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Sample records for adult cardiac myocytes

  1. Isolation and Genetic Manipulation of Adult Cardiac Myocytes for Confocal Imaging

    OpenAIRE

    Kaestner, Lars; Scholz, Anke; Hammer, Karin; Vecerdea, Anne; Ruppenthal, Sandra; Lipp, Peter

    2009-01-01

    Cardiac myocytes isolated from adult hearts are widely accepted as a model somewhere half way between embryonic and neonatal muscle cells on one side and a working heart on the other. Thus, cardiomyocytes serve as good models for cardiac cellular physiology and pathophysiology, for pharmaceutical investigations as well as for the exploration of transgenic animal models. Here we describe a method of isolating the cells from the heart. Furthermore we show how a genetic manipulation on cardiac m...

  2. Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy.

    Science.gov (United States)

    Corda, S; Mebazaa, A; Gandolfini, M P; Fitting, C; Marotte, F; Peynet, J; Charlemagne, D; Cavaillon, J M; Payen, D; Rappaport, L; Samuel, J L

    1997-11-01

    Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9 +/- 8.2% [n = 17]; serum, +14.9 +/- 6.5% [n = 13]; both P < .01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P < .01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-beta (TGF-beta), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass-dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-beta. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass-dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy. PMID:9351441

  3. Expression and protective effects of urocortin in cardiac myocytes.

    Science.gov (United States)

    Okosi, A; Brar, B K; Chan, M; D'Souza, L; Smith, E; Stephanou, A; Latchman, D S; Chowdrey, H S; Knight, R A

    1998-04-01

    Reverse transcription PCR showed that mRNA encoding the CRH-like molecule, urocortin, is expressed in a rat cardiac myocyte cell line and in primary cultures of cardiac myocytes. Identity of the amplified with the published sequence was established by restriction mapping and direct sequencing. Expression of urocortin mRNA was increased 12-18 h after thermal injury. Urocortin peptide protected cardiac myocytes from cell death induced by hypoxia. The data suggest that urocortin is an endogenous cardiac myocyte peptide which modulates the cellular response to stress. PMID:9639256

  4. Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

    DEFF Research Database (Denmark)

    Hofgaard, Johannes P; Banach, Kathrin; Mollerup, Sarah;

    2008-01-01

    Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis...

  5. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Icli, Basak [Department of Medicine, Cardiovascular Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Bharti, Ajit [Center of Molecular Stress Response Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, MA 02118 (United States); Pentassuglia, Laura; Peng, Xuyang [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States); Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

  6. Sensing Cardiac Electrical Activity With a Cardiac Myocyte--Targeted Optogenetic Voltage Indicator

    NARCIS (Netherlands)

    Chang Liao, Mei-Ling; de Boer, Teun P; Mutoh, Hiroki; Raad, Nour; Richter, Claudia; Wagner, Eva; Downie, Bryan R; Unsöld, Bernhard; Arooj, Iqra; Streckfuss-Bömeke, Katrin; Döker, Stephan; Luther, Stefan; Guan, Kaomei; Wagner, Stefan; Lehnart, Stephan E; Maier, Lars S; Stühmer, Walter; Wettwer, Erich; van Veen, Toon; Morlock, Michael M; Knöpfel, Thomas; Zimmermann, Wolfram-Hubertus

    2015-01-01

    RATIONALE: Monitoring and controlling cardiac myocyte activity with optogenetic tools offer exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac

  7. Calcium binding to cardiac myocytes protected from proteolytic enzyme activity.

    Science.gov (United States)

    Bailey, L E; Fawzi, A B

    1985-04-17

    Excitation-contraction coupling in cardiac muscle is dependent on extracellular calcium and calcium bound to the surface of the myocardial cell. In this study, we examined the physical characteristics of calcium binding to adult guinea pig ventricular myocytes disaggregated mechanically in oxygenated tissue culture medium containing a proteinase inhibitor (aprotinin), and separated from cellular debris by Cytodex beads. Cells prepared in this manner excluded Trypan blue and showed no evidence of spontaneous contraction or contracture. Scatchard plots of calcium binding determined by continuous flow equilibrium dialysis revealed a high-affinity, low-capacity pool, Ka = 65 X 10(3) M-1 and Bt = 1.3 nmol X mg-1 and a low-affinity, high-capacity pool, Ka = 141 M-1 and Bt = 138 nmol X mg-1. The low-affinity pool was not detectable after lanthanum, trypsin or collagenase treatment or in cells prepared without aprotinin in the isolation medium. Both neuraminidase and phospholipase C reduced Bt of the low-affinity pool by one half, but only neuraminidase affected the affinity constant of this pool. Ka was increased to 516.7 M-1, similar to the apparent affinity constant for calcium binding estimated from dP/dtmax measured at several extracellular calcium concentrations (470 M-1). The results suggest that calcium bound to sarcolemmal phospholipids represents the superficial calcium involved in excitation-contraction coupling in the heart.

  8. Nanomaterials for Cardiac Myocyte Tissue Engineering

    OpenAIRE

    Rodolfo Amezcua; Ajay Shirolkar; Carolyn Fraze; David A. Stout

    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 possib...

  9. Improving cardiac myocytes performance by CNTs platforms

    Directory of Open Access Journals (Sweden)

    Valentina eMartinelli

    2013-09-01

    Full Text Available The application of nanotechnology to the cardiovascular system has increasingly caught scientists’ attention as a potentially powerful tool for the development of new generation devices able to interface, repair or boost the performance of cardiac tissue. Carbon nanotubes (CNTs are considered as promising materials for nanomedicine applications in general and have been recently tested towards excitable cell growth. CNTs are cylindrically shaped structures made up of rolled-up graphene sheets, with unique electrical, thermal and mechanical properties, able to effectively conducting electrical current in electrochemical interfaces. CNTs-based scaffolds have been recently found to support the in vitro growth of cardiac cells: in particular, their ability to improve cardiomyocytes proliferation, maturation and electrical behavior are making CNTs extremely attractive for the development and exploitation of interfaces able to impact on cardiac cells physiology and function.

  10. Finite Element Model to Study One Dimensional Calcium Dyanmics in Cardiac Myocytes

    Science.gov (United States)

    Pathak, Kunal B.; Adlakha, Neeru

    2015-12-01

    The multi physical process involving calcium ions regulate expansion and contraction of cardiac myocytes. This mechanism of expansion and contraction of cardiac myocytes is responsible for contraction and expansion of heart for pumping of blood into arteries and receiving blood into heart from vein. Thus calcium dynamics in cardiac myocytes is responsible for the activities of the myocytes cells and functioning of the heart. The specific spatiotemporal calcium ion dynamics is required to trigger, sustain and terminate activity of the cell. In this paper an attempt has been done to propose a model to study calcium dynamics in cardiac myocytes for a one-dimensional unsteady state case. The model incorporates the process like diffusion, reaction involving source and excess buffers. Appropriate boundary conditions and initial conditions have been framed. The finite element method has been employed to obtain the solution. The numerical results have been used to study the effect of buffers and source influx on calcium dynamics in cardiac myocytes.

  11. Isoprenaline enhances local Ca2+ release in cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Jian-xin SHEN

    2006-01-01

    Aim: Contraction of cardiac myocytes is controlled by the generation and amplification of intracellular Ca2+ signals. The key step of this process is the coupling between sarcolemma L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR). β-Adrenergic stimulation is an important regulatory mechanism for this coupling process. But the details underlied the global level, which require local Ca2+ release study are still unclear. The present study is to explore the effects of β-adrenergic stimulation on local Ca2+ release. Methods: Using confocal microscopy combined with loose-seal patch-clamp approaches, effects of isoprenaline (1 μmol·L-1), a β-adrenergic agonist, on local SR Ca2+ release triggered by Ca2+ influx through LCCs in intact rat cardiac myocytes were investigated. Results: Isoprenaline increased the intensity of ensemble averaged local Ca2+ transients, the peak of which displayed a typical bell-shaped voltage-dependence over the membrane voltages ranging from ~-40mV to ~+35mV. Further analysis showed that this enhancement could be explained by the increased coupling fidelity (which refers the increased probability of RyRs activation upon depolarization), and the increased amplitude of evoked Ca2+ sparks (due to more Ca2+ releases through local RyRs). In addition, isoprenaline decreased the first latency, which displayed a typical "U"-shaped voltage-dependence, showing the available acceleration and synchronization of β-adrenergic stimulation on intracellular calcium release. Conclusions: Isoprenaline enhances local Ca2+ release in cardiac myocytes. These results underscore the importance of regulation of β-adrenergic stimulation on local intermolecular signals between LCCs and RyRs in heart cells.

  12. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Xiao HAN; Jian-xun LIU; Xin-zhi LI

    2011-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes.Methods: Cardiac myocytes were incubated under starvation conditions (GD) for O, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sat B (50 μmol/L) in the presence or absence of chloro-quine (3 μmol/L) under GD 3 h, the amount of LC3-11, the abundance of LC3-positive fluorescent dots in cells, cell viability and cellular ATP levels were determined using immunoblotting, immunofluorescence microscopy, MTT assay and luminometer, respectively. More-over, electron microscopy (EM) and immunofluorescent duel labeling of LC3 and Caspase-8 were used to examine the characteristics of autophagy and apoptosis.Results: Immunoblot analysis showed that the amount of LC3-11 in starving cells increased in a time-dependent manner accompanied by increased LC3-positive fluorescence and decreased cell viability and ATP content. Sal B (50 μmol/L) inhibited the increase in LC3-11, reduced the abundance of LC3 immunofluorescence and intensity of Caspase-8 fluorescence, and enhanced cellular viability and ATP levels in myocytes under GD 3 h, regardless of whether chloroquine was present.Conclusion: Autophagy induced by starvation for 3 h led to cell injury. Sal B protected starving cells by blocking the early stage of autophagic flux and inhibiting apoptosis that occurred during autophagy.

