β-adrenergic activation in old mice due to decreased AMPK activity.

    PubMed

    Wang, Jingjing; Song, Yao; Li, Hao; Shen, Qiang; Shen, Jing; An, Xiangbo; Wu, Jimin; Zhang, Jianshu; Wu, Yunong; Xiao, Han; Zhang, Youyi

    2016-11-01

    Senescent hearts exhibit defective responses to β-adrenergic receptor (β-AR) over-activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in protecting against ageing-associated cardiac remodelling in mice upon β-AR over-activation. 10-week-old (young) and 18-month-old (old) mice were subcutaneously injected with the β-AR agonist isoproterenol (ISO; 5 mg/kg). More extensive cardiac fibrosis was found in old mice upon ISO exposure than in young mice. Meanwhile, ISO treatment decreased AMPK activity and increased β-arrestin 1, but not β-arrestin 2, expression, and the effects of ISO on AMPK and β-arrestin 1 were greater in old mice than in young mice. Similarly, young AMPKα2-knockout (KO) mice showed more extensive cardiac fibrosis upon ISO exposure than that was observed in age-matched wild-type (WT) littermates. The extent of cardiac fibrosis in WT old mice was similar to that in young KO mice. Additionally, AMPK activities were decreased and β-arrestin 1 expression increased in KO mice. In contrast, the AMPK activator metformin decreased β-arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure. In conclusion, more severe cardiac fibrosis is induced by ISO in old mice than in young mice. A decrease in AMPK activity, which further increases β-arrestin 1 expression, is the central mechanism underlying the ageing-related cardiac fibrosis induced by ISO. The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon β-AR over-activation.

  6. Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities.

    PubMed

    Norman, Catalina; Rall, Jack A; Tikunova, Svetlana B; Davis, Jonathan P

    2007-10-01

    We investigated whether changing thin filament Ca(2+) sensitivity alters the rate of contraction, either during normal cross-bridge cycling or when cross-bridge cycling is increased by inorganic phosphate (P(i)). We increased or decreased Ca(2+) sensitivity of force production by incorporating into rat skinned cardiac trabeculae the troponin C (TnC) mutants V44QTnC(F27W) and F20QTnC(F27W). The rate of isometric contraction was assessed as the rate of force redevelopment (k(tr)) after a rapid release and restretch to the original length of the muscle. Both in the absence of added P(i) and in the presence of 2.5 mM added P(i) 1) Ca(2+) sensitivity of k(tr) was increased by V44QTnC(F27W) and decreased by F20QTnC(F27W) compared with control TnC(F27W); 2) k(tr) at submaximal Ca(2+) activation was significantly faster for V44QTnC(F27W) and slower for F20QTnC(F27W) compared with control TnC(F27W); 3) at maximum Ca(2+) activation, k(tr) values were similar for control TnC(F27W), V44QTnC(F27W), and F20QTnC(F27W); and 4) k(tr) exhibited a linear dependence on force that was indistinguishable for all TnCs. In the presence of 2.5 mM P(i), k(tr) was faster at all pCa values compared with the values for no added P(i) for TnC(F27W), V44QTnC(F27W), and F20QTnC(F27W). This study suggests that TnC Ca(2+) binding properties modulate the rate of cardiac muscle contraction at submaximal levels of Ca(2+) activation. This result has physiological relevance considering that, on a beat-to-beat basis, the heart contracts at submaximal Ca(2+) activation.

  7. Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated With Cardiac and Skeletal Muscle Pathology.

    PubMed

    Sato, Yohei; Kobayashi, Hiroshi; Higuchi, Takashi; Shimada, Yohta; Ida, Hiroyuki; Ohashi, Toya

    2016-08-18

    : Pompe disease (PD) is a lysosomal storage disease that is caused by a deficiency of the acid α-glucosidase, which results in glycogen accumulation in the lysosome. The major clinical symptoms of PD include skeletal muscle weakness, respiratory failure, and cardiac hypertrophy. Based on its severity and symptom onset, PD is classified into infantile and late-onset forms. Lysosomal accumulation of glycogen can promote many types of cellular dysfunction, such as autophagic dysfunction, endoplasmic reticulum stress, and abnormal calcium signaling within skeletal muscle. However, the disease mechanism underlying PD cardiomyopathy is not fully understood. Several researchers have shown that PD induced pluripotent stem cell (iPSC)-derived cardiomyocytes successfully replicate the disease phenotype and are useful disease models. We have analyzed the metabolomic profile of late-onset PD iPSC-derived cardiomyocytes and found that oxidative stress and mitochondrial dysfunction are likely associated with cardiac complications. Furthermore, we have validated that these disease-specific changes were also observed in the cardiomyocytes and skeletal muscle of a genetically engineered murine PD model. Oxidative stress may contribute to skeletal muscle and cardiomyocyte dysfunction in PD mice; however, NF-E2-related factor 2 was downregulated in cardiomyocytes and skeletal muscle, despite evidence of oxidative stress. We hypothesized that oxidative stress and an impaired antioxidative stress response mechanism may underlie the molecular pathology of late-onset PD.

  8. The low-affinity Ca2(+)-binding sites in cardiac/slow skeletal muscle troponin C perform distinct functions: site I alone cannot trigger contraction.

    PubMed Central

    Sweeney, H L; Brito, R M; Rosevear, P R; Putkey, J A

    1990-01-01

    Both troponin C (TnC) and calmodulin share a remarkably similar tertiary motif that may be common to other Ca2(+)-binding proteins with activator activity. TnC plays a critical role in regulating muscle contraction and is particularly well-suited for structural analysis by site-directed mutation. Fast-twitch skeletal muscle TnC has two low-affinity Ca2(+)-binding sites (sites I and II), while in cardiac and slow-twitch skeletal muscle TnC site I is inactive. Recently, using protein engineering, we directly demonstrated that binding of Ca2+ to the low-affinity site(s) initiates muscle contraction. In the present study, we use mutagenesis to determine whether either of the low-affinity sites in cardiac TnC can trigger contraction in slow-twitch skeletal muscle fibers. In one Ca2(+)-binding mutant, Ca2(+)-binding to the dormant low-affinity site I was restored (CBM+I). In a second mutant, site I was activated while site II was inactivated (CBM+I-IIA). Both proteins had the predicted CA2(+)-binding characteristics, and both were able to associate with troponin I and troponin T to form a troponin complex and integrate into permeabilized slow-twitch skeletal muscle fibers. A comparison of NMR spectra shows the aromatic regions in the two proteins to be qualitatively similar without divalent cations but markedly different with Ca2+. Mutant CBM+I supported force generation in skinned slow skeletal muscle fibers but had Sr2+ and Ca2+ sensitivities similar to fast skeletal TnC. Mutant CBM+I-IIA was unable to restore Ca2(+)-dependent contraction to TnC-depleted skinned slow muscle fibers. The data directly demonstrate that low-affinity sites I and II have distinct functions and that only site II in cardiac TnC can trigger muscle contraction in slow-twitch skeletal muscle fibers. This principle of distinct, modular activities for Ca2(+)-binding sites in the same protein may apply to other members of the TnC/calmodulin family. Images PMID:2263608

  9. Myosin types and fiber types in cardiac muscle. II. Atrial myocardium

    PubMed Central

    1982-01-01

    Antibodies were produced against myosins isolated from the left atrial myocardium (anti-bAm) and the left ventricular myocardium (anti-bVm) of the bovine heart. Cross-reactive antibodies were removed by cross- absorption. Absorbed anti-bAm and anti-bVm were specific for the myosin heavy chains when tested by enzyme immunoassay combined with SDS gel electrophoresis. Indirect immunofluorescence was used to determine the reactivity of atrial muscle fibers to the two antibodies. Three populations of atrial muscle fibers were distinguished in the bovine heart: (a) fibers reactive with anti-bAm and unreactive with anti-bVm, like most fibers in the left atrium; (b) fibers reactive with both antibodies, especially numerous in the right atrium; (c) fibers reactive with anti-bVm and unreactive with anti-bAm, present only in the interatrial septum and in specific regions of the right atrium, such as the crista terminalis. These findings can be accounted for by postulating the existence of two distinct types of atrial myosin heavy chains, one of which is antigenically related to ventricular myosin. The tendency for fibers labeled by anti-bVm to occur frequently in bundles and their preferential distribution in the crista terminalis, namely along one of the main conduction pathways between the sinus node and the atrioventricular node, and in the interatrial septum, where different internodal tracts are known to converge, suggests that these fibers may be specialized for faster conduction. PMID:6218175

  10. Predicting Effects of Tropomyosin Mutations on Cardiac Muscle Contraction through Myofilament Modeling

    PubMed Central

    Sewanan, Lorenzo R.; Moore, Jeffrey R.; Lehman, William; Campbell, Stuart G.

    2016-01-01

    Point mutations to the human gene TPM1 have been implicated in the development of both hypertrophic and dilated cardiomyopathies. Such observations have led to studies investigating the link between single residue changes and the biophysical behavior of the tropomyosin molecule. However, the degree to which these molecular perturbations explain the performance of intact sarcomeres containing mutant tropomyosin remains uncertain. Here, we present a modeling approach that integrates various aspects of tropomyosin's molecular properties into a cohesive paradigm representing their impact on muscle function. In particular, we considered the effects of tropomyosin mutations on (1) persistence length, (2) equilibrium between thin filament blocked and closed regulatory states, and (3) the crossbridge duty cycle. After demonstrating the ability of the new model to capture Ca-dependent myofilament responses during both dynamic and steady-state activation, we used it to capture the effects of hypertrophic cardiomyopathy (HCM) related E180G and D175N mutations on skinned myofiber mechanics. Our analysis indicates that the fiber-level effects of the two mutations can be accurately described by a combination of changes to the three tropomyosin properties represented in the model. Subsequently, we used the model to predict mutation effects on muscle twitch. Both mutations led to increased twitch contractility as a consequence of diminished cooperative inhibition between thin filament regulatory units. Overall, simulations suggest that a common twitch phenotype for HCM-linked tropomyosin mutations includes both increased contractility and elevated diastolic tension. PMID:27833562

  11. [The influence of small doses of exogenic nitrite on oxidative modifications of water-soluble proteins of rat cardiac and skeletal muscle].

    PubMed

    Kuleva, N V; Krasovskaia, I E; Shumilova, T E

    2014-01-01

    The influence of small doses of exogenic nitrite on reversible and irreversible oxidative modifications of water-soluble proteins of rat cardiac and skeletal muscle was studied with the aid of redox 2D-electrophoresis and colorimetric determination of protein carbonyl group, correspondingly. To explain the absence of significant changes under hypoxia induced by nitrite the known hypothesis about nitrite inhibition of some sites of mitochondrial electron transporting chain decreasing free radical quantity was discussed.

  12. Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program

    PubMed Central

    Hermes, Bárbara Maria; Cardoso, Dannuey Machado; Gomes, Tiago José Nardi; dos Santos, Tamires Daros; Vicente, Marília Severo; Pereira, Sérgio Nunes; Barbosa, Viviane Acunha; de Albuquerque, Isabella Martins

    2015-01-01

    Objective To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program. Methods A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II cardiac rehabilitation program: inspiratory muscle training program associated with combined training (aerobic and resistance) group (GCR + IMT, n=12) and combined training with respiratory exercises group (GCR, n=12), over a period of 12 weeks, with two sessions per week. Before and after intervention, the following measurements were obtained: maximal inspiratory and expiratory pressures (PImax and PEmax), peak oxygen consumption (peak VO2) and quality of life scores. Data were compared between pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student's t-test, except the categorical variables, which were compared using the Chi-square test. Values of P<0.05 were considered statistically significant. Results Compared to GCR, the GCR + IMT group showed larger increments in PImax (P<0.001), PEmax (P<0.001), peak VO2 (P<0.001) and quality of life scores (P<0.001). Conclusion The present study demonstrated that the addition of inspiratory muscle training, even when applied for a short period, may potentiate the effects of combined aerobic and resistance training, becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation. PMID:27163422

  13. Skeletal muscle metabolic response to exercise in horses with 'tying-up' due to polysaccharide storage myopathy.

    PubMed

    Valberg, S J; Macleay, J M; Billstrom, J A; Hower-Moritz, M A; Mickelson, J R

    1999-01-01

    Polysaccharide storage myopathy (PSSM) is a distinct cause of exertional rhabdomyolysis in Quarter Horses that results in glycogen and abnormal polysaccharide accumulation. The purpose of this study was to determine if excessive glycogen storage in PSSM is due to a glycolytic defect that impairs utilisation of this substrate during exercise. Muscle biopsies, blood lactates and serum CK were obtained 1) at rest from 5 PSSM Quarter Horses, 4 normal Quarter Horses (QH controls) and 6 Thoroughbreds with recurrent exertional rhabdomyolysis (TB RER) and 2) after a maximal treadmill exercise test in PSSM and QH controls. In addition, 3 PSSM horses performed a submaximal exercise test. At rest, muscle glycogen concentrations were 2.4x and 1.9x higher in PSSM vs. QH controls or TB RER, respectively. Muscle lactates at rest were similar between PSSM and QH controls but significantly higher in PSSM vs. TB RER. Muscle glucose-6-phosphate concentrations were also higher in PSSM horses than controls combined. During maximal exercise, mean muscle glycogen concentrations declined 2.7x more and mean lactate increased 2x more in PSSM vs. QH controls; however, differences were not statistically significant. Blood lactate concentrations after maximal exercise did not reflect generally higher muscle lactate in PSSM vs. QH controls. No change in blood lactate concentrations occurred in PSSM horses with submaximal exercise. Serum CK activity increased significantly 4 h after maximal and submaximal exercise and was significantly higher in PSSM vs. QH controls. These results show that during maximal exercise, PSSM horses utilised muscle glycogen and produce lactic acid via a functional glycolytic pathway and that during submaximal exercise oxidative metabolism was unimpaired. The excessive glycogen storage and formation of abnormal polysaccharide in PSSM horses therefore appear to reflect increased glycogen synthesis rather than decreased utilisation. The specific subset of horses with

  14. Permeability alteration of sarcolemmal membrane in catecholamine-induced cardiac muscle cell injury. In vivo studies with fine structural diffusion tracer horse radish peroxidase.

    PubMed

    Boutet, M; Hüttner, I; Rona, G

    1976-05-01

    Cardiac muscle cell injury was produced in male Sprague-Dawley rats weighing 300 to 450 gm. with catecholamines, norepinephrine, and isoproterenol; sarcolemmal membrane alteration was tested in vivo using the extracellular macromolecular tracer, horseradish peroxidase. Norepinephrine was administered in continuous intravenous infusion in a dose of 4 to 6 mug. per 100 gm. of body weight per minute, whereas isoproterenol was given as a single subcutaneous injection in a dose of 8.5 mg. per 100 gm. of body weight. Horseradish peroxidase was injected intravenously and localized in the right ventricular myocardium following 6 and 30 minutes of circulation time by light and electron microscopy. As early as 10 minutes after norepinephrine infusion, horseradish peroxidase appeared within cardiac muscle cells possessing normal fine structure. Selective deposition of the tracer on normal and altered myofilaments was noted. Similar observations were made in the isoproterenol model at 60 to 90 minutes. The results indicate that sarcolemmal membrane permeability alteration is an early event in catecholamine-induced cardiac muscle injury. The possible functional significance of the findings is discussed.

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

    PubMed

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

    2002-06-07

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

  16. Acquired torticollis due to primary pyomyositis of the paraspinal muscles in an 11-year-old boy.

    PubMed

    Ray, S; Iyer, A; Avula, S; Kneen, R

    2016-03-18

    Torticollis is characterised by tilting and rotation of the cervical spine in opposite directions. Causes can be congenital or acquired. Primary pyomyositis is a rare subacute deep bacterial infection of skeletal muscles that typically affects individuals under 20 years of age from tropical countries. Infrequently, pyomyositis occurs in individuals from temperate regions, usually in immunocompromised adults, and this is defined as secondary pyomyositis. We report a case of acquired torticollis due to primary pyomyositis of the paraspinal muscles in a previously healthy boy from the UK. A prolonged course of antibiotics and physiotherapy led to a complete resolution of his illness. We review how to differentiate pyomyositis from focal myositis, a more common inflammatory muscular cause of acquired torticollis.

  17. Reorganised motor control strategies of trunk muscles due to acute low back pain.

    PubMed

    Hirata, R P; Salomoni, S E; Christensen, S W; Graven-Nielsen, T

    2015-06-01

    This study assessed how the low back motor control strategies were affected by experimental pain. In twelve volunteers the right m. longissimus was injected by hypertonic and isotonic (control) saline. The pain intensity was assessed on a visual analog scale (VAS). Subjects were seated on a custom-designed chair including a 3-dimensional force sensor adjusted to the segmental height of T1. Electromyography (EMG) was recorded bilaterally from longissimus, multifidus, rectus abdominis, and external oblique muscles. Isometric trunk extensions were performed before, during, and after the saline injections at 5%, 10%, and 20% of maximum voluntary contraction force. Visual feedback of the extension force was provided whereas the tangential force components were recorded. Compared with isotonic saline, VAS scores were higher following hypertonic saline injections (P<.01). Experimental low back pain reduced the EMG activity bilaterally of the rectus abdominis muscles during contractions at 10% and 20% MVC (P<.01) although force accuracy and tangential force variability was not affected. Increased variability in the tangential force composition was found during pain compared with the non-painful condition (P<.05). The immediate adaptation to pain was sufficient to maintain the quality of the task performance; however the long-term consequence of such adaptation is unknown and may overload other structures.

  18. 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

  19. Mechanical control of the rising phase of contraction of frog skeletal and cardiac muscle

    PubMed Central

    1977-01-01

    The effect of shortening on contractile activity was studied in experiments in which shortening during the rising phase of an isotonic contraction was suddenly stopped. At the same muscle length and the same time after stimulation the rise in tension was much faster, if preceded by shortening, than during an isometric contraction, demonstrating an increase in contractile activity. In this experiment the rate of tension rise determined in various phases of contraction was proportional to the rate of isotonic shortening at the same time after stimulation. Therefore, the time course of the isotonic rising phase could be derived from the tension rise after shortening. The rate of isotonic shortening was found to be unrelated to the tension generated at various lengths and to correspond closely to the activation process induced by shortening. The length response explains differences between isotonic and isometric contractions with regard to energy release (Fenn effect) and time relations. These results extend previous work which showed that shortening during later phases of a twitch prolongs, while lengthening abbreviates contraction. Thus the length responses, which have been called shortening activation and lengthening deactivation, control activity throughout an isotonic twitch. PMID:591919

  20. Intrauterine structure of foot muscles in talipes equinovarus due to high-level myelomeningocele: a light microscopic study in fetal cadavers.

    PubMed

    Omeroğlu, Suna; Peker, Tuncay; Omeroğlu, Hakan; Gülekon, Nadir; Mungan, Tamer; Danişman, Nuri

    2004-07-01

    The purpose of this study was to investigate the light microscopic structure of extrinsic foot muscles in talipes equinovarus (TEV) deformity that developed during intrauterine life due to high-level myelomeningocele. Ten feet of five fetal cadavers ranging in age from 18 to 20 weeks were dissected. Five feet had typical TEV deformity and the other five feet did not have any deformity (control group). Under light microscopic examination quantitative measurement of both muscle fiber sizes and fibrosis in the muscle tissue were performed to investigate the denervation muscle atrophy. Mean muscle fiber size of the TEV group was found to be significantly lower than that of the control group in all foot muscles except the gastrocnemius muscle. The proportion of fibrosis due to denervation atrophy was significantly higher in the TEV group than in the control group in all muscles. This situation was most evident in the peroneus longus muscle. It was concluded that muscular imbalance due to significant muscular atrophy might be the cause of TEV deformity that developed during intrauterine life due to high-level myelomeningocele.

  1. Two cases of delayed cardiac tamponade due to pericarditis after pulmonary vein (PV) isolation for atrial fibrillation.

    PubMed

    Torihashi, Sadayoshi; Shiraishi, Hirokazu; Hamaoka, Tetsuro; Imai, Mikimasa; Kuroyanagi, Akira; Nakanishi, Naohiko; Nakamura, Takeshi; Yamano, Tetsuhiro; Matsumuro, Akiyoshi; Shirayama, Takeshi

    2015-01-01

    Catheter ablation is an established treatment for atrial fibrillation (AF). The incidence of major complications related to the procedure is reported to be 4.5%, and delayed cardiac tamponade (DCT) is a rare, although recently recognized, complication. However, the mechanisms underlying the development of DCT remain unclear. We herein report the cases of two men, both 49 years of age, who developed cardiac tamponade requiring pericardiocentesis a few weeks after undergoing pulmonary vein isolation for persistent AF. Physicians should explain to the patient the potential for DCT as a complication prior to performing catheter ablation and provide careful follow-up for at least a few weeks after the session.

  2. The new compound, LASSBio 294, increases the contractility of intact and saponin-skinned cardiac muscle from Wistar rats

    PubMed Central

    Sudo, R T; Zapata-Sudo, G; Barreiro, E J

    2001-01-01

    A new compound designated as LASSBio 294 (L-294), 3,4-methylenedioxybenzoyl-2-thienylhydrazone, was synthesized as an alternative therapeutic for cardiac dysfunction. L-294 increased in a dose-dependent manner the spontaneous contractions of isolated hearts from Wistar rats with maximal effect (128.0±0.7% of control) observed at 25 μM. The positive inotropic effect of L-294 was also observed in electrically stimulated cardiac tissues from Wistar rats. The maximal increment of twitches, at 200 μM, was 163.1±18.4% for atrial, 153.5±28.5% for papillary and 201.5±18.5% for ventricular muscles. In saponin skinned ventricular cells: (a) L-294 present in the period of sarcoplasmic reticulum (SR) loading with Ca2+ shifted the dose and caffeine-induced contracture curve; (b) L-294 (100 μM) increased 40% the Ca2+ uptake into SR; (c) L-294 did not significantly alter the sensitivity of contractile proteins to Ca2+ in SR-disrupted skinned ventricular cells. Retrograde perfusion of the isolated heart from Wistar rats with L-294 (100 μM) did not cause any significant change in rhythm, heart rate (control, 220±14.7 b.p.m.; 246±24.6 b.p.m. for L-294), PR interval (control, 66.0±2.4 ms; 64.0±2.3 ms for L-294) or QRS duration (control, 28.8±3.4 ms; 32.0±2.0 ms for L-294). These results suggest a novel mechanism for a positive cardioinotropic effect through an interaction with the Ca2+ uptake/release process of the SR. The effect of L-294 could be explained by a pronounced increased accumulation of Ca2+ into the SR. PMID:11588115

  3. Reciprocal regulation of microRNA-1 and IGF-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions

    PubMed Central

    Elia, Leonardo; Contu, Riccardo; Quintavalle, Manuela; Varrone, Francesca; Chimenti, Cristina; Russo, Matteo Antonio; Cimino, Vincenzo; De Marinis, Laura; Frustaci, Andrea; Catalucci, Daniele; Condorelli, Gianluigi

    2010-01-01

    Background MicroRNAs (miRNAs/miRs) are small conserved RNA molecules of 22 nucleotides, which negatively modulate gene expression primarily through base paring to the 3′ untranslated region (UTR) of target mRNAs. The muscle-specific miR-1 has been implicated in cardiac hypertrophy, heart development, cardiac stem cell differentiation, and arrhythmias through targeting of regulatory proteins. In this study, we investigated the molecular mechanisms through which miR-1 intervenes in regulation of muscle cell growth and differentiation. Methods and Results Based on bioinformatics tools, biochemical assays and in vivo models, we demonstrate that 1) IGF-I and insulin growth factor 1 receptor (IGF-1R) are targets of miR-1; 2) miR-1 and IGF-1 protein levels are inversely correlated in models of cardiac hypertrophy and failure as well as in the C2C12 skeletal muscle cell model of differentiation; 3) the activation state of the IGF-1 signal transduction cascade reciprocally regulates miR-1 expression through the Foxo3a transcription factor; and 4) miR-1 expression inversely correlates with cardiac mass and thickness in myocardial biopsies of acromegalic patients, in which IGF-1 is overproduced following aberrant synthesis of growth hormone. Conclusions Our results reveal a critical role of miR-1 in mediating the effects of the IGF-1 pathway and demonstrate a feedback loop between miR-1 expression and the IGF-1 signal transduction cascade. PMID:19933931

  4. Increase in ( sup 3 H)PN 200-110 binding to cardiac muscle membrane in streptozocin-induced diabetic rats

    SciTech Connect

    Nishio, Y.; Kashiwagi, A.; Ogawa, T.; Asahina, T.; Ikebuchi, M.; Kodama, M.; Shigeta, Y. )

    1990-09-01

    Voltage-sensitive Ca2+ channels in cardiac left ventricular muscle membranes isolated from nondiabetic control and diabetic rats were measured with (3H)PN 200-110, a dihydropyridine derivative, as a ligand. The binding site (Bmax) of (3H)PN 200-110 in cardiac membranes isolated from streptozocin-induced diabetic (STZ-D) rats (128 +/- 10 fmol/mg protein) significantly (P less than 0.01) increased by 64% compared with that of control rats (78 +/- 4 fmol/mg protein) 10 wk after STZ administration without a significant change in Kd. However, the significant increase in Bmax of (3H)PN 200-110 binding in diabetic rats depended on the duration of diabetes such that the increase was not found until 6 wk after STZ injection. An 8-wk intensive insulin treatment, which was initiated 2 wk after STZ injection, normalized the increase in (3H)PN 200-110 binding in STZ-D rats to control levels (85 +/- 4 fmol/mg protein). Furthermore, (3H)PN 200-110 binding to control cardiac membranes was dose-dependently inhibited in the presence of verapamil, a phenylalkylamine Ca2+ antagonist, but that was not the case in cardiac membranes isolated from STZ-D rats. These results indicate that voltage-sensitive Ca2+ channels in cardiac muscle isolated from STZ-D rats are quantitatively and qualitatively altered, because the course of diabetes and the increase in the channels can be prevented by treatment with insulin.

  5. Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: the basis of W7 as an inhibitor of cardiac muscle contraction.

    PubMed

    Oleszczuk, Marta; Robertson, Ian M; Li, Monica X; Sykes, Brian D

    2010-05-01

    The solution structure of Ca(2+)-bound regulatory domain of cardiac troponin C (cNTnC) in complex with the switch region of troponin I (cTnI(147-163)) and the calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfinamide (W7), has been determined by NMR spectroscopy. The structure reveals that the W7 naphthalene ring interacts with the terminal methyl groups of M47, M60, and M81 as well as aliphatic and aromatic side chains of several other residues in the hydrophobic pocket of cNTnC. The H3 ring proton of W7 also contacts the methyl groups of I148 and M153 of cTnI(147-163). The N-(6-aminohexyl) tail interacts primarily with the methyl groups of V64 and M81, which are located on the C- and D-helices of cNTnC. Compared to the structure of the cNTnC*Ca(2+)*W7 complex (Hoffman, R. M. B. and Sykes, B. D. (2009) Biochemistry 48, 5541-5552), the tail of W7 reorients slightly toward the surface of cNTnC while the ring remains in the hydrophobic pocket. The positively charged -NH(3)(+) group from the tail of W7 repels the positively charged R147 of cTnI(147-163). As a result, the N-terminus of the peptide moves away from cNTnC and the helical content of cTnI(147-163) is diminished, when compared to the structure of cNTnC*Ca(2+)*cTnI(147-163) (Li, M. X., Spyracopoulos, L., and Sykes B. D. (1999) Biochemistry 38, 8289-8298). Thus the ternary structure cNTnC*Ca(2+)*W7*cTnI(147-163) reported in this study offers an explanation for the approximately 13-fold affinity reduction of cTnI(147-163) for cNTnC*Ca(2+) in the presence of W7 and provides a structural basis for the inhibitory effect of W7 in cardiac muscle contraction. This generates molecular insight into structural features that are useful for the design of cTnC-specific Ca(2+)-desensitizing drugs.

  6. Effects of endurance exercise training on heart rate variability and susceptibility to sudden cardiac death: protection is not due to enhanced cardiac vagal regulation.

    PubMed

    Billman, George E; Kukielka, Monica

    2006-03-01

    Low heart rate variability (HRV) is associated with an increased susceptibility to ventricular fibrillation (VF). Exercise training can increase HRV (an index of cardiac vagal regulation) and could, thereby, decrease the risk for VF. To test this hypothesis, a 2-min coronary occlusion was made during the last min of a 18-min submaximal exercise test in dogs with healed myocardial infarctions; 20 had VF (susceptible), and 13 did not (resistant). The dogs then received either a 10-wk exercise program (susceptible, n=9; resistant, n=8) or an equivalent sedentary period (susceptible, n=11; resistant, n=5). HRV was evaluated at rest, during exercise, and during a 2-min occlusion at rest and before and after the 10-wk period. Pretraining, the occlusion provoked significantly (P<0.01) greater increases in HR (susceptible, 54.9+/-8.3 vs. resistant, 25.0+/-6.1 beats/min) and greater reductions in HRV (susceptible, -6.3+/-0.3 vs. resistant, -2.8+/-0.8 ln ms2) in the susceptible dogs compared with the resistant animals. Similar response differences between susceptible and resistant dogs were noted during submaximal exercise. Training significantly reduced the HR and HRV responses to the occlusion (HR, 17.9+/-11.5 beats/min; HRV, -1.2+/-0.8, ln ms2) in the susceptible dogs; similar response reductions were noted during exercise. In contrast, these variables were not altered in the sedentary susceptible dogs. Posttraining, VF could no longer be induced in the susceptible dogs, whereas four sedentary susceptible dogs died during the 10-wk control period, and the remaining seven animals still had VF when tested. Atropine decreased HRV but only induced VF in one of eight trained susceptible dogs. Thus exercise training increased cardiac vagal activity, which was not solely responsible for the training-induced VF protection.