  13. Cardiac fibroblasts are predisposed to convert into myocyte phenotype: Specific effect of transforming growth factor. beta

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    Eghbali, M.; Tomek, R.; Woods, C.; Bhambi, B. (Univ. of Chicago, IL (United States))

    1991-02-01

    Cardiac fibroblasts are mainly responsible for the synthesis of major extracellular matrix proteins in the heart, including fibrillar collagen types I and III and fibronectin. In this report we show that these cells, when stimulated by transforming growth factor {beta}{sub 1} (TGF-{beta}{sub 1}), acquire certain myocyte-specific properties. Cultured cardiac fibroblasts from adult rabbit heart were treated with TGF-{beta}{sub 1}, (10-15 ng/ml) for different periods of time. Northern hybridization analysis of total RNA showed that cells treated with TGF-{beta}{sub 1} became stained with a monoclonal antibody to muscle-specific actin. After treatment of quiescent cells with TGF-{beta}{sub 1}, cell proliferation (as measured by ({sup 3}H)thymidine incorporation) was moderately increased. Cultured cardiac fibroblasts at the subconfluent stage, when exposed to TGF-{beta}{sub 1} in the presence of 10% fetal bovine serum, gave rise to a second generation of slowly growing cells that expressed muscle-specific actin filaments. The findings demonstrate that cardiac fibroblasts can be made to differentiate into cells that display many characteristics of cardiac myocytes. TGF-{beta}{sub 1} seems to be a specific inducer of such conversion.

  14. Microfluidic partitioning of the extracellular space around single cardiac myocytes.

    Science.gov (United States)

    Klauke, Norbert; Smith, Godfrey L; Cooper, Jonathan M

    2007-02-01

    This paper describes the partitioning of the extracellular space around an electrically activated single cardiac myocyte, constrained within a microfluidic device. Central to this new method is the production of a hydrophobic gap-structure, which divides the extracellular space into two distinct microfluidic pools. The content of these pools was controlled using a pair of concentric automated pipets (subsequently called "dual superfusion pipet"), each providing the ability to dispense (i.e., the source, inner pipet) and aspirate (the sink, outer pipet) a buffer solution (perfusate) into each of the two pools. For rapid solution switching around the cell, additional dual superfusion pipets were inserted into the microchannel for defined time periods using a piezostepper, enabling us to add a test solution, such as a drug. Three distinct areas of the cell were manipulated, namely, the microfluidic environment, the cellular membrane, and the intracellular space. Planar integrated microelectrodes enabled the electrical stimulation of the cardiomyocyte and the recording of the evoked action potential. The device was mounted on an inverted microscope to allow simultaneous sarcomere length and epifluorescence measurements during evoked electrical activity, including, for example, the response of the stimulated end of the cardiac myocyte in comparison with the untreated cell end.

  15. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  16. Insulin improves cardiac myocytes contractile function recovery in simulated ischemia-reperfusion: Key role of Akt

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; ZHANG Haifeng; FAN Qian; MA Xinliang; GAO Feng

    2003-01-01

    The present study examined cardiac myocyte contractile and Ca2+ transient responses to insulin during simulated ischemia/reperfusion (I/R) and furtherinvestigated the role of protein kinase B (Akt) in the insulin- induced inotropic effect. Ventricular myocytes were enzymatically isolated from adult Sprague-Dawley rats and perfused with Tyrode solution while electrically field-stimulated. Simulated I/R was induced by perfusing the cells with chemical anoxic solution including sodium cyanide-sodium lactate for 15 min followed by reperfusion with normal oxygenated Tyrode solution with or without insulin. It is found that insulin only at concentration as high as 10 IU/L could increase cell shortening (16±5%, P < 0.05) in normal myocytes, whereas it concentration-dependently (0.01-10 IU/L) increased the contraction,the velocity of shortening/releng- theningand Ca2+ transient in I/R myocytes. In addition, insulin treatment (1 IU/L) increased Akt phosphorylation of I/R cardiomyocytes by 2.4-fold compared with that of the control (P < 0.01). Most importantly, pretreatment with LY 294002, a specific inhibitor of phosphatidylinositol 3′-kinase (PI3-kinase), significantly inhibited both Akt phosphorylation and the positive inotropic response to insulin in the I/R cardiomyocytes. These results suggest that insulin exerts direct positive inotropic effect by increasing Ca2+ transient of cardiomyocytes, which is enhanced in the pathological condition of I/R. Akt activation plays an important role in the insulin-induced improvement of myocyte contractile function following I/R.

  17. New dynamic model for non-Fickian diffusion of calcium spark in cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    TAN Wenchang; LIU Shiqiang; GUO Jingjing; WANG Shiqiang; CHENG Heping; T. Masuoka

    2003-01-01

    A new dynamic model for non-Fickian diffusion of calcium spark in cardiac myocytes was developed by introducing time lags on the basis of the microscale mass transport theory. Numerical simulation showed that the size of the calcium spark produced by the new dynamic model was larger than that of Fick diffusion and was in more agreement with experimental results. In addition, the time lags of the calcium spark in cardiac myocytes were about 0.1-0.8 ms. These results can be used to understand the mechanism of calcium spark diffusion in cardiac myocytes.

  18. Angiotensin II type 1 receptor signalling regulates microRNA differentially in cardiac fibroblasts and myocytes

    DEFF Research Database (Denmark)

    Jeppesen, Pia Lindgren; Christensen, Gitte Lund; Schneider, Mikael;

    2011-01-01

    analogue, [Sar1, Ile4, Ile8] Ang II (SII Ang II), which selectively activates Gaq/11-independent signalling, failed to regulate miRNAs in HEK293N cells Furthermore, Ang II induced miRNA regulation was blocked following Gaq/11 and Mek1 inhibition. The observed Ang II regulation of miRNA was confirmed...... in primary cultures of adult cardiac fibroblasts. Interestingly, Ang II did not regulate miRNA expression in cardiac myocytes, but SII Ang II significantly downregulated miR-129-3p. Conclusions and implications: Five miRNAs were regulated by Ang II through mechanisms depending on Gaq/11 and Erk1/2 activation...

  19. Stochastic Alternating Dynamics for Synchronous EAD-Like Beating Rhythms in Cultured Cardiac Myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ning; ZHANG Hui-Min; LIU Zhi-Qiang; DING Xue-Li; YANG Ming-Hao; GU Hua-Guang; REN Wei

    2009-01-01

    Dissolved cardiac myocytes can couple together and generate synchronous beatings in culture. We observed a synchronized early after-depolarization(EAD)-like rhythm in cultured cardiac myocytes and reproduced the experimental observation in a network mathematical model whose dynamics are close to a Hopf bifurcation. The mechanism for this EAD-like rhythm is attributed to noised-induced stochastic alternatings between the focus and the limit cycle. These results provide novel understandings for pathological heart rhythms like the early immature beatings.

  20. Finite element model to study two dimensional unsteady state calcium distribution in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    Kunal Pathak

    2016-09-01

    Full Text Available The calcium signaling plays a crucial role in expansion and contraction of cardiac myocytes. This calcium signaling is achieved by calcium diffusion, buffering mechanisms and influx in cardiac myocytes. The various calcium distribution patterns required for achieving calcium signaling in myocytes are still not well understood. In this paper an attempt has been made to develop a model of calcium distribution in myocytes incorporating diffusion of calcium, point source and excess buffer approximation. The model has been developed for a two dimensional unsteady state case. Appropriate boundary conditions and initial condition have been framed. The finite element method has been employed to obtain the solution. The numerical results have been used to study the effect of buffers and source amplitude on calcium distribution in myocytes.

  1. Construction of calcium release sites in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    Alexandra eZahradnikova

    2012-08-01

    Full Text Available Local character of calcium release in cardiac myocytes, as defined by confocal recordings of calcium sparks, implies independent activation of individual calcium release sites based on ryanodine receptor (RyR channel recruitment. We constructed virtual calcium release sites (vCRSs composed of a variable number of RyR channels distributed in clusters in accordance with the experimentally observed cluster size distribution. The vCRSs consisted either of a single virtual calcium release unit, in which all clusters shared a common dyadic space, or of multiple virtual calcium release units containing one cluster each and having separate dyadic spaces. We explored the stochastic behavior of vCRSs to understand the activation and recruitment of RyRs during calcium sparks. RyRs were represented by the published allosteric gating model that included regulation by cytosolic Ca2+ and Mg2+. The interaction of Mg2+ with the RyR Ca2+-binding sites and the refractory period of vCRSs were optimized to accord with the experimentally observed calcium dependence of calcium spark frequency. The Mg2+-binding parameters of RyRs that provided the best description of spark frequency depended on the number of RyRs assembled in the virtual calcium release sites. Adequate inhibitory effect of Mg2+ on the calcium dependence of RyR open probability was achieved if the virtual calcium release sites contained at least three clusters. For the distribution of the number of open RyRs in evoked calcium sparks to correspond to the experimentally observed distribution of spark calcium release fluxes, at least 3 clusters had to share a common virtual calcium release unit, in which ~ 3 RyRs open to form an average spark. These results reconcile the small cluster size and stochastic placement of RyRs in the release sites with the estimates of the amount of RyR protein, volume density of calcium release sites, and the size of calcium release sites in rat cardiac myocytes.

  2. 5-azacytidine promotes the transdifferentiation of cardiac cells to skeletal myocytes.

    Science.gov (United States)

    Kaur, Keerat; Yang, Jinpu; Eisenberg, Carol A; Eisenberg, Leonard M

    2014-10-01

    The DNA methylation inhibitor 5-azacytidine is widely used to stimulate the cardiac differentiation of stem cells. However, 5-azacytidine has long been employed as a tool for stimulating skeletal myogenesis. Yet, it is unclear whether the ability of 5-azacytidine to promote both cardiac and skeletal myogenesis is dependent strictly on the native potential of the starting cell population or if this drug is a transdifferentiation agent. To address this issue, we examined the effect of 5-azacytidine on cultures of adult mouse atrial tissue, which contains cardiac but not skeletal muscle progenitors. Exposure to 5-azacytidine caused atrial cells to elongate and increased the presence of fat globules within the cultures. 5-Azacytidine also induced expression of the skeletal myogenic transcription factors MyoD and myogenin. 5-Azacytidine pretreatments allowed atrial cells to undergo adipogenesis or skeletal myogenesis when subsequently cultured with either insulin and dexamethasone or low-serum media, respectively. The presence of skeletal myocytes in atrial cultures was indicated by dual staining for myogenin and sarcomeric α-actin. These data demonstrate that 5-azacytidine converts cardiac cells to noncardiac cell types and suggests that this drug has a compromised efficacy as a cardiac differentiation factor. PMID:25090621

  3. VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes.

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    Ferlito, Marcella; Fulton, William B; Zauher, Mohamed A; Marbán, Eduardo; Steenbergen, Charles; Lowenstein, Charles J

    2010-11-01

    ANP is a peptide released by cardiac myocytes that regulates blood pressure and natriuresis. However, the molecular mechanisms controlling ANP release from cardiac myocytes are not defined. We now identify three components of the exocytic machinery that regulate ANP release from atrial myocytes. We found that cardiac myocytes express N-ethylmaleimide sensitive factor (NSF), soluble NSF attachment protein (α-SNAP), and SNAP receptors (SNAREs). Additionally we found that specific SNARE molecules, VAMP-1 and VAMP-2, both co-sediment and co-localize with ANP. Also, one SNARE molecule, syntaxin-4, partially co-sediments and partially co-localizes with ANP. Furthermore, these three SNAREs, syntaxin-4 and VAMP-1 and VAMP-2, form a SNARE complex inside cardiac myocytes. Finally, knockdown of VAMP-1, VAMP-2, or syntaxin-4 blocks regulated release of ANP. In contrast, silencing of VAMP-3 did not have an effect on ANP release. Our data suggest that three specific SNAREs regulate cardiac myocyte exocytosis of ANP. Pathways that modify the exocytic machinery may influence natriuresis and blood pressure.

  4. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Min, E-mail: chenminyx@gmail.com [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Yunnan Centers for Diseases Prevention and Control, Kunming 650022 (China); Wang, Yanru [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Qu, Aijuan [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  5. The pharmacology of three inwardly rectifying potassium Channels in neonatal rat cardiac myocytes.

    OpenAIRE

    Azam, R.

    1999-01-01

    The aim of the present study was to investigate the pharmacology of three inwardly rectifying K+-channels in neonatal rat cardiac myocytes, IKAch, IKI, IKAtp- using whole cell voltage clamp techniques. Cells were held at -50mV. A previous study has shown that clotrimazole, an antimycotic agent, and cetiedil, an antisickling agent are potent against the IKACch in atrial myocytes. Structural analogues of these compounds were tested on the three inward rectifiers. UCL1880, an a...

  6. Myoglobin-mediated oxygen delivery to mitochondria of isolated cardiac myocytes.

    OpenAIRE

    Wittenberg, B A; Wittenberg, J. B.

    1987-01-01

    Myoglobin-mediated oxygen delivery to intracellular mitochondria is demonstrated in cardiac myocytes isolated from the hearts of mature rats. Myocytes are held at high ambient oxygen pressure, 40-340 torr (5-45 kPa); sarcoplasmic myoglobin is fully oxygenated. In this condition oxygen availability does not limit respiratory rate; myoglobin-facilitated diffusion contributes no additional oxygen flux and, since oxygen consumption is measured in steady states, the storage function of myoglobin v...

  7. Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in Heart Failure

    Science.gov (United States)

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A.; Liang, Bruce T.

    2014-01-01

    Background Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Methods and Results Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation–induced postinfarct or transverse aorta constriction–induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N5-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. Conclusions This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. PMID:24622244

  8. Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

    Science.gov (United States)

    Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

    1995-01-01

    Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

  9. Uptake and metabolism of the novel peptide angiotensin-(1-12 by neonatal cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmad

    Full Text Available BACKGROUND: Angiotensin-(1-12 [Ang-(1-12] functions as an endogenous substrate for the productions of Ang II and Ang-(1-7 by a non-renin dependent mechanism. This study evaluated whether Ang-(1-12 is incorporated by neonatal cardiac myocytes and the enzymatic pathways of ¹²⁵I-Ang-(1-12 metabolism in the cardiac myocyte medium from WKY and SHR rats. METHODOLOGY/PRINCIPAL FINDINGS: The degradation of ¹²⁵I-Ang-(1-12 (1 nmol/L in the cultured medium of these cardiac myocytes was evaluated in the presence and absence of inhibitors for angiotensin converting enzymes 1 and 2, neprilysin and chymase. In both strains uptake of ¹²⁵I-Ang-(1-12 by myocytes occurred in a time-dependent fashion. Uptake of intact Ang-(1-12 was significantly greater in cardiac myocytes of SHR as compared to WKY. In the absence of renin angiotensin system (RAS enzymes inhibitors the hydrolysis of labeled Ang-(1-12 and the subsequent generation of smaller Ang peptides from Ang-(1-12 was significantly greater in SHR compared to WKY controls. ¹²⁵I-Ang-(1-12 degradation into smaller Ang peptides fragments was significantly inhibited (90% in WKY and 71% in SHR in the presence of all RAS enzymes inhibitors. Further analysis of peptide fractions generated through the incubation of Ang-(1-12 in the myocyte medium demonstrated a predominant hydrolytic effect of angiotensin converting enzyme and neprilysin in WKY and an additional role for chymase in SHR. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that neonatal myocytes sequester angiotensin-(1-12 and revealed the enzymes involved in the conversion of the dodecapeptide substrate to biologically active angiotensin peptides.

  10. IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB

    International Nuclear Information System (INIS)

    Hyperosmotic stress stimulates a rapid and pronounced apoptosis in cardiac myocytes which is attenuated by insulin-like growth factor-1 (IGF-1). Because in these cells IGF-1 induces intracellular Ca2+ increase, we assessed whether the cyclic AMP response element-binding protein (CREB) is activated by IGF-1 through Ca2+-dependent signalling pathways. In cultured cardiac myocytes, IGF-1 induced phosphorylation (6.5 ± 1.0-fold at 5 min), nuclear translocation (30 min post-stimulus) and DNA binding activity of CREB. IGF-1-induced CREB phosphorylation was mediated by MEK1/ERK, PI3-K, p38-MAPK, as well as Ca2+/calmodulin kinase and calcineurin. Exposure of cardiac myocytes to hyperosmotic stress (sorbitol 600 mOsm) decreased IGF-1-induced CREB activation Moreover, overexpression of a dominant negative CREB abolished the anti-apoptotic effects of IGF-1. Our results suggest that IGF-1 activates CREB through a complex signalling pathway, and this transcription factor plays an important role in the anti-apoptotic action of IGF-1 in cultured cardiac myocytes

  11. ROLE OF CALCINEURIN IN ANGIOTENSIN II INDUCED CARDIAC MYOCYTE HYPERTROPHY OF RATS

    Institute of Scientific and Technical Information of China (English)

    符民桂; 张继峰; 许松; 庞永政; 刘乃奎; 唐朝枢

    2001-01-01

    Objective. The present study investigated the role of calcineurin in angiotensin II(AngII) induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H leucine incorporation; atrial natriuretic factor(ANF) Mrna level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13% ,57% (P< 0.05) and 228% (P< 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H leucine incorporation in AngII treated cardiomyocytes in a dose dependent manner. It was also found that CsA slightly reduced the Mrna level of ANF gene in AngII stimulated cardiomyocytes. Conclusion. During AngII induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII induced myocardial hypertrophy of rats.

  12. C-Reactive Protein Inhibits Survivin Expression via Akt/mTOR Pathway Downregulation by PTEN Expression in Cardiac Myocytes

    OpenAIRE

    Beom Seob Lee; Soo Hyuk Kim; Jaewon Oh; Taewon Jin; Eun Young Choi; Sungha Park; Sang-Hak Lee; Ji Hyung Chung; Seok-Min Kang

    2014-01-01

    C-reactive protein (CRP) is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We ...

  13. Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl

  14. Cardiac Myocyte Diversity and a Fibroblast Network in the Junctional Region of the Zebrafish Heart Revealed by Transmission and Serial Block-Face Scanning Electron Microscopy

    KAUST Repository

    Lafontant, Pascal J.

    2013-08-23

    The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart. © 2013 Lafontant et al.

  15. Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

    Energy Technology Data Exchange (ETDEWEB)

    Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

    2014-09-01

    Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

  16. Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

    International Nuclear Information System (INIS)

    Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility

  17. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure.

    Science.gov (United States)

    Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K; Sinha-Hikim, Amiya P

    2011-06-01

    This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15-21 (E15-E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15-E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure. PMID:21424555

  18. Ca2+ Alternans in a Cardiac Myocyte Model that Uses Moment Equations to Represent Heterogeneous Junctional SR Ca2+

    OpenAIRE

    Huertas, Marco A; Smith, Gregory D.; Györke, Sándor

    2010-01-01

    Multiscale whole-cell models that accurately represent local control of Ca2+-induced Ca2+ release in cardiac myocytes can reproduce high-gain Ca2+ release that is graded with changes in membrane potential. Using a recently introduced formalism that represents heterogeneous local Ca2+ using moment equations, we present a model of cardiac myocyte Ca2+ cycling that exhibits alternating sarcoplasmic reticulum (SR) Ca2+ release when periodically stimulated by depolarizing voltage pulses. The model...

  19. Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

    Directory of Open Access Journals (Sweden)

    Tianruo Guo

    2013-01-01

    Full Text Available A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

  20. Ionic diffusion in voltage-clamped isolated cardiac myocytes. Implications for Na,K-pump studies.

    OpenAIRE

    Mogul, D J; Singer, D H; ten Eick, R E

    1989-01-01

    The whole-cell voltage-clamp technique employing electrolyte-filled micro-pipette suction electrodes is widely used to investigate questions requiring an electrophysiological approach. With this technique, the ionic composition of the cytosol is assumed to be strongly influenced (as result of diffusion) by the ionic composition of the solution contained in the electrode. If this assumption is valid for isolated cardiac myocytes, the technique would be particularly powerful for studying the de...

  1. Titanium Dioxide Nanoparticles Induced Proinflammation of Primary Cultured Cardiac Myocytes of Rat

    OpenAIRE

    Wei Song; Jiangxue Wang; Meili Liu; Ping Li; Gang Zhou; Zhou Li; Yubo Fan

    2013-01-01

    Titanium dioxide (TiO2) nanoparticles are widely used in electronics, biology, and medicine owing to their special properties. However, during TiO2 nanoparticles exposure, nanoparticles may enter the blood circulation and translocate to the heart, and they may result in negative effects on the cardiovascular system. In this study, we demonstrated that the anatase and rutile TiO2 nanoparticles had potential toxicological effects on primary cultured cardiac myocytes of rat. After incubating wit...