  7. Autophagy plays an important role in Sunitinib-mediated cell death in H9c2 cardiac muscle cells

    SciTech Connect

    Zhao Yuqin; Xue Tao; Yang Xiaochun; Zhu Hong; Ding Xiaofei; Lou Liming; Lu Wei; Yang Bo; He Qiaojun

    2010-10-01

    Sunitinib, which is a multitargeted tyrosine-kinase inhibitor, exhibits antiangiogenic and antitumor activity, and extends survival of patients with metastatic renal-cell carcinoma (mRCC) and gastrointestinal stromal tumors (GIST). This molecule has also been reported to be associated with cardiotoxicity at a high frequency, but the mechanism is still unknown. In the present study, we observed that Sunitinib showed high anti-proliferative effect on H9c2 cardiac muscle cells measured by PI staining and the MTT assay. But apoptotic markers (PARP cleavage, caspase 3 cleavage and chromatin condensation) were uniformly negative in H9c2 cells after Sunitinib treatment for 48 h, indicating that another cell death pathway may be involved in Sunitinib-induced cardiotoxicity. Here we found Sunitinib dramatically increased autophagic flux in H9c2 cells. Acidic vesicle fluorescence and high expression of LC3-II in H9c2 cells identified autophagy as a Sunitinib-induced process that might be associated with cytotoxicity. Furthermore, knocking down Beclin 1 by RNA-interference to block autophagy in H9c2 cells revealed that the death rate was decreased when treated with Sunitinib in comparison to control cells. These results confirmed that autophagy plays an important role in Sunitinib-mediated H9c2 cells cytotoxicity. Taken together, the data presented here strongly suggest that autophagy is associated with Sunitinib-induced cardiotoxicity, and that inhibition of autophagy constitutes a viable strategy for reducing Sunitinib-induced cardiomyocyte death thereby alleviating Sunitinib cardiotoxicity.

  8. Dynamic cardiac output regulation at rest, during exercise, and muscle metaboreflex activation: impact of congestive heart failure.

    PubMed

    Ichinose, Masashi; Sala-Mercado, Javier A; Coutsos, Matthew; Li, Zhenhua; Ichinose, Tomoko K; Dawe, Elizabeth; Fano, Dominic; O'Leary, Donal S

    2012-10-01

    We tested whether mild and moderate dynamic exercise and muscle metaboreflex activation (MMA) affect dynamic baroreflex control of heart rate (HR) and cardiac output (CO), and the influence of stroke volume (SV) fluctuations on CO regulation in normal (N) and pacing-induced heart failure (HF) dogs by employing transfer function analyses of the relationships between spontaneous changes in left ventricular systolic pressure (LVSP) and HR, LVSP and CO, HR and CO, and SV and CO at low and high frequencies (Lo-F, 0.04-0.15 Hz; Hi-F, 0.15-0.6 Hz). In N dogs, both workloads significantly decreased the gains for LVSP-HR and LVSP-CO in Hi-F, whereas only moderate exercise also reduced the LVSP-CO gain in Lo-F. MMA during mild exercise further decreased the gains for LVSP-HR in both frequencies and for LVSP-CO in Lo-F. MMA during moderate exercise further reduced LVSP-HR gain in Lo-F. Coherence for HR-CO in Hi-F was decreased by exercise and MMA, whereas that in Lo-F was sustained at a high level (>0.8) in all settings. HF significantly decreased dynamic HR and CO regulation in all situations. In HF, the coherence for HR-CO in Lo-F decreased significantly in all settings; the coherence for SV-CO in Lo-F was significantly higher. We conclude that dynamic exercise and MMA reduces dynamic baroreflex control of HR and CO, and these are substantially impaired in HF. In N conditions, HR modulation plays a major role in CO regulation. In HF, influence of HR modulation wanes, and fluctuations of SV dominate in CO variations.

  9. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  10. Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy.

    PubMed

    Sivaguru, Mayandi; Fried, Glenn; Sivaguru, Barghav S; Sivaguru, Vignesh A; Lu, Xiaochen; Choi, Kyung Hwa; Saif, M Taher A; Lin, Brian; Sadayappan, Sakthivel

    2015-11-01

    The ability to image the entire adult mouse heart at high resolution in 3-D would provide enormous advantages in the study of heart disease. However, a technique for imaging nuclear/cellular detail as well as the overall structure of the entire heart in 3-D with minimal effort is lacking. To solve this problem, we modified the benzyl alcohol:benzyl benzoate (BABB) clearing technique by labeling mouse hearts with periodic acid Schiff (PAS) stain. We then imaged the hearts with a combination of two-photon fluorescence microscopy and automated tile-scan imaging/stitching. Utilizing the differential spectral properties of PAS, we could identify muscle and nuclear compartments in the heart. We were also able to visualize the differences between a 3-month-old normal mouse heart and a mouse heart that had undergone heart failure due to the expression of cardiac myosin binding protein-C (cMyBP-C) gene mutation (t/t). Using 2-D and 3-D morphometric analysis, we found that the t/t heart had anomalous ventricular shape, volume, and wall thickness, as well as a disrupted sarcomere pattern. We further validated our approach using decellularized hearts that had been cultured with 3T3 fibroblasts, which were tracked using a nuclear label. We were able to detect the 3T3 cells inside the decellularized intact heart tissue, achieving nuclear/cellular resolution in 3-D. The combination of labeling, clearing, and two-photon microscopy together with tiling eliminates laborious and time-consuming physical sectioning, alignment, and 3-D reconstruction.

  11. The relation between cardiac output kinetics and skeletal muscle oxygenation during moderate exercise in moderately impaired patients with chronic heart failure.

    PubMed

    Spee, Ruud F; Niemeijer, Victor M; Schoots, Thijs; Wijn, Pieter F; Doevendans, Pieter A; Kemps, Hareld M

    2016-07-01

    Oxygen uptake (V̇o2) kinetics are prolonged in patients with chronic heart failure (CHF). This may be caused by impaired oxygen delivery or skeletal muscle derangements. We investigated whether impaired cardiac output (Q̇) kinetics limit skeletal muscle oxygen delivery relative to the metabolic demands at submaximal exercise in CHF patients by evaluating the relation between Q̇ kinetics and skeletal muscle deoxygenation. Forty-three CHF patients, NYHA II-III, performed a constant-load exercise test at 80% of the ventilatory aerobic threshold (VAT) to assess V̇o2 kinetics (τV̇o2). Q̇ kinetics (τQ̇) were assessed by a radial artery pulse contour analysis method. Skeletal muscle deoxygenation was assessed by near infrared spectroscopy at the m. vastus lateralis, using the minimal value of the tissue saturation index during onset of exercise (TSImin). Patients were categorized in slow and normal Q̇ responders relative to metabolic demands (τQ̇/V̇o2 ≥1 and τQ̇/V̇o2 <1, respectively), τQ̇ (62 ± 29 s), and τV̇o2 (60 ± 21 s) were significantly related (r = 0.66, P = 0.001). There was a significant correlation between τQ̇ and TSImin in the slow Q̇ responders [rs= -0.57, P = 0.005, n = 22 (51%)]. In conclusion, in moderately impaired CHF patients with relatively slow Q̇ kinetics, central hemodynamics may limit skeletal muscle oxygenation during moderate-intensity exercise.

  12. Intracellular angiotensin-(1–12) changes the electrical properties of intact cardiac muscle

    PubMed Central

    Dell’Itallia, L. J.; Varagic, J.; Ferrario, C. M.

    2016-01-01

    In the present work, the influence of intracellular injection of angiotensin-(1–12) [Ang-(1–12)] on the electrical properties of the intact left ventricle of Wistar Kyoto rats was investigated with electrophysiological methods. Particular attention was given to the role of chymostatin on the effect of the peptide. The results indicated that intra-cellular administration of the peptide elicited a depolarization of the surface cell membrane and an increase of duration of the action potential followed by the generation of early afterdepolarizations. The increment of action potential duration caused by Ang-(1–12) (100 nM) was due to a decrease of total potassium current recorded from single cardiomyocytes using the whole cell configuration of pCAMP. The decrease of potassium current was related to the activation of protein kinase C (PKC) because the specific inhibitor of kinase C, Bis-1 (10−9 M), abolished Ang-(1–12) effects on the potassium current. The question of whether the effect of Ang-(1–12) was related to the formation of Ang II by chymase was investigated. The results revealed that the intracellular administration of chymostatin, a chymase inhibitor (10−9 M) abolished the effect of intracellular Ang-(1–12) on the potassium current. Moreover, intracellular Ang II (100 nM), by itself, reduced the potassium current, an effect decreased by intracellular valsartan (100 nM). Valsartan (10–9 M) dialyzed into the cell abolished the effect of Ang-(1–12) (100 nM). These observations demonstrate that the effect of Ang-(1–12) on potassium current was related to the formation of Ang II and that the peptide has arrhythmogenic properties. PMID:27590241

  13. [A case of cardiac tamponade due to malignant pericarditis with lung adenocarcinoma, effectively treated with pericardial drainage and pemetrexed plus cisplatin chemotherapy].

    PubMed

    Yoshida, Kazufumi; Teramoto, Shinji

    2015-01-01

    A 68-year-old man was diagnosed with non small cell lung cancer in May 2013. Although the patient was negative for EGFR mutation, he wished to undergo treatment with gefitinib and erlotinib as first-line therapy. However, one year later, he was admitted to our hospital because of cardiac tamponade due to malignant pericarditis. He received pericardial drainage, after which his condition was stabilized. He was diagnosed with lung adenocarcinoma by cytology of pericardial effusion and treated with pemetrexed plus cisplatin as second-line therapy. Thereafter, the malignant effusion was decreased and the primary lesion was regressed. He received six courses of chemotherapy, however, brain metastases and bone metastases appeared. The brain metastases were controlled with gamma knife radiosurgery and he received carboptatin-paclitaxel plus bevacizumab as third-line therapy. The patient is currently receiving chemotherapy without any recurrence of malignant pericarditis or cardiac tamponade.

  14. Cardiac Involvement Classification and Therapeutic Management in Patients with Duchenne Muscular Dystrophy.

    PubMed

    Fayssoil, Abdallah; Abasse, Soumeth; Silverston, Katy

    2017-01-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. The clinical picture included peripheral muscle weakness, cardiomyopathy and chronic respiratory insufficiency. In this paper, the authors review cardiac involvement in patients with DMD, propose a cardiac impairment classification and discuss therapeutic management options.

  15. Cardiac Involvement Classification and Therapeutic Management in Patients with Duchenne Muscular Dystrophy

    PubMed Central

    Fayssoil, Abdallah; Abasse, Soumeth; Silverston, Katy

    2017-01-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. The clinical picture included peripheral muscle weakness, cardiomyopathy and chronic respiratory insufficiency. In this paper, the authors review cardiac involvement in patients with DMD, propose a cardiac impairment classification and discuss therapeutic management options. PMID:28269790

  16. Role of heart rate and stroke volume during muscle metaboreflex-induced cardiac output increase: differences between activation during and after exercise.

    PubMed

    Crisafulli, Antonio; Piras, Francesco; Filippi, Michele; Piredda, Carlo; Chiappori, Paolo; Melis, Franco; Milia, Raffaele; Tocco, Filippo; Concu, Alberto

    2011-09-01

    We hypothesized that the role of stroke volume (SV) in the metaboreflex-induced cardiac output (CO) increase was blunted when the metaboreflex was stimulated by exercise muscle ischemia (EMI) compared with post-exercise muscle ischemia (PEMI), because during EMI heart rate (HR) increases and limits diastolic filling. Twelve healthy volunteers were recruited and their hemodynamic responses to the metaboreflex evoked by EMI, PEMI, and by a control dynamic exercise were assessed. The main finding was that the blood pressure increment was very similar in the EMI and PEMI settings. In both conditions the main mechanism used to raise blood pressure was a CO elevation. However, during the EMI test CO was increased as a result of HR elevation whereas during the PEMI test CO was increased as a result of an increase in SV. These results were explainable on the basis of the different HR behavior between the two settings, which in turn led to different diastolic time and myocardial performance.

  17. Mifepristone is a Vasodilator Due to the Inhibition of Smooth Muscle Cells L-Type Ca2+ Channels.

    PubMed

    Mariana, Melissa; Feiteiro, Joana; Cairrao, Elisa; Verde, Ignacio

    2016-06-01

    Derived from the estrane progestins, mifepristone was the first synthetic steroid of this class employed as abortifacient in the first months of pregnancy. Mifepristone reduces high potassium-induced contraction and prevents calcium-induced contraction. At the vascular level, mifepristone induces direct relaxation in rat and human arteries, and this effect seems to be endothelium- and NO independent, suggesting that the vascular smooth muscle is its target. Moreover, mifepristone's effect could involve the modulation of different calcium channels. The aim of the present study is to analyze the involvement of calcium channels in the relaxation induced by mifepristone on vascular smooth muscle cells (VSMCs). Planar cell surface area (PCSA) technique was used to analyze the effect of mifepristone on the VSMC contractility, and the whole cell configuration of patch-clamp technique to measure the activity of L-type Ca(2+) channels (LTCC) in A7r5 cells. Regarding the PCSA technique, mifepristone induced relaxation of the VSMC previously contracted by different agents. Also, a rapid inhibitory effect on basal and BAY K8644-stimulated calcium current was observed, which indicates that this drug has the ability to block LTCC. These results suggest that mifepristone induces relaxation on the VSMCs due to the inhibition of the calcium channels.

  18. Variability of hemodynamic responses to acute digitalization in chronic cardiac failure due to cardiomyopathy and coronary artery disease.

    PubMed

    Cohn, K; Selzer, A; Kersh, E S; Karpman, L S; Goldschlager, N

    1975-04-01

    Eight patients with chronic congestive heart failure (four with cardiomyopathy and four with ischemic heart disease) underwent hemodynamic studies during acute administration of digoxin, given intravenously in two 0-5 mg doses 2 hours apart. Observations were made before administration of digitalis (control period) and serially therafter for 4 hours after the first dose. Resting mean cardiac index and pulmonary arterial wedge pressure were as follows: 2.0 liters/min per m2 and 23 mm Hg (control period); 2.1 and 24 (at 1 hour); 2.0 and 23 (at 2 hours); 2.7 and 19 (at 3 hours); and 2.3 and 20 (at 4 hours). Exercise responses of mean cardiac index and pulmonary arterial wedge pressure in five patients were: 3.1 liters/min per m2 and 36 mm Hg (control period); 3.2 and 33 (at 1 hour); 3.2 and 28 (at 2 hours); 3.1 and 27 (at.3 hours); and 3.4 and 31 (at 4 hours). The pulmonary arterial wedge pressure remained elevated during exercise in all cases. Arrhythmias were seen in five patients after administration of 0.5 mg of digoxin. Hemodynamic improvement at 4 hours involving both reduced filling pressure and increased blood flow was observed in only two patients at rest and in one additional patient during exercise. Acute deterioration of cardiac function (elevated pulmonary arterial wedge pressure of decreased cardiac index) occurred 30 minutes after administration of digoxin in four patients, concomitantly with increased systemic resistance. In six patients, a peak hemodynamic effect appeared 1 to 1 1/2 hours after administration of digoxin, with partial or total loss of initial benefit by 2 and 4 hours. In previously performed studies observations have seldom exceeded 1 hour; the results of this 4 hour study suggest that, in patients with cardiomyopathy or coronary artery disease and chronic congestive heart failure, acute digitalization does not necessarily lead to consistent, marked or lasting hemodynamic improvement. Thus, current concepts of the use of digitalis is

  19. The Scaffold Protein Muscle A-Kinase Anchoring Protein β Orchestrates Cardiac Myocyte Hypertrophic Signaling Required for the Development of Heart Failure

    PubMed Central

    Kritzer, Michael D.; Li, Jinliang; Passariello, Catherine L.; Gayanilo, Marjorie; Thakur, Hrishikesh; Dayan, Joseph; Dodge-Kafka, Kimberly; Kapiloff, Michael S.

    2014-01-01

    Background Cardiac myocyte hypertrophy is regulated by an extensive intracellular signal transduction network. In vitro evidence suggests that the scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) serves as a nodal organizer of hypertrophic signaling. However, the relevance of mAKAPβ signalosomes to pathological remodeling and heart failure in vivo remains unknown. Methods and Results Using conditional, cardiac myocyte–specific gene deletion, we now demonstrate that mAKAPβ expression in mice is important for the cardiac hypertrophy induced by pressure overload and catecholamine toxicity. mAKAPβ targeting prevented the development of heart failure associated with long-term transverse aortic constriction, conferring a survival benefit. In contrast to 29% of control mice (n=24), only 6% of mAKAPβ knockout mice (n=31) died in the 16 weeks of pressure overload (P=0.02). Accordingly, mAKAPβ knockout inhibited myocardial apoptosis and the development of interstitial fibrosis, left atrial hypertrophy, and pulmonary edema. This improvement in cardiac status correlated with the attenuated activation of signaling pathways coordinated by the mAKAPβ scaffold, including the decreased phosphorylation of protein kinase D1 and histone deacetylase 4 that we reveal to participate in a new mAKAP signaling module. Furthermore, mAKAPβ knockout inhibited pathological gene expression directed by myocyte-enhancer factor-2 and nuclear factor of activated T-cell transcription factors that associate with the scaffold. Conclusions mAKAPβ orchestrates signaling that regulates pathological cardiac remodeling in mice. Targeting of the underlying physical architecture of signaling networks, including mAKAPβ signalosome formation, may constitute an effective therapeutic strategy for the prevention and treatment of pathological remodeling and heart failure. PMID:24812305

  20. Delayed evacuatory function due to specific smooth muscle reactivity in the gastrointestinal tracts of tacrine-treated rats.

    PubMed

    Krustev, A; Sirakov, V; Turiiski, V; Getova, D; Velkova, K; Prissadova, N

    2008-01-01

    Most of the side effects induced by tacrine are associated with the gastrointestinal (GI) tract. The aim of the study was to analyze the nature of radiographically registered, tacrine-induced changes in evacuatory function, as well as to find a possible correlation with the immediate in vitro action of the drug on smooth muscles from the GI tracts of rats. The tacrine dose we used reliably delayed GI passage: contrast matter was not fully evacuated, predominantly from the stomach and cecum. The delay resulted from changes in tone and peristaltic activity, specific for the various regions of the tract. These changes were associated with a superposing of the responses due to the anticholinesterase and noncholinergic action of tacrine.

  1. Evidence towards improved estimation of respiratory muscle effort from diaphragm mechanomyographic signals with cardiac vibration interference using sample entropy with fixed tolerance values.

    PubMed

    Sarlabous, Leonardo; Torres, Abel; Fiz, José A; Jané, Raimon

    2014-01-01

    The analysis of amplitude parameters of the diaphragm mechanomyographic (MMGdi) signal is a non-invasive technique to assess respiratory muscle effort and to detect and quantify the severity of respiratory muscle weakness. The amplitude of the MMGdi signal is usually evaluated using the average rectified value or the root mean square of the signal. However, these estimations are greatly affected by the presence of cardiac vibration or mechanocardiographic (MCG) noise. In this study, we present a method for improving the estimation of the respiratory muscle effort from MMGdi signals that is robust to the presence of MCG. This method is based on the calculation of the sample entropy using fixed tolerance values (fSampEn), that is, with tolerance values that are not normalized by the local standard deviation of the window analyzed. The behavior of the fSampEn parameter was tested in synthesized mechanomyographic signals, with different ratios between the amplitude of the MCG and clean mechanomyographic components. As an example of application of this technique, the use of fSampEn was explored also in recorded MMGdi signals, with different inspiratory loads. The results with both synthetic and recorded signals indicate that the entropy parameter is less affected by the MCG noise, especially at low signal-to-noise ratios. Therefore, we believe that the proposed fSampEn parameter could improve estimates of respiratory muscle effort from MMGdi signals with the presence of MCG interference.

  2. Evidence towards Improved Estimation of Respiratory Muscle Effort from Diaphragm Mechanomyographic Signals with Cardiac Vibration Interference Using Sample Entropy with Fixed Tolerance Values

    PubMed Central

    Sarlabous, Leonardo; Torres, Abel; Fiz, José A.; Jané, Raimon

    2014-01-01

    The analysis of amplitude parameters of the diaphragm mechanomyographic (MMGdi) signal is a non-invasive technique to assess respiratory muscle effort and to detect and quantify the severity of respiratory muscle weakness. The amplitude of the MMGdi signal is usually evaluated using the average rectified value or the root mean square of the signal. However, these estimations are greatly affected by the presence of cardiac vibration or mechanocardiographic (MCG) noise. In this study, we present a method for improving the estimation of the respiratory muscle effort from MMGdi signals that is robust to the presence of MCG. This method is based on the calculation of the sample entropy using fixed tolerance values (fSampEn), that is, with tolerance values that are not normalized by the local standard deviation of the window analyzed. The behavior of the fSampEn parameter was tested in synthesized mechanomyographic signals, with different ratios between the amplitude of the MCG and clean mechanomyographic components. As an example of application of this technique, the use of fSampEn was explored also in recorded MMGdi signals, with different inspiratory loads. The results with both synthetic and recorded signals indicate that the entropy parameter is less affected by the MCG noise, especially at low signal-to-noise ratios. Therefore, we believe that the proposed fSampEn parameter could improve estimates of respiratory muscle effort from MMGdi signals with the presence of MCG interference. PMID:24586436

  3. Cardiac catheterization

    MedlinePlus

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

  4. Single adult rabbit and rat cardiac myocytes retain the Ca2+- and species-dependent systolic and diastolic contractile properties of intact muscle

    PubMed Central

    1986-01-01

    conclude that the widely divergent, Ca2+-dependent systolic and diastolic properties of intact rat and rabbit cardiac muscle are retained with a high degree of fidelity in the majority of viable single myocytes isolated from the myocardium of these species, and that these myocytes are thus a valid model for studies of Ca2+-dependent excitation- contraction mechanisms in the heart. PMID:3783125

  5. Fatal delayed cardiac tamponade due to rupture of micropseudoaneurysm of left anterior descending coronary artery following stab to the chest.

    PubMed

    Xing, Jingjun; Li, Shangxun; Zhang, Lin; Yang, Yi; Duan, Yijie; Li, Wenhe; Zhou, Yiwu

    2015-01-01

    Traumatic coronary pseudoaneurysm has been described to be mainly associated to iatrogenic lesion of the coronary arteries. However, chest-stab-wound-related coronary pseudoaneurysm caused by isolated partial incision of a coronary artery giving rise to fatal delayed cardiac tamponade is very rare. We describe an autopsy case in which this potentially fatal complication developed 8 days later after a thoracic stab wound. Unfortunately, the imaging examination failed to detect this defect during hospitalization. Postmortem examination revealed that the posterior wall of the left anterior descending coronary artery was intact but that the anterior wall was incised, forming a micropseudoaneurysm which had ruptured. This case highlights that isolated coronary artery injuries must be considered in any patient with a penetrating wound to the thorax, and coronary pseudoaneurysms should not be missed in these patients.

  6. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats.

    PubMed

    Dolinsky, Vernon W; Jones, Kelvin E; Sidhu, Robinder S; Haykowsky, Mark; Czubryt, Michael P; Gordon, Tessa; Dyck, Jason R B

    2012-06-01

    Exercise training (ET) improves endurance capacity by increasing both skeletal muscle mitochondrial number and function, as well as contributing to favourable cardiac remodelling.Interestingly, some of the benefits of regular exercise can also be mimicked by the naturally occurring polyphenol, resveratrol (RESV). However, it is not known whether RESV enhances physiological adaptations to ET. To investigate this, male Wistar rats were randomly assigned to a control chow diet or a chow diet that contained RESV (4 g kg⁻¹ of diet) and subsequently subjected to a programme of progressive treadmill running for 12 weeks. ET-induced improvements in exercise performance were enhanced by 21% (P <0.001) by the addition of RESV to the diet. In soleus muscle, ET+RESV increased both the twitch (1.8-fold; P <0.05) and tetanic(1.2-fold; P <0.05) forces generated during isometric contraction, compared to ET alone. In vivo echocardiography demonstrated that ET+RESV also increased the resting left ventricular ejection fraction by 10% (P <0.05), and reduced left ventricular wall stress compared to ET alone.These functional changes were accompanied by increased cardiac fatty acid oxidation (1.2-fold;P <0.05) and favourable changes in cardiac gene expression and signal transduction pathways that optimized the utilization of fatty acids in ET+RESV compared to ET alone. Overall, our findings provide evidence that the capacity for fatty acid oxidation is augmented by the addition of RESV to the diet during ET, and that this may contribute to the improved physical performance of rats following ET.

  7. Hypophosphatemia and phosphorus depletion in respiratory and peripheral muscles of patients with respiratory failure due to COPD.

    PubMed

    Fiaccadori, E; Coffrini, E; Fracchia, C; Rampulla, C; Montagna, T; Borghetti, A

    1994-05-01

    In 22 patients (19 men, 3 women; mean [+/- SD] age, 63 +/- 6 years) with chronic obstructive pulmonary disease (COPD), phosphorus content was measured by spectrophotometric methods on muscle fragments of both peripheral (quadriceps femoris needle biopsy in 22 patients) and respiratory muscles (external intercostal muscle surgical biopsy in 14 patients). Thirty age- and sex-matched subjects were used as controls (19 for quadriceps femoris muscle biopsy and 11 for intercostal muscle biopsy). Serum phosphorus levels, as well as the main determinants of overall phosphorus metabolism (dietary intake of phosphorus and renal phosphate handling), were also obtained in all patients and control subjects. Muscle phosphorus content of both respiratory and peripheral muscles was significantly reduced in the COPD patient group, no matter what reference index was used (fat-free dry muscle weight or muscle fragment DNA content); muscle phosphorus depletion was present in about 50 percent of patients with COPD. In the same patient group, a significant relationship between muscle and serum phosphorus levels was demonstrable in the case of peripheral muscles only. No relationship was found between phosphorus content of both types of skeletal muscles and dietary phosphorus intake levels or with nutritional status, even though patients with COPD had significantly reduced anthropometric, biochemical, and immunologic indices as compared with controls. Renal phosphorus handling indices of the COPD patient group were compatible with a condition of inadequacy of the renal compensatory mechanism to hypophosphatemia and phosphorus depletion (low percent tubular reabsorption of phosphorus, low renal threshold concentration values). Our study suggests that phosphorus depletion occurs frequently in COPD, but in this clinical condition serum phosphorus levels are not representative of cellular phosphorus levels. Phosphorus depletion, which is equally severe in respiratory and peripheral muscles

  8. Diffusion tensor imaging of the human calf muscle: distinct changes in fractional anisotropy and mean diffusion due to passive muscle shortening and stretching.

    PubMed

    Schwenzer, Nina F; Steidle, Günter; Martirosian, Petros; Schraml, Christina; Springer, Fabian; Claussen, Claus D; Schick, Fritz

    2009-12-01

    The influence of passive shortening and stretching of the calf muscles on diffusion characteristics was investigated. The diffusion tensor was measured in transverse slices through the lower leg of eight healthy volunteers (29 +/- 7 years) on a 3 T whole-body MR unit in three different positions of the foot (40 degrees plantarflexion, neutral ankle position (0 degrees ), and -10 degrees dorsiflexion in the ankle). Maps of the mean diffusivity, the three eigenvalues of the tensor and fractional anisotropy (FA) were calculated. Results revealed a distinct dependence of the mean diffusivity and FA on the foot position and the related shortening and stretching of the muscle groups. The tibialis anterior muscle showed a significant increase of 19% in FA with increasing dorsiflexion, while the FA of the antagonists significantly decreased ( approximately 20%). Regarding the mean diffusivity of the diffusion tensor, the muscle groups showed an opposed response to muscle elongation and shortening. Regarding the eigenvalues of the diffusion tensor, lambda(2) and lambda(3) showed significant changes in relation to muscle length. In contrast, no change in lambda(1) could be found. This work reveals significant changes in diffusional characteristics induced by passive muscle shortening and stretching.

  9. A case of tricuspid valve endocarditis due to Cardiobacterium hominis which emphasizes the shift between the poverty of clinical symptoms and the severity of cardiac damages.

    PubMed

    Molet, Lucie; Revest, Matthieu; Fournet, Maxime; Donal, Erwan; Bonnaure-Mallet, Martine; Minet, Jacques; Le Bars, Hervé

    2016-12-01

    Infectious endocarditis due to Cardiobacterium hominis is an uncommon event, accounting for less than 2% of all cases of infectious endocarditis. The infection of the tricuspid valve as it is reported here is extremely rare. We report the case of a tricuspid endocarditis due to Cardiobacterium hominis in a 56 year-old man who was admitted to hospital with pelvic and scapular pain. The diagnosis was established through positive blood cultures and echographic detection of a large tricuspid vegetation. Despite efficient antibiotic therapy, valve replacement was required. The clinical course of Cardiobacterium endocarditis is usually subacute, and the diagnosis may therefore be delayed. This case emphasizes the shift between the poverty of clinical symptoms and severity of cardiac damages, what we could call the Cardiobacterium paradox.