  2. Direct, differential effects of tamoxifen, 4-hydroxytamoxifen, and raloxifene on cardiac myocyte contractility and calcium handling.

    Directory of Open Access Journals (Sweden)

    Michelle L Asp

    Full Text Available Tamoxifen (Tam, a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. High Tam doses have been used for treatment of gliomas and cancers with multiple drug resistance, but long QT Syndrome is a side effect. Tam is also used experimentally in mice for inducible gene knockout in numerous tissues, including heart; however, the potential direct effects of Tam on cardiac myocyte mechanical function are not known. The goal of this study was to determine the direct, acute effects of Tam, its active metabolite 4-hydroxytamoxifen (4OHT, and related drug raloxifene (Ral on isolated rat cardiac myocyte mechanical function and calcium handling. Tam decreased contraction amplitude, slowed relaxation, and decreased Ca²⁺ transient amplitude. Effects were primarily observed at 5 and 10 μM Tam, which is relevant for high dose Tam treatment in cancer patients as well as Tam-mediated gene excision in mice. Myocytes treated with 4OHT responded similarly to Tam-treated cells with regard to both contractility and calcium handling, suggesting an estrogen-receptor independent mechanism is responsible for the effects. In contrast, Ral increased contraction and Ca²⁺ transient amplitudes. At 10 μM, all drugs had a time-dependent effect to abolish cellular contraction. In conclusion, Tam, 4OHT, and Ral adversely and differentially alter cardiac myocyte contractility and Ca²⁺ handling. These findings have important implications for understanding the Tam-induced cardiomyopathy in gene excision studies and may be important for understanding effects on cardiac performance in patients undergoing high-dose Tam therapy.

  3. FINITE ELEMENT ANALYSIS OF CARDIAC MYOCYTE DEBONDING AND REORIENTATION DURING CYCLIC SUBSTRATE STRETCH EXPERIMENTS

    Institute of Scientific and Technical Information of China (English)

    Tao Tang; Jun Qiu; Meng Zhang; Zhuo Zhuang

    2009-01-01

    The substrate stretch experiment, which is carried out on several kinds of adherent cells, is usually used to catch the physiological variation and morphological response to cyclic substrate deformation. In this paper, stretch loading was exerted on cardiac myocytes cultured on silica substrates using a custom-made substrate stretch device. The effect of stretch on the alignment orientation of cardiac myocytes was studied through morphocytological statistics. Under cyclic stretch stimulus, the long axes of cardiac myocytes oriented perpendicularly to the stretch direction for continuous stretch acting. However, the mechanism underlying these behaviors is not well understood from such in vitro tests. Finite element (FE) model was developed in the analysis to investigate these behaviors. Xu-Needleman formulation was used to define the interaction behavior for contact surfaces between cell and substrate. The role of cell viscoelasticity nature is studied in adherent cell debonding with the substrate and aligning perpendicular to the stretch direction during long time cyclic stretch stimulation. There were four different strain magnitudes considered in the simulation to find out the cell debonding affected by the cyclic strains. The potential role of cyclic strain frequency in regulating cell debonding and alignment was also studied using FE analysis.

  4. Modeling Calcium Wave Based on Anomalous Subdiffusion of Calcium Sparks in Cardiac Myocytes

    Science.gov (United States)

    Chen, Xi; Kang, Jianhong; Fu, Ceji; Tan, Wenchang

    2013-01-01

    sparks and waves play important roles in calcium release and calcium propagation during the excitation-contraction (EC) coupling process in cardiac myocytes. Although the classical Fick’s law is widely used to model sparks and waves in cardiac myocytes, it fails to reasonably explain the full-width at half maximum(FWHM) paradox. However, the anomalous subdiffusion model successfully reproduces sparks of experimental results. In this paper, in the light of anomalous subdiffusion of sparks, we develop a mathematical model of calcium wave in cardiac myocytes by using stochastic release of release units (CRUs). Our model successfully reproduces calcium waves with physiological parameters. The results reveal how concentration waves propagate from an initial firing of one CRU at a corner or in the middle of considered region, answer how large in magnitude of an anomalous spark can induce a wave. With physiological currents (2pA) through CRUs, it is shown that an initial firing of four adjacent CRUs can form a wave. Furthermore, the phenomenon of calcium waves collision is also investigated. PMID:23483894

  5. PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Koji Isodono

    Full Text Available To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1. While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER. In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease.

  6. Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-zhong; GE Chang-jiang; LIU Jing-hua; L(U) Shu-zheng; L(U) Yun; GUO Cheng-jun; ZHAO Dong-hui; FANG Dong-ping; HE Dong-fang; ZHOU Yuan

    2011-01-01

    Background It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial.This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes.Methods The β-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed.Results The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95±2..41) U/g or (29.28±3.65) U/g vs. (0.84-0.21) U/g, P <0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95e2.41) U/g vs. (29.28±3.65)U/g, P <0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced 3-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35±11.21) U/g protein vs. (14.13±2.58) U/g protein, P<0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63±7.65)U/g vs. (14.13±2.58) U/g, P<0.05 ).Conclusions

  7. Cell-specific promoter in adenovirus vector for transgenic expression of SERCA1 ATPase in cardiac myocytes.

    Science.gov (United States)

    Inesi, G; Lewis, D; Sumbilla, C; Nandi, A; Strock, C; Huff, K W; Rogers, T B; Johns, D C; Kessler, P D; Ordahl, C P

    1998-03-01

    Adenovirus-mediated transfer of cDNA encoding the chicken skeletal muscle sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) yielded selective expression in cultured chick embryo cardiac myocytes under control of a segment (-268 base pair) of the cell-specific cardiac troponin T (cTnT) promoter or nonselective expression in myocytes and fibroblasts under control of a constitutive viral [cytomegalovirus (CMV)] promoter. Under optimal conditions nearly all cardiac myocytes in culture were shown to express transgenic SERCA1 ATPase. Expression was targeted to intracellular membranes and was recovered in subcellular fractions with a pattern identical to that of the endogenous SERCA2a ATPase. Relative to control myocytes, transgenic SERCA1 expression increased up to four times the rates of ATP-dependent (and thapsigargin-sensitive) Ca2+ transport activity of cell homogenates. Although the CMV promoter was more active than the cTnT promoter, an upper limit for transgenic expression of functional enzyme was reached under control of either promoter by adjustment of the adenovirus plaque-forming unit titer of infection media. Cytosolic Ca2+ concentration transients and tension development of whole myocytes were also influenced to a similar limit by transgenic expression of SERCA1 under control of either promoter. Our experiments demonstrate that a cell-specific protein promoter in recombinant adenovirus vectors yields highly efficient and selective transgene expression of a membrane-bound and functional enzyme in cardiac myocytes.

  8. Effects of simulated microgravity on nitric oxide level in cardiac myocytes and its mechanism

    Institute of Scientific and Technical Information of China (English)

    XIONG; Jianghui; (熊江辉); LI; Yinghui; (李莹辉); NIE; Jielin; (聂捷琳)

    2003-01-01

    The depression of cardiac contractility induced by space microgravity is an important issue of aerospace medicine research, while its precise mechanism is still unknown. In the present study, we explored effects of simulated microgravity on nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) expression and related regulative mechanism using electron spin resonance (ESR) spectroscopy, immunocytochemistry and in situ hybridization. We found a remarkable increase of NO level and up-regulation of iNOS and iNOS mRNA expression in rat cardiac myocytes under simulated microgravity. Staurosporine (a nonselective protein kinase inhibitor), calphostin C (a selective protein kinase C inhibitor), partially inhibited the effect of simulated microgravity. Thus regulative effect of simulated microgravity on iNOS expression is mediated at least partially via activation of protein kinase C. These results indicate that NO system in cardiac myocytes is sensitive to simulated microgravity and may play an important role in the depression of cardiac contractility induced by simulated microgravity.

  9. Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits

    OpenAIRE

    Tong, XiaoYong; Porter, Lisa M.; Liu, GongXin; Dhar-Chowdhury, Piyali; Srivastava, Shekhar; Pountney, David J.; Yoshida, Hidetada; Artman, Michael; Fishman, Glenn I.; Yu, Cindy; Iyer, Ramesh; Morley, Gregory E.; Gutstein, David E.; Coetzee, William A.

    2006-01-01

    Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits. Am J Physiol Heart Circ Physiol 291: H543–H551, 2006. First published February 24, 2006; doi:10.1152/ajpheart.00051.2006.—Cardiac ATP-sensitive K+ (KATP) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression ...

  10. Down-regulation of C-type natriuretic peptide receptor by vasonatrin peptide in cardiac myocytes and fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Shun-yan L(U); Miao-zhang ZHU; Dian-shi WANG; Jun YU; Hai-tao GUO; Yu-zhen HU; Qi-ming WEI

    2004-01-01

    AIM: To investigate the regulatory effects of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in cultured neonatal rat cardiac myocytes and fibroblasts. METHODS: Quantitative RTPCR was undertaken to evaluate the levels of NPR-C mRNA and radioimmunoassay was used to determine the formation of intracellular cGMP. RESULTS: Twenty-four hours hypoxic exposure increased the level of NPR-C mRNA in cardiomyocytes, while did not alter the expression of NPR-C in cardiac fibroblasts. VNP (1 × l0-8-1×10-6 mol/L) reduced the levels of NPR-C mRNA in cardiac myocytes induced by hypoxia in a concentration-dependent manner, and with high concentration (1×10-6 mol/L) also decreased the expression of NPR-C in cardiac fibroblasts and air-control cardiac myocytes. The inhibitory effects of VNP on the expression of NPR-C was mimicked by 8-bromo-cGMP 1×10-6 mol/L (a membrane permeable analog of cGMP). VNP (1×10-8-1×10-6 mol/L) increased the formation of intracellular guanosine-3',5'-cyclic monophosphate (cGMP) in both cardiac myocytes and fibroblasts.HS-142-1, the particulate guanylyl cyclase-coupled receptor antagonist, partially abrogated the above effects of VNP. CONCLUSION: Hypoxic exposure for 24 h up-regulated the expression of NPR-C in cultured neonatal rat cardiac myocytes. VNP decreased the expression of NPR-C in cardiac myocytes and fibroblasts under both aircontrol and hypoxic condition, which was at least partially mediated by guanylate cyclase linked natriuretic peptide receptors through increasing the intracellular cGMP.

  11. Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture.

    Science.gov (United States)

    Berger, H J; Prasad, S K; Davidoff, A J; Pimental, D; Ellingsen, O; Marsh, J D; Smith, T W; Kelly, R A

    1994-01-01

    To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.

  12. Inorganic polyphosphate in cardiac myocytes: from bioenergetics to the permeability transition pore and cell survival.

    Science.gov (United States)

    Dedkova, Elena N

    2016-02-01

    Inorganic polyphosphate (polyP) is a linear polymer of Pi residues linked together by high-energy phosphoanhydride bonds as in ATP. PolyP is present in all living organisms ranging from bacteria to human and possibly even predating life of this planet. The length of polyP chain can vary from just a few phosphates to several thousand phosphate units long, depending on the organism and the tissue in which it is synthesized. PolyP was extensively studied in prokaryotes and unicellular eukaryotes by Kulaev's group in the Russian Academy of Sciences and by the Nobel Prize Laureate Arthur Kornberg at Stanford University. Recently, we reported that mitochondria of cardiac ventricular myocytes contain significant amounts (280±60 pmol/mg of protein) of polyP with an average length of 25 Pi and that polyP is involved in Ca(2+)-dependent activation of the mitochondrial permeability transition pore (mPTP). Enzymatic polyP depletion prevented Ca(2+)-induced mPTP opening during ischaemia; however, it did not affect reactive oxygen species (ROS)-mediated mPTP opening during reperfusion and even enhanced cell death in cardiac myocytes. We found that ROS generation was actually enhanced in polyP-depleted cells demonstrating that polyP protects cardiac myocytes against enhanced ROS formation. Furthermore, polyP concentration was dynamically changed during activation of the mitochondrial respiratory chain and stress conditions such as ischaemia/reperfusion (I/R) and heart failure (HF) indicating that polyP is required for the normal heart metabolism. This review discusses the current literature on the roles of polyP in cardiovascular health and disease. PMID:26862184

  13. Na/K pump current in aggregates of cultured chick cardiac myocytes

    OpenAIRE

    1990-01-01

    Spontaneously beating aggregates of cultured embryonic chick cardiac myocytes, maintained at 37 degrees C, were voltage clamped using a single microelectrode switching clamp to measure the current generated by the Na/K pump (Ip). In resting, steady-state preparations an ouabain- sensitive current of 0.46 +/- 0.03 microA/cm2 (n = 22) was identified. This current was not affected by 1 mM Ba, which was used to reduce inward rectifier current (IK1) and linearize the current-voltage relationship. ...

  14. Intracellular sodium affects ouabain interaction with the Na/K pump in cultured chick cardiac myocytes

    OpenAIRE

    1990-01-01

    Whether a given dose of ouabain will produce inotropic or toxic effects depends on factors that affect the apparent affinity (K0.5) of the Na/K pump for ouabain. To accurately resolve these factors, especially the effect of intracellular Na concentration (Nai), we have applied three complementary techniques for measuring the K0.5 for ouabain in cultured embryonic chick cardiac myocytes. Under control conditions with 5.4 mM Ko, the value of the K0.5 for ouabain was 20.6 +/- 1.2, 12.3 +/- 1.7, ...

  15. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure

    OpenAIRE

    Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; GELFAND, ROBERT; Mahata, Sushil K.; Sinha-Hikim, Amiya P.

    2011-01-01

    This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15–21 (E15–E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocyc...

  16. Effect of Sodium Tanshinone Ⅱ A Sulfonate on Cardiac Myocyte Hypertrophy and Its Underlying Mechanism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective:To investigate the effects of sodium tanshinone Ⅱ A sulfonate (STS) on the hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ) in primary cultured neonatal rat cardiac myocytes.Methods:The effect of STS on cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-3,5-phenytetrazoliumromide (MTT) assay.As indexes for cardiocyte hypertrophy,cell size was determined by phase contrast microscopy and protein synthesis rate was measured by 3H-leucine incorporation.The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction (RT-PCR).Results:STS could inhibit cardiocyte hypertrophy,increase the protein synthesis rate and enhance proto-oncogene c-los mRNA expression in cardiocytes induced by Ang Ⅱ (P<0.01),with an effect similar to that of Valsartan,the Ang Ⅱ receptor antagonist.Conclusion:STS can prevent the hypertrophy of cardiac myocytes induced by Ang Ⅱ,which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.

  17. Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis.

    Science.gov (United States)

    Zhang, Xiaohui; Zhang, Xiaohua; Xiong, Yiqun; Xu, Chaoying; Liu, Xinliang; Lin, Jian; Mu, Guiping; Xu, Shaogang; Liu, Wenhe

    2016-09-01

    The sarcolemmal ATP-sensitive K+ (sarcKATP) channel plays a cardioprotective role during stress. However, the role of the sarcKATP channel in the apoptosis of cardiomyocytes and association with mitochondrial calcium remains unclear. For this purpose, we developed a model of LPS-induced sepsis in neonatal rat cardiomyocytes (NRCs). The TUNEL assay was performed in order to detect the apoptosis of cardiac myocytes and the MTT assay was performed to determine cellular viability. Exposure to LPS significantly decreased the viability of the NRCs as well as the expression of Bcl-2, whereas it enhanced the activity and expression of the apoptosis-related proteins caspase-3 and Bax, respectively. The sarcKATP channel blocker, HMR-1098, increased the apoptosis of NRCs, whereas the specific sarcKATP channel opener, P-1075, reduced the apoptosis of NRCs. The mitochondrial calcium uniporter inhibitor ruthenium red (RR) partially inhibited the pro-apoptotic effect of HMR-1098. In order to confirm the role of the sarcKATP channel, we constructed a recombinant adenovirus vector carrying the sarcKATP channel mutant subunit Kir6.2AAA to inhibit the channel activity. Kir6.2AAA adenovirus infection in NRCs significantly aggravated the apoptosis of myocytes induced by LPS. Elucidating the regulatory mechanisms of the sarcKATP channel in apoptosis may facilitate the development of novel therapeutic targets and strategies for the management of sepsis and cardiac dysfunction. PMID:27430376

  18. Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis.

    Science.gov (United States)

    Shiraishi, J; Tatsumi, T; Keira, N; Akashi, K; Mano, A; Yamanaka, S; Matoba, S; Asayama, J; Yaoi, T; Fushiki, S; Fliss, H; Nakagawa, M

    2001-10-01

    Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation. PMID:11557554

  19. C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Beom Seob Lee

    Full Text Available C-reactive protein (CRP is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.

  20. Effects of hypoxia on promoter of telomerase reverse transcriptase and cell cycle distribution in neonatal rat cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    XU Shun-lin; HUANG Jun; ZHU Jing; CAO Ke-jiang; DING Gui-peng; ZHU Yi; XU Lu

    2005-01-01

    @@ On the hypothesis that telomerase reverse transcriptase (TERT) of cardiac myocytes (CMs) is consistent with cell cycle distribution as well as tumour cells, we plan to investigate the expression of TERT in CMs and how TERT is in keeping with CMs cycle distribution after birth and under hypoxia, and roughly understand how hypoxia affects activity of TERT promoter.

  1. Modeling beta-adrenergic control of cardiac myocyte contractility in silico

    Science.gov (United States)

    Saucerman, Jeffrey J.; Brunton, Laurence L.; Michailova, Anushka P.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.

  2. The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study.

    Science.gov (United States)

    Greisas, Ariel; Zlochiver, Sharon

    2016-09-01

    Cardiac fibroblast proliferation and concomitant collagenous matrix accumulation (fibrosis) develop during multiple cardiac pathologies. Recent studies have demonstrated direct electrical coupling between myocytes and fibroblasts in vitro, and assessed the electrophysiological implications of such coupling. However, in the living tissues, such coupling has not been demonstrated, and only indirect coupling via the extracellular space is likely to exist. In this study we employed a multi-domain model to assess the modulation of the cardiac electrophysiological properties by neighboring fibroblasts assuming only indirect coupling. Numerical simulations in 1D and 2D human atrial models showed that extracellular coupling sustains a significant impact on conduction velocity (CV) and a less significant effect on the action potential duration. Both CV and the slope of the CV restitution increased with increasing fibroblast density. This effect was more substantial for lower extracellular conductance. In 2D, spiral waves exhibited reduced frequency with increasing fibroblast density, and the propensity of wavebreaks and complex dynamics at high pacing rates significantly increased. PMID:27150222

  3. Carbon nanotubes instruct physiological growth and functionally mature syncytia: nongenetic engineering of cardiac myocytes.

    Science.gov (United States)

    Martinelli, Valentina; Cellot, Giada; Toma, Francesca Maria; Long, Carlin S; Caldwell, John H; Zentilin, Lorena; Giacca, Mauro; Turco, Antonio; Prato, Maurizio; Ballerini, Laura; Mestroni, Luisa

    2013-07-23

    Myocardial tissue engineering currently represents one of the most realistic strategies for cardiac repair. We have recently discovered the ability of carbon nanotube scaffolds to promote cell division and maturation in cardiomyocytes. Here, we test the hypothesis that carbon nanotube scaffolds promote cardiomyocyte growth and maturation by altering the gene expression program, implementing the cell electrophysiological properties and improving networking and maturation of functional syncytia. In our study, we combine microscopy, biological and electrophysiological methodologies, and calcium imaging, to verify whether neonatal rat ventricular myocytes cultured on substrates of multiwall carbon nanotubes acquire a physiologically more mature phenotype compared to control (gelatin). We show that the carbon nanotube substrate stimulates the induction of a gene expression profile characteristic of terminal differentiation and physiological growth, with a 2-fold increase of α-myosin heavy chain (P carbon nanotubes appear to exert a protective effect against the pathologic stimulus of phenylephrine. Finally, cardiomyocytes on carbon nanotubes demonstrate a more mature electrophysiological phenotype of syncytia and intracellular calcium signaling. Thus, carbon nanotubes interacting with cardiomyocytes have the ability to promote physiological growth and functional maturation. These properties are unique in the current vexing field of tissue engineering, and offer unprecedented perspectives in the development of innovative therapies for cardiac repair.