  10. Muscle-specific AMPK β1β2-null mice display a myopathy due to loss of capillary density in nonpostural muscles.

    PubMed

    Thomas, Melissa M; Wang, David C; D'Souza, Donna M; Krause, Matthew P; Layne, Andrew S; Criswell, David S; O'Neill, Hayley M; Connor, Michael K; Anderson, Judy E; Kemp, Bruce E; Steinberg, Gregory R; Hawke, Thomas J

    2014-05-01

    AMP-activated protein kinase (AMPK) is a master regulator of metabolism. While muscle-specific AMPK β1β2 double-knockout (β1β2M-KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary β1β2M-KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial- and fiber-type-specific etiology to the myopathy was ruled out. However, β1β2M-KO TA muscles displayed significant (P<0.05) increases in platelet aggregation and apoptosis within myofibers and surrounding interstitium (P<0.05). These changes correlated with a 45% decrease in capillary density (P<0.05). We hypothesized that the β1β2M-KO myopathy in resting muscle resulted from impaired AMPK-nNOSμ signaling, causing increased platelet aggregation, impaired vasodilation, and, ultimately, ischemic injury. Consistent with this hypothesis, AMPK-specific phosphorylation (Ser1446) of nNOSμ was decreased in β1β2M-KO compared to wild-type (WT) mice. The AMPK-nNOSμ relationship was further demonstrated by administration of 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) to β1β2-MKO muscles and C2C12 myotubes. AICAR significantly increased nNOSμ phosphorylation and nitric oxide production (P<0.05) within minutes of administration in WT muscles and C2C12 myotubes but not in β1β2M-KO muscles. These findings highlight the importance of the AMPK-nNOSμ pathway in resting skeletal muscle.

  11. Muscle Weakness and Fibrosis Due to Cell Autonomous and Non-cell Autonomous Events in Collagen VI Deficient Congenital Muscular Dystrophy.

    PubMed

    Noguchi, Satoru; Ogawa, Megumu; Malicdan, May Christine; Nonaka, Ikuya; Nishino, Ichizo

    2017-02-01

    Congenital muscular dystrophies with collagen VI deficiency are inherited muscle disorders with a broad spectrum of clinical presentation and are caused by mutations in one of COL6A1-3 genes. Muscle pathology is characterized by fiber size variation and increased interstitial fibrosis and adipogenesis. In this study, we define critical events that contribute to muscle weakness and fibrosis in a mouse model with collagen VI deficiency. The Col6a1(GT/GT) mice develop non-progressive weakness from younger age, accompanied by stunted muscle growth due to reduced IGF-1 signaling activity. In addition, the Col6a1(GT/GT) mice have high numbers of interstitial skeletal muscle mesenchymal progenitor cells, which dramatically increase with repeated myofiber necrosis/regeneration. Our results suggest that impaired neonatal muscle growth and the activation of the mesenchymal cells in skeletal muscles contribute to the pathology of collagen VI deficient muscular dystrophy, and more importantly, provide the insights on the therapeutic strategies for collagen VI deficiency.

  12. Cardiac Cephalgia

    PubMed Central

    Wassef, Nancy; Ali, Ali Turab; Katsanevaki, Alexia-Zacharoula; Nishtar, Salman

    2014-01-01

    Although most of the patients presenting with ischemic heart disease have chest pains, there are other rare presenting symptoms like cardiac cephalgia. In this report, we present a case of acute coronary syndrome with an only presentation of exertional headache. It was postulated as acute presentation of coronary artery disease, due to previous history of similar presentation associated with some chest pains with previous left coronary artery stenting. We present an unusual case with cardiac cephalgia in a young patient under the age of 50 which was not reported at that age before. There are four suggested mechanisms for this cardiac presentation. PMID:28352454

  13. Single myosin cross-bridge orientation in cardiac papillary muscle detects lever-arm shear strain in transduction.

    PubMed

    Burghardt, Thomas P; Josephson, Matthew P; Ajtai, Katalin

    2011-09-13

    Myosin motors transduce ATP free energy into mechanical work. Transduction models allocate specific functions to motor structural domains beginning with ATP hydrolysis in the active site and ending in a lever-arm rotating power-stroke. Myosin light chains, regulatory (RLC) and essential (ELC), bind IQ-domains on the lever-arm and track its movement. Strong evidence exists that light chains stabilize the lever-arm and that light chain mutation undermines stability. Human ventricular RLC tagged with photoactivatable GFP (HCRLC-PAGFP) replaces native RLC in porcine papillary muscle fibers, restores native contractility, and situates PAGFP for single molecule orientation tracking within the crowded fiber lattice. The spatial emission pattern from single photoactivated PAGFP tagged myosins was observed in z-stacks fitted simultaneously to maximize accuracy in estimated dipole orientation. Emitter dipole polar and azimuthal angle pair scatter plots identified an area where steric and molecular crowding constraints depopulated orientations unfavorable for actin interaction. Transitions between pre- and post-power-stroke states represent the lever-arm trajectory sampled by the data and quantify lever-arm shear strain in transduction at three tension levels. These data identify forces acting on myosin in the in situ fiber system due to crowding, steric hindrance, and actomyosin interaction. They induce lever-arm shear strain observed with single molecule orientation detection. A single myosin work histogram reveals discretized power-stroke substates reminiscent of the Huxley-Simmons model for myosin based contraction [Huxley and Simmons ( 1971 ) Nature 233 , 533]. RLC or ELC mutation, should it impact lever-arm shear strain, will be detected as changes in single myosin shear strain or power-stroke substate distribution.

  14. Single Myosin Cross-Bridge Orientation in Cardiac Papillary Muscle Detects Lever-Arm Shear Strain in Transduction

    PubMed Central

    Burghardt, Thomas P.; Josephson, Matthew P.; Ajtai, Katalin

    2011-01-01

    Myosin motors transduce ATP free energy into mechanical work. Transduction models allocate specific functions to motor structural domains beginning with ATP hydrolysis in the active site and ending in a lever-arm rotating power-stroke. Myosin light chains, regulatory (RLC) and essential (ELC), bind IQ-domains on the lever-arm and track its movement. Strong evidence exists that light chains stabilize the lever-arm and that light chain mutation undermines stability. Human ventricular RLC tagged with photoactivatable GFP (HCRLC-PAGFP) replaces native RLC in porcine papillary muscle fibers, restores native contractility, and situates PAGFP for single molecule orientation tracking within the crowded fiber lattice. The spatial emission pattern from single photoactivated PAGFP tagged myosins was observed in z-stacks fitted simultaneously to maximize accuracy in estimated dipole orientation. Emitter dipole polar and azimuthal angle pair scatter plots identified an area where steric and molecular crowding constraints depopulated orientations unfavorable for actin interaction. Transitions between pre- and post-power-stroke states represent the lever-arm trajectory sampled by the data and quantify lever-arm shear strain in transduction at three tension levels. These data identify forces acting on myosin in the in situ fiber system due to crowding, steric hindrance, and actomyosin interaction. They induce lever-arm shear strain observed with single molecule orientation detection. A single myosin work histogram reveals discretized power-stroke substates reminiscent of the Huxley–Simmons model for myosin based contraction [Huxley and Simmons (1971) Nature 233, 533]. RLC or ELC mutation, should it impact lever-arm shear strain, will be detected as changes in single myosin shear strain or power-stroke substate distribution. PMID:21819137

  15. Stem cell sources for cardiac regeneration.

    PubMed

    Roccio, M; Goumans, M J; Sluijter, J P G; Doevendans, P A

    2008-03-01

    Cell-based cardiac repair has the ambitious aim to replace the malfunctioning cardiac muscle developed after myocardial infarction, with new contractile cardiomyocytes and vessels. Different stem cell populations have been intensively studied in the last decade as a potential source of new cardiomyocytes to ameliorate the injured myocardium, compensate for the loss of ventricular mass and contractility and eventually restore cardiac function. An array of cell types has been explored in this respect, including skeletal muscle, bone marrow derived stem cells, embryonic stem cells (ESC) and more recently cardiac progenitor cells. The best-studied cell types are mouse and human ESC cells, which have undisputedly been demonstrated to differentiate into cardiomyocyte and vascular lineages and have been of great help to understand the differentiation process of pluripotent cells. However, due to their immunogenicity, risk of tumor development and the ethical challenge arising from their embryonic origin, they do not provide a suitable cell source for a regenerative therapy approach. A better option, overcoming ethical and allogenicity problems, seems to be provided by bone marrow derived cells and by the recently identified cardiac precursors. This report will overview current knowledge on these different cell types and their application in cardiac regeneration and address issues like implementation of delivery methods, including tissue engineering approaches that need to be developed alongside.

  16. The emergence of Pax7-expressing muscle stem cells during vertebrate head muscle development

    PubMed Central

    Nogueira, Julia Meireles; Hawrot, Katarzyna; Sharpe, Colin; Noble, Anna; Wood, William M.; Jorge, Erika C.; Goldhamer, David J.; Kardon, Gabrielle; Dietrich, Susanne

    2015-01-01

    Pax7 expressing muscle stem cells accompany all skeletal muscles in the body and in healthy individuals, efficiently repair muscle after injury. Currently, the in vitro manipulation and culture of these cells is still in its infancy, yet muscle stem cells may be the most promising route toward the therapy of muscle diseases such as muscular dystrophies. It is often overlooked that muscular dystrophies affect head and body skeletal muscle differently. Moreover, these muscles develop differently. Specifically, head muscle and its stem cells develop from the non-somitic head mesoderm which also has cardiac competence. To which extent head muscle stem cells retain properties of the early head mesoderm and might even be able to switch between a skeletal muscle and cardiac fate is not known. This is due to the fact that the timing and mechanisms underlying head muscle stem cell development are still obscure. Consequently, it is not clear at which time point one should compare the properties of head mesodermal cells and head muscle stem cells. To shed light on this, we traced the emergence of head muscle stem cells in the key vertebrate models for myogenesis, chicken, mouse, frog and zebrafish, using Pax7 as key marker. Our study reveals a common theme of head muscle stem cell development that is quite different from the trunk. Unlike trunk muscle stem cells, head muscle stem cells do not have a previous history of Pax7 expression, instead Pax7 expression emerges de-novo. The cells develop late, and well after the head mesoderm has committed to myogenesis. We propose that this unique mechanism of muscle stem cell development is a legacy of the evolutionary history of the chordate head mesoderm. PMID:26042028

  17. The protective effects of Chinese herb-Taikong Yangxin Prescription on the atrophic remodeling of cardiac muscle in rats induced by hindlimb unloading through activating Akt/GSK-3beta signaling pathway

    NASA Astrophysics Data System (ADS)

    Ming, Yuan; Min, Yuan; Jianfeng, Zhang; Zhili, Li; Huijuan, Wang; Desheng, Wang; Yinghui, Li; Yongzhi, Li; Shizhong, Jiang

    Objective To test the hypothesis that traditional Chinese herb-TaiKong Yangxin Prescrip-tion can activate the Akt/GSK-3β signaling pathway and alleviate the atrophic remodeling of cardiac muscle in rats induced by hindlimb unloading. Methods The physiological effects of simulated microgravity was induced by 7d hindlimb unloading in rats. TaiKong Yangxin Pre-scription was given daily by gastric irrigation as countermeasure against effects of simulated microgravity. The frozen sections of left ventricular cardiac muscles were stained by FITC la-beled lectin and visualized by laser scanning confocal microscopy, the cross section areas(CSA) of cardiomyocytes were calculated by IPP6.0 Image software. The protein expression of TnI, phosphorylation level of Akt and GSK-3β were measured by Western blot. Results Simulated microgravity decreased the CSA of cardiomyocytes and protein expression of TnI in left ven-tricular cardiac muscles, inhibited the phosphorylation level of Akt at serine 473 and GSK-3β at serine 9. The traditional Chinese herb-TaiKong Yangxin Prescription alleviated the atrophic remodeling of cardiac muscles, reversed the declined protein expression of TnI and phosphoryla-tion levels of Akt at serine 473 and GSK-3β at serine 9 in hindlimb-unloading rats. Conclusion The traditional Chinese herb-TaiKong Yangxin Prescription has significant countermeasure effects on the atrophic remodeling of cardiac muscle induced by hindlimb unloading in rats, in which activating Akt/GSK-3β signaling pathway plays an important role.(Funded by Advanced space medico-engineering research project of China, grant NO. 2005SY5206005 and SJ200801)

  18. Radiofrequency energy loop primes cardiac, neuronal, and skeletal muscle differentiation in mouse embryonic stem cells: a new tool for improving tissue regeneration.

    PubMed

    Maioli, Margherita; Rinaldi, Salvatore; Santaniello, Sara; Castagna, Alessandro; Pigliaru, Gianfranco; Gualini, Sara; Fontani, Vania; Ventura, Carlo

    2012-01-01

    Radiofrequency (RF) waves from Wi-Fi (wireless fidelity) technologies have become ubiquitous, with Internet access spreading into homes, and public areas. The human body harbors multipotent stem cells with various grading of potentiality. Whether stem cells may be affected by Wi-Fi RF energy remains unknown. We exposed mouse embryonic stem (ES) cells to a Radio Electric Asymmetric Conveyer (REAC), an innovative device delivering Wi-Fi RF of 2.4 GHz with its conveyer electrodes immersed into the culture medium. Cell responses were investigated by real-time PCR, Western blot, and confocal microscopy. Single RF burst duration, radiated power, electric and magnetic fields, specific absorption rate, and current density in culture medium were monitored. REAC stimulation primed transcription of genes involved in cardiac (GATA4, Nkx-2.5, and prodynorphin), skeletal muscle (myoD) and neuronal (neurogenin1) commitment, while downregulating the self renewal/pluripotency-associated genes Sox2, Oct4, and Nanog. REAC exposure enhanced the expression of cardiac, skeletal, and neuronal lineage-restricted marker proteins. The number of spontaneously beating ES-derived myocardial cells was also increased. In conclusion, REAC stimulation provided a "physical milieu" optimizing stem cell expression of pluripotentiality and the attainment of three major target lineages for regenerative medicine, without using chemical agonists or vector-mediated gene delivery.

  19. [Histopathological and immunohistochemical features of cardiac myxomas].

    PubMed

    Hernández-Bringas, Omar; Ortiz-Hidalgo, Carlos

    2013-01-01

    Mixomas are the most common primary cardiac tumors with an estimate incidence of 0,5-1 per 10(6) individuals per year. These tumors have generated interest due to their unique location (left side of the atrial septum near the fossa ovalis), variable clinical presentation and undefined histogenesis. Most cardiac myxomas occur sporadically while approximately 10% of diagnosed cases develop as part of Carney complex. This neoplasm is of uncertain histogenesis, however, endothelial, neurogenic, fibroblastic, and cardiac and smooth muscle cells differentiation has been proposed, and rarely glandular differentiation has been observed. Recently, due to the expression of certain cardiomyocyte-specific factors, an origin of mesenchymal cardiomyocytes progenitor cells has been suggested. Histologically cardiac myxomas are mainly composed of stellated, fusiform and polygonal cells, immersed in an amorphous myxoid matrix. Immunohistochemically some endothelial markers, such as CD31, CD34, FVIIIAg, are present. Positive staining has also been reported for S-100 protein, calretinin, vimentin, desmin, smooth muscle myosin, CD56, α1 antitrypsin and α 1antichymotrypsin. Surgical resection is currently the only treatment of choice. We present in this article a histopathological and immunohistochemical review of cardiac myxomas.

  20. An Objective Functional Characterisation of Head Movement Impairment in Individuals with Neck Muscle Weakness Due to Amyotrophic Lateral Sclerosis

    PubMed Central

    Pancani, Silvia; Tindale, Wendy; Shaw, Pamela J.

    2017-01-01

    Background Neck muscle weakness and head drop are well recognised in patients with Amyotrophic lateral sclerosis (ALS), but an objective characterisation of the consequent head movement impairment is lacking. The aim of this study was to quantitatively characterise head movements in ALS compared to aged matched controls. Methods We evaluated two groups, one of thirteen patients with ALS and one of thirteen age-matched controls, during the execution of a series of controlled head movements, performed while wearing two inertial sensors attached on the forehead and sternum, respectively. We quantified the differences between the two groups from the sensor data using indices of velocity, smoothness and movement coupling (intended as a measure of undesired out of plane movements). Findings Results confirmed a general limitation in the ability of the ALS patients to perform and control head movements. High inter-patient variability was observed due to a wide range of observed functional impairment levels. The ability to extend the head backward and flex it laterally were the most compromised, with significantly lower angular velocity (P < 0.05, Cohen’s d > 0.8), reduced smoothness and greater presence of coupled movements with respect to the controls. A significant reduction of angular velocity (P < 0.05, Cohen’s d > 0.8) in extension, axial rotation and lateral flexion was observed when patients were asked to perform the movements as fast as possible. Interpretation This pilot study is the first study providing a functional objective quantification of head movements in ALS. Further work involving different body areas and correlation with existing methods of evaluating neuromuscular function, such as dynamometry and EMG, is needed to explore the use of this approach as a marker of disease progression in ALS. PMID:28068376

  1. Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia.

    PubMed

    Yoshida, Tadashi; Tabony, A Michael; Galvez, Sarah; Mitch, William E; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

    2013-10-01

    Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5' AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

  2. Studies of the voltage-sensitive calcium channels in smooth muscle, neuronal, and cardiac tissues using 1,4-dihydropyridine calcium channel antagonists and activators

    SciTech Connect

    Wei, X.

    1988-01-01

    This study describes the investigation of the voltage-sensitive Ca{sup +} channels in vascular and intestinal smooth muscle, chick neural retina cells and neonatal rat cardiac myocytes using 1,4-dihydropyridine Ca{sup 2+} channel antagonists and activators. In rat aorta, the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) produced Ca{sup 2+}-dependent contractile responses. The responses to TPA were blocked by the Ca{sup 2+} channel antagonists. The effects of the enantiomers of Bay K 8644 and 202-791 were characterized in both rat tail artery and guinea pig ileal longitudinal smooth muscle preparations using pharmacologic and radioligand binding assays. The (S)-enantiomers induced contraction and potentiated the responses to K{sup +} depolarization. The (R)-enantiomers inhibited the tension responses to K{sup +}. All the enantiomers inhibited specific ({sup 3}H)nitrendipine binding. The pharmacologic activities of both activator and antagonist ligands correlated on a 1:1 basis with the binding affinities. In chick neural retina cells the (S)-enantiomers of Bay K 8644 and 202-791 enhanced Ca{sup 2+} influx. In contrast, the (R)-enantiomers inhibited Ca{sup 2+} influx. The enantiomers of Bay K 8644 and 202-791 inhibited specific ({sup 3}H)PN 200-110 binding competitively. Binding of 1,4-dihydropyridines was characterized in neonatal rat heart cells.

  3. Determination of cardiac size following space missions of different durations - The second manned Skylab mission

    NASA Technical Reports Server (NTRS)

    Nicogossian, A.; Hoffler, G. W.; Johnson, R. L.; Gowen, R. J.

    1976-01-01

    A simple method to estimate cardiac size from single frontal plane chest roentgenograms has been described. Pre- and postflight chest X-rays from Apollo 17, and Skylab 2 and 3 have been analyzed for changes in the cardiac silhouette size. The data obtained from the computed cardiothoracic areal ratios compared well with the clinical cardiothoracic diametral ratios (r = .86). Though an overall postflight decrease in cardiac size is evident, the mean difference was not statistically significant (n = 8). The individual decreases in the cardiac silhouette size postflight are thought to be due to decrements in intracardiac chamber volumes rather than in myocardial muscle mass.

  4. Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development

    PubMed Central

    Brunt, Lucy H.; Norton, Joanna L.; Bright, Jen A.; Rayfield, Emily J.; Hammond, Chrissy L.

    2015-01-01

    Abnormal joint morphogenesis is linked to clinical conditions such as Developmental Dysplasia of the Hip (DDH) and to osteoarthritis (OA). Muscle activity is known to be important during the developmental process of joint morphogenesis. However, less is known about how this mechanical stimulus affects the behaviour of joint cells to generate altered morphology. Using zebrafish, in which we can image all joint musculoskeletal tissues at high resolution, we show that removal of muscle activity through anaesthetisation or genetic manipulation causes a change to the shape of the joint between the Meckel's cartilage and Palatoquadrate (the jaw joint), such that the joint develops asymmetrically leading to an overlap of the cartilage elements on the medial side which inhibits normal joint function. We identify the time during which muscle activity is critical to produce a normal joint. Using Finite Element Analysis (FEA), to model the strains exerted by muscle on the skeletal elements, we identify that minimum principal strains are located at the medial region of the joint and interzone during mouth opening. Then, by studying the cells immediately proximal to the joint, we demonstrate that biomechanical strain regulates cell orientation within the developing joint, such that when muscle-induced strain is removed, cells on the medial side of the joint notably change their orientation. Together, these data show that biomechanical forces are required to establish symmetry in the joint during development. PMID:26253758

  5. Dosimetric perturbations due to an implanted cardiac pacemaker in MammoSite{sup Registered-Sign} treatment

    SciTech Connect

    Sung, Wonmo; Kim, Siyong; Kim, Jung-in; Lee, Jae-gi; Shin, Young-Joo; Jung, Jae-Yong; Ye, Sung-Joon

    2012-10-15

    Purpose: To investigate dose perturbations for pacemaker-implanted patients in partial breast irradiation using high dose rate (HDR) balloon brachytherapy. Methods: Monte Carlo (MC) simulations were performed to calculate dose distributions involving a pacemaker in Ir-192 HDR balloon brachytherapy. Dose perturbations by varying balloon-to-pacemaker distances (BPD = 50 or 100 mm) and concentrations of iodine contrast medium (2.5%, 5.0%, 7.5%, and 10.0% by volume) in the balloon were investigated for separate parts of the pacemaker (i.e., battery and substrate). Relative measurements using an ion-chamber were also performed to confirm MC results. Results: The MC and measured results in homogeneous media without a pacemaker agreed with published data within 2% from the balloon surface to 100 mm BPD. Further their dose distributions with a pacemaker were in a comparable agreement. The MC results showed that doses over the battery were increased by a factor of 3, compared to doses without a pacemaker. However, there was no significant dose perturbation in the middle of substrate but up to 70% dose increase in the substrate interface with the titanium capsule. The attenuation by iodine contrast medium lessened doses delivered to the pacemaker by up to 9%. Conclusions: Due to inhomogeneity of pacemaker and contrast medium as well as low-energy photons in Ir-192 HDR balloon brachytherapy, the actual dose received in a pacemaker is different from the homogeneous medium-based dose and the external beam-based dose. Therefore, the dose perturbations should be considered for pacemaker-implanted patients when evaluating a safe clinical distance between the balloon and pacemaker.

  6. Residues of sulfadiazine and doxycycline in broiler liver and muscle tissue due to cross-contamination of feed.

    PubMed

    Vandenberge, V; Delezie, E; Huyghebaert, G; Delahaut, P; Daeseleire, E; Croubels, S

    2012-01-01

    Veterinary drugs, such as antimicrobial compounds, are widely used in poultry and may lead to the presence of residues in matrices of animal origin, such as muscle and liver tissue. In this study, broilers received an experimental feed containing sulfadiazine or doxycycline at cross-contamination levels of 2.5, 5 and 10% of the therapeutic dose in feed. Breast and thigh muscle and liver samples were collected during treatment and depletion period and analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations reached a plateau phase 3-5 days after the start of experimental feeding. A rapid depletion of residues was noted after withdrawal of the experimental feed. No significant differences in measured concentrations were observed between the various muscle types. Residue concentrations for some experimental groups; the 10% group of sulfadiazine and the 5 and 10% group of doxycycline, however, exceeded their corresponding maximum residue limits (MRLs).

  7. HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect.

    PubMed

    Guiraud, Simon; Migeon, Tiffany; Ferry, Arnaud; Chen, Zhiyong; Ouchelouche, Souhila; Verpont, Marie-Christine; Sado, Yoshikazu; Allamand, Valérie; Ronco, Pierre; Plaisier, Emmanuelle

    2017-03-01

    Collagen IV is a major component of basement membranes (BMs). The α1(IV) chain, encoded by the COL4A1 gene, is expressed ubiquitously and associates with the α2(IV) chain to form the α1α1α2(IV) heterotrimer. Several COL4A1 mutations affecting a conformational domain containing integrin-binding sites are responsible for the systemic syndrome of hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC). To analyze the pathophysiology of HANAC, Col4a1 mutant mice bearing the p.Gly498Val mutation were generated. Analysis of the skeletal muscles of Col4a1(G498V) mutant animals showed morphologic characteristics of a muscular dystrophy phenotype with myofiber atrophy, centronucleation, focal inflammatory infiltrates, and fibrosis. Abnormal ultrastructural aspects of muscle BMs was associated with reduced extracellular secretion of the mutant α1α1α2(IV) trimer. In addition to muscular dystrophic features, endothelial cell defects of the muscle capillaries were observed, with intracytoplasmic accumulation of the mutant α1α1α2(IV) molecules, endoplasmic reticulum cisternae dilation, and up-regulation of endoplasmic reticulum stress markers. Induction of the unfolded protein response in Col4a1 mutant muscle tissue resulted in an excess of apoptosis in endothelial cells. HANAC mutant animals also presented with a muscular functional impairment and increased serum creatine kinase levels reflecting altered muscle fiber sarcolemma. This extensive description of the muscular phenotype of the Col4a1 HANAC murine model suggests a potential contribution of primary endothelial cell defects, together with muscle BM alterations, to the development of COL4A1-related myopathy.

  8. Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis.

    PubMed

    Cox, P M; Brueton, L A; Murphy, K W; Worthington, V C; Bjelogrlic, P; Lazda, E J; Sabire, N J; Sewry, C A

    1999-09-10

    We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. Autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester.

  9. Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction.

    PubMed

    Bednar, Frantisek; Kroupa, Josef; Ondrakova, Martina; Osmancik, Pavel; Kopa, Milos; Motovska, Zuzana

    2016-05-01

    Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

  10. A conserved MADS-box phosphorylation motif regulates differentiation and mitochondrial function in skeletal, cardiac, and smooth muscle cells.

    PubMed

    Mughal, W; Nguyen, L; Pustylnik, S; da Silva Rosa, S C; Piotrowski, S; Chapman, D; Du, M; Alli, N S; Grigull, J; Halayko, A J; Aliani, M; Topham, M K; Epand, R M; Hatch, G M; Pereira, T J; Kereliuk, S; McDermott, J C; Rampitsch, C; Dolinsky, V W; Gordon, J W

    2015-10-29

    Exposure to metabolic disease during fetal development alters cellular differentiation and perturbs metabolic homeostasis, but the underlying molecular regulators of this phenomenon in muscle cells are not completely understood. To address this, we undertook a computational approach to identify cooperating partners of the myocyte enhancer factor-2 (MEF2) family of transcription factors, known regulators of muscle differentiation and metabolic function. We demonstrate that MEF2 and the serum response factor (SRF) collaboratively regulate the expression of numerous muscle-specific genes, including microRNA-133a (miR-133a). Using tandem mass spectrometry techniques, we identify a conserved phosphorylation motif within the MEF2 and SRF Mcm1 Agamous Deficiens SRF (MADS)-box that regulates miR-133a expression and mitochondrial function in response to a lipotoxic signal. Furthermore, reconstitution of MEF2 function by expression of a neutralizing mutation in this identified phosphorylation motif restores miR-133a expression and mitochondrial membrane potential during lipotoxicity. Mechanistically, we demonstrate that miR-133a regulates mitochondrial function through translational inhibition of a mitophagy and cell death modulating protein, called Nix. Finally, we show that rodents exposed to gestational diabetes during fetal development display muscle diacylglycerol accumulation, concurrent with insulin resistance, reduced miR-133a, and elevated Nix expression, as young adult rats. Given the diverse roles of miR-133a and Nix in regulating mitochondrial function, and proliferation in certain cancers, dysregulation of this genetic pathway may have broad implications involving insulin resistance, cardiovascular disease, and cancer biology.

  11. The effect of eight weeks resistance and aerobic training on myostatin and follistatin expression in cardiac muscle of rats

    PubMed Central

    Rashidlamir, Amir; Attarzadeh Hosseini, Seyyed Reza; Hejazi, Keyvan; Motevalli Anberani, Seyyed Mohamad

    2016-01-01

    Introduction: The clinical studies have shown that the myostatin gene expression and its serum density occur more frequently in heart patients than in healthy individuals. The purpose of this study is to investigate the influence of 8-week resistance and aerobic exercise on the myostatin and follistatin gene expression of myocardium muscle of healthy male Wistar rats. Methods: In this experimental study, 20 five-week-old adult Wistar rats (250 ± 26.5 g) were divided into three groups: healthy control group (n = 6), resistance exercise group (n = 7), and aerobic exercise group (n = 7). The resistance and aerobic exercise plan consisted of 8 weeks and 3 sessions per week. The resistance exercise group performed climbing a one-meter 26-stair ladder with a slope of 85 degrees for 3 sets of 5 repetitions per session. The aerobic exercise group performed running at a speed of 12 meters per minute for 30 minutes during the first sessions gradually increasing up to a speed of 30 meters per minute for 60 minutes during the final sessions (equivalent to 70% to 80% of maximum oxygen consumption). The differences between the groups were evaluated using a one-way analysis of variance (ANOVA) test. When appropriate, LSD post-hoc test was used. The significance level for the study was less than 0.05. Results: The results of this study shows that after 8 weeks of exercise, there is no significant difference between myostatin mRNA gene expression levels of the heart muscle among the three groups of control, resistance exercise, and aerobic exercise (P = 0.172, F = 1.953). However, the mean differences between follistatin mRNA levels of the heart muscle among the three groups of control, resistance exercise, and aerobic exercise are statistically significant (F = 38.022, P = 0.001). Furthermore, the ratio of follistatin to myostatin mRNA gene expression of the heart muscle (P = 0.001, F = 10.288) shows significant difference among the three groups. Conclusion: Our results indicate

  12. The effect of eight weeks resistance and aerobic training on myostatin and follistatin expression in cardiac muscle of rats.