  4. Toward an integrative computational model of the Guinea pig cardiac myocyte.

    Science.gov (United States)

    Gauthier, Laura Doyle; Greenstein, Joseph L; Winslow, Raimond L

    2012-01-01

    The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca(2+)) release occurs at the nanodomain level, where openings of single L-type Ca(2+) channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca(2+) transient is a smooth continuous function of influx of Ca(2+) through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca(2+) release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca(2+) and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca(2+) transients, thus influencing tissue level electromechanical function. PMID:22783206

  5. Towards an integrative computational model of the guinea pig cardiac myocyte

    Directory of Open Access Journals (Sweden)

    Laura Doyle Gauthier

    2012-07-01

    Full Text Available The local control theory of excitation-contraction (EC coupling asserts that regulation of calcium (Ca2+ release occurs at the nanodomain level, where openings of single L-type Ca2+ channels (LCCs trigger openings of small clusters of ryanodine receptors (RyRs co-localized within the dyad. A consequence of local control is that the whole-cell Ca2+ transient is a smooth continuous function of influx of Ca2+ through LCCs. While this so-called graded release property has been known for some time, it’s functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically-based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca2+ release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally-observed causal relationship between action potential (AP shape and timing of Ca2+ and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca2+ transients, thus influencing tissue-level electro-mechanical function.

  6. Contraction and relaxation of isolated cardiac myocytes of the frog under varying mechanical loads.

    Science.gov (United States)

    Parikh, S S; Zou, S Z; Tung, L

    1993-02-01

    The mechanics of cardiac systole and relaxation have been studied primarily at the level of the whole heart or intact muscle. End-systolic pressure-volume relations of frog hearts have been found to be load dependent, whereas those of the mammal are relatively load independent. On the other hand, myocardial relaxation as studied at the muscle level is load independent in the frog but markedly load dependent in the mammal. Interpretation of these studies is complicated because of the unknown contribution of extracellular connective tissue, neurohumoral factors, and, in the case of the heart, the complex chamber geometry. Therefore, it is valuable to study cardiac mechanics at the level of the basic unit of contractile activity--the isolated myocyte. The goal of this study was to subject isolated frog cardiomyocytes to mechanical loading paradigms that mimic those presented to the cells within the heart. In the first part of this study, the afterload and preload of contracting cells were varied to study their effects on the end-systolic force-length relation, which was consistently found to be load independent over the range of isotonic shortening tested (typically 5%). We also investigated the force-length-time response of the cells to test the concept of the heart behaving as a time-varying elastance. Our results suggest that in this regard the frog myocyte behaves like mammalian muscle, and they are consistent with the presence of a small viscosity within the cell. We conclude that the tissue structure of the frog heart may contribute to disparity in mechanical behavior at the different structural levels. In the second part of this study, we subjected isolated frog cardiomyocytes to four different loading paradigms to test the hypothesis that myocardial relaxation in the frog is independent of load. These sequences consisted of afterloaded contractions followed by conventional isotonic-isometric relaxation (ACCR) or afterloaded contractions followed by

  7. FAK-related nonkinase attenuates hypertrophy induced by angiotensin-Ⅱ in cultured neonatal rat cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Jin QIN; Zheng-xiang LIU

    2006-01-01

    Aim: To examine the inhibitory effect of FAK-related nonkinase (FRNK) in cardiac hypertrophy in vitro and investigate the possible mechanisms. Methods: A functional fragment of FRNK cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into the vector pcDNA3.1. Hypertrophy in neonatal rat cardiac myocytes was established with angiotensin-Ⅱ stimulation. The pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes by Lipofectamine 2000. The surface area and mRNA expression of atrial natriuretic peptide (ANP) of myocytes were employed to detect cardiac hypertrophy. NF-κB p65 protein in nuclear extracts, phosphorylation levels of ERK1/2 (p-ERK1/2) and AKT (p-AKT), as well as total ERK1/2, and AKT in variant treated cardiomyocytes were determined by Western blot. Results: Under the stimulation of angiotensin Ⅱ, the surface area of myocytes and levels of ANP mRNA were significantly increased. But transient transfection with pcDNA3.1-FRNK in advance may reduce the surface area and expression of ANP mRNA of hypertrophic myocytes. The protein levels of NF-κB p65 in nuclear extracts and p-ERK1/2, p-AKT in FRNK treated cardiomyocytes were significantly decreased compared with that in angiotensin-Ⅱ induced cardiomyocytes, while different treatments had little effect on total ERK1/2 and AKT. Conclusion: FRNK may inhibit angiotensin-Ⅱ-induced cardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 and AKT, consequently downregulating nuclear translocation of NF-κB p65.

  8. Gene Product Expression of Cyclin D2 and p16 During the Transition from Cardiac Myocyte Hyperplasia to Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The current study was to investigate mRNA expression of cyclin D2 and p16 during the transition from cardiac myocyte hyperplasia to hypertrophy. Cultured cardiac myocytes (CM) and fibroblasts (FC) obtained from 1-day-old Sparague-Dawley rats were used in this study. We have determined (1) hyperplasia by cell growth curve and fluorescence activated cell sorting (FACS); and (2) ultrastructure by electron microscope observation; and (3) expressions of cyclin D2 mRNA and p16 mRNA by using in situ hybridization and image analysis. The results were shown (1) Results of cell growth curve and FACS analysis showed CM could proliferate in the first 3 cultured days (4 days in postnatal development). But the ability decreased quickly, concomitant with the differentiation. (2) The ultrastructure of CM showed the large amount of myofilaments and mitochondrion and FC showed moderate amount of rough endoplasmic reticulum. (3) The expression of cyclin D2 mRNA in 3-, 4-, 5-day CM group was 0.89 times(p<0.05), 0.80 times (p<0.05)and 0.56 times (p<0.01)of that in 1-day group respectively. P16 mRNA in 2-, 3-, 4-, 5-day CM group were 1.63 times(p<0.01),1.72 times(p<0.01),1.99 times (p<0.01)and 2.84 times (p<0.01) of that in 1-day group respectively. It can be concluded that cultured neonatal rat cardiac myocytes could proliferate during the first 3 cultured days, but the ability of proliferation decreased, from the fourth day, concomitant with differentiation. Cyclin D2 and p16 have the key roles during the transition from myocyte hyperplasia to hypertrophy.

  9. Remodeling of the sarcomeric cytoskeleton in cardiac ventricular myocytes during heart failure and after cardiac resynchronization therapy.

    Science.gov (United States)

    Lichter, Justin G; Carruth, Eric; Mitchell, Chelsea; Barth, Andreas S; Aiba, Takeshi; Kass, David A; Tomaselli, Gordon F; Bridge, John H; Sachse, Frank B

    2014-07-01

    Sarcomeres are the basic contractile units of cardiac myocytes. Recent studies demonstrated remodeling of sarcomeric proteins in several diseases, including genetic defects and heart failure. Here we investigated remodeling of sarcomeric α-actinin in two models of heart failure, synchronous (SHF) and dyssynchronous heart failure (DHF), as well as a model of cardiac resynchronization therapy (CRT). We applied three-dimensional confocal microscopy and quantitative methods of image analysis to study isolated cells from our animal models. 3D Fourier analysis revealed a decrease of the spatial regularity of the α-actinin distribution in both SHF and DHF versus control cells. The spatial regularity of α-actinin in DHF cells was reduced when compared with SHF cells. The spatial regularity of α-actinin was partially restored after CRT. We found longitudinal depositions of α-actinin in SHF, DHF and CRT cells. These depositions spanned adjacent Z-disks and exhibited a lower density of α-actinin than in the Z-disk. Differences in the occurrence of depositions between the SHF, CRT and DHF models versus control were significant. Also, CRT cells exhibited a higher occurrence of depositions versus SHF, but not DHF cells. Other sarcomeric proteins did not accumulate in the depositions to the same extent as α-actinin. We did not find differences in the expression of α-actinin protein and its encoding gene in our animal models. In summary, our studies indicate that HF is associated with two different types of remodeling of α-actinin and only one of those was reversed after CRT. We suggest that these results can guide us to an understanding of remodeling of structures and function associated with sarcomeres.

  10. Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes

    OpenAIRE

    Shenouda, Sylvia K.; Varner, Kurt J.; Carvalho, Felix; Lucchesi, Pamela A.

    2009-01-01

    Repeated administration of MDMA (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown; oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included: al...

  11. Contribution of NHE-1 to cell length cardiac shortening of normal and failing rabbit myocytes

    NARCIS (Netherlands)

    M.M.G.J. van Borren; J.G. Zegers; A. Baartscheer; J.H. Ravesloot

    2006-01-01

    At the same intracellular pH (pH(i)) Na+/H+ exchange (NHE-1) fluxes of ventricular myocytes of hypertrophied failing hearts (HFH) are increased. We assessed how NHE-1 affected cell length shortening. pH(i) was measured fluorimetrically in resting and twitching (1 - 3 Hz)normal and HFH rabbit myocyte

  12. Regional electroporation of single cardiac myocytes in a focused electric field.

    Science.gov (United States)

    Klauke, Norbert; Smith, Godfrey; Cooper, Jonathan M

    2010-01-15

    There is now a significant interest in being able to locate single cells within geometrically defined regions of a microfluidic chip and to gain intracellular access through the local electroporation of the cell membrane. This paper describes the microfabrication of electroporation devices which can enable the regional electroporation of adult ventricular myocytes, in order to lower the local electrical resistance of the cell membrane. Initially three different devices, designed to suit the characteristic geometry of the cardiomyocyte, were investigated (all three designs serve to focus the electric field to selected regions of the cell). We demonstrate that one of these three devices revealed the sequence of cellular responses to field strengths of increasing magnitudes, namely, cell contraction, hypercontraction, and lysis. This same device required a reduced threshold voltage for each of these events, including in particular membrane breakdown. We were not only able to show the gradual regional increase in the electric conductivity of the cell membrane but were also able to avoid changes in the local intra- and extracellular pH (by preventing the local generation of protons at the electrode surface, as a consequence of the reduced threshold voltage). The paper provides evidence for new strategies for achieving robust and reproducible regional electroporation, a technique which, in future, may be used for the insertion of large molecular weight molecules (including genes) as well as for on-chip voltage clamping of the primary adult cardiomyocyte.