    PubMed

    Rashidlamir, Amir; Attarzadeh Hosseini, Seyyed Reza; Hejazi, Keyvan; Motevalli Anberani, Seyyed Mohamad

    2016-01-01

    Introduction: The clinical studies have shown that the myostatin gene expression and its serum density occur more frequently in heart patients than in healthy individuals. The purpose of this study is to investigate the influence of 8-week resistance and aerobic exercise on the myostatin and follistatin gene expression of myocardium muscle of healthy male Wistar rats. Methods: In this experimental study, 20 five-week-old adult Wistar rats (250 ± 26.5 g) were divided into three groups: healthy control group (n = 6), resistance exercise group (n = 7), and aerobic exercise group (n = 7). The resistance and aerobic exercise plan consisted of 8 weeks and 3 sessions per week. The resistance exercise group performed climbing a one-meter 26-stair ladder with a slope of 85 degrees for 3 sets of 5 repetitions per session. The aerobic exercise group performed running at a speed of 12 meters per minute for 30 minutes during the first sessions gradually increasing up to a speed of 30 meters per minute for 60 minutes during the final sessions (equivalent to 70% to 80% of maximum oxygen consumption). The differences between the groups were evaluated using a one-way analysis of variance (ANOVA) test. When appropriate, LSD post-hoc test was used. The significance level for the study was less than 0.05. Results: The results of this study shows that after 8 weeks of exercise, there is no significant difference between myostatin mRNA gene expression levels of the heart muscle among the three groups of control, resistance exercise, and aerobic exercise (P = 0.172, F = 1.953). However, the mean differences between follistatin mRNA levels of the heart muscle among the three groups of control, resistance exercise, and aerobic exercise are statistically significant (F = 38.022, P = 0.001). Furthermore, the ratio of follistatin to myostatin mRNA gene expression of the heart muscle (P = 0.001, F = 10.288) shows significant difference among the three groups. Conclusion: Our results indicate

  13. TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: Co-localization at z-discs, costameres and intercalated discs

    PubMed Central

    Andrei, Spencer R.; Sinharoy, Pritam; Bratz, Ian N.; Damron, Derek S.

    2016-01-01

    ABSTRACT Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) and vanilloid subtype-1 (TRPV1) are structurally related, non-selective cation channels that show a high permeability to calcium. Previous studies indicate that TRP channels play a prominent role in the regulation of cardiovascular dynamics and homeostasis, but also contribute to the pathophysiology of many diseases and disorders within the cardiovascular system. However, no studies to date have identified the functional expression and/or intracellular localization of TRPA1 in primary adult mouse ventricular cardiomyocytes (CMs). Although TRPV1 has been implicated in the regulation of cardiac function, there is a paucity of information regarding functional expression and localization of TRPV1 in adult CMs. Our current studies demonstrate that TRPA1 and TRPV1 ion channels are co-expressed at the protein level in CMs and both channels are expressed throughout the endocardium, myocardium and epicardium. Moreover, immunocytochemical localization demonstrates that both channels predominantly colocalize at the Z-discs, costameres and intercalated discs. Furthermore, specific TRPA1 and TRPV1 agonists elicit dose-dependent, transient rises in intracellular free calcium concentration ([Ca2+]i) that are abolished in CMs obtained from TRPA1−/− and TRPV1−/− mice. Similarly, we observed a dose-dependent attenuation of the TRPA1 and TRPV1 agonist-induced increase in [Ca2+]i when WT CMs were pretreated with increasing concentrations of selective TRPA1 or TRPV1 channel antagonists. In summary, these findings demonstrate functional expression and the precise ultrastructural localization of TRPA1 and TRPV1 ion channels in freshly isolated mouse CMs. Crosstalk between TRPA1 and TRPV1 may be important in mediating cellular signaling events in cardiac muscle. PMID:27144598

  14. TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: Co-localization at z-discs, costameres and intercalated discs.

    PubMed

    Andrei, Spencer R; Sinharoy, Pritam; Bratz, Ian N; Damron, Derek S

    2016-09-02

    Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) and vanilloid subtype-1 (TRPV1) are structurally related, non-selective cation channels that show a high permeability to calcium. Previous studies indicate that TRP channels play a prominent role in the regulation of cardiovascular dynamics and homeostasis, but also contribute to the pathophysiology of many diseases and disorders within the cardiovascular system. However, no studies to date have identified the functional expression and/or intracellular localization of TRPA1 in primary adult mouse ventricular cardiomyocytes (CMs). Although TRPV1 has been implicated in the regulation of cardiac function, there is a paucity of information regarding functional expression and localization of TRPV1 in adult CMs. Our current studies demonstrate that TRPA1 and TRPV1 ion channels are co-expressed at the protein level in CMs and both channels are expressed throughout the endocardium, myocardium and epicardium. Moreover, immunocytochemical localization demonstrates that both channels predominantly colocalize at the Z-discs, costameres and intercalated discs. Furthermore, specific TRPA1 and TRPV1 agonists elicit dose-dependent, transient rises in intracellular free calcium concentration ([Ca(2+)]i) that are abolished in CMs obtained from TRPA1(-/-) and TRPV1(-/-) mice. Similarly, we observed a dose-dependent attenuation of the TRPA1 and TRPV1 agonist-induced increase in [Ca(2+)]i when WT CMs were pretreated with increasing concentrations of selective TRPA1 or TRPV1 channel antagonists. In summary, these findings demonstrate functional expression and the precise ultrastructural localization of TRPA1 and TRPV1 ion channels in freshly isolated mouse CMs. Crosstalk between TRPA1 and TRPV1 may be important in mediating cellular signaling events in cardiac muscle.

  15. [Parameters of cardiac muscle repolarization on the electrocardiogram when changing anatomical and electric position of the heart].

    PubMed

    Chaĭkovskiĭ, I A; Baum, O V; Popov, L A; Voloshin, V I; Budnik, N N; Frolov, Iu A; Kovalenko, A S

    2014-01-01

    While discussing the diagnostic value of the single channel electrocardiogram a set of theoretical considerations emerges inevitably, one of the most important among them is the question about dependence of the electrocardiogram parameters from the direction of electrical axis of heart. In other words, changes in what of electrocardiogram parameters are in fact liable to reflect pathological processes in myocardium, and what ones are determined by extracardiac factors, primarily by anatomic characteristics of patients. It is arguable that while analyzing electrocardiogram it is necessary to orient to such physiologically based informative indexes as ST segment displacement. Also, symmetry of the T wave shape is an important parameter which is independent of patients anatomic features. The results obtained are of interest for theoretical and applied aspects of the biophysics of the cardiac electric field.

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  17. Binding of a Calcium Antagonist, [3H]Nitrendipine, to High Affinity Sites in Bovine Aortic Smooth Muscle and Canine Cardiac Membranes

    PubMed Central

    Williams, Lewis T.; Tremble, Patrice

    1982-01-01

    [3H]Nitrendipine, a potent calcium channel antagonist [3-ethyl-5-methyl-1-1,4-dihydro-2,6 - dimethyl - 4 - (3 - nitrophenyl) - 3,5 - pyridine carboxylate], was used to label high affinity binding sites on membranes prepared from bovine aortic smooth muscle. The binding of [3H]nitrendipine is rapid (t1/2 < 5 min) and reversible at 37°C. The binding sites have a high affinity for [3H]nitrendipine with an equilibrium dissociation constant of 2.1 nM. The density of sites is 40-60 fmol/mg of membrane protein. Analogues of nitrendipine compete for the binding sites with affinities consistent with their known biological effects as calcium antagonists. Nisoldipine, [isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine carboxylate], a calcium antagonist more potent than nifedipine [2,6-dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4-dihydropyridine] in relaxing vascular smooth muscle, has an affinity three-fold higher than that of nifedipine in competing for the binding sites. A biologically inactive derivative of nifedipine does not compete for [3H]nitrendipine binding. Verapamil (α-isopropyl-α[(N-methyl - N-homoveratryl) -α-aminopropyl]-3,4-dimethyoxyphenyl acetonitrile), a structurally different calcium antagonist, only partially (25%) inhibits binding at high concentrations (1 μM). Prazosin, an alpha adrenergic antagonist does not compete for [3H]nitrendipine binding sites. The binding of [3H]nitrendipine is not affected by 1.5 mM calcium. Canine cardiac membranes also have high affinity [3H]nitrendipine binding sites, (KD = 6 nM) but bovine erythrocytes do not. The relative affinities of nisoldipine and nifedipine for the cardiac membrane binding sites reflect the relative activities of these compounds as calcium channel antagonists. These results suggest that the [3H]nitrendipine binding sites are the sites through which dihydropyridines act as calcium channel antagonists. PMID:6282938

  18. Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle.

    PubMed

    Asayama, K; Dobashi, K; Hayashibe, H; Kato, K

    1989-10-01

    To determine whether beta-blockade protects rat heart against thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.

  19. Expression of the atrial natriuretic peptide gene in the cardiac muscle of rat extrapulmonary and intrapulmonary veins.

    PubMed Central

    Springall, D R; Bhatnagar, M; Wharton, J; Hamid, Q; Gulbenkian, S; Hedges, M; Meleagros, L; Bloom, S R; Polak, J M

    1988-01-01

    Atrial natriuretic peptide is a peptide regulating salt and water balance, originally isolated from the cardiac atrium, where it is synthesised as part of a precursor molecule in specialised myocardial cells. The myocardium extends into the extrapulmonary part of the pulmonary veins in many species, including man. In some small mammals, however, such as the rat, mouse, and bat, it extends further to veins in the peripheral parts of the lung. Since this myocardial layer is continuous with that in the atrium, we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats. Strong immunoreactivity was seen for both the peptide and the N terminal sequence (cardiodilatin) of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point, where it was localised in the dense cored granules by electron microscopy; in situ hybridisation showed atrial natriuretic peptide messenger RNA at identical sites. Chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved (precursor molecule) form. Thus the peptide is synthesised in veins both outside and inside the lung, and these extra-atrial sites may be an important additional source of circulating atrial natriuretic peptide. Images PMID:2965426

  20. Tissue- and fibre-specific modifications of insulin-signalling molecules in cardiac and skeletal muscle of diabetic rats.

    PubMed

    Ekladous, Demiana; Mehdi, Mohamad Z; Costa, Myriam; Srivastava, Ashok K; Chiasson, Jean-Louis; Coderre, Lise

    2008-08-01

    1. Levels of insulin-signalling molecules are altered in streptozotocin (STZ)-induced diabetes, a model of Type 1 diabetes. However, the tissue-specific regulation of these changes and the effect of insulin supplementation on signalling molecule protein levels have not been well characterized. 2. In the present study, we evaluated the level of proximal insulin-signalling intermediates in the heart and in red and white gastrocnemius muscles of 2 week diabetic rats and diabetic rats supplemented with insulin. 3. Diabetes augmented levels of the insulin receptor and the p85 regulatory subunit of phosphatidylinositol 3-kinase in the red gastrocnemius, but not in the white gastrocnemius or the heart. Furthermore, diabetes reduced insulin receptor substrate-1 levels in both the red and white gastrocnemius, but not in the heart. Examination of the levels and basal activities of distal insulin-signalling intermediates (protein kinase B (PKB)/Akt, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (MAPK)) also failed to reveal a specific pattern in these changes. Thus, diabetes reduced basal ERK1/2 and PKB/Akt phosphorylation in the heart and white gastrocnemius, respectively, whereas it augmented basal p38 MAPK activity in the red gastrocnemius. Insulin supplementation normalized the levels and activities of some but not all proteins. 4. In conclusion, the results of the present study demonstrate that adaptation to STZ-induced diabetes varies among skeletal muscle fibre types and the heart, emphasizing the complex tissue-specific responses to diabetes.

  1. Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation.

    PubMed

    Hoy, Andrew J; Brandon, Amanda E; Turner, Nigel; Watt, Matthew J; Bruce, Clinton R; Cooney, Gregory J; Kraegen, Edward W

    2009-07-01

    Type 2 diabetes is characterized by hyperlipidemia, hyperinsulinemia, and insulin resistance. The aim of this study was to investigate whether acute hyperlipidemia-induced insulin resistance in the presence of hyperinsulinemia was due to defective insulin signaling. Hyperinsulinemia (approximately 300 mU/l) with hyperlipidemia or glycerol (control) was produced in cannulated male Wistar rats for 0.5, 1 h, 3 h, or 5 h. The glucose infusion rate required to maintain euglycemia was significantly reduced by 3 h with lipid infusion and was further reduced after 5 h of infusion, with no difference in plasma insulin levels, indicating development of insulin resistance. Consistent with this finding, in vivo skeletal muscle glucose uptake (31%, P < 0.05) and glycogen synthesis rate (38%, P < 0.02) were significantly reduced after 5 h compared with 3 h of lipid infusion. Despite the development of insulin resistance, there was no difference in the phosphorylation state of multiple insulin-signaling intermediates or muscle diacylglyceride and ceramide content over the same time course. However, there was an increase in cumulative exposure to long-chain acyl-CoA (70%) with lipid infusion. Interestingly, although muscle pyruvate dehydrogenase kinase 4 protein content was decreased in hyperinsulinemic glycerol-infused rats, this decrease was blunted in muscle from hyperinsulinemic lipid-infused rats. Decreased pyruvate dehydrogenase complex activity was also observed in lipid- and insulin-infused animals (43%). Overall, these results suggest that acute reductions in muscle glucose metabolism in rats with hyperlipidemia and hyperinsulinemia are more likely a result of substrate competition than a significant early defect in insulin action or signaling.

  2. Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.

    PubMed

    Salem, K A; Adrian, T E; Qureshi, M A; Parekh, K; Oz, M; Howarth, F C

    2012-12-01

    There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0

  3. Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy

    PubMed Central

    Frade, Amanda Farage; Teixeira, Priscila Camilo; Ianni, Barbara Maria; Pissetti, Cristina Wide; Saba, Bruno; Wang, Lin Hui Tzu; Kuramoto, Andréia; Nogueira, Luciana Gabriel; Buck, Paula; Dias, Fabrício; Giniaux, Helene; Llored, Agnes; Alves, Sthefanny; Schmidt, Andre; Donadi, Eduardo; Marin-Neto, José Antonio; Hirata, Mario; Sampaio, Marcelo; Fragata, Abílio; Bocchi, Edimar Alcides; Stolf, Antonio Noedir; Fiorelli, Alfredo Inacio; Santos, Ronaldo Honorato Barros; Rodrigues, Virmondes; Pereira, Alexandre Costa; Kalil, Jorge; Cunha-Neto, Edecio; Chevillard, Christophe

    2013-01-01

    Aims Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. Methods and Results We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5’ region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. Conclusions Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions. PMID:24367596

  4. Variations in tendon stiffness due to diets with different glycotoxins affect mechanical properties in the muscle-tendon unit.

    PubMed

    Grasa, J; Calvo, B; Delgado-Andrade, C; Navarro, M P

    2013-03-01

    Passive elastic behavior of tendon tissue from rats subjected to different dietary treatments was characterized. For that purpose, twenty-four weanling Wistar rats (41.02 ± 0.16 g) were randomly distributed into four groups. During 88 days each group was fed on different diets: control diet and diets containing advanced glycation end products (AGEs) from glucose-lysine model system, from bread crust and bread dough, respectively. After the trial animals were sacrificed and tendon samples were extracted and tested mechanically to fracture in a uniaxial tensile test machine. A transversely-hyperelastic model was formulated based on stress-strain relationships and its parameters were fit to the experimental data using the Levenberg-Marquardt optimization algorithm. Material parameters were incorporated in a finite element model to study different stress-strain distributions in a muscle-tendon unit. Results show higher strains and stresses in the muscle belly when properties of a stiffer tendon associated with a diet rich in AGEs are included in the model. A real increase in this mechanical response of the tissue could imply possible pain in joint mobility.

  5. The spectral changes in EMG during a second bout eccentric contraction could be due to adaptation in muscle fibres themselves: a simulation study.

    PubMed

    Dimitrov, V G; Arabadzhiev, T I; Dimitrova, N A; Dimitrov, G V

    2012-04-01

    The mechanism of marked reduction in damage symptoms after repeated bout of similar eccentric contractions is still unknown. The neuronal adaptation leading to reduction of muscle fibre propagation velocity (MFPV) due to increased activation of slow-twitch motor units (MUs), decrease in activation of fast-twitch MUs, and/or increase in MU synchronization was suggested as a cause for lower EMG frequency characteristics. However, the repeated bout effect could occur also after electrically stimulated exercise. Prolonged elevation of cytoplasmic Ca(2+) due to the increased membrane permeability after eccentric contractions was reported. Elevated Ca(2+) induced peripheral changes that included alteration of intracellular action potential and MFPV reduction. We simulated and compared changes in EMG frequency characteristics related to effects of central nervous system (CNS) or to peripheral changes. The simulations were performed for different electrode arrangements and positions. The results showed that the peripheral effects could be similar or even stronger than the effects related to CNS. We hypothesised that the repeated bout effect was a consequence of the adaptation in muscle fibres necessary for avoiding Ca(2+)-induced protein and lipid degradation due to Ca(2+) overload resulting from the increased membrane permeability after eccentric contraction. The possibilities for noninvasive testing of this hypothesis were discussed.

  6. A false positive case due to matrix interference in the analysis of ronidazole residues in muscle tissue using LC-MS/MS.

    PubMed

    Kumar, Praveen; Rúbies, Antoni; Centrich, Francesc; Companyó, Ramon

    2014-06-01

    In contrast with the information of the inspection body concerning the use of ronidazole, several non compliant muscle samples were detected using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in accordance with confirmation criteria of Decision 2002/657/EC. This led to the suspicion that non compliance could be due to false positive results. In this context, a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed and sample extracts were re-analyzed, resolving the co eluting isobaric interfering peak, which also has an interfering product ion with the transition product (m/z 201>140).

  7. Phentolamine suppresses the increase in arteriolar vasomotion frequency due to systemic hypoxia in hamster skeletal muscle microcirculation.

    PubMed

    Colantuoni, A; Bertuglia, S; Marchiafava, P L

    2001-07-20

    Systemic hypoxia (8%, 11% and 15% oxygen gas mixture inspiration) has been shown to increase the frequency of arteriolar rhythmic diameter changes in hamster skeletal muscle microcirculation. The effects of phentolamine on vasomotion frequency during systemic hypoxia were studied in Syrian hamsters implanted with a plastic chamber in the dorsum skin. Phentolamine (50 microg/100 g body wt.) was injected intravenously before the 20-min exposure to 11% oxygen gas mixture. The microvessels were studied with a fluorescent microscopy technique, using fluorescein isothiocyanate bound to dextran (mol. wt. 150,000) as a tracer. Vessel diameters were measured with a shearing method. Fourier transform and autoregressive modeling were used to assess the time variant features of diameter changes. Under baseline conditions, the arterioles were characterized by rhythmic diameter changes with fundamental frequency related to vessel size. The terminal branchings were dominated by order 3 vessel activity (frequency: 0.08-0.16 Hz) spreading downstream to all daughter arterioles. Systemic hypoxia caused an increase in vasomotion frequency of order 3 arterioles up to 0.3-0.5 Hz (average: 0.40 +/- 0.06 Hz) and a significant decrease in mean diameter (-28 +/- 5%). Phentolamine completely suppressed the rhythmic changes in diameter of order 3 arterioles that dilated significantly (+ 30 +/- 4%). Therefore, the effects of systemic hypoxia on arteriolar vasomotion appear to be triggered by an increase in sympathetic nervous discharge that induces a rise in frequency up to 0.3-0.5 Hz.

  8. Controlled Cardiac Computed Tomography

    PubMed Central

    Wang, Chenglin; Liu, Ying; Wang, Ge

    2006-01-01

    Cardiac computed tomography (CT) has been a hot topic for years because of the clinical importance of cardiac diseases and the rapid evolution of CT systems. In this paper, we propose a novel strategy for controlled cardiac CT that may effectively reduce image artifacts due to cardiac and respiratory motions. Our approach is radically different from existing ones and is based on controlling the X-ray source rotation velocity and powering status in reference to the cardiac motion. We theoretically show that by such a control-based intervention the data acquisition process can be optimized for cardiac CT in the cases of periodic and quasiperiodic cardiac motions. Specifically, we formulate the corresponding coordination/control schemes for either exact or approximate matches between the ideal and actual source positions, and report representative simulation results that support our analytic findings. PMID:23165017

  9. Effects on shortening velocity of rabbit skeletal muscle due to variations in the level of thin-filament activation.

    PubMed Central

    Moss, R L

    1986-01-01

    The effect of Ca2+ upon maximum shortening velocity (Vmax) has been investigated in skinned single fibres from rabbit psoas muscles. Vmax was obtained at 15 degrees C by measuring the amounts of time (delta t) required to take up various amounts of slack (delta l) imposed at one end of the fibre. During maximal activation with Ca2+, plots of delta l vs. delta t were well fitted by a single straight line. Calculation of Vmax from the slopes of the fitted lines yielded a Vmax of 4.44 +/- 0.15 (S.E. of mean) muscle lengths per second (m.l./s). However, at lower levels of Ca2+ activation, plots of delta l vs. delta t were biphasic, containing an initial phase of steady high-velocity shortening and a subsequent phase of steady low-velocity shortening. The transition between these two phases occurred following active shortening equivalent to 60-80 nm/half-sarcomere. Vmax during the high-velocity phase was relatively insensitive to Ca2+ concentration between pCas (i.e. -log [Ca2+]) of 4.5 and 6.0; however, Vmax fell to 3.58 +/- 0.40 m.l./s at pCa 6.1 and further to 1.02 +/- 0.30 m.l./s at pCa 6.2. Vmax during the low-velocity phase decreased as Ca2+ was lowered within the entire range of pCas studied to a minimum value of 0.35 +/- 0.09 m.l./s at pCa 6.2. The degree of thin-filament activation at a particular pCa was varied by partial extraction of troponin-C, which resulted in a permanent though reversible inactivation of parts of the thin filaments. Partial extraction of troponin-C altered the plots of delta l vs. delta t obtained at pCa 4.5 to a biphasic form. In addition, Vmax during the high- and low-velocity phases of shortening was reduced at each pCa greater than 4.5. Vmax values obtained in control fibres at low Ca2+ concentrations and extracted fibres were in good agreement when generated isometric tensions were equivalent. This was the case for both the high- and low-velocity phases of shortening. Fibres were also activated in the absence of Ca2+ by partial

  10. Adipose stromal cells differentiation toward smooth muscle cell phenotype diminishes their vasculogenic activity due to induction of activin A secretion.

    PubMed

    Merfeld-Clauss, Stephanie; Lease, Benjamin R; Lu, Hongyan; March, Keith L; Traktuev, Dmitry O

    2016-09-16

    Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs' SMC-lineage commitment affects their subsequent communication with ECs is unknown. The vasculogenic characteristics of human ASCs in progenitor stage and after differentiation towards SMC phenotype were analysed in the present study. Exposure to transforming growth factor β1 (TGFβ1 ) or activin A has induced expression of SMC markers in ASCs. Analysis performed after treatment withdrawal revealed that secretome of pre-differentiated ASCs had a reduced potency to support EC survival and these ASCs had diminished ability to support EC vasculogenesis in vitro. Vascularization of subcutaneous implants carrying a mixture of ECs and ASCs was 50% lower when, instead of control, pre-differentiated ASCs were used. Pre-differentiated ASCs had an inferior mitogenic response to EC-produced factors. Differentiation of ASCs was accompanied by upregulation of vascular endothelial growth factor and a decrease in hepatocyte growth factor (HGF) production; however, addition of HGF to the co-culture incubation media did not improve vasculogenesis. In parallel, ASC treatment with TGFβ1 induced secretion of activin A. Augmenting co-culture incubation media with anti-activin A IgG restored the ability of pre-differentiated ASCs to support vasculogenesis to the same degree as control ASCs. The present study suggests that TGFβ1 or activin A-induced ASC commitment to SMC phenotype negatively affects the ability of ASCs to support EC vasculogenesis in applications based on EC and ASC co-injection into target tissues. Copyright © 2016 John Wiley & Sons, Ltd.

  11. [Effect of gravitation loading and retabolil on development of atrophy in muscles and bones of rats due to suspension].

    PubMed

    KaplanskiI, A S; Il'ina-Kakueva, E I; Durnova, G N; Alekseev, E A; Loginov, V I

    1999-01-01

    In a 3-wk experiment with tail-suspended rats histological and histomorphometric methods were used to determine the effects of graded gravitational loading (GGL) and anabolic steroid retabolil (nortestosterone decanoate) on the course of atrophy in soleus m. (SM), gastrocnemius m. (GM), tibia and humerus, and functioning of somatotrophic hormones (STH) of the pituitary and thyrocytes of the thyroid. Suspension was found to produce atrophy in SM and, to a less degree, in GM, partial transformation of SM slow fibers into the fast ones, suppression of the tibial longitudinal growth, demineralization of the tibial and humeral spongious metaphyses; besides, functional activities of STH-cells and thyrocytes were inhibited. Graded gravitational loading of rats by intermittence of suspension for 2 hrs slowed down atrophy in both muscles and osteopenia in tibia, stimulated the synthetic and secretory functions of STH-cells without any marked effect on thyrocytes or humeral osteopenia. GGL failed to influence the slow-to-fast transformation of SM fibers. Two injections of retabolil at the total dose of 3 mg/kg of the body mass somewhat interfered with the SM atrophy and humoral osteopenia, and were favorable to the synthetic but not secretory activity of STH-cells. Neither SM and tibial atrophies nor thyroid activity of the gland were improved. The prophylactic action of GGL upon the SM and humeral atrophies was significantly higher when combined with retabolil, whereas GM and tibia were not noticeably cured by retabolil. Inhibition of the SM atrophy and humeral osteopenia in rats treated with GGL and retabolil concurred with elevated activities of STH-cells and thyrocytes indirectly suggesting their more intensive production of the growth hormone and thyroid hormones, respectively.

  12. Symmetry of cardiac function assessment

    PubMed Central

    Bai, Xu-Fang; Ma, Amy X

    2016-01-01

    Both right and left ventricles are developed from two adjacent segments of the primary heart tube. Though they are different with regard to shape and power, they mirror each other in terms of behavior. This is the first level of symmetry in cardiac function assessment. Both cardiac muscle contraction and relaxation are active. This constructs the second level of symmetry in cardiac function assessment. Combination of the two levels will help to find some hidden indexes or approaches to evaluate cardiac function. In this article, four major indexes from echocardiography were analyzed under this principal, another seventeen indexes or measurement approaches came out of the shadow, which is very helpful in the assessment of cardiac function, especially for the right cardiac function and diastolic cardiac function. PMID:27582768

  13. Cardiac arrest due to intracranial hypotension following pseudohypoxic brain swelling induced by negative suction drainage in a cranioplasty patient: a case report

    PubMed Central

    Kim, Su Ryun; Kim, Seon Ju

    2016-01-01

    Pseudohypoxic brain swelling (PHBS) is known to be an uncommon event that may occur during and following an uneventful brain surgery, when negative suction drainage is used. The cerebrospinal fluid loss related to suction drainage can evoke intracranial hypotension that progress to PHBS. The main presentations of PHBS are sudden unexpected circulatory collapses, such as severe bradycardia, hypotension, cardiac arrest, consciousness deterioration and diffuse brain swelling as seen with brain computerized tomography (CT). We present a stuporous 22-year-old patient who underwent cranioplasty under general anesthesia. The entire course of the general anesthesia and operation progressed favorably. However, the time of scalp suture completion, sudden bradycardia and hypotension occurred, followed by cardiac arrest immediately after initiation of subgaleal and epidural suction drainage. After successful resuscitation, the comatose patient was transferred to the neurosurgical intensive care unit and PHBS was confirmed using brain CT. PMID:27274378

  14. Combination of veno-arterial extracorporeal membrane oxygenation and hypothermia for out-of-hospital cardiac arrest due to Taxus intoxication.

    PubMed

    Thooft, Aurélie; Goubella, Ahmed; Fagnoul, David; Taccone, Fabio S; Brimioulle, Serge; Vincent, Jean-Louis; De Backer, Daniel

    2014-11-01

    A young woman presented with cardiac arrest following ingestion of yew tree leaves of the Taxus baccata species. The toxin in yew tree leaves has negative inotropic and dromotropic effects. The patient had a cardiac rhythm that alternated between pulseless electrical activity with a prolonged QRS interval and ventricular fibrillation. When standard resuscitation therapy including digoxin immune Fab was ineffective, a combination of extracorporeal membrane oxygenation (ECMO) and hypothermia was initiated. The total duration of low flow/no flow was 82 minutes prior to the initiation of ECMO. After 36 hours of ECMO (including 12 hours of electrical asystole), the patient's electrocardiogram had normalized and the left ventricular ejection fraction was 50%. At this time, dobutamine and the ECMO were stopped. The patient had a full neurologic recovery and was discharged from the intensive care unit after 5 days and from the hospital 1 week later.

  15. Orofacial pain of cardiac origin: Review literature and clinical cases

    PubMed Central

    Garcia-Vicente, Laia; Jané-Salas, Enric; Estrugo-Devesa, Albert; Chimenos-Küstner, Eduardo; Roca-Elias, Josep

    2012-01-01

    The most common types of orofacial pain originate at the dental or periodontal level or in the musculoskeletal structures. However, the patient may present pain in this region even though the source is located elsewhere in the body. One possible source of heterotopic pain is of cardiac origin. Objectives: Report two cases of orofacial pain of cardiac origin and review the clinical cases described in the literature. Study Design: Description of clinical cases and review of clinical cases. Results and conclusions: Nine cases of atypical pain of cardiac origin are recorded, which include 5 females and 4 males. In craniofacial structures, pain of cardiac origin is usually bilateral. At the craniofacial level, the most frequent location described is in the throat and jaw. Pain of cardiac origin is considered atypical due to its location, although roughly 10% of the cases of cardiac ischemia manifest primarily in craniofacial structures. Finally, the differential diagnosis of pain of odontogenic origin must be taken into account with pain of non-odontogenic origin (muscle, psychogenic, neuronal, cardiac, sinus and neurovascular pain) in order to avoid diagnostic errors in the dental practice as well as unnecessary treatments. Key words:Orofacial pain, ischemic heart disease, heterotopic pain, odontalgia. PMID:22322488

  16. Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders

    PubMed Central

    Jiménez-Jáimez, Juan; Palomino Doza, Julián; Ortega, Ángeles; Macías-Ruiz, Rosa; Perin, Francesca; Rodríguez-Vázquez del Rey, M. Mar; Ortiz-Genga, Martín; Monserrat, Lorenzo; Barriales-Villa, Roberto; Blanca, Enrique; Álvarez, Miguel; Tercedor, Luis

    2016-01-01

    Background Calmodulin 1, 2 and 3 (CALM) mutations have been found to cause cardiac arrest in children at a very early age. The underlying aetiology described is long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and idiopathic ventricular fibrillation (IVF). Little phenotypical data about CALM2 mutations is available. Objectives The aim of this paper is to describe the clinical manifestations of the Asn98Ser mutation in CALM2 in two unrelated children in southern Spain with apparently unexplained cardiac arrest/death. Methods Two unrelated children aged 4 and 7, who were born to healthy parents, were studied. Both presented with sudden cardiac arrest. The first was resuscitated after a VF episode, and the second died suddenly. In both cases the baseline QTc interval was within normal limits. Peripheral blood DNA was available to perform targeted gene sequencing. Results The surviving 4-year-old girl had a positive epinephrine test for LQTS, and polymorphic ventricular ectopic beats were seen on a previous 24-hour Holter recording from the deceased 7-year-old boy, suggestive of a possible underlying CPVT phenotype. A p.Asn98Ser mutation in CALM2 was detected in both cases. This affected a highly conserved across species residue, and the location in the protein was adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain, predicting a high pathogenic effect. Conclusions Human calmodulin 2 mutation p.Asn98Ser is associated with sudden cardiac death in childhood with a variable clinical penetrance. Our results provide new phenotypical information about clinical behaviour of this mutation. PMID:27100291

  17. Comparison of skin and muscle biopsies before and after pentoxifylline treatment in patients with leg ulcers due to deep venous incompetence.

    PubMed

    Angelides, N S; von der Ahe, C W; Themistocleus, P

    1991-01-01

    The aim of this study was to understand the possible mechanisms by which deep venous insufficiency and venous hypertension are associated with trophic skin changes and ulceration and to explain the therapeutic effect of Pentoxifylline in patients with leg ulcers due to deep venous incompetence. Twenty patients were included in this pilot study. They were graded into two groups: group 1, included 10 patients (5 F and 5 M) with deep venous incompetence and normal arteries; group 2, included 10 patients (1 F and 9 M) with deep venous incompetence and moderate arterial disease. Skin and muscle biopsies were carried out before and after the oral administration of 1,200 mg of Pentoxifylline daily (400 mg t.d.s). The following parameters were investigated by means of light microscopy and immunofluorescence tests: engorgement of venous stroma; decrease of intimal elastica; hyaline degeneration; floccular degeneration; pericapillary fibrin deposits and fibrin degradation products; inflammation and fat necrosis; myofibril degeneration; fibrous scar; regeneration and reconstitution of muscle fibres. The results indicated that local inflammation at the ulcer's area cause accumulation of white blood cells in the capillaries and the interstitial fluid, where there is also accumulation of fibrinogen. These changes may lead to chronic tissue ischaemia and ulceration. The known favourable effect of Pentoxifylline on red cells and leucocyte function as well as its lowering effect on plasma fibrinogen level, may be responsible for the observed therapeutic effect of Pentoxifylline on venous leg ulcers.

  18. Age-associated impairement in endpoint accuracy of goal-directed contractions performed with two fingers is due to altered activation of the synergistic muscles.

    PubMed

    Chen, Yen-Ting; Pinto Neto, Osmar; de Miranda Marzullo, Ana Carolina; Kennedy, Deanna M; Fox, Emily J; Christou, Evangelos A

    2012-07-01

    The purpose of this study was to determine whether older adults compared with young adults exhibit impaired end-point accuracy during a two-finger task due to altered activation of the contributing synergistic muscles. Nine young (21.3 years ± 1.6 years, 4 men) and 9 older (73.1 years ± 6.4 years, 5 men) were instructed to accurately match the center of a target with concurrent abduction of the index and little fingers (synergistic two-finger task). The target comprised of 20% MVC and 200 ms. Visual feedback of the force trajectory and target was provided 1s after each trial. Subjects completed 40 trials and the last 10 were used for analysis. Endpoint accuracy was quantified as the normalized deviation from the target in terms of peak force (peak force error), time-to-peak force (time-to-peak force error), and a combination of the two (overall error). Motor output variability was quantified as the standard deviation and coefficient of variation (CV) of peak force and time to peak force. The neural activation of the involved synergist muscles (first dorsal interosseus (FDI) and abductor digiti minimi (ADM)) was quantified with the electromyography (EMG) amplitude (root mean square) and its frequency structure (wavelet analysis). Older adults exhibited significantly greater peak force (46.7 ± 10% vs. 24.9 ± 3.2%) and overall endpoint error (68.5 ± 9.7% vs. 41.7 ± 4.3%), whereas the time to peak force error was similar for the two age groups. Older adults also exerted greater peak force variability than young adults, as quantified by the CV of peak force (34.3 ± 3.5% vs. 24.1 ± 2.3%). The greater peak force error in older adults was associated with changes in the activation of the ADM muscle but not the FDI. Specifically, greater peak force error was associated with greater power from 13-30 Hz and lesser power from 30-60 Hz. These results, therefore, suggest that older adults compared with young adults exhibit impaired endpoint force accuracy during a two

  19. Cardiac Electrophysiology: Normal and Ischemic Ionic Currents and the ECG

    ERIC Educational Resources Information Center

    Klabunde, Richard E.

    2017-01-01

    Basic cardiac electrophysiology is foundational to understanding normal cardiac function in terms of rate and rhythm and initiation of cardiac muscle contraction. The primary clinical tool for assessing cardiac electrical events is the electrocardiogram (ECG), which provides global and regional information on rate, rhythm, and electrical…

  20. Hypokalemia and sudden cardiac death.

    PubMed

    Kjeldsen, Keld

    2010-01-01

    Worldwide, approximately three million people suffer sudden cardiac death annually. These deaths often emerge from a complex interplay of substrates and triggers. Disturbed potassium homeostasis among heart cells is an example of such a trigger. Thus, hypokalemia and, also, more transient reductions in plasma potassium concentration are of importance. Hypokalemia is present in 7% to 17% of patients with cardiovascular disease. Furthermore, up to 20% of hospitalized patients and up to 40% of patients on diuretics suffer from hypokalemia. Importantly, inadequate management of hypokalemia was found in 24% of hospitalized patients. Hypokalemia is associated with increased risk of arrhythmia in patients with cardiovascular disease, as well as increased all-cause mortality, cardiovascular mortality and heart failure mortality by up to 10-fold. Long-term potassium homeostasis depends on renal potassium excretion. However, skeletal muscles play an important role in short-term potassium homeostasis, primarily because skeletal muscles contain the largest single pool of potassium in the body. Moreover, due to the large number of Na(+)/K(+) pumps and K(+) channels, the skeletal muscles possess a huge capacity for potassium exchange. In cardiovascular patients, hypokalemia is often caused by nonpotassium-sparing diuretics, insufficient potassium intake and a shift of potassium into stores by increased potassium uptake stimulated by catecholamines, beta-adrenoceptor agonists and insulin. Interestingly, drugs with a proven significant positive effect on mortality and morbidity rates in heart failure patients all increase plasma potassium concentration. Thus, it may prove beneficial to pay more attention to hypokalemia and to maintain plasma potassium levels in the upper normal range. The more at risk of fatal arrhythmia and sudden cardiac death a patient is, the more attention should be given to the potassium homeostasis.

  1. The effect of moderate-intensity exercise on the expression of HO-1 mRNA and activity of HO in cardiac and vascular smooth muscle of spontaneously hypertensive rats.

    PubMed

    Ren, Cailing; Qi, Jie; Li, Wanwei; Zhang, Jun

    2016-04-01

    The objective of this study was to observe the effects of moderate-intensity training on the activity of heme oxygenase (HO) and expression of HO-1 mRNA in the aorta and the cardiac muscle of spontaneously hypertensive rats (SHRs). After 9 weeks of swimming exercise, the activity of HO and expression of HO-1 mRNA in the SHRs were measured. The resting blood pressure in the exercise group was increased by 1.7% (P > 0.05), whereas it was significantly elevated by 10.3% (P < 0.01) in the SHR rats. Compared with animals in the control and sedentary groups, the expression level of HO-1 mRNA of aorta and cardiac muscle in the exercise group was significantly enhanced (P < 0.01). The HO activity and the content of plasma carbon monoxide (CO) in the sedentary group were dramatically decreased (P < 0.05 and P < 0.01, respectively) compared with the control group. HO activity and content of plasma CO in the exercise group were significantly higher compared with those in the sedentary group (P < 0.05 and P < 0.01, respectively). The HO/CO metabolic pathway might be involved in the regulation of blood pressure of the SHR models.

  2. The Role of Cardiac Side Population Cells in Cardiac Regeneration

    PubMed Central

    Yellamilli, Amritha; van Berlo, Jop H.

    2016-01-01

    The heart has a limited ability to regenerate. It is important to identify therapeutic strategies that enhance cardiac regeneration in order to replace cardiomyocytes lost during the progression of heart failure. Cardiac progenitor cells are interesting targets for new regenerative therapies because they are self-renewing, multipotent cells located in the heart. Cardiac side population cells (cSPCs), the first cardiac progenitor cells identified in the adult heart, have the ability to differentiate into cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts. They become activated in response to cardiac injury and transplantation of cSPCs into the injured heart improves cardiac function. In this review, we will discuss the current literature on the progenitor cell properties and therapeutic potential of cSPCs. This body of work demonstrates the great promise cSPCs hold as targets for new regenerative strategies. PMID:27679798

  3. Cardiac mechanics: Physiological, clinical, and mathematical considerations

    NASA Technical Reports Server (NTRS)

    Mirsky, I. (Editor); Ghista, D. N.; Sandler, H.

    1974-01-01

    Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

  4. Cardiac catheterization - discharge

    MedlinePlus

    Catheterization - cardiac - discharge; Heart catheterization - discharge: Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization discharge; CAD - cardiac catheterization discharge; Coronary artery disease - cardiac catheterization ...

  5. Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes

    PubMed Central

    Banerjee, Ranjan; He, Jun; Spaniel, Carolyn; Quintana, Megan T.; Wang, Zhongjing; Bain, James; Newgard, Christopher B.; Muehlbauer, Michael J.; Willis, Monte S.

    2017-01-01

    The muscle-specific ubiquitin ligases MuRF1, MuRF2, MuRF3 have been reported to have overlapping substrate specificities, interacting with each other as well as proteins involved in metabolism and cardiac function. In the heart, all three MuRF family proteins have proven critical to cardiac responses to ischemia and heart failure. The non-targeted metabolomics analysis of MuRF1-/-, MuRF2-/-, and MuRF3-/- hearts was initiated to investigate the hypothesis that MuRF1, MuRF2, and MuRF3 have a similarly altered metabolome, representing alterations in overlapping metabolic processes. Ventricular tissue was flash frozen and quantitatively analyzed by GC/MS using a library built upon the Fiehn GC/MS Metabolomics RTL Library. Non-targeted metabolomic analysis identified significant differences (via VIP statistical analysis) in taurine, myoinositol, and stearic acid for the three MuRF-/- phenotypes relative to their matched controls. Moreover, pathway enrichment analysis demonstrated that MuRF1-/- had significant changes in metabolite(s) involved in taurine metabolism and primary acid biosynthesis while MuRF2-/- had changes associated with ascorbic acid/aldarate metabolism (via VIP and t-test analysis vs. sibling-matched wildtype controls). By identifying the functional metabolic consequences of MuRF1, MuRF2, and MuRF3 in the intact heart, non-targeted metabolomics analysis discovered common pathways functionally affected by cardiac MuRF family proteins in vivo. These novel metabolomics findings will aid in guiding the molecular studies delineating the mechanisms that MuRF family proteins regulate metabolic pathways. Understanding these mechanism is an important key to understanding MuRF family proteins' protective effects on the heart during cardiac disease.

  6. Cardiomyocyte-specific perilipin 5 overexpression leads to myocardial steatosis and modest cardiac dysfunction1[S

    PubMed Central

    Wang, Hong; Sreenivasan, Urmila; Gong, Da-Wei; O'Connell, Kelly A.; Dabkowski, Erinne R.; Hecker, Peter A.; Ionica, Nicoleta; Konig, Manige; Mahurkar, Anup; Sun, Yezhou; Stanley, William C.; Sztalryd, Carole

    2013-01-01

    Presence of ectopic lipid droplets (LDs) in cardiac muscle is associated to lipotoxicity and tissue dysfunction. However, presence of LDs in heart is also observed in physiological conditions, such as when cellular energy needs and energy production from mitochondria fatty acid β-oxidation are high (fasting). This suggests that development of tissue lipotoxicity and dysfunction is not simply due to the presence of LDs in cardiac muscle but due at least in part to alterations in LD function. To examine the function of cardiac LDs, we obtained transgenic mice with heart-specific perilipin 5 (Plin5) overexpression (MHC-Plin5), a member of the perilipin protein family. Hearts from MHC-Plin5 mice expressed at least 4-fold higher levels of plin5 and exhibited a 3.5-fold increase in triglyceride content versus nontransgenic littermates. Chronic cardiac excess of LDs was found to result in mild heart dysfunction with decreased expression of peroxisome proliferator-activated receptor (PPAR)α target genes, decreased mitochondria function, and left ventricular concentric hypertrophia. Lack of more severe heart function complications may have been prevented by a strong increased expression of oxidative-induced genes via NF-E2-related factor 2 antioxidative pathway. Perilipin 5 regulates the formation and stabilization of cardiac LDs, and it promotes cardiac steatosis without major heart function impairment. PMID:23345411

  7. Cardiac Hegemony of Senescence

    PubMed Central

    Siddiqi, Sailay; Sussman, Mark A.

    2013-01-01

    Cardiac senescence and age-related disease development have gained general attention and recognition in the past decades due to increased accessibility and quality of health care. The advancement in global civilization is complementary to concerns regarding population aging and development of chronic degenerative diseases. Cardiac degeneration has been rigorously studied. The molecular mechanisms of cardiac senescence are on multiple cellular levels and hold a multilayer complexity level, thereby hampering development of unambiguous treatment protocols. In particular, the synergistic exchange of the senescence phenotype through a senescence secretome between myocytes and stem cells appears complicated and is of great future therapeutic value. The current review article will highlight hallmarks of senescence, cardiac myocyte and stem cell senescence, and the mutual exchange of senescent secretome. Future cardiac cell therapy approaches require a comprehensive understanding of myocardial senescence to improve therapeutic efficiency as well as efficacy. PMID:24349878

  8. Cardiac myofilaments: mechanics and regulation

    NASA Technical Reports Server (NTRS)

    de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

    2003-01-01

    The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

  9. Cardiac involvement in hereditary myopathy with early respiratory failure

    PubMed Central

    Steele, Hannah E.; Harris, Elizabeth; Barresi, Rita; Marsh, Julie; Beattie, Anna; Bourke, John P.; Straub, Volker

    2016-01-01

    Objective: To assess whether hereditary myopathy with early respiratory failure (HMERF) due to the c.951434T>C; (p.Cys31712Arg) TTN missense mutation also includes a cardiac phenotype. Method: Clinical cohort study of our HMERF cohort using ECG, 2D echocardiogram, and cross-sectional cardiac imaging with MRI or CT. Results: We studied 22 participants with the c.951434T>C; (p.Cys31712Arg) TTN missense mutation. Three were deceased. Cardiac conduction abnormalities were identified in 7/22 (32%): sustained atrioventricular tachycardia (n = 2), atrial fibrillation (n = 2), nonsustained atrial tachycardia (n = 1), premature supraventricular complexes (n = 1), and unexplained sinus bradycardia (n = 1). In addition, 4/22 (18%) had imaging evidence of otherwise unexplained cardiomyopathy. These findings are supported by histopathologic correlation suggestive of myocardial cytoskeletal remodeling. Conclusions: Coexisting cardiac and skeletal muscle involvement is not uncommon in patients with HMERF arising due to the c.951434T>C; (p.Cys31712Arg) TTN mutation. All patients with pathogenic or putative pathogenic TTN mutations should be offered periodic cardiac surveillance. PMID:27511179

  10. Green tea polyphenols improve cardiac muscle mRNA, and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiologic studies indicate that the consumption of green tea polyphenols (GTP) may reduce the risk of coronary artery disease. To explore the underlying mechanisms of action at the molecular level, we examined the effects of GTP on cardiac mRNA and protein levels of genes involved in insulin an...

  11. Paracrine Effects of IGF-1 Overexpression on the Functional Decline Due to Skeletal Muscle Disuse: Molecular and Functional Evaluation in Hindlimb Unloaded MLC/mIgf-1 Transgenic Mice

    PubMed Central

    Cannone, Maria; Liantonio, Antonella; De Bellis, Michela; Digennaro, Claudio; Gramegna, Gianluca; De Luca, Annamaria; Germinario, Elena; Danieli-Betto, Daniela; Betto, Romeo; Dobrowolny, Gabriella; Rizzuto, Emanuele; Musarò, Antonio; Desaphy, Jean-François; Camerino, Diana Conte

    2013-01-01

    Slow-twitch muscles, devoted to postural maintenance, experience atrophy and weakness during muscle disuse due to bed-rest, aging or spaceflight. These conditions impair motion activities and can have survival implications. Human and animal studies demonstrate the anabolic role of IGF-1 on skeletal muscle suggesting its interest as a muscle disuse countermeasure. Thus, we tested the role of IGF-1 overexpression on skeletal muscle alteration due to hindlimb unloading (HU) by using MLC/mIgf-1 transgenic mice expressing IGF-1 under the transcriptional control of MLC promoter, selectively activated in skeletal muscle. HU produced atrophy in soleus muscle, in terms of muscle weight and fiber cross-sectional area (CSA) reduction, and up-regulation of atrophy gene MuRF1. In parallel, the disuse-induced slow-to-fast fiber transition was confirmed by an increase of the fast-type of the Myosin Heavy Chain (MHC), a decrease of PGC-1α expression and an increase of histone deacetylase-5 (HDAC5). Consistently, functional parameters such as the resting chloride conductance (gCl) together with ClC-1 chloride channel expression were increased and the contractile parameters were modified in soleus muscle of HU mice. Surprisingly, IGF-1 overexpression in HU mice was unable to counteract the loss of muscle weight and the decrease of fiber CSA. However, the expression of MuRF1 was recovered, suggesting early effects on muscle atrophy. Although the expression of PGC-1α and MHC were not improved in IGF-1-HU mice, the expression of HDAC5 was recovered. Importantly, the HU-induced increase of gCl was fully contrasted in IGF-1 transgenic mice, as well as the changes in contractile parameters. These results indicate that, even if local expression does not seem to attenuate HU-induced atrophy and slow-to-fast phenotype transition, it exerts early molecular effects on gene expression which can counteract the HU-induced modification of electrical and contractile properties. MuRF1 and HDAC5

  12. Biomarker panel of cardiac and skeletal muscle troponins, fatty acid binding protein 3 and myosin light chain 3 for the accurate diagnosis of cardiotoxicity and musculoskeletal toxicity in rats.

    PubMed

    Tonomura, Yutaka; Matsushima, Shuuichi; Kashiwagi, Emi; Fujisawa, Kae; Takagi, Shingo; Nishimura, Yoko; Fukushima, Ryou; Torii, Mikinori; Matsubara, Mitsunobu

    2012-12-16

    Cardiotoxicity and musculoskeletal toxicity can be life-threatening, and thus have strong impact on both the development and marketing of drugs. Because the conventional biomarkers such as aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) have low detection power, there has been increasing interest in developing biomarkers with higher detection power. The current study examined the usefulness of several promising biomarkers, cardiac and skeletal muscle troponins (cTnI, cTnT and sTnI), fatty acid binding protein 3 (FABP3) and myosin light chain 3 (MYL3), and compared the obtained data to AST, LDH and CK in rat models treated with various myotoxic and non-myotoxic compounds (isoproterenol, metaproterenol, doxorubicin, mitoxantrone, allylamine, cyclosporine A, cyclophosphamide, aminoglutethimide, acetaminophen, methapyrilene, allylalcohol and α-naphthylisothiocyanate). These promising biomarkers were found to be superior to the conventional biomarkers, as they had a specific and abundant distribution within the heart and/or skeletal muscles; exhibited a positive correlation between the amplitude of increases and the degree of pathological alterations; had higher diagnostic accuracy for detecting pathological alterations; and had the additive effect of improving the diagnostic accuracy of conventional biomarkers. However, these promising biomarkers have several drawbacks including a rapid clearance, the fact that they are affected by renal dysfunction, and different reactivity to the mode of action of individual myotoxicants. In conclusion, the promising biomarkers cTnI, cTnT, FABP3, MYL3, and sTnI demonstrated sensitivity and specificity for cardiac and skeletal myotoxicity that was superior to those of conventional biomarkers, while we should pay attention to the drawbacks of these biomarkers when used in toxicity studies.

  13. Quantitative assessment of brain microvascular and tissue oxygenation during cardiac arrest and resuscitation in pigs.

    PubMed

    Yu, J; Ramadeen, A; Tsui, A K Y; Hu, X; Zou, L; Wilson, D F; Esipova, T V; Vinogradov, S A; Leong-Poi, H; Zamiri, N; Mazer, C D; Dorian, P; Hare, G M T

    2013-07-01

    Cardiac arrest is associated with a very high rate of mortality, in part due to inadequate tissue perfusion during attempts at resuscitation. Parameters such as mean arterial pressure and end-tidal carbon dioxide may not accurately reflect adequacy of tissue perfusion during cardiac resuscitation. We hypothesised that quantitative measurements of tissue oxygen tension would more accurately reflect adequacy of tissue perfusion during experimental cardiac arrest. Using oxygen-dependent quenching of phosphorescence, we made measurements of oxygen in the microcirculation and in the interstitial space of the brain and muscle in a porcine model of ventricular fibrillation and cardiopulmonary resuscitation. Measurements were performed at baseline, during untreated ventricular fibrillation, during resuscitation and after return of spontaneous circulation. After achieving stable baseline brain tissue oxygen tension, as measured using an Oxyphor G4-based phosphorescent microsensor, ventricular fibrillation resulted in an immediate reduction in all measured parameters. During cardiopulmonary resuscitation, brain oxygen tension remained unchanged. After the return of spontaneous circulation, all measured parameters including brain oxygen tension recovered to baseline levels. Muscle tissue oxygen tension followed a similar trend as the brain, but with slower response times. We conclude that measurements of brain tissue oxygen tension, which more accurately reflect adequacy of tissue perfusion during cardiac arrest and resuscitation, may contribute to the development of new strategies to optimise perfusion during cardiac resuscitation and improve patient outcomes after cardiac arrest.

  14. An E-box/M-CAT hybrid motif and cognate binding protein(s) regulate the basal muscle-specific and cAMP-inducible expression of the rat cardiac alpha-myosin heavy chain gene.

    PubMed

    Gupta, M P; Gupta, M; Zak, R

    1994-11-25

    Expression of the cardiac myosin heavy chain (MHC) genes is regulated developmentally and by numerous epigenetic factors. Here we report the identification of a cis-regulatory element and cognate nuclear binding protein(s) responsible for cAMP-induced expression of the rat cardiac alpha-MHC gene. By Northern blot analysis, we found that, in primary cultures of fetal rat heart myocytes, the elevation of intracellular levels of cAMP results in up-regulation of alpha-MHC and down-regulation of beta-MHC mRNA expression. This effect of cAMP was dependent upon the basal level of expression of both MHC transcripts and was sensitive to cycloheximide. In transient expression analysis employing a series of alpha-MHC/CAT constructs, we identified a 31-base pair fragment located in the immediate upstream region (-71 to -40), which confers both muscle-specific and cAMP-inducible expression of the gene. Within this 31-base pair fragment there are two regions, an AT-rich portion and a hybrid motif which contains overlapping sequences of E-box and M-CAT binding sites (GGCACGTGGAATG). By substitution mutation analysis, both elements were found important for the basal muscle-specific expression; however, the cAMP-inducible expression of the gene is conferred only by the E-box/M-CAT hybrid motif (EM element). Using mobility gel shift competition assay, immunoblotting, and UV-cross-linking analyses, we found that a protein binding to the EM element is indistinguishable from the transcription enhancer factor-1 (TEF-1) in terms of sequence recognition, molecular mass, and immunoreactivity. Methylation interference and point mutation analyses indicate that, besides M-CAT sequences, center CG dinucleotides of the E-box motif CACGTG are essential for protein binding to the EM element and for its functional activity. Furthermore, our data also show that, in addition to TEF-1, another HF-1a-related factor may be recognized by the alpha-MHC gene EM element. These results are first to

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. The Effects of Increased Cardiac Output, Surgical Isolation and Countercurrent Exchange at the Femoral Artery on the Residence Time of Xenon in Muscle

    DTIC Science & Technology

    1993-11-01

    Correct positioning was confirmed by a continuous pressure recording (Gould). We removed the skin and subcutaneous tissues of the left gastrocnemius muscle...hypoxemia persisted and was resistant to efforts to correct it ( recessing the endotracheal tube, increasing airway pressures) for the duration of the

  17. Myocardial damage in dogs affected by heartworm disease (Dirofilaria immitis): immunohistochemical study of cardiac myoglobin and troponin I in naturally infected dogs.

    PubMed

    Carretón, E; Grandi, G; Morchón, R; Simón, F; Passeri, B; Cantoni, A M; Kramer, L; Montoya-Alonso, J A

    2012-10-26

    It has recently been reported that dogs affected by canine heartworm disease (Dirofilaria immitis) can show an increase in plasma levels of myoglobin and cardiac troponin I, two markers of muscle/myocardial injury. In order to determine if this increase is due to myocardial damage, the right ventricle of 24 naturally infected dogs was examined by routine histology and immunohistochemistry with anti-myoglobin and anti-cardiac troponin I antibodies. Microscopic lesions included necrosis and myocyte vacuolization, and were associated with loss of staining for one or both proteins. Results confirm that increased levels of myoglobin and cardiac troponin I are indicative of myocardial damage in dogs affected by heartworm disease.

  18. Changes of calf muscle-tendon properties due to stretching and active movement of children with cerebral palsy--a pilot study.

    PubMed

    Zhao, Heng; Wu, Yi-Ning; Liu, Jie; Ren, Yupeng; Gaebler-Spira, Deborah J; Zhang, Li-Qun

    2009-01-01

    A portable ankle rehabilitation robot with intelligent stretching and game-based active movement training was used to treat the spastic impaired ankle of children with cerebral palsy over six weeks. The subject's calf muscles and Achilles tendon properties were evaluated before and after treatment using ultrasonography and biomechanical measures. It was found that there were decreased Achilles tendon resting length (2.5%), increased cross-sectional area (5.5%), increased stiffness (22.9%), increased Young's modulus (13.8%), decreased soleus muscle fascicular stiffness (53.7%), and decreased medial gastrocnemius fascicular stiffness (46.1%).

  19. Mitochondrial biogenesis in cardiac pathophysiology.

    PubMed

    Rimbaud, Stéphanie; Garnier, Anne; Ventura-Clapier, Renée

    2009-01-01

    Cardiac performance depends on a fine balance between the work the heart has to perform to satisfy the needs of the body and the energy that it is able to produce. Thus, energy production by oxidative metabolism, the main energy source of the cardiac muscle, has to be strictly regulated to adapt to cardiac work. Mitochondrial biogenesis is the mechanism responsible for mitochondrial component synthesis and assembly. This process controls mitochondrial content and thus correlates with energy production that, in turn, sustains cardiac contractility. Mitochondrial biogenesis should be finely controlled to match cardiac growth and cardiac work. When the heart is subjected to an increase in work in response to physiological and pathological challenges, it adapts by increasing its mass and expressing a new genetic program. In response to physiological stimuli such as endurance training, mitochondrial biogenesis seems to follow a program involving increased cardiac mass. But in the context of pathological hypertrophy, the modifications of this mechanism remain unclear. What appears clear is that mitochondrial biogenesis is altered in heart failure, and the imbalance between cardiac work demand and energy production represents a major factor in the development of heart failure.

  20. Cardiac Sarcoidosis.

    PubMed

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  1. Low oxygen tension induces positive inotropy and decreases a(i)Na in isolated guinea-pig cardiac ventricular papillary muscles.

    PubMed

    Jao, M J; Yang, J M

    1998-06-30

    Effects of low oxygen on contractile force, intracellular Na+ activity (aiNa), and action potential were simultaneously measured in isolated guinea-pig ventricular papillary muscles. Reduction of oxygen from control 488 to 150 mmHg biphasically increased and decreased the twitch tension, and decreased aiNa in muscles driven at 60 beats/min. The action potential duration (APD) was decreased but the maximum rate of upstroke (Vmax) was increased. In control, 1 microM epinephrine significantly increased the the action potential amplitude and twitch tension with decreases in the time to twitch peak (TTP), time for 50% relaxation (RT50), and aiNa. After exposure to low oxygen for 10 min, with twitch tension elevated and TTP and RT90 increased, 1 microM epinephrine significantly increased the twitch tension and Vmax, and decreased the APD and aiNa. Pretreatment with reserpine inhibited the twitch tension, both at control and in the presence of epinephrine. But changes of action potential and aiNa in response to low oxygen and epinephrine were similar to those in control. Our results indicate that the isolated guinea-pig ventricular muscle needs a high oxygen tension to maintain a normal contractile function. Reduction of oxygen deteriorates the electrical and mechanical activities, most likely, by a coaxial graded hypoxia. The decreased aiNa, not associated with endogenous catecholamines, suggests that the activity of the Na(+)-K+ pump can be maintained in the superficial muscle cells despite of core-central hypoxia.