  13. Temperature dependence of intracellular free calcium in cardiac myocytes from rat and ground squirrel measured by confocal microscopy

    Institute of Scientific and Technical Information of China (English)

    王世强; 周曾铨; 钱洪

    1999-01-01

    The temperature-dependence of infraeeliular free caleimn (Ca) was investigated in mdo-1 loaded ventricular myocytes from the ral, a non-hibernator, and from the ground squirrel, a hibernator. The dissociation constant of indo-l at different temperatures was calibrated both al pll-tat and at @-stat . and the result demonstrated that the @-stat ralibration should be prettrred . Analysis of the fluoreseent image showed a striking increase of Ca2 as well as spontaneous caleiuni waves in ral cells, indicating an overloaded cakuum. In contrast, cardiac myocytes of the ground sqnirraf were found to keep a constant (Ca2+) without caleium overload regardless of temperature variation. It is be-lieved that understanding of the mechanisms underlying the interccllular caleima homeostasis of hibrernators may lead to solutions of some medical questions .

  14. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy.

    Science.gov (United States)

    Defer, Nicole; Wan, Jinghong; Souktani, Richard; Escoubet, Brigitte; Perier, Magali; Caramelle, Philippe; Manin, Sylvie; Deveaux, Vanessa; Bourin, Marie-Claude; Zimmer, Andreas; Lotersztajn, Sophie; Pecker, Françoise; Pavoine, Catherine

    2009-07-01

    Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction. Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR. Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts. The infarct size was increased 24 h after IR in CB2(-/-) vs. wild-type (WT) hearts and decreased when WT hearts were injected with the CB2 agonist JWH133 (3 mg/kg) at reperfusion. Compared with WT hearts, CB2(-/-) hearts showed widespread injury 3 d after IR, with enhanced apoptosis and remodeling affecting the remote myocardium. Finally, CB2(-/-) hearts exhibited exacerbated fibrosis, associated with left ventricular dysfunction 4 wk after IR, whereas their WT counterparts recovered normal function. Cardiac myocytes and fibroblasts isolated from CB2(-/-) hearts displayed a higher H(2)O(2)-induced death than WT cells, whereas 1 microM JWH133 triggered survival effects. Furthermore, H(2)O(2)-induced myofibroblast activation was increased in CB2(-/-) fibroblasts but decreased in 1 microM JWH133-treated WT fibroblasts, compared with that in WT cells. Therefore, CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation.

  15. Microfluidic systems to examine intercellular coupling of pairs of cardiac myocytes.

    Science.gov (United States)

    Klauke, Norbert; Smith, Godfrey; Cooper, Jonathan M

    2007-06-01

    In this paper we describe a microfluidic environment that enables us to explore cell-to-cell signalling between longitudinally linked primary heart cells. We have chosen to use pairs (or doublets) of cardiac myocyte as a model system, not only because of the importance of cell-cell signalling in the study of heart disease but also because the single cardiomyocytes are both mechanically and electrically active and their synchronous activation due to the intercellular coupling within the doublet can be readily monitored on optical and electrical recordings. Such doublets have specialised intercellular contact structures in the form of the intercalated discs, comprising the adhesive junction (fascia adherens and macula adherens or desmosome) and the connecting junction (known as gap junction). The latter structure enables adjacent heart cells to share ions, second messengers and small metabolites (<1 kDa) between them and thus provides the structural basis for the synchronous (syncytical) behaviour of connected cardiomyocytes. Using the unique environment provided by the microfluidic system, described in this paper, we explore the local ionic conditions that enable the propagation of Ca(2+) waves between two heart cells. We observe that the ability of intracellular Ca(2+) waves to traverse the intercalated discs is dependent on the relative concentrations of diastolic Ca(2+) in the two adjacent cells. These experiments rely upon our ability to independently control both the electrical stimulation of each of the cells (using integrated microelectrodes) and to rapidly change (or switch) the local concentrations of ions and drugs in the extracellular buffer within the microfluidic channel (using a nanopipetting system). Using this platform, it is also possible to make simultaneous optical recordings (including fluorescence and cell contraction) to explore the effect of drugs on one or both cells, within the doublet.

  16. Design-based stereological estimation of the total number of cardiac myocytes in histological sections

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Nyengaard, Jens Randel

    2005-01-01

    in LV was 34.1 x 10(6) (0.08) (mean (coefficient of variation)), and the mean number of nuclei per myocyte 1.85 (0.03). Combining these estimates the total number of myocytes in LV was calculated to be 18.5 x 10(6) (0.09). CONCLUSIONS: This new method is applicable to a range of experiments focusing...

  17. Cardiac Rehabilitation in Older Adults.

    Science.gov (United States)

    Schopfer, David W; Forman, Daniel E

    2016-09-01

    The biology of aging and the pathophysiology of cardiovascular disease (CVD) overlap, with the effect that CVD is endemic in the growing population of older adults. Moreover, CVD in older adults is usually complicated by age-related complexities, including multimorbidity, polypharmacy, frailty, and other intricacies that add to the risks of ambiguous symptoms, deconditioning, iatrogenesis, falls, disability, and other challenges. Cardiac rehabilitation (CR) is a comprehensive lifestyle program that can have particular benefit for older patients with cardiovascular conditions. Although CR was originally designed primarily as an exercise training program for younger adults after a myocardial infarction or coronary artery bypass surgery, it has evolved as a comprehensive lifestyle program (promoting physical activity as well as education, diet, risk reduction, and adherence) for a broader range of CVD (coronary heart disease, heart failure, and valvular heart disease). It provides a valuable opportunity to address and moderate many of the challenges pertinent for the large and growing population of older adults with CVD. Cardiac rehabilitation promotes physical function (cardiorespiratory fitness as well as strength and balance) that helps overcome disease and deconditioning as well as related vulnerabilities such as disability, frailty, and falls. Similarly, CR facilitates education, monitoring, and guidance to reduce iatrogenesis and promote adherence. Furthermore, CR fosters cognition, socialization, and independence in older patients. Yet despite all its conceptual benefits, CR is significantly underused in older populations. This review discusses benefits and the paradoxical underuse of CR, as well as evolving models of care that may achieve greater application and efficacy. PMID:27297002

  18. Difference of Sodium Currents between Pediatric and Adult Human Atrial Myocytes: Evidence for Developmental Changes of Sodium Channels

    Directory of Open Access Journals (Sweden)

    Benzhi Cai, Xiaoqin Mu, Dongmei Gong, Shulin Jiang, Jianping Li, Qingxin Meng, Yunlong Bai, Yanju Liu, Xinyue Wang, Xueying Tan, Baofeng Yang, Yanjie Lu

    2011-01-01

    Full Text Available Voltage-gated calcium currents and potassium currents were shown to undergo developmental changes in postnatal human and animal cardiomocytes. However, so far, there is no evidence whether sodium currents also presented the developmental changes in postnatal human atrial cells. The aim of this study was to observe age-related changes of sodium currents between pediatric and adult atrial myocytes. Human atrial myocytes were acutely isolated and the whole-cell patch clamp technique was used to record sodium currents isolated from pediatric and adult atrial cardiomocytes. The peak amplitude of sodium currents recorded in adult atrial cells was significantly larger than that in pediatric atrial myocytes. However, there was no significant difference of the activation voltage for peak sodium currents between two kinds of atrial myocytes. The time constants for the activation and inactivation of sodium currents were smaller in adult atria than pediatric atria. The further study revealed that the voltage-dependent inactivation of sodium currents were more slow in adult atrial cardiomyocytes than pediatric atrial cells. A significant difference was also observed in the recovery process of sodium channel from inactivation. In summary, a few significant differences were demonstrated in sodium currents characteristics between pediatric and adult atrial myocytes, which indicates that sodium currents in human atria also undergo developmental changes.

  19. Tribulosin suppresses apoptosis via PKC epsilon and ERK1/2 signaling pathway during hypoxia/reoxygenation in neonatal rat ventricular cardiac myocytes.

    Science.gov (United States)

    Zhang, Shuang; Li, Hong; Yang, Shi-Jie

    2011-12-01

    Tribulosin (tigogenin 3-O-β-D-xylopyranosyl(1-2)-[β-D-xylopyranosyl (1-3)]-β-D-glucopyranosyl (1-4)-[a-L-rhamnopyranosyl(1-2)]-β-D-galactopyranoside), a component of gross saponins of Tribulus terrestris, has been shown to produce cytoprotective effects in heart. Yet, the precise mechanisms are not fully understood. We examined the mechanisms of tribulosin on myocardial protection. Ventricular myocytes were isolated from the heart of neonatal rats and were exposed to 3 h of hypoxia followed by 2 h reoxygenation. Apoptosis was induced by hypoxia/reoxygenation (H/R), and the expression of protein kinase C epsilon (PKCϵ) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured neonatal rat cardiac myocytes was detected. The results indicated that treatment with tribulosin in the culture medium protected cardiac myocytes against apoptosis induced by H/R. PKCϵ and ERK1/2 expression increased after pretreated with tribulosin. In the presence of PKCϵ inhibitor co-treated with tribulosin, the expression of ERK1/2 was decreased in H/R cardiac myocytes. While preconditioned with PD98059, ERK1/2 inhibitor, no effects on the expression of PKCϵ were detected. Tribulosin has protective effects on cardiac myocytes against apoptosis induced by H/R injury via PKCϵ and ERK1/2 signaling pathway. PMID:22115037

  20. Effects of adiponectin on oxidative stress and apoptosis in human cardiac myocytes cultured with high glucose

    Institute of Scientific and Technical Information of China (English)