  2. Botulinum neurotoxin type A injection of the pelvic floor muscle in pain due to spasticity: a review of the current literature.

    PubMed

    Bhide, Alka A; Puccini, Federica; Khullar, Vik; Elneil, Suzy; Digesu, G Alessandro

    2013-09-01

    The role of muscle spasm is not a new concept in the genesis of pain. Botulinum neurotoxin type A (BoNTA) has been successfully employed in a variety of muscular and inflammatory conditions. The aim of our study was to review the published literature on the role of BoNTA injection of the pelvic floor muscle in the management of women with chronic pelvic pain (CPP). A systematic search of the literature published up to June 2012 on the use of BoNTA in the treatment of female pelvic floor muscle spasm was carried out using relevant search terms in MEDLINE and EMBASE databases. The results were limited to full-text English language articles. Relevant trials as well as relevant reviews were selected and analyzed by two independent reviewers. Five studies (2 case reports, 1 prospective pilot study, 1 retrospective study and 1 randomised double-blind placebo controlled study) were included in this systematic review. Overall, BoNTA has shown to be beneficial in relieving CPP related to pelvic floor spasm. The role of BoNTA as a treatment of CPP has been recognized for more than 10 years. Although data are still scarce preliminary results are encouraging. BoNTA is an attractive option for refractory CPP related to pelvic floor muscle spasm, but further studies using validated and reproducible outcome measures are needed, to establish its effectiveness, safeness, technique, optimal dosage, and duration of symptom relief.

  3. Dose-Dependent Decrease in Mortality with No Cognitive or Muscle Function Improvements Due to Dietary EGCG Supplementation in Aged Mice.

    PubMed

    Pence, Brandt D; Bhattacharya, Tushar K; Park, Pul; Rytych, Jennifer L; Allen, Jacob M; Sun, Yi; McCusker, Robert H; Kelley, Keith W; Johnson, Rodney W; Rhodes, Justin S; Woods, Jeffrey A

    2017-01-05

    We have previously shown that a diet containing epigallocatechin gallate (EGCG) and beta-alanine is not effective in improving either cognitive or muscle function in aged (18 month) mice (Gibbons et al. Behav Brain Res 2014, Pence et al. Appl Physiol Nutr Metab 2016). However, this diet reduced oxidative stress in the brain, and previous studies using longer-term interventions and other doses have documented beneficial effects in cognitive and muscle function, especially with EGCG. Here we hypothesized that a different dose of EGCG or longer feeding period would be more efficacious in improving cognition. Aged (21-25 mo) Balb/cByJ male mice underwent 63 days of feeding with EGCG at 0, 0.09, or 3.67 mg/g AIN-93M diet and were then subjected to a battery of cognitive and muscle function tests. EGCG feeding at either of the two doses did not alter preference for novel versus familiar arm in the Y-maze test (p=0.29) and did not affect learning in the active avoidance test (p=0.76). Similarly, EGCG did not affect preference for novel versus familiar mice in a social exploration test (p=0.17). Likewise, there was no effect of EGCG on muscle function by grip strength (p=0.16), rotarod (p=0.18) or treadmill test to exhaustion (p=0.25). EGCG reduced mortality in a dose-dependent fashion (p=0.05, log rank test for trend), with 91% of high EGCG, 72% of low EGCG, and 55% of control mice surviving to the end of the study. In conclusion, EGCG improves survival in aged mice but does not affect cognitive or muscle function.

  4. Discovery and progress of direct cardiac reprogramming.

    PubMed

    Kojima, Hidenori; Ieda, Masaki

    2017-02-14

    Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

  5. Novel myosin-based therapies for congenital cardiac and skeletal myopathies

    PubMed Central

    Ochala, Julien; Sun, Yin-Biao

    2016-01-01

    The dysfunction in a number of inherited cardiac and skeletal myopathies is primarily due to an altered ability of myofilaments to generate force and motion. Despite this crucial knowledge, there are, currently, no effective therapeutic interventions for these diseases. In this short review, we discuss recent findings giving strong evidence that genetically or pharmacologically modulating one of the myofilament proteins, myosin, could alleviate the muscle pathology. This should constitute a research and clinical priority. PMID:27412953

  6. Your Muscles

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Muscles KidsHealth > For Kids > Your Muscles A A A ... and skeletal (say: SKEL-uh-tul) muscle. Smooth Muscles Smooth muscles — sometimes also called involuntary muscles — are ...

  7. Role of magnesium in etiology of hypertension and atherosclerosis: is Mg/sup 2+/ a second messenger in cardiac and vascular muscle

    SciTech Connect

    Altura, B.M.; Altura, B.T.

    1988-01-01

    Evidence is reviewed which implicates a modulatory role for magnesium (Mg) in the control of arterial blood pressure, vascular tone and lipid metabolism. The evidence is beginning to become persuasive in implicating lower than normal dietary intake of Mg in the etiology of some forms of hypertension, ischemic heart disease (IHD) and atherosclerosis. Hypomagnesemic states in hospitalized patients, particularly those subjects with cardiovascular disease, is becoming more frequent and a serious risk factor for cardiac arrhythmias and stroke. Experimental evidence is presented which demonstrates that Mg deficiency can lead to hypertension, atheromas and coronary vasospasm. Therapy with Mg in several forms of experimental hypertension and atherosclerosis is efficacious. Evidence is also presented to indicate that the (Mg/sup 2+/)/degree/ controls myocardial cellular bioenergetics at the cytosolic and mitochondrial levels. Lastly, the data implicates Mg/sup 2+/ as a true intracellular regulatory cation and most likely as a second messenger.

  8. Slow inactivation in human cardiac sodium channels.

    PubMed Central

    Richmond, J E; Featherstone, D E; Hartmann, H A; Ruben, P C

    1998-01-01

    The available pool of sodium channels, and thus cell excitability, is regulated by both fast and slow inactivation. In cardiac tissue, the requirement for sustained firing of long-duration action potentials suggests that slow inactivation in cardiac sodium channels may differ from slow inactivation in skeletal muscle sodium channels. To test this hypothesis, we used the macropatch technique to characterize slow inactivation in human cardiac sodium channels heterologously expressed in Xenopus oocytes. Slow inactivation was isolated from fast inactivation kinetically (by selectively recovering channels from fast inactivation before measurement of slow inactivation) and structurally (by modification of fast inactivation by mutation of IFM1488QQQ). Time constants of slow inactivation in cardiac sodium channels were larger than previously reported for skeletal muscle sodium channels. In addition, steady-state slow inactivation was only 40% complete in cardiac sodium channels, compared to 80% in skeletal muscle channels. These results suggest that cardiac sodium channel slow inactivation is adapted for the sustained depolarizations found in normally functioning cardiac tissue. Complete slow inactivation in the fast inactivation modified IFM1488QQQ cardiac channel mutant suggests that this impairment of slow inactivation may result from an interaction between fast and slow inactivation. PMID:9635748

  9. Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration.

    PubMed

    Zeng, Bin; Tong, Suiyang; Ren, Xiaofeng; Xia, Hao

    2016-08-01

    Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were co-localized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2'-deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury.

  10. Oxidative capacities of cardiac and skeletal muscles of heart transplant recipients: mitochondrial effects of cyclosporin-A and its vehicle Cremophor-EL.

    PubMed

    N' Guessan, Benoit Banga; Sanchez, Hervé; Zoll, Joffrey; Ribera, Florence; Dufour, Stéphane; Lampert, Eliane; Kindo, Michel; Geny, Bernard; Ventura-Clapier, Renée; Mettauer, Bertrand

    2014-04-01

    Chronic immunosuppressive treatment was suspected to alter maximal muscle oxidative capacity (Vmax ) of heart transplant recipients, leading to a limitation of their exercise tolerance. It remains undefined whether the mitochondrial respiratory chain (MRC) of right ventricle (RV) and vastus lateralis (VL) muscles were altered by immunosuppressants and/or their vehicles. Vmax was measured polarographically in saponin-skinned fibres of RV and VL biopsies of patients and compared with Vmax of healthy VL and myocardium. Effects of increasing concentrations (1-10-100 μM) of Sandimmune(®) , its vehicle, Cyclosporine (CsA) in ethanol (EtOH), or EtOH alone were tested. The vehicle's effects on MRC complexes were investigated using specific substrates and inhibitors. Ten months after grafting, Vmax of RV and VL of immunosuppressed patients were similar to their Vmax at time of transplantation and to that of control tissues. In Vitro, Sandimmune(®) significantly decreased Vmax while CsA in EtOH or EtOH exerted small and similar effects. Effects of the vehicle were higher than (RV) or identical to (VL) those of Sandimmune(®) . The sites of action of the vehicle on MRC were located on complexes I and IV. While unchanged under chronic immunosuppressive therapy, Vmax of RV and VL muscles was depressed by acute exposure to intravenous Sandimmune(®) in vitro, an effect attributed to its vehicle by inhibition of complexes I and IV of the MRC. This work provides an in vitro proof of a toxic effect on the mitochondria respiratory chain of the vehicle used in the intravenous formulation of Sandimmune(®) but with no clinical consequences in chronically immunosuppressed patients.

  11. Effect of tighter glycemic control on cardiac function, exercise capacity, and muscle strength in heart failure patients with type 2 diabetes: a randomized study

    PubMed Central

    Nielsen, Roni; Wiggers, Henrik; Thomsen, Henrik Holm; Bovin, Ann; Refsgaard, Jens; Abrahamsen, Jan; Møller, Niels; Bøtker, Hans Erik; Nørrelund, Helene

    2016-01-01

    Objectives In patients with type 2 diabetes (T2D) and heart failure (HF), the optimal glycemic target is uncertain, and evidence-based data are lacking. Therefore, we performed a randomized study on the effect of optimized glycemic control on left ventricular function, exercise capacity, muscle strength, and body composition. Design and methods 40 patients with T2D and HF (left ventricular ejection fraction (LVEF) 35±12% and hemoglobin A1c (HbA1c) 8.4±0.7% (68±0.8 mmol/mol)) were randomized to either 4-month optimization (OPT group) or non-optimization (non-OPT group) of glycemic control. Patients underwent dobutamine stress echocardiography, cardiopulmonary exercise test, 6 min hall-walk test (6-MWT), muscle strength examination, and dual X-ray absorptiometry scanning at baseline and at follow-up. Results 39 patients completed the study. HbA1c decreased in the OPT versus the non-OPT group (8.4±0.8% (68±9 mmol/mol) to 7.6±0.7% (60±7 mmol/mol) vs 8.3±0.7% (67±10 mmol/mol) to 8.4±1.0% (68±11 mmol/mol); p<0.001). There was no difference between the groups with respect to changes in myocardial contractile reserve (LVEF (p=0.18)), oxygen consumption (p=0.55), exercise capacity (p=0.12), and 6-MWT (p=0.84). Muscle strength decreased in the non-OPT compared with the OPT group (37.2±8.1 to 34.8±8.3 kg vs 34.9±10.2 to 35.4±10.7 kg; p=0.01), in line with a non-significant decrease in lean (p=0.07) and fat (p=0.07) tissue mass in the non-OPT group. Hypoglycemia and fluid retention did not differ between groups. Conclusions 4 months of optimization of glycemic control was associated with preserved muscle strength and lean body mass in patients with T2D and HF compared with lenient control, and had no deleterious effect on left ventricular contractile function and seemed to be safe. Trial registration number NCT01213784; pre-results. PMID:27158520

  12. Depression of Ca2+ insensitive tension due to reduced pH in partially troponin-extracted skinned skeletal muscle fibers.

    PubMed Central

    Metzger, J M; Moss, R L

    1988-01-01

    Previous studies on skinned muscle fibers have demonstrated a direct effect of elevated levels of H+ ion to depress force production; however, the molecular basis for this effect is presently unknown. Here, whole troponin complexes were removed from skinned single fiber preparations of rat slow-twitch and fast-twitch muscles, and the effect of H+ ions on the resultant Ca2+-insensitive force was examined. The effect of H+ ions to depress force was found to be virtually identical in untreated control fibers activated in the presence of Ca2+ and in fibers activated in the absence of Ca2+ by troponin removal. Thus, the effect of H+ ions to depress force occurs at a step in activation beyond the disinhibition of the thin filament by Ca2+, probably involving reductions in the number of attached cross-bridges or in the force per attachment. PMID:3233271

  13. Factors affecting the reactivation of the oligomycin-sensitive adenosine 5'-triphosphatase and the release of ATPase inhibitor protein during the re-energization of intact mitochondria from ischemic cardiac muscle.

    PubMed

    Rouslin, W

    1987-03-15

    In the present study we examined factors affecting the reversal of the ischemia-induced protonic inhibition of the mitochondrial ATPase described earlier (Rouslin, W. (1983) J. Biol. Chem. 258, 9657-9661). It was found that ATPase reactivation and accompanying inhibitor protein release during the re-energization of intact mitochondria isolated from 20-min ischemic canine heart muscle could be blocked completely by either carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or nigericin but was unaffected by valinomycin at 35 mM K+. At higher K+ concentrations, valinomycin also blocked ATPase reactivation but not quite as completely as did nigericin. These observations suggest that ATPase reactivation and inhibitor protein release are particularly dependent upon either the trans-inner membrane pH gradient (delta pH) or possibly upon matrix pH per se and slightly less dependent upon membrane potential (delta psi) in intact cardiac muscle mitochondria. The addition of FCCP at the end of the re-energization incubations limited partially the extent of both ATPase reactivation and inhibitor protein release. This latter effect appears to have been mediated by a partial reassociation of the inhibitor protein with the enzyme, and it was accentuated (when FCCP was added at the end of the incubations) or mimicked (when FCCP was absent) by lowering the pH of the re-energization medium. A close examination of the first 10 min of the time course of enzyme activation and of inhibitor protein release revealed that while the former process was essentially finished in 1 min or less, the latter required approximately 10 min for completion. This observation led to the proposal of a two-site model of enzyme-inhibitor interaction which is discussed.

  14. Acute rhabdomyolysis of the soleus muscle induced by a lightning strike: magnetic resonance and scintigraphic findings.

    PubMed

    Watanabe, Naofumi; Inaoka, Tsutomu; Shuke, Noriyuki; Takahashi, Koji; Aburano, Tamio; Chisato, Naoyuki; Nochi, Hitoshi; Go, Kazutomo

    2007-07-01

    Among natural disasters, a lightning strike is a rare but potentially life-threatening phenomenon. If victims survive a cardiac arrest due to instantaneous passage of an exceptionally high voltage electric charge through the whole body, they may be afflicted with various complications such as muscle necrosis resulting in acute renal failure. In this article, we report a case of a 54-year-old man with acute rhabdomyolysis of the left soleus muscle associated with a lightning strike. T2-weighted and short-tau inversion recovery MR images showed a high signal intensity in the left soleus muscle. A whole-body bone scintigram showed abnormal uptakes in the left soleus muscle and the dorsal aspect of the left foot. MR and scintigraphic evaluations were very useful in depicting the site and extent of muscle damage. Since the patient showed a surprisingly high level of serum creatine kinase, the added information was very valuable for determining the patient's management.

  15. Use of flow, electrical, and mechanical stimulation to promote engineering of striated muscles.

    PubMed

    Rangarajan, Swathi; Madden, Lauran; Bursac, Nenad

    2014-07-01

    The field of tissue engineering involves design of high-fidelity tissue substitutes for predictive experimental assays in vitro and cell-based regenerative therapies in vivo. Design of striated muscle tissues, such as cardiac and skeletal muscle, has been particularly challenging due to a high metabolic demand and complex cellular organization and electromechanical function of the native tissues. Successful engineering of highly functional striated muscles may thus require creation of biomimetic culture conditions involving medium perfusion, electrical and mechanical stimulation. When optimized, these external cues are expected to synergistically and dynamically activate important intracellular signaling pathways leading to accelerated muscle growth and development. This review will discuss the use of different types of tissue culture bioreactors aimed at providing conditions for enhanced structural and functional maturation of engineered striated muscles.

  16. Use of flow, electrical, and mechanical stimulation to promote engineering of striated muscles

    PubMed Central

    Rangarajan, Swathi; Madden, Lauran; Bursac, Nenad

    2014-01-01

    The field of tissue engineering involves design of high-fidelity tissue substitutes for predictive experimental assays in vitro and cell-based regenerative therapies in vivo. Design of striated muscle tissues, such as cardiac and skeletal muscle, has been particularly challenging due to a high metabolic demand and complex cellular organization and electromechanical function of the native tissues. Successful engineering of highly functional striated muscles may thus require creation of biomimetic culture conditions involving medium perfusion, electrical and mechanical stimulation. When optimized, these external cues are expected to synergistically and dynamically activate important intracellular signaling pathways leading to accelerated muscle growth and development. This review will discuss the use of different types of tissue culture bioreactors aimed at providing conditions for enhanced structural and functional maturation of engineered striated muscles. PMID:24366526

  17. Nuclear cardiac

    SciTech Connect

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

  18. Cardiac cameras.

    PubMed

    Travin, Mark I

    2011-05-01

    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  19. Mechanism of the Frank-Starling law--a simulation study with a novel cardiac muscle contraction model that includes titin and troponin I.

    PubMed

    Schneider, Natalie S; Shimayoshi, Takao; Amano, Akira; Matsuda, Tetsuya

    2006-09-01

    A stretch-induced increase of active tension is one of the most important properties of the heart, known as the Frank-Starling law. Although a variation of myofilament Ca(2+) sensitivity with sarcomere length (SL) change was found to be involved, the underlying molecular mechanisms are not fully clarified. Some recent experimental studies indicate that a reduction of the lattice spacing between thin and thick filaments, through the increase of passive tension caused by the sarcomeric protein titin with an increase in SL within the physiological range, promotes formation of force-generating crossbridges (Xbs). However, the mechanism by which the Xb concentration determines the degree of cooperativity for a given SL has so far evaded experimental elucidation. In this simulation study, a novel, rather simple molecular-based cardiac contraction model, appropriate for integration into a ventricular cell model, was designed, being the first model to introduce experimental data on titin-based radial tension to account for the SL-dependent modulation of the interfilament lattice spacing and to include a conformational change of troponin I (TnI). Simulation results for the isometric twitch contraction time course, the length-tension and the force-[Ca(2+)] relationships are comparable to experimental data. A complete potential Frank-Starling mechanism was analyzed by this simulation study. The SL-dependent modulation of the myosin binding rate through titin's passive tension determines the Xb concentration which then alters the degree of positive cooperativity affecting the rate of the TnI conformation change and causing the Hill coefficient to be SL-dependent.

  20. Ichthyophonus-induced cardiac damage: a mechanism for reduced swimming stamina in salmonids

    USGS Publications Warehouse

    Kocan, R.; LaPatra, S.; Gregg, J.; Winton, J.; Hershberger, P.

    2006-01-01

    Swimming stamina, measured as time-to-fatigue, was reduced by approximately two-thirds in rainbow trout experimentally infected with Ichthyophonus. Intensity of Ichthyophonus infection was most severe in cardiac muscle but multiple organs were infected to a lesser extent. The mean heart weight of infected fish was 40% greater than that of uninfected fish, the result of parasite biomass, infiltration of immune cells and fibrotic (granuloma) tissue surrounding the parasite. Diminished swimming stamina is hypothesized to be due to cardiac failure resulting from the combination of parasite-damaged heart muscle and low myocardial oxygen supply during sustained aerobic exercise. Loss of stamina in Ichthyophonus-infected salmonids could explain the poor performance previously reported for wild Chinook and sockeye salmon stocks during their spawning migration. ?? 2006 Blackwell Publishing Ltd.

  1. Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF.

    PubMed

    Sarma, Satyam; Levine, Benjamin D

    2015-09-15

    Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests "peripheral," i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.

  2. Differential Expression of Cardiac Troponin T and I in a Patient with Isolated Skeletal Muscular Sarcoidosis

    PubMed Central

    Mannoji, Hiroshi; Hayashi, Fumie; Kubota, Toru; Ikeda, Yoshihiko; Ishibashi-Ueda, Hatsue; Kato, Seiya; Tahara, Nobuhiro; Fukutomi, Takayoshi; Yamada, Takeshi; Okabe, Masanori; Yamamoto, Yusuke

    2016-01-01

    A 49-year-old female was referred to our hospital due to high serum creatine kinase (CK) (2,605 IU/L) and serum cardiac troponin T (cTnT) (0.342 ng/mL) levels. She had no other complaints and further examinations suggested no signs of cardiac disease. Additionally, the serum cardiac troponin I (cTnI) levels were normal. She reported having gradually felt difficulty in walking upstairs. A biopsy indicated skeletal muscle sarcoidosis with positive staining for cTnT. Steroid therapy immediately resolved her muscular symptoms with a normalization of the serum CK levels. Since the serum levels of cTnI were normal, the concomitant measurement of cTnT/cTnI might be useful to diagnose skeletal muscular disease biochemically in such cases. PMID:27803423

  3. Comparative changes in antioxidant enzymes and oxidative stress in cardiac, fast twitch and slow twitch skeletal muscles following endurance exercise training

    PubMed Central

    Hyatt, Hayden W; Smuder, Ashley J; Sollanek, Kurt J; Morton, Aaron B; Roberts, Michael D; Kavazis, Andreas N

    2016-01-01

    The aim of this study was to evaluate exercise-induced transcriptional and protein responses of heart, soleus (slow oxidative), and plantaris (fast glycolytic) muscle in response to ten days of endurance exercise training. Four-month old female Sprague-Dawley rats were assigned to either a sedentary (SED) or endurance exercise-training (EXE) group (n=8 per group). The heart, plantaris, and soleus were excised and used for biochemical analyses. Our results show that heart and plantaris from EXE animals had higher protein levels of superoxide dismutase 2 (SOD2) compared to SED animals (P<0.05). Also, the protein levels of catalase were higher in plantaris of EXE animals compared to SED animals (P<0.05). No significant differences existed for 4 hydroxynonenal (4HNE) conjugated proteins (index of oxidative damage) in the three tissues between SED and EXE animals. mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were higher in plantaris of EXE animals compared to SED animals (P<0.05), and mRNA levels of estrogen-related receptor alpha (ERRα) were lower in the heart of EXE animals compared to SED animals. In conclusion, heart and plantaris are responsive to ten days of treadmill training, while greater exercise intensities or durations may be needed to elicit alterations in soleus. PMID:28078055

  4. Association between exposure to emissions from the oil and gas industry and pathology of the immune, nervous, and respiratory systems, and skeletal and cardiac muscle in beef calves.

    PubMed

    Waldner, Cheryl L; Clark, Edward G

    2009-01-01

    To determine potential associations between emissions from oil and gas field facilities and the risk of lesions in the immune, nervous, and respiratory systems of beef calves, researchers examined tissue samples collected from 1,531 cases with exposure data, which included aborted fetuses, stillbirths, and calf mortalities from 203 cow-calf herds, by means of histopathology. The researchers prospectively measured exposure to sulfur dioxide, hydrogen sulfide, and volatile organic compounds by using air-monitoring data from passive monitors. They used the density of facilities surrounding each pasture as a second measure of exposure. Each tissue was classified by the presence or absence of a series of specified lesions, including those associated with degeneration, necrosis, infection, inflammation, anomaly, lympholysis (for lymphoid tissue), and proliferation (for the respiratory system). Exposure was not associated with the risk of lesions to tissues of either the immune or nervous system in calves that were aborted or died in spring 2002. Exposures to sulfur dioxide and hydrogen sulfide were not significantly associated with the risk of lesions to respiratory tissues in calves that were born alive in spring 2002. Increasing postnatal exposures to volatile organic compounds measured as benzene and toluene were associated with increased odds of respiratory lesions. The association between volatile organic compounds measured as benzene and respiratory lesions was significant for calves older than 3 weeks. During gestation, increasing exposure to sulfur dioxide was associated with increased odds of lesions in either the skeletal muscle or myocardium.

  5. Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding

    PubMed Central

    Urashima, Takashi; Shimura, Daisuke; Amemiya, Erika; Miyasaka, Genki; Yokota, Shunsuke; Fujimoto, Yoshitaka; Akaike, Toru; Inoue, Takahiro; Minamisawa, Susumu

    2017-01-01

    Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling) has not yet been clarified. We developed an animal model of right ventricular (RV) hypertrophy with fibrosis by pulmonary artery (PA) banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca2+ concentration of RV papillary muscles were simultaneously measured (n = 33). The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca2+ responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca2+ had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca2+ responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1) the decrease in Ca2+ responsiveness and 2) the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication. PMID:28068381

  6. Normal cardiac function in mice with supraphysiological cardiac creatine levels.

    PubMed

    Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O

    2014-02-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

  7. Direct Cardiac Reprogramming: From Developmental Biology to Cardiac Regeneration

    PubMed Central

    Qian, Li; Srivastava, Deepak

    2013-01-01

    Heart disease affects millions worldwide and is a progressive condition involving loss of cardiomyocytes. The human heart has limited endogenous regenerative capacity and is thus an important target for novel regenerative medicine approaches. While cell-based regenerative therapies hold promise, cellular reprogramming of endogenous cardiac fibroblasts, which represent more than half of the cells in the mammalian heart, may be an attractive alternative strategy for regenerating cardiac muscle. Recent advances leveraging years of developmental biology point to the feasibility of generating de novo cardiomyocyte-like cells from terminally differentiated non-myocytes in the heart in situ after ischemic damage. Here, we review the progress in cardiac reprogramming methods and consider the opportunities and challenges that lie ahead in refining this technology for regenerative medicine. PMID:24030021

  8. Cardiac atrophy after bed rest and spaceflight

    NASA Technical Reports Server (NTRS)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  9. Nanomaterials for Cardiac Myocyte Tissue Engineering

    PubMed Central

    Amezcua, Rodolfo; Shirolkar, Ajay; Fraze, Carolyn; Stout, David A.

    2016-01-01

    Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials. PMID:28335261

  10. Mechanical analysis of Drosophila indirect flight and jump muscles

    PubMed Central

    Swank, Douglas M.

    2011-01-01

    The genetic advantages of Drosophila make it a very appealing choice for investigating muscle development, muscle physiology and muscle protein structure and function. To take full advantage of this model organism, it has been vital to develop isolated Drosophila muscle preparations that can be mechanically evaluated. We describe techniques to isolate, prepare and mechanically analyze skinned muscle fibers from two Drosophila muscle types, the indirect flight muscle and the jump muscle. The function of the indirect flight muscle is similar to vertebrate cardiac muscle, to generate power in an oscillatory manner. The indirect flight muscle is ideal for evaluating the influence of protein mutations on muscle and cross-bridge stiffness, oscillatory power, and deriving cross-bridge rate constants. Jump muscle physiology and structure are more similar to skeletal vertebrate muscle than indirect flight muscle, and it is ideal for measuring maximum shortening velocity, force-velocity characteristics and steady-state power generation. PMID:22079350

  11. Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells.

    PubMed

    Lee, Kunwoo; Yu, Pengzhi; Lingampalli, Nithya; Kim, Hyun Jin; Tang, Richard; Murthy, Niren

    2015-01-01

    The treatment of myocardial infarction is a major challenge in medicine due to the inability of heart tissue to regenerate. Direct reprogramming of endogenous cardiac fibroblasts into functional cardiomyocytes via the delivery of transcription factor mRNAs has the potential to regenerate cardiac tissue and to treat heart failure. Even though mRNA delivery to cardiac fibroblasts has the therapeutic potential, mRNA transfection in cardiac fibroblasts has been challenging. Herein, we develop an efficient mRNA transfection in cultured mouse cardiac fibroblasts via a polyarginine-fused heart-targeting peptide and lipofectamine complex, termed C-Lipo and demonstrate the partial direct reprogramming of cardiac fibroblasts towards cardiomyocyte cells. C-Lipo enabled the mRNA-induced direct cardiac reprogramming due to its efficient transfection with low toxicity, which allowed for multiple transfections of Gata4, Mef2c, and Tbx5 (GMT) mRNAs for a period of 2 weeks. The induced cardiomyocyte-like cells had α-MHC promoter-driven GFP expression and striated cardiac muscle structure from α-actinin immunohistochemistry. GMT mRNA transfection of cultured mouse cardiac fibroblasts via C-Lipo significantly increased expression of the cardiomyocyte marker genes, Actc1, Actn2, Gja1, Hand2, and Tnnt2, after 2 weeks of transfection. Moreover, this study provides the first direct evidence that the stoichiometry of the GMT reprogramming factors influence the expression of cardiomyocyte marker genes. Our results demonstrate that mRNA delivery is a potential approach for cardiomyocyte generation.

  12. Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

    PubMed

    Zhang, Li-Fan; Sun, Biao; Cao, Xin-Sheng; Liu, Chun; Yu, Zhi-Bin; Zhang, Le-Ning; Cheng, Jiu-Hua; Wu, Yan-Hong; Wu, Xing-Yu

    2003-07-01

    This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.

  13. Automated cardiac sarcomere analysis from second harmonic generation images

    NASA Astrophysics Data System (ADS)

    Garcia-Canadilla, Patricia; Gonzalez-Tendero, Anna; Iruretagoyena, Igor; Crispi, Fatima; Torre, Iratxe; Amat-Roldan, Ivan; Bijnens, Bart H.; Gratacos, Eduard

    2014-05-01

    Automatic quantification of cardiac muscle properties in tissue sections might provide important information related to different types of diseases. Second harmonic generation (SHG) imaging provides a stain-free microscopy approach to image cardiac fibers that, combined with our methodology of the automated measurement of the ultrastructure of muscle fibers, computes a reliable set of quantitative image features (sarcomere length, A-band length, thick-thin interaction length, and fiber orientation). We evaluated the performance of our methodology in computer-generated muscle fibers modeling some artifacts that are present during the image acquisition. Then, we also evaluated it by comparing it to manual measurements in SHG images from cardiac tissue of fetal and adult rabbits. The results showed a good performance of our methodology at high signal-to-noise ratio of 20 dB. We conclude that our automated measurements enable reliable characterization of cardiac fiber tissues to systematically study cardiac tissue in a wide range of conditions.

  14. Cardiac Amyloidosis

    MedlinePlus

    ... In the normal heart, the muscle fibers (stained pink in this slide) are close together with little ... amount of amyloid deposited between them (staining light pink-purple). (Images courtesy of Dr Paul VanderLaan, Brigham ...

  15. Cardiac Rehabilitation

    MedlinePlus

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  16. Limited Expression of Slow Tonic Myosin Heavy Chain in Human Cranial Muscles

    PubMed Central

    Sokoloff, Alan J.; Li, Haiyan; Burkholder, Thomas J.

    2013-01-01

    Recent reports of slow tonic myosin heavy chain (MHCst) in human masticatory and laryngeal muscles suggest that MHCst may have a wider distribution in humans than previously thought. Because of the novelty of this finding, we sought to confirm the presence of MHCst in human masticatory and laryngeal muscles by reacting tissue from these muscles and controls from extraocular, intrafusal, cardiac, appendicular and developmental muscle with antibodies (Abs) ALD-58 and S46 considered highly specific for MHCst. At Ab dilutions producing minimal reaction to muscle fibers positive for MHCI, only extraocular, intrafusal and fetal tongue tissue reacted with Ab S46 had strong immunoreaction in an appreciable number of muscle fibers. In immunoblots Ab S46, but not Ab ALD-58, labeled adult extraocular muscles; no other muscles were labeled with either Ab. We conclude that, in humans, Ab S46 has greater specificity for MHCst than does Ab ALD-58. We suggest that reports of MHCst in human masticatory and laryngeal muscles reflect false-positive identification of MHCst due to cross-reactivity of Ab ALD-58 with another MHC isoform. PMID:17486578

  17. Smooth muscle hyperplasia due to loss of smooth muscle α-actin is driven by activation of focal adhesion kinase, altered p53 localization and increased levels of platelet-derived growth factor receptor-β

    PubMed Central

    Papke, Christina L.; Cao, Jiumei; Kwartler, Callie S.; Villamizar, Carlos; Byanova, Katerina L.; Lim, Soon-Mi; Sreenivasappa, Harini; Fischer, Grant; Pham, John; Rees, Meredith; Wang, Miranda; Chaponnier, Christine; Gabbiani, Giulio; Khakoo, Aarif Y.; Chandra, Joya; Trache, Andreea; Zimmer, Warren; Milewicz, Dianna M.

    2013-01-01

    Mutations in ACTA2, encoding the smooth muscle cell (SMC)-specific isoform of α-actin (α-SMA), cause thoracic aortic aneurysms and dissections and occlusive vascular diseases, including early onset coronary artery disease and stroke. We have shown that occlusive arterial lesions in patients with heterozygous ACTA2 missense mutations show increased numbers of medial or neointimal SMCs. The contribution of SMC hyperplasia to these vascular diseases and the pathways responsible for linking disruption of α-SMA filaments to hyperplasia are unknown. Here, we show that the loss of Acta2 in mice recapitulates the SMC hyperplasia observed in ACTA2 mutant SMCs and determine the cellular pathways responsible for SMC hyperplasia. Acta2−/− mice showed increased neointimal formation following vascular injury in vivo, and SMCs explanted from these mice demonstrated increased proliferation and migration. Loss of α-SMA induced hyperplasia through focal adhesion (FA) rearrangement, FA kinase activation, re-localization of p53 from the nucleus to the cytoplasm and increased expression and ligand-independent activation of platelet-derived growth factor receptor beta (Pdgfr-β). Disruption of α-SMA in wild-type SMCs also induced similar cellular changes. Imatinib mesylate inhibited Pdgfr-β activation and Acta2−/− SMC proliferation in vitro and neointimal formation with vascular injury in vivo. Loss of α-SMA leads to SMC hyperplasia in vivo and in vitro through a mechanism involving FAK, p53 and Pdgfr-β, supporting the hypothesis that SMC hyperplasia contributes to occlusive lesions in patients with ACTA2 missense mutations. PMID:23591991

  18. Smooth muscle hyperplasia due to loss of smooth muscle α-actin is driven by activation of focal adhesion kinase, altered p53 localization and increased levels of platelet-derived growth factor receptor-β.

    PubMed

    Papke, Christina L; Cao, Jiumei; Kwartler, Callie S; Villamizar, Carlos; Byanova, Katerina L; Lim, Soon-Mi; Sreenivasappa, Harini; Fischer, Grant; Pham, John; Rees, Meredith; Wang, Miranda; Chaponnier, Christine; Gabbiani, Giulio; Khakoo, Aarif Y; Chandra, Joya; Trache, Andreea; Zimmer, Warren; Milewicz, Dianna M

    2013-08-01

    Mutations in ACTA2, encoding the smooth muscle cell (SMC)-specific isoform of α-actin (α-SMA), cause thoracic aortic aneurysms and dissections and occlusive vascular diseases, including early onset coronary artery disease and stroke. We have shown that occlusive arterial lesions in patients with heterozygous ACTA2 missense mutations show increased numbers of medial or neointimal SMCs. The contribution of SMC hyperplasia to these vascular diseases and the pathways responsible for linking disruption of α-SMA filaments to hyperplasia are unknown. Here, we show that the loss of Acta2 in mice recapitulates the SMC hyperplasia observed in ACTA2 mutant SMCs and determine the cellular pathways responsible for SMC hyperplasia. Acta2(-/-) mice showed increased neointimal formation following vascular injury in vivo, and SMCs explanted from these mice demonstrated increased proliferation and migration. Loss of α-SMA induced hyperplasia through focal adhesion (FA) rearrangement, FA kinase activation, re-localization of p53 from the nucleus to the cytoplasm and increased expression and ligand-independent activation of platelet-derived growth factor receptor beta (Pdgfr-β). Disruption of α-SMA in wild-type SMCs also induced similar cellular changes. Imatinib mesylate inhibited Pdgfr-β activation and Acta2(-/-) SMC proliferation in vitro and neointimal formation with vascular injury in vivo. Loss of α-SMA leads to SMC hyperplasia in vivo and in vitro through a mechanism involving FAK, p53 and Pdgfr-β, supporting the hypothesis that SMC hyperplasia contributes to occlusive lesions in patients with ACTA2 missense mutations.

  19. The effect of Mg2+ on cardiac muscle function: Is CaATP the substrate for priming myofibril cross-bridge formation and Ca2+ reuptake by the sarcoplasmic reticulum?

    PubMed Central

    Smith, G A; Vandenberg, J I; Freestone, N S; Dixon, H B

    2001-01-01

    of the kinetics of the cardiac sarcoplasmic reticulum ATPase to those of the myofibril, in particular the positive co-operativity of both Mg2+ inhibition and Ca2+ activation, leads to the conclusion that this ATPase also has an initiation step that utilizes CaATP. The first-order activation by sub-millimolar [Mg2+], similar to that of the myofibril, may be explained by Mg2+ involvement in the phosphate-release step of the ATPase. The inhibition of both the myofibril and sarcoplasmic reticulum Ca2+ transporting ATPases by Mg2+ offers an explanation for the specific requirement for phosphocreatine (PCr) for full activity of both enzymes in situ and its effect on their apparent affinities for ATP. This explanation is based on the slow diffusion of Mg2+ within the myofibril and on the contrast of PCr with both ATP and phosphoenolpyruvate, in that PCr does not bind Mg2+ under physiological conditions, whereas both the other two bind it more tightly than the products of their hydrolysis do. The switch to supply of energy by diffusion of MgATP into the myofibril when depletion of PCr raises [ATP]/[PCr] greatly, e.g. during anoxia, results in a local [Mg2+] increase, which inhibits the ATPase. It is possible that mechanisms similar to those described above occur in skeletal muscle but the Ca2+ co-operativity involved would be masked by the presence of two Ca2+ binding sites on each troponin. PMID:11237858

  20. Human embryonic stem cells and cardiac repair.

    PubMed

    Zhu, Wei-Zhong; Hauch, Kip D; Xu, Chunhui; Laflamme, Michael A

    2009-01-01

    The muscle lost after a myocardial infarction is replaced with noncontractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. Human embryonic stem cell-derived cardiomyocytes exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-derived cardiomyocytes and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges.

  1. Muscle Cramps

    MedlinePlus

    Muscle cramps are sudden, involuntary contractions or spasms in one or more of your muscles. They often occur after exercise or at night, ... to several minutes. It is a very common muscle problem. Muscle cramps can be caused by nerves ...

  2. Muscle Disorders

    MedlinePlus

    Your muscles help you move and help your body work. Different types of muscles have different jobs. There are many problems that can affect muscles. Muscle disorders can cause weakness, pain or even ...

  3. Your Muscles

    MedlinePlus

    ... of the heart because it controls the heartbeat. Skeletal Muscle Now, let's talk about the kind of muscle ... soccer ball into the goal. These are your skeletal muscles — sometimes called striated (say: STRY-ay-tud) muscle ...

  4. Hepato-cardiac disorders

    PubMed Central

    Fouad, Yasser Mahrous; Yehia, Reem

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases PMID:24653793

  5. Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function

    PubMed Central

    2014-01-01

    Background Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. Materials and methods Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. Results Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway. Conclusions Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of

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

    PubMed

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

    2017-02-01

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

  7. The Physics of Cardiac Fibrillation: Strings that kill

    NASA Astrophysics Data System (ADS)

    Bodenschatz, Eberhard

    2009-03-01

    Fibrillation is a state of spatio-temporal chaos in a 3d-biological excitable medium, namely the heart muscle. The building blocks are wave-emitting three-dimensional topological singularities in the electric excitation field of the tissue. These string like singularities send out a rotating wave fields with very fast frequencies (up to 10 times normal heart rate) and thus dominate over the pacemaker. The incoherent electrical excitation of the spatio-temporal chaotic dynamics leads to an unsynchronized contraction of the cardiac muscle and to the loss of the pumping action, and if untreated to death. Due to the topological nature of the spatio-temporal chaotic state it is very difficult to control. Current defibrillation technologies use strong electric field pulses (1 kV, 30 A, 12 ms) to reset the whole muscle. Here we report that natural muscle heterogeneities act as wave emitting sites when a weak electric field pulse is applied across the tissue. We report theoretical predictions on the physics and support the findings by results from experiment. This work was conducted in collaboration with Stefan Luther (MPIDS), Falvio Fenton ( Cornell), Amgad Squires (Cornell), Robert Gilmour (Cornell), Valentin Krinsky (MPIDS), Alain Pumir (NIce).

  8. Inhibition of autophagy inhibits the conversion of cardiac fibroblasts to cardiac myofibroblasts

    PubMed Central

    Gupta, Shivika S.; Zeglinski, Matthew R.; Rattan, Sunil G.; Landry, Natalie M.; Ghavami, Saeid; Wigle, Jeffrey T.; Klonisch, Thomas; Halayko, Andrew J.; Dixon, Ian M.C.

    2016-01-01

    The incidence of heart failure with concomitant cardiac fibrosis is very high in developed countries. Fibroblast activation in heart is causal to cardiac fibrosis as they convert to hypersynthetic cardiac myofibroblasts. There is no known treatment for cardiac fibrosis. Myofibroblasts contribute to the inappropriate remodeling of the myocardial interstitium, which leads to reduced cardiac function and ultimately heart failure. Elevated levels of autophagy have been linked to stress-induced ventricular remodeling and other cardiac diseases. Previously, we had shown that TGF-β1 treatment of human atrial fibroblasts both induced autophagy and enhanced the fibrogenic response supporting a linkage between the myofibroblast phenotype and autophagy. We now demonstrate that with in vitro culture of primary rat cardiac fibroblasts, inhibition of autophagy represses fibroblast to myofibroblast phenoconversion. Culturing unpassaged cardiac fibroblasts for 72 hours on plastic tissue culture plates is associated with elevated α-smooth muscle actin (α-SMA) expression. This activation parallels increased microtubule-associated protein 1A/1B-light chain 3 (LC-3β II) protein expression. Inhibition of autophagy with bafilomycin-A1 (Baf-A1) and chloroquine (CQ) in cardiac fibroblasts significantly reduces α-SMA and extracellular domain A fibronectin (ED-A FN) protein vs untreated controls. Myofibroblast cell migration and contractility were significantly reduced following inhibition of autophagy. These data support the possibility of a causal link between cardiac fibroblast-to-myofibroblast phenoconversion and autophagy. PMID:27705938

  9. Artificial muscle: the human chimera is the future.

    PubMed

    Tozzi, P

    2011-12-14

    Severe heart failure and cerebral stroke are broadly associated with the impairment of muscular function that conventional treatments struggle to restore. New technologies enable the construction of "smart" materials that could be of great help in treating diseases where the main problem is muscle weakness. These materials "behave" similarly to biological systems, because the material directly converts energy, for example electrical energy into movement. The extension and contraction occur silently like in natural muscles. The real challenge is to transfer this amazing technology into devices that restore or replace the mechanical function of failing muscle. Cardiac assist devices based on artificial muscle technology could envelope a weak heart and temporarily improve its systolic function, or, if placed on top of the atrium, restore the atrial kick in chronic atrial fibrillation. Artificial sphincters could be used to treat urinary incontinence after prostatectomy or faecal incontinence associated with stomas. Artificial muscles can restore the ability of patients with facial paralysis due to stroke or nerve injury to blink. Smart materials could be used to construct an artificial oesophagus including peristaltic movement and lower oesophageal sphincter function to replace the diseased oesophagus thereby avoiding the need for laparotomy to mobilise stomach or intestine. In conclusion, in the near future, smart devices will integrate with the human body to fill functional gaps due to organ failure, and so create a human chimera.

  10. Inactivation of Myosin Binding Protein C Homolog in Zebrafish as a Model for Human Cardiac Hypertrophy and Diastolic Dysfunction

    PubMed Central

    Chen, Yau‐Hung; Pai, Chiung‐Wen; Huang, Shu‐Wei; Chang, Sheng‐Nan; Lin, Lian‐Yu; Chiang, Fu‐Tien; Lin, Jiunn‐Lee; Hwang, Juey‐Jen; Tsai, Chia‐Ti

    2013-01-01

    Background Sudden cardiac death due to malignant ventricular arrhythmia is a devastating manifestation of cardiac hypertrophy. Sarcomere protein myosin binding protein C is functionally related to cardiac diastolic function and hypertrophy. Zebrafish is a better model to study human electrophysiology and arrhythmia than rodents because of the electrophysiological characteristics similar to those of humans. Methods and Results We established a zebrafish model of cardiac hypertrophy and diastolic dysfunction by genetic knockdown of myosin binding protein C gene (mybpc3) and investigated the electrophysiological phenotypes in this model. We found expression of zebrafish mybpc3 restrictively in the heart and slow muscle, and mybpc3 gene was evolutionally conservative with sequence homology between zebrafish and human mybpc3 genes. Zebrafish with genetic knockdown of mybpc3 by morpholino showed ventricular hypertrophy with increased myocardial wall thickness and diastolic heart failure, manifesting as decreased ventricular diastolic relaxation velocity, pericardial effusion, and dilatation of the atrium. In terms of electrophysiological phenotypes, mybpc3 knockdown fish had a longer ventricular action potential duration and slower ventricular diastolic calcium reuptake, both of which are typical electrophysiological features in human cardiac hypertrophy and heart failure. Impaired calcium reuptake resulted in increased susceptibility to calcium transient alternans and action potential duration alternans, which have been proved to be central to the genesis of malignant ventricular fibrillation and a sensitive marker of sudden cardiac death. Conclusions mybpc3 knockdown in zebrafish recapitulated the morphological, mechanical, and electrophysiological phenotypes of human cardiac hypertrophy and diastolic heart failure. Our study also first demonstrated arrhythmogenic cardiac alternans in cardiac hypertrophy. PMID:24047589

  11. Cardiac optogenetics

    PubMed Central

    2013-01-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart. PMID:23457014

  12. Cardiac Surgery

    PubMed Central

    Weisse, Allen B.

    2011-01-01

    Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of coronary artery bypass grafting greatly aided the treatment of coronary heart disease. Cardiac transplantation, attempts to use the total artificial heart, and the application of ventricular assist devices have brought us to the present day. Although progress in the field of cardiovascular surgery appears to have slowed when compared with the halcyon times of the past, substantial challenges still face cardiac surgeons. It can only be hoped that sufficient resources and incentive can carry the triumphs of the 20th century into the 21st. This review covers past developments and future opportunities in cardiac surgery. PMID:22163121

  13. Effects of mechanical stimulation induced by compression and medium perfusion on cardiac tissue engineering.

    PubMed

    Shachar, Michal; Benishti, Nessi; Cohen, Smadar

    2012-01-01

    Cardiac tissue engineering presents a challenge due to the complexity of the muscle tissue and the need for multiple signals to induce tissue regeneration in vitro. We investigated the effects of compression (1 Hz, 15% strain) combined with fluid shear stress (10(-2) -10(-1) dynes/cm(2) ) provided by medium perfusion on the outcome of cardiac tissue engineering. Neonatal rat cardiac cells were seeded in Arginine-Glycine-Aspartate (RGD)-attached alginate scaffolds, and the constructs were cultivated in a compression bioreactor. A daily, short-term (30 min) compression (i.e., "intermittent compression") for 4 days induced the formation of cardiac tissue with typical striation, while in the continuously compressed constructs (i.e., "continuous compression"), the cells remained spherical. By Western blot, on day 4 the expression of the gap junction protein connexin 43 was significantly greater in the "intermittent compression" constructs and the cardiomyocyte markers (α-actinin and N-cadherin) showed a trend of better preservation compared to the noncompressed constructs. This regime of compression had no effect on the proliferation of nonmyocyte cells, which maintained low expression level of proliferating cell nuclear antigen. Elevated secretion levels of basic fibroblast growth factor and transforming growth factor-β in the daily, intermittently compressed constructs likely attributed to tissue formation. Our study thus establishes the formation of an improved cardiac tissue in vitro, when induced by combined mechanical signals of compression and fluid shear stress provided by perfusion.

  14. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.

    PubMed

    Jang, Jinah; Park, Hun-Jun; Kim, Seok-Won; Kim, Heejin; Park, Ju Young; Na, Soo Jin; Kim, Hyeon Ji; Park, Moon Nyeo; Choi, Seung Hyun; Park, Sun Hwa; Kim, Sung Won; Kwon, Sang-Mo; Kim, Pum-Joon; Cho, Dong-Woo

    2017-01-01

    Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo. The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.

  15. Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

    NASA Astrophysics Data System (ADS)

    Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

    1988-03-01

    A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

  16. [Cardiac rehabilitation in women].

    PubMed

    Ghannem, M; Ghannem, L; Lamouchi, S; Justin, K D; Meimoun, P; Ghannem, L

    2016-12-01

    Coronary artery disease (CAD) occurs later in life in women when compared to men (10 years later). The FAST-MI study has shown that the profile of women with CAD has changed in the past 15 years, they are younger, more obese, and usually smokers. Whatever the age at which CAD occurs in women, the prognosis tends to be worse than in men, despite a higher frequency of acute coronary syndrome (ACS) with angiographically normal coronary arteries in women. In women without significant lesion at coronary angiography, the WISE study has shown abnormalities of the coronary vasomotricy. Despite its beneficial effect on morbidity and mortality, cardiac rehabilitation is underused particularly in women. Indeed, several factors do not encourage a woman to follow a cardiac rehabilitation program, even after an ACS. These factors may be cultural, domestic, familial, orthopedic, or even the fear of exercising. Therefore, physicians have to be particularly convincing in women, in order to have them participating in rehabilitation programs. Physical capacity is lower in women when compared to men. However, the weaker the physical capacity, the better the benefit of cardiac rehabilitation. Physical endurance training continuously or in interval, associated to muscle strengthening can improve the physical capacity in women. Vascular risk factors correction is also an important step for the management of women with CAD. Therapeutic education and several available workshops help women to better understand their disease and to improve their self-management when they return home. Anxiety, depression, and sexual dysfunction frequently deteriorate the quality of life of our patients. Therefore, psychological management is also essential in our departments.

  17. Serum cardiac troponin T after repeated endurance exercise events.

    PubMed

    Bonetti, A; Tirelli, F; Albertini, R; Monica, C; Monica, M; Tredici, G

    1996-05-01

    Recently Dr. Rowe made a hypothesis according to which small areas of myocardial necrosis can be caused by microvascular spasm, related to high catecholamine concentrations and other mechanisms, following extraordinary unremitting endurance exercises or due to the cumulative effect of several endurance events. It was this last suggestion which prompted us to investigate 25 top cyclists, taking part in the 77th Giro d'Italia. Blood samples were obtained the day before the start of the competition and once a week thereafter until the end. We measured myoglobin, lactic dehydrogenase, total creatine kinase, creatine kinase isoenzyme MB and serum cardiac troponin T (Tn-T), a highly sensitive and specific method for the detection of myocardial injury. While at measuring time points which followed we found a significant increase in the serum indicators of muscle damage, compared with their values at the beginning of the race, creatine kinase isoenzyme MB did not rise significantly and cardiac Tn-T was found in the serum of only 5 athletes, repeatedly in some cases, but always below the cut off values considered as indicating myocardial ischemia. On the basis of the behaviour of creatine kinase isoenzyme MB and, above all, of cardiac Tn-T, we can conclude that heavy endurance exercises, repeated daily for 22 days, as was the case in our study, do not seem able to produce, in top athletes, permanent heart damage by means of acute myocardial injury.

  18. Nitric oxide synthase in cardiac sarcoplasmic reticulum.

    PubMed

    Xu, K Y; Huso, D L; Dawson, T M; Bredt, D S; Becker, L C

    1999-01-19

    NO. is a free radical that modulates heart function and metabolism. We report that a neuronal-type NO synthase (NOS) is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles and that endogenous NO. produced by SR-associated NOS inhibits SR Ca2+ uptake. Ca2+-dependent biochemical conversion of L-arginine to L-citrulline was observed from isolated rabbit cardiac SR vesicles in the presence of NOS substrates and cofactors. Endogenous NO. was generated from the vesicles and detected by electron paramagnetic resonance spin-trapping measurements. Immunoelectron microscopy demonstrated labeling of cardiac SR vesicles by using anti-neuronal NOS (nNOS), but not anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies, whereas skeletal muscle SR vesicles had no nNOS immunoreactivity. The nNOS immunoreactivity also displayed a pattern consistent with SR localization in confocal micrographs of sections of human myocardium. Western blotting demonstrated that cardiac SR NOS is larger than brain NOS (160 vs. 155 kDa). No immunodetection was observed in cardiac SR vesicles from nNOS knockout mice or with an anti-nNOS mu antibody, suggesting the possibility of a new nNOS-type isoform. 45Ca uptake by cardiac SR vesicles, catalyzed by Ca2+-ATPase, was inhibited by NO. produced endogenously from cardiac SR NOS, and 7-nitroindazole, a selective nNOS inhibitor, completely prevented this inhibition. These results suggest that a cardiac muscle nNOS isoform is located on SR of cardiac myocytes, where it may respond to intracellular Ca2+ concentration and modulate SR Ca2+ ion active transport in the heart.

  19. Nitric oxide synthase in cardiac sarcoplasmic reticulum

    PubMed Central

    Xu, Kai Y.; Huso, David L.; Dawson, Ted M.; Bredt, David S.; Becker, Lewis C.

    1999-01-01

    NO⋅ is a free radical that modulates heart function and metabolism. We report that a neuronal-type NO synthase (NOS) is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles and that endogenous NO⋅ produced by SR-associated NOS inhibits SR Ca2+ uptake. Ca2+-dependent biochemical conversion of l-arginine to l-citrulline was observed from isolated rabbit cardiac SR vesicles in the presence of NOS substrates and cofactors. Endogenous NO⋅ was generated from the vesicles and detected by electron paramagnetic resonance spin-trapping measurements. Immunoelectron microscopy demonstrated labeling of cardiac SR vesicles by using anti-neuronal NOS (nNOS), but not anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies, whereas skeletal muscle SR vesicles had no nNOS immunoreactivity. The nNOS immunoreactivity also displayed a pattern consistent with SR localization in confocal micrographs of sections of human myocardium. Western blotting demonstrated that cardiac SR NOS is larger than brain NOS (160 vs. 155 kDa). No immunodetection was observed in cardiac SR vesicles from nNOS knockout mice or with an anti-nNOSμ antibody, suggesting the possibility of a new nNOS-type isoform. 45Ca uptake by cardiac SR vesicles, catalyzed by Ca2+-ATPase, was inhibited by NO⋅ produced endogenously from cardiac SR NOS, and 7-nitroindazole, a selective nNOS inhibitor, completely prevented this inhibition. These results suggest that a cardiac muscle nNOS isoform is located on SR of cardiac myocytes, where it may respond to intracellular Ca2+ concentration and modulate SR Ca2+ ion active transport in the heart. PMID:9892689

  20. The transgenic expression of human follistatin-344 increases skeletal muscle mass in pigs.

    PubMed

    Chang, Fei; Fang, Rui; Wang, Meng; Zhao, Xin; Chang, Wen; Zhang, Zaihu; Li, Ning; Meng, Qingyong

    2017-02-01

    Follistatin (FST), which was first found in the follicles of cattle and pigs, has been shown to be an essential regulator for muscle development. Mice that were genetically engineered to overexpress Fst specifically in muscle had at least twice the amount of skeletal muscle mass as controls; these findings are similar to earlier results obtained in myostatin-knockout mice. However, the role of follistatin in skeletal muscle development has yet to be clarified in livestock. Here, we describe transgenic Duroc pigs that exogenously express Fst specifically in muscle tissue. The transgenic pigs exhibited an increased proportion of skeletal muscle and a reduced proportion of body fat that were similar to those reported in myostatin-null cattle. The lean percentage of lean meat was significantly higher in the F1 generation of TG pigs (72.95 ± 1.0 %) than in WT pigs (69.18 ± 0.97 %) (N = 16, P < 0.05). Myofiber hypertrophy was also observed in the longissimus dorsi of transgenic pigs, possibly contributing to the increased skeletal muscle mass. Western blot analysis showed a significantly reduced level of Smad2 phosphorylation and an increased level of Akt(S473) phosphorylation in the skeletal muscle tissue of the transgenic pigs. Moreover, no cardiac muscle hypertrophy or reproductive abnormality was observed. These findings indicate that muscle-specific Fst overexpression in pigs enhances skeletal muscle growth, at least partly due to myofiber hypertrophy and providing a promising approach to increase muscle mass in pigs and other livestock.

  1. Does Resistance Training Stimulate Cardiac Muscle Hypertrophy?

    ERIC Educational Resources Information Center

    Bloomer, Richard J.

    2003-01-01

    Reviews the literature on the left ventricular structural adaptations induced by resistance/strength exercise, focusing on human work, particularly well-trained strength athletes engaged in regular, moderate- to high-intensity resistance training (RT). The article discusses both genders and examines the use of anabolic-androgenic steroids in…

  2. Calcium versus strontium handling by the heart muscle.

    PubMed

    Hendrych, Michal; Olejnickova, Veronika; Novakova, Marie

    2016-01-01

    Calcium plays a crucial role in numerous processes in living systems, from both intracellular and intercellular signalling to blood clotting. Calcium can be replaced by strontium in various intracellular processes due to high level of their similarity and strontium thus may serve as a valuable tool for different experimental studies. On the other hand, strontium is also used in clinical medicine and is commonly taken to the human body with food and water. The negative cardiac side effects of strontium therapy of osteoporosis and bone metastases are well known, but still not fully explained. This fact explains enhanced interest in this element and its impact on human body. This article reviews effects of calcium and strontium on several biochemical and physiological processes, with special emphasis on cardiac muscle.

  3. About Cardiac Arrest

    MedlinePlus

    ... Thromboembolism Aortic Aneurysm More About Cardiac Arrest Updated:Mar 10,2017 What is cardiac arrest? Cardiac arrest is the abrupt loss of heart function in a person who may or may not have diagnosed heart ...

  4. Seasonal variations of cardiac output in rats.

    PubMed

    Back, G; Strubelt, O

    1975-11-15

    Cardiac output of rats shows seasonal variations with low values in spring and summer and high ones in autumn and winter. The stroke volume was much more implicated in these changes than the heart rate. The seasonal changes of cardiac output are probably due to changes of thyroid function.

  5. Sudden cardiac death – Historical perspectives

    PubMed Central

    Abhilash, S.P.; Namboodiri, Narayanan

    2014-01-01

    Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. It is believed to be involved in nearly a quarter of human deaths, with ventricular fibrillation being the most common mechanism. It is estimated that more than 7 million lives per year are lost to SCD worldwide. Historical perspectives of SCD are analyzed with a brief description on how the developments in the management of sudden cardiac arrest evolved over time. PMID:24568828

  6. Muscle Deoxygenation Causes Muscle Fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

    1999-01-01

    Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

  7. Muscle disorder

    MedlinePlus

    Myopathic changes; Myopathy; Muscle problem ... Blood tests sometimes show abnormally high muscle enzymes. If a muscle disorder might also affect other family members, genetic testing may be done. When someone has symptoms and signs ...

  8. Muscle aches

    MedlinePlus

    ... common cause of muscle aches and pain is fibromyalgia , a condition that causes tenderness in your muscles ... imbalance, such as too little potassium or calcium Fibromyalgia Infections, including the flu, Lyme disease , malaria , muscle ...

  9. Genetic dissection of cardiac growth control pathways

    NASA Technical Reports Server (NTRS)

    MacLellan, W. R.; Schneider, M. D.

    2000-01-01

    Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.

  10. Cardiac tissue engineering: state of the art.

    PubMed

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

    2014-01-17

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

  11. The ECG vertigo in diabetes and cardiac autonomic neuropathy.

    PubMed

    Voulgari, Christina; Tentolouris, Nicholas; Stefanadis, Christodoulos

    2011-01-01

    The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have diabetes, and its prevalence is steadily increasing. The decrease in cardiac mortality in people with diabetes is lagging behind that of the general population. Cardiovascular disease is a broad term which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves, and cardiac rhythm. The ECG offers a quick, noninvasive clinical and research screen for the early detection of cardiovascular disease in diabetes. In this paper, the clinical and research value of the ECG is readdressed in diabetes and in the presence of cardiac autonomic neuropathy.

  12. Low Dose Sarin Leads To Murine Cardiac Dysfunction

    DTIC Science & Technology

    2010-03-01

    reduced heart rate at smooth muscle level; at exocrine glands , it causes secretions in the lung, nasal, oral, and sweat glands . Among clinical effects...smooth muscles, skeletal muscles, most exocrine glands , the central nervous system (CNS), and the cardiac system (central and ganglionic afferents...sarin need to 8 be critically analyzed at low doses to help provide early diagnosis. Similarly, functional and structural changes in the heart

  13. MUSCLE INJURIES IN ATHLETES

    PubMed Central

    Barroso, Guilherme Campos; Thiele, Edilson Schwansee

    2015-01-01

    This article had the aim of demonstrating the physiology, diagnosis and treatment of muscle injuries, focusing on athletes and their demands and expectations. Muscle injuries are among the most common complaints in orthopedic practice, occurring both among athletes and among non-athletes. These injuries present a challenge for specialists, due to the slow recovery, during which time athletes are unable to take part in training and competitions, and due to frequent sequelae and recurrences of the injuries. Most muscle injuries (between 10% and 55% of all injuries) occur during sports activities. The muscles most commonly affected are the ischiotibial, quadriceps and gastrocnemius. These muscles go across two joints and are more subject to acceleration and deceleration forces. The treatment for muscle injuries varies from conservative treatment to surgery. New procedures are being used, like the hyperbaric chamber and the use of growth factors. However, there is still a high rate of injury recurrence. Muscle injury continues to be a topic of much controversy. New treatments are being researched and developed, but prevention through muscle strengthening, stretching exercises and muscle balance continues to be the best “treatment”. PMID:27027021

  14. MUSCLE INJURIES IN ATHLETES.

    PubMed

    Barroso, Guilherme Campos; Thiele, Edilson Schwansee

    2011-01-01

    This article had the aim of demonstrating the physiology, diagnosis and treatment of muscle injuries, focusing on athletes and their demands and expectations. Muscle injuries are among the most common complaints in orthopedic practice, occurring both among athletes and among non-athletes. These injuries present a challenge for specialists, due to the slow recovery, during which time athletes are unable to take part in training and competitions, and due to frequent sequelae and recurrences of the injuries. Most muscle injuries (between 10% and 55% of all injuries) occur during sports activities. The muscles most commonly affected are the ischiotibial, quadriceps and gastrocnemius. These muscles go across two joints and are more subject to acceleration and deceleration forces. The treatment for muscle injuries varies from conservative treatment to surgery. New procedures are being used, like the hyperbaric chamber and the use of growth factors. However, there is still a high rate of injury recurrence. Muscle injury continues to be a topic of much controversy. New treatments are being researched and developed, but prevention through muscle strengthening, stretching exercises and muscle balance continues to be the best "treatment".

  15. Mathematical Models of Cardiac Pacemaking Function

    NASA Astrophysics Data System (ADS)

    Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

    2013-10-01

    Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  16. A severe penetrating cardiac injury in the absence of cardiac tamponade.

    PubMed

    Connelly, Tara M; Kolcow, Walenty; Veerasingam, Dave; DaCosta, Mark

    2016-10-26

    Penetrating cardiac injury is rare and frequently not survivable. Significant haemorrhage resulting in cardiac tamponade commonly ensues. Such cardiac tamponade is a clear clinical, radiological and sonographic indicator of significant underlying injury. In the absence of cardiac tamponade, diagnosis can be more challenging. In this case of a 26-year old sailor stabbed at sea, a significant pericardial effusion and cardiac tamponade did not occur despite an injury transversing the pericardium. Instead, the pericardial haemorrhage drained into the left pleural cavity resulting in a haemothorax. This case is notable due to a favourable outcome despite a delay in diagnosis due to a lack of pericardial effusion, a concomitant cerebrovascular event and a long delay from injury to appropriate medical treatment in the presence of a penetrating cardiac wound deep enough to cause a muscular ventricular septal defect and lacerate a primary chordae of the anterior mitral leaflet.

  17. Evaluation and adaptive attenuation of the cardiac vibration interference in mechanomyographic signals.

    PubMed

    Sarlabous, Leonardo; Torres, Abel; Fiz, Jose Antonio; Morera, Josep; Jane, Raimon

    2012-01-01

    The study of the mechanomyographic signal of the diaphragm muscle (MMGdi) is a promising technique in order to evaluate the respiratory muscles effort. The relationship between amplitude and frequency parameters of this signal with the respiratory effort performed during respiration is of great interest for researchers and physicians due to its diagnostic potentials. However, MMGdi signals are frequently contaminated by a cardiac vibration or mechanocardiographic (MCG) signal. An adaptive noise cancellation (ANC) can be used to reduce the MCG interference in the recorded MMGdi activity. In this paper, it is evaluated the proposed ANC scheme by means of a synthetic MMGdi signal with a controlled MCG interference. The Pearson's correlation coefficient (PCC) between both root mean square (RMS) and mean frequency (fm) of the synthetic MMGdi signal are considerably reduced with the presence of cardiac vibration noise (from 0.95 to 0.87, and from 0.97 to 0.76, respectively). With the ANC algorithm proposed the effect of the MCG noise on the amplitude and frequency of MMG parameters is reduced considerably (PCC of 0.93 and 0.97 for the RMS and fm, respectively). The ANC method proposed in this work is an interesting technique to attenuate the cardiac interference in respiratory MMG signals. Further investigation should be carried out to evaluate the performance of the ANC algorithm in real MMGdi signals.

  18. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

    PubMed Central

    Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

  19. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    PubMed

    Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

  20. Fibroblast growth factor 21 is induced upon cardiac stress and alters cardiac lipid homeostasis

    PubMed Central

    Brahma, Manoja K.; Adam, Rene C.; Pollak, Nina M.; Jaeger, Doris; Zierler, Kathrin A.; Pöcher, Nadja; Schreiber, Renate; Romauch, Matthias; Moustafa, Tarek; Eder, Sandra; Ruelicke, Thomas; Preiss-Landl, Karina; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2014-01-01

    Fibroblast growth factor 21 (FGF21) is a PPARα-regulated gene elucidated in the liver of PPARα-deficient mice or PPARα agonist-treated mice. Mice globally lacking adipose triglyceride lipase (ATGL) exhibit a marked defect in TG catabolism associated with impaired PPARα-activated gene expression in the heart and liver, including a drastic reduction in hepatic FGF21 mRNA expression. Here we show that FGF21 mRNA expression is markedly increased in the heart of ATGL-deficient mice accompanied by elevated expression of endoplasmic reticulum (ER) stress markers, which can be reversed by reconstitution of ATGL expression in cardiac muscle. In line with this assumption, the induction of ER stress increases FGF21 mRNA expression in H9C2 cardiomyotubes. Cardiac FGF21 expression was also induced upon fasting of healthy mice, implicating a role of FGF21 in cardiac energy metabolism. To address this question, we generated and characterized mice with cardiac-specific overexpression of FGF21 (CM-Fgf21). FGF21 was efficiently secreted from cardiomyocytes of CM-Fgf21 mice, which moderately affected cardiac TG homeostasis, indicating a role for FGF21 in cardiac energy metabolism. Together, our results show that FGF21 expression is activated upon cardiac ER stress linked to defective lipolysis and that a persistent increase in circulating FGF21 levels interferes with cardiac and whole body energy homeostasis. PMID:25176985

  1. [Overactive muscles: it can be more serious than common myalgia or cramp].

    PubMed

    Molenaar, Joery P F; Snoeck, Marc M J; Voermans, Nicol C; van Engelen, Baziel G M

    2016-01-01

    Positive muscle phenomena are due to muscle overactivity. Examples are cramp, myalgia, and stiffness. These manifestations have mostly acquired causes, e.g. side-effects of medication, metabolic disorders, vitamin deficiency, excessive caffeine intake or neurogenic disorders. We report on three patients with various positive muscle phenomena, to illustrate the clinical signs that indicate an underlying myopathy. Patient A, a 56-year-old man, was diagnosed with muscle cramp in the context of excessive coffee use and previous lumbosacral radiculopathy. Patient B, a 71-year-old man, was shown to have RYR1-related myopathy. Patient C, a 42-year-old man, suffered from Brody myopathy. We propose for clinicians to look out for a number of 'red flags' that can point to an underlying myopathy, and call for referral to neurology if indicated. Red flags include second wind phenomenon, familial occurrence of similar complaints, marked muscle stiffness, myotonia, muscle weakness, muscle hypertrophy, and myoglobinuria. Establishing a correct diagnosis is important for proper treatment. Certain myopathies call for cardiac or respiratory screening.

  2. Systemic therapy for cardiac sarcomas.

    PubMed

    Ravi, Vinod; Benjamin, Robert S

    2010-01-01

    Cardiac sarcomas create 2 risks: local problems and metastatic disease. Most frequently, the histologies are angiosarcoma and high-grade pleomorphic unclassified sarcoma (formerly called MFH or malignant fibrous histiocytoma). There is also a clinical-pathological entity without distinctive histological features of tumors that originate in the pulmonary artery and are referred to as pulmonary artery sarcomas or intimal sarcomas of the pulmonary artery. Conventional wisdom indicates that soft-tissue sarcomas are poorly responsive to chemotherapy. Luckily, that is not the case. Attempts to concentrate on the local problem only with therapies up to and including cardiac transplantation have been unsuccessful due to the high rate of fatal metastatic disease.

  3. Modulation of the cardiac membrane-bound cyclic nucleotide phosphodiesterase: inhibition due to a contamination of TLC purified S-adenosyl-L-(methyl-/sup 3/H) methionine by Zn/sup + +/ ions

    SciTech Connect

    Dubois, M.; Prigent, A.F.; Nemoz, G.; Fougier, S.; Pacheco, H.

    1985-07-29

    Cardiac membranes pretreated with S-Adenosyl-L-(methyl-/sup 3/H) methionine((/sup 3/H) SAM) purified on TLC silica gel 60 F/sub 254/ plates exhibited a marked decrease in cyclic AMP and cyclic GMP phosphodiesterase activity. However, this inhibition did not appear when membranes were incubated with either (/sup 14/C) SAM or unlabelled SAM. The authors showed that, during the TLC purification of (/sup 3/H) SAM, which involved an acidic elution step, minute amounts of the fluorescent indicator F/sub 254/ (Zn sulfur) were eluted. The contaminating Zn/sup + +/ ions strongly inhibited cyclic nucleotide phosphodiesterase activity and phospholipid methylation with I/sub 50/ values in micromolar range. 17 references, 4 figures, 2 tables.

  4. Effect of Statins on Skeletal Muscle: Exercise, Myopathy, and Muscle Outcomes

    PubMed Central

    Parker, Beth A.; Thompson, Paul D.

    2012-01-01

    Statins are effective for reducing low-density lipoprotein cholesterol and cardiac events, but can produce muscle side effects. We have hypothesized that statin-related muscle complaints are exacerbated by exercise and influenced by factors including mitochondrial dysfunction, membrane disruption and/or calcium handling. The interaction between statins, exercise and muscle symptoms may be more effectively diagnosed and treated as rigorous scientific studies accumulate. PMID:23000957

  5. Cardiac energetic impairment in heart disease and the potential role of metabolic modulators: a review for clinicians.

    PubMed

    Singh, Satnam; Schwarz, Konstantin; Horowitz, John; Frenneaux, Michael

    2014-10-01

    Cardiac energetic impairment is a frequent finding in patients with both inherited and acquired diseases of heart muscle. In this review the mechanisms of energy generation in the healthy heart and their disturbances in heart muscle diseases are described. Therapeutic agents targeted at correcting cardiac energetic impairment are discussed.

  6. Influence of aging on the activity of mice Sca-1+CD31− cardiac stem cells

    PubMed Central

    Pu, Shiming; Qin, Liu; Li, Yun; Zhou, Zuping

    2017-01-01

    Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31− subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31− subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending. PMID:27980224

  7. Cardiac xenotransplantation.

    PubMed

    DiSesa, V J

    1997-12-01

    Heart failure is an important medical and public health problem. Although medical therapy is effective for many people, the only definitive therapy is heart transplantation, which is limited severely by the number of donors. Mechanical devices presently are used as "bridges" to transplantation. Their widespread use may solve the donor shortage problem, but at present, mechanical devices are limited by problems related to blood clotting, power supply, and foreign body infection. Cardiac xenotransplantation using animal donors is a potential biologic solution to the donor organ shortage. The immune response, consisting of hyperacute rejection, acute vascular rejection, and cellular rejection, currently prevents clinical xenotransplantation. Advances in the solution of these problems have been made using conventional immunosuppressive drugs and newer agents whose use is based on an understanding of important steps in xenoimmunity. The most exciting approaches use tools of molecular biology to create genetically engineered donors and to induce states of donor and recipient bone marrow chimerism and tolerance in xenogeneic organ recipients. The successful future strategy may use a combination of a genetically engineered donor and a chimeric recipient with or without nonspecific immunosuppressive drugs.

  8. The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

    PubMed Central

    Mezentseva, Nadejda V.; Yang, Jinpu; Kaur, Keerat; Iaffaldano, Grazia; Rémond, Mathieu C.; Eisenberg, Carol A.

    2013-01-01

    Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76, 276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype. PMID:22994322

  9. The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells.

    PubMed

    Mezentseva, Nadejda V; Yang, Jinpu; Kaur, Keerat; Iaffaldano, Grazia; Rémond, Mathieu C; Eisenberg, Carol A; Eisenberg, Leonard M

    2013-02-15

    Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76, 276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype.

  10. Cardiac manifestations in Behcet's disease

    PubMed Central

    Demirelli, Selami; Degirmenci, Husnu; Inci, Sinan; Arisoy, Arif

    2015-01-01

    Summary Behcet's disease (BD) is a chronic inflammatory disorder, with vasculitis underlying the pathophysiology of its multisystemic effects. Venous pathology and thrombotic complications are hallmarks of BD. However, it has been increasingly recognised that cardiac involvement and arterial complications are also important aspects of the course of the disease. Cardiac lesions include pericarditis, endocarditis, intracardiac thrombosis, myocardial infarction, endomyocardial fibrosis, and myocardial aneurysm. Treatment of cardiovascular involvement in BD is largely empirical, and is aimed towards suppressing the vasculitis. The most challenging aspect seems to be the treatment of arterial aneurysms and thromboses due to the associated risk of bleeding. When the prognosis of cardiac involvement in BD is not good, recovery can be achieved through oral anticoagulation, immunosuppressive therapy, and colchicine use. In this review, we summarise the cardiovascular involvement, different manifestations, and treatment of BD. PMID:25984424

  11. Murine Muscle Engineered from Dermal Precursors: An In Vitro Model for Skeletal Muscle Generation, Degeneration, and Fatty Infiltration

    PubMed Central

    García-Parra, Patricia; Naldaiz-Gastesi, Neia; Maroto, Marcos; Padín, Juan Fernando; Goicoechea, María; Aiastui, Ana; Fernández-Morales, José Carlos; García-Belda, Paula; Lacalle, Jaione; Álava, Jose Iñaki; García-Verdugo, José Manuel; García, Antonio G.

    2014-01-01

    Skeletal muscle can be engineered by converting dermal precursors into muscle progenitors and differentiated myocytes. However, the efficiency of muscle development remains relatively low and it is currently unclear if this is due to poor characterization of the myogenic precursors, the protocols used for cell differentiation, or a combination of both. In this study, we characterized myogenic precursors present in murine dermospheres, and evaluated mature myotubes grown in a novel three-dimensional culture system. After 5–7 days of differentiation, we observed isolated, twitching myotubes followed by spontaneous contractions of the entire tissue-engineered muscle construct on an extracellular matrix (ECM). In vitro engineered myofibers expressed canonical muscle markers and exhibited a skeletal (not cardiac) muscle ultrastructure, with numerous striations and the presence of aligned, enlarged mitochondria, intertwined with sarcoplasmic reticula (SR). Engineered myofibers exhibited Na+- and Ca2+-dependent inward currents upon acetylcholine (ACh) stimulation and tetrodotoxin-sensitive spontaneous action potentials. Moreover, ACh, nicotine, and caffeine elicited cytosolic Ca2+ transients; fiber contractions coupled to these Ca2+ transients suggest that Ca2+ entry is activating calcium-induced calcium release from the SR. Blockade by d-tubocurarine of ACh-elicited inward currents and Ca2+ transients suggests nicotinic receptor involvement. Interestingly, after 1 month, engineered muscle constructs showed progressive degradation of the myofibers concomitant with fatty infiltration, paralleling the natural course of muscular degeneration. We conclude that mature myofibers may be differentiated on the ECM from myogenic precursor cells present in murine dermospheres, in an in vitro system that mimics some characteristics found in aging and muscular degeneration. PMID:23631552

  12. Sudden cardiac death: A reappraisal.

    PubMed

    Steinberg, Christian; Laksman, Zachary W M; Krahn, Andrew D

    2016-11-01

    Sudden cardiac death (SCD) is still among the leading causes of death in women and men, accounting for over 50% of all fatal cardiovascular events in the United States. Two arrhythmia mechanisms of SCD can be distinguished as follows: shockable rhythms (ventricular fibrillation and pulseless ventricular tachycardia) and non-shockable rhythms including asystole or pulseless electrical activity. The overall prognosis of cardiac arrest due to shockable rhythms is significantly better. While the majority of SCDs is attributed to coronary artery disease or other structural heart disease, no obvious cause can be identified in 5% of all events, and those events are labeled as sudden unexplained deaths (SUD). Those unexplained events are typically caused by rare hereditary electrical disorders or arrhythmogenic cardiomyopathies. A systematic approach to the diagnosis of cardiac arrest followed by tailored therapy based on etiology has emerged in the last 10-15 years, with significant changes of medical practice and risk management of cardiac arrest victims. The aim of this review is to summarize our contemporary understanding of SCD/SUD in adults and to discuss current concepts of management and secondary prevention in cardiac arrest victims. A full discussion of the topic of primary prevention of SCD is beyond the scope of this article.

  13. [Cardiac surgery in the elderly].

    PubMed

    Wiegmann, B; Ismail, I; Haverich, A

    2017-02-01

    Due to the increasing demographic changes and the fact that cardiovascular diseases are still the leading cause of death, the mean chronological age of patients undergoing cardiac surgery is steadily increasing. In 2015, 14.8% of these patients were aged 80 years and older. This meta-analysis reviewed if and under what circumstances elderly patients benefit from cardiac surgical procedures without running the risk of limitations in the quality of life and high rates of morbidity and mortality. Generally, the chronological age was not a risk factor for higher perioperative and postoperative morbidity and mortality but the biological age was the critical factor, in particular the associated comorbidities of patients and the timing of the surgical procedure in the course of the disease. The result is that elective operations resulted in a better outcome than operations in a symptomatic or decompensated stage of a disease. Compared to patients receiving conventional medicinal therapy, elderly patients undergoing cardiac surgery had an improved life expectancy. A significant increase in the quality of life could also be identified and was ultimately comparable to those of younger patients after cardiac surgery; therefore, elderly patients even those over 80 years old benefit in all aspects of cardiac surgery, as long as individually adapted operative techniques are considered.

  14. Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro

    PubMed Central

    Tolmachov, Oleg; Ma, Yu-Ling; Themis, Michael; Patel, Pravina; Spohr, Hilmar; MacLeod, Kenneth T; Ullrich, Nina D; Kienast, Yvonne; Coutelle, Charles; Peters, Nicholas S

    2006-01-01

    Background Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro. Methods To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin® and the polycation transduction enhancer Transfectam®. The EGFP-positive transduced cells were then enriched by flow cytometry. Results More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than

  15. Cardiac alternans and intracellular calcium cycling

    PubMed Central

    Edwards, Joshua N.; Blatter, Lothar A.

    2014-01-01

    Cardiac alternans refers to a condition in which there is a periodic beat-to-beat oscillation in electrical activity and the strength of cardiac muscle contraction at a constant heart rate. Clinically, cardiac alternans occurs in settings that are typical for cardiac arrhythmias and has been causally linked to these conditions. At the cellular level, alternans is defined as beat-to-beat alternations in contraction amplitude (mechanical alternans), action potential duration (APD; electrical or APD alternans), and Ca2+ transient amplitude (Ca2+ alternans). The cause of alternans is multifactorial, however alternans always originate from disturbances of the bi-directional coupling between membrane voltage (Vm) and intracellular calcium ([Ca2+]i). Bi-directional coupling refers to the fact that in cardiac cells, Vm depolarization and the generation of action potentials cause the elevation of [Ca2+]i that is required for contraction (a process referred to as excitation-contraction coupling), the changes of [Ca2+]i on the other hand control Vm because important membrane currents are Ca2+-dependent. Evidence is mounting that alternans is ultimately caused by disturbances of cellular Ca2+ signaling. Here we review how two key factors of cardiac cellular Ca2+ cycling - the release of Ca2+ from internal stores and the capability of clearing the cytosol from Ca2+ after each beat - determine the conditions under which alternans occurs. The contributions from key Ca2+ handling proteins - surface membrane channels, ion pumps and transporters, and internal Ca2+ release channels - are discussed. PMID:25040398

  16. Cardiac MRI in restrictive cardiomyopathy.

    PubMed

    Gupta, A; Singh Gulati, G; Seth, S; Sharma, S

    2012-02-01

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  17. Dipyridamole cardiac imaging

    SciTech Connect

    Iskandrian, A.S.; Heo, J.; Askenase, A.; Segal, B.L.; Auerbach, N.

    1988-02-01

    Dipyridamole cardiac imaging is a useful alternative technique to exercise stress testing in the evaluation of patients with ischemic heart disease. Intravenous dipyridamole is still in the investigational phase, while oral dipyridamole is widely available. The hemodynamic effects of dipyridamole include an increase in coronary blood flow (due to coronary vasodilation) which is in excess of the increase in myocardial oxygen consumption and cardiac output. The disparity in the increase in coronary blood flow relative to the cardiac output results in an increase in myocardial thallium activity and an increase in the myocardial/background activity ratio. The quality of the thallium images is better or similar to that of exercise thallium images. The optimal dose of intravenous dipyridamole is 0.56 mg/kg, and of the oral dose it is 300 to 400 mg, although higher doses may be necessary in some patients. Analysis of the thallium images has been to a large extent based on visual inspection of the planar images. Delayed images are helpful to establish the nature of the perfusion abnormalities (transient or fixed). The process of redistribution is based on disparate rates of washout from the normal and abnormal zones. The sensitivity and specificity of dipyridamole thallium imaging, whether intravenous or oral, have been shown in a number of studies to be quite adequate and comparable to that achieved during exercise thallium imaging. Dipyridamole two-dimensional echocardiography has also been used in the detection of coronary artery disease; transient (new or worsening of preexisting) wall motion abnormalities have been found to be a specific marker of coronary artery disease. Transmural as well as regional coronary steal phenomena have been postulated as the mechanism for dipyridamole-induced regional wall motion abnormalities. 65 references.

  18. Usefulness of cardiac resynchronisation therapy devices and implantable cardioverter defibrillators in the treatment of heart failure due to severe systolic dysfunction: systematic review of clinical trials and network meta-analysis

    PubMed Central

    García García, M A; Rosero Arenas, M A; Ruiz Granell, R; Chorro Gascó, F J; Martínez Cornejo, A

    2016-01-01

    Aim To assess the effectiveness of cardiac resynchronisation therapy (CRT), implantable cardioverter defibrillator (ICD) therapy, and the combination of these devices (CRT+ICD) in adult patients with left ventricular dysfunction and symptomatic heart failure. Methods A comprehensive systematic review of randomised clinical trials was conducted. Several electronic databases (PubMed, Embase, Ovid, Cochrane, ClinicalTrials.gov) were reviewed. The mortality rates between treatments were compared. A network was established comparing the various options, and direct, indirect and mixed comparisons were made using multivariate meta-regression. The degree of clinical and statistical homogeneity was assessed. Results 43 trials involving 13 017 patients were reviewed. Resynchronisation therapy, defibrillators, and combined devices (CRT+ICD) are clearly beneficial compared to optimal medical treatment, showing clear benefit in all of these cases. In a theoretical order of efficiency, the first option is combined therapy (CRT+ICD), the second is CRT, and the third is defibrillator implantation (ICD). Given the observational nature of these comparisons, and the importance of the overlapping CIs, we cannot state that the combined option (CRT+ICD) offers superior survival benefit compared to the other two options. Conclusions The combined option of CRT+ICD seems to be better than the option of CRT alone, although no clear improvement in survival was found for the combined option. It would be advisable to perform a direct comparative study of these two options. PMID:27326223

  19. Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4.

    PubMed

    Ounzain, Samir; Kobayashi, Satoru; Peterson, Richard E; He, Aibin; Motterle, Anna; Samani, Nilesh J; Menick, Donald R; Pu, William T; Liang, Qiangrong; Chong, Nelson W

    2012-05-01

    Ms1/STARS is a novel muscle-specific actin-binding protein that specifically modulates the myocardin-related transcription factor (MRTF)-serum response factor (SRF) regulatory axis within striated muscle. This ms1/STARS-dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and postnatal cardiac function/homeostasis. The dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter, gain-of-function, and loss-of-function approaches. Through this integrated analysis, we have identified three evolutionarily conserved regions (ECRs), α, SINA, and DINA, that act as cis-regulatory modules and confer differential cardiac cell-specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall, our results demonstrate that within embryonic, neonatal, and adult hearts, GATA4 represses ms1/STARS expression with the pathologically associated depletion of GATA4 (type 1/type 2 diabetic models), resulting in ms1/STARS upregulation. This GATA4-dependent repression of ms1/STARS expression has major implications for MRTF-SRF signaling in the context of cardiac development and disease.

  20. Exploring cardiac biophysical properties.

    PubMed

    Ait Mou, Younss; Bollensdorff, Christian; Cazorla, Olivier; Magdi, Yacoub; de Tombe, Pieter P

    2015-01-01

    The heart is subject to multiple sources of stress. To maintain its normal function, and successfully overcome these stresses, heart muscle is equipped with fine-tuned regulatory mechanisms. Some of these mechanisms are inherent within the myocardium itself and are known as intrinsic mechanisms. Over a century ago, Otto Frank and Ernest Starling described an intrinsic mechanism by which the heart, even ex vivo, regulates its function on a beat-to-beat basis. According to this phenomenon, the higher the ventricular filling is, the bigger the stroke volume. Thus, the Frank-Starling law establishes a direct relationship between the diastolic and systolic function of the heart. To observe this biophysical phenomenon and to investigate it, technologic development has been a pre-requisite to scientific knowledge. It allowed for example to observe, at the cellular level, a Frank-Starling like mechanism and has been termed: Length Dependent Activation (LDA). In this review, we summarize some experimental systems that have been developed and are currently still in use to investigate cardiac biophysical properties from the whole heart down to the single myofibril. As a scientific support, investigation of the Frank-Starling mechanism will be used as a case study.

  1. Exploring cardiac biophysical properties

    PubMed Central

    Mou, Younss Ait; Bollensdorff, Christian; Cazorla, Olivier; Magdi, Yacoub; de Tombe, Pieter P.

    2015-01-01

    The heart is subject to multiple sources of stress. To maintain its normal function, and successfully overcome these stresses, heart muscle is equipped with fine-tuned regulatory mechanisms. Some of these mechanisms are inherent within the myocardium itself and are known as intrinsic mechanisms. Over a century ago, Otto Frank and Ernest Starling described an intrinsic mechanism by which the heart, even ex vivo, regulates its function on a beat-to-beat basis. According to this phenomenon, the higher the ventricular filling is, the bigger the stroke volume. Thus, the Frank-Starling law establishes a direct relationship between the diastolic and systolic function of the heart. To observe this biophysical phenomenon and to investigate it, technologic development has been a pre-requisite to scientific knowledge. It allowed for example to observe, at the cellular level, a Frank-Starling like mechanism and has been termed: Length Dependent Activation (LDA). In this review, we summarize some experimental systems that have been developed and are currently still in use to investigate cardiac biophysical properties from the whole heart down to the single myofibril. As a scientific support, investigation of the Frank-Starling mechanism will be used as a case study. PMID:26779498

  2. Physiology: postprandial cardiac hypertrophy in pythons.

    PubMed

    Andersen, Johnnie B; Rourke, Bryan C; Caiozzo, Vincent J; Bennett, Albert F; Hicks, James W

    2005-03-03

    Oxygen consumption by carnivorous reptiles increases enormously after they have eaten a large meal in order to meet metabolic demands, and this places an extra load on the cardiovascular system. Here we show that there is an extraordinarily rapid 40% increase in ventricular muscle mass in Burmese pythons (Python molurus) a mere 48 hours after feeding, which results from increased gene expression of muscle-contractile proteins. As this fully reversible hypertrophy occurs naturally, it could provide a useful model for investigating the mechanisms that lead to cardiac growth in other animals.

  3. Iliopsoas muscle injury in dogs.