    LI Xing; LI Mei-rong; GUO Zhi-xin

    2012-01-01

    Background Diabetic cardiomyopathy is the major cause of morbidity and mortality in diabetic patients.Oxidative stress plays an important role in diabetic cardiomyopathy.This study aimed to investigate the effects of adiponectin on oxidative stress and apoptosis in human cardiac myocytes (HCM) cultured with high glucose.Methods The cells were assigned to three group: control group,high glucose group and high glucose plus adiponectin group.After culture for 24,48,72 hours,oxidative stress was evaluated by detecting levels of malondialdehyde (MDA)and superoxide dismutase (SOD) in the supernatant of culture media.The expression of p66Shc and Heme oxygenase-1 (HO-1) was detected by real-time polymerase chain reaction (PCR).Flow cytometry was designed to observe and detect cellular apoptosis.Results Our findings showed significant increase in MDA levels and decrease in SOD activity in the high glucose group compared with the control group (P <0.05).However,MDA levels were significantly decreased and SOD activity was significantly increased in the adiponectin group compared with those in the high-glucose group (P <0.05).The mRNA expression of HO-1 in the high glucose group was significantly increased in a time-dependent manner compared with that in the control group (P <0.05).Adiponectin further increased the mRNA expression of HO-1 induced by high glucose in a time-dependent manner (P <0.05).The expression of p66Shc was significantly increased in high glucose group compared with that in the control group (P <0.05).Adiponectin significantly suppressed the upregulation of p66Shc induced by high glucose (P <0.05).The apoptotic rate of cardiomyocytes was significantly increased in the high glucose group compared with that in the control group while the apoptotic rate in the adiponectin group was remarkably declined in comparison with that in the high glucose group.Conclusion Adiponectin reduces high glucose-induced oxidative stress and apoptosis and plays a

  1. Recording of calcium transient and analysis of calcium removal mechanisms in cardiac myocytes from rats and ground squirrels

    Institute of Scientific and Technical Information of China (English)

    王世强; 周曾铨; 钱洪

    2000-01-01

    With confocal microscopy, we recorded calcium transients and analyzed calcium removal rate at different temperatures in cardiac myocytes from the rat, a non-hibernator, and the ground squirrel, a hibernator. The results showed a remarkable increase of the diastolic level of calcium transients in the rat but no detectable change in the ground squirrel. Calcium transient of the ground squirrel, compared with that of the rat at the same temperature, had a shorter duration and showed a faster calcium removal. As indicated by the pharmacological effect of cyclopiazonic acid, calcium uptake by sarcoplasmic reticulum (SR) was the major mechanism of calcium removal, and was faster in the ground squirrel than in the rat. Our results confirmed the essential role of SR in hypothermia-tolerant adaptation, and negated the importance of Na-Ca exchange. We postulated the possibility to improve hypothermia-tolerance of the cardiac tissue of non-hibernating mammals.

  2. S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes

    DEFF Research Database (Denmark)

    Schneider, Mikael; Kostin, Sawa; Strøm, Claes C;

    2007-01-01

    RNA expression was increased in hypertrophic rat hearts and that it has pro-cardiomyogenic effects in embryonic stem cell-derived embryoid bodies. We therefore hypothesized that S100A4 could play a supportive role in the injured heart. METHODS AND RESULTS: Here we verify by quantitative real-time PCR...... and immunoblotting that S100A4 mRNA and protein is upregulated in hypertrophic rat and human hearts and show by way of confocal microscopy that S100A4 protein, but not mRNA, appears in cardiac myocytes only in the border zone after an acute ischemic event in rat and human hearts. In normal rat and human hearts, S100...... after injury. Promisingly, recombinant S100A4 protein elicited a robust hypertrophic response and increased the number of viable cells in cardiac myocyte cultures by inhibiting apoptosis. We also found that ERK1/2 activation was necessary for both the hypertrophy and survival effects of S100A4 in vitro...

  3. Two functionally different Na/K pumps in cardiac ventricular myocytes

    OpenAIRE

    1995-01-01

    The whole-cell patch-clamp technique was used to voltage clamp acutely isolated myocytes at -60 mV and study effects of ionic environment on Na/K pump activity. In quiescent guinea pig myocytes, normal intracellular Na+ is approximately 6 mM, which gives a total pump current of 0.25 +/- 0.09 pA/pF, and an inward background sodium current of 0.75 +/- 0.26 pA/pF. The average capacitance of a cell is 189 +/- 61 pF. Our main conclusion is the total Na/K pump current comprises currents from two di...

  4. Image Processing Techniques for Assessing Contractility in Isolated Neonatal Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Carlos Bazan

    2011-01-01

    employed in determining myocyte contractility almost simultaneously with the acquisition of the Ca2+ transient and other correlates of cell contraction. The proposed methodology can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease models, transgeneity, or other common applications of neonatal cardiocytes.

  5. Morphological Modifications in Myofibrils by Suppressing Tropomyosin 4α in Chicken Cardiac Myocytes.

    Science.gov (United States)

    Toyota, Naoji; Fujitsuka, Chiaki; Ishibashi, Goushi; S Yoshida, Lucia; Takano-Ohmuro, Hiromi

    2016-01-01

    Tropomyosin (TPM) localizes along F-actin and, together with troponin T (TnT) and other components, controls calcium-sensitive muscle contraction. The role of the TPM isoform (TPM4α) that is expressed in embryonic and adult cardiac muscle cells in chicken is poorly understood. To analyze the function of TPM4α in myofibrils, the effects of TPM4α-suppression were examined in embryonic cardiomyocytes by small interference RNA transfection. Localization of myofibril proteins such as TPM, actin, TnT, α-actinin, myosin and connectin was examined by immunofluorescence microscopy on day 5 when almost complete TPM4α-suppression occurred in culture. A unique large structure was detected, consisting of an actin aggregate bulging from the actin bundle, and many curved filaments projecting from the aggregate. TPM, TnT and actin were detected on the large structure, but myosin, connectin, α-actinin and obvious myofibril striations were undetectable. It is possible that TPM4α-suppressed actin filaments are sorted and excluded at the place of the large structure. This suggests that TPM4α-suppression significantly affects actin filament, and that TPM4α plays an important role in constructing and maintaining sarcomeres and myofibrils in cardiac muscle. PMID:27118431

  6. Morphological Modifications in Myofibrils by Suppressing Tropomyosin 4α in Chicken Cardiac Myocytes.

    Science.gov (United States)

    Toyota, Naoji; Fujitsuka, Chiaki; Ishibashi, Goushi; S Yoshida, Lucia; Takano-Ohmuro, Hiromi

    2016-01-01

    Tropomyosin (TPM) localizes along F-actin and, together with troponin T (TnT) and other components, controls calcium-sensitive muscle contraction. The role of the TPM isoform (TPM4α) that is expressed in embryonic and adult cardiac muscle cells in chicken is poorly understood. To analyze the function of TPM4α in myofibrils, the effects of TPM4α-suppression were examined in embryonic cardiomyocytes by small interference RNA transfection. Localization of myofibril proteins such as TPM, actin, TnT, α-actinin, myosin and connectin was examined by immunofluorescence microscopy on day 5 when almost complete TPM4α-suppression occurred in culture. A unique large structure was detected, consisting of an actin aggregate bulging from the actin bundle, and many curved filaments projecting from the aggregate. TPM, TnT and actin were detected on the large structure, but myosin, connectin, α-actinin and obvious myofibril striations were undetectable. It is possible that TPM4α-suppressed actin filaments are sorted and excluded at the place of the large structure. This suggests that TPM4α-suppression significantly affects actin filament, and that TPM4α plays an important role in constructing and maintaining sarcomeres and myofibrils in cardiac muscle.

  7. Effects of rutin from leaves and flowers of buckwheat (Fagopyrum esculentum Moench.) on angiotensin II-induced hypertrophy of cardiac myocytes and proliferation of fibroblasts

    OpenAIRE

    Han, Shu-ying; Chu, Jin-Xiu; Li, Guang-min; Zhu, Li-Sha; Shi, Rui-Fang

    2010-01-01

    Rutin was isolated from dried leaves and flowers of buckwheat (Fagopyrum esculentum Moench.). The effects of rutin on angiotensin II-induced hypertrophy of cultured cardiac myocytes and proliferation of cardiac fibroblasts of neonatal rats were evaluated by analyzing the cell surface area, measuring the protein synthesis rate through 3H-leucine incorporation, and the MTT method. Rutin (0.8 to 8.0 mg/l) exhibited a strong inhibition on the hypertrophy and proliferation. The results...

  8. Spectrally resolved time-correlated single photon counting: a novel approach for characterization of endogenous fluorescence in isolated cardiac myocytes.

    Science.gov (United States)

    Chorvat, D; Chorvatova, A

    2006-12-01

    A new setup for time-resolved fluorescence micro-spectroscopy of cells, based on multi-dimensional time-correlated single photon counting, was designed and tested. Here we demonstrate that the spectrometer allows fast and reproducible measurements of endogenous flavin fluorescence measured directly in living cardiac cells after excitation with visible picosecond laser diodes. Two complementary approaches for the analysis of spectrally- and time-resolved autofluorescence data are presented, comprising the fluorescence decay fitting by exponential series and the time-resolved emission spectroscopy analysis. In isolated cardiac myocytes, we observed three distinct lifetime pools with characteristic lifetime values spanning from picosecond to nanosecond range and the time-dependent red shift of the autofluorescence emission spectra. We compared obtained results to in vitro recordings of free flavin adenine dinucleotide (FAD) and FAD in lipoamide dehydrogenase (LipDH). The developed setup combines the strength of both spectral and fluorescence lifetime analysis and provides a solid base for the study of complex systems with intrinsic fluorescence, such as identification of the individual flavinoprotein components in living cardiac cells. This approach therefore constitutes an important instrumental advancement towards redox fluorimetry of living cardiomyocytes, with the perspective of its applications in the investigation of oxidative metabolic state under pathophysiological conditions, such as ischemia and/or metabolic disorders. PMID:17033778

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-12-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE. PMID:27263018

  11. Ca(2+ release events in cardiac myocytes up close: insights from fast confocal imaging.

    Directory of Open Access Journals (Sweden)

    Vyacheslav M Shkryl

    Full Text Available The spatio-temporal properties of Ca(2+ transients during excitation-contraction coupling and elementary Ca(2+ release events (Ca(2+ sparks were studied in atrial and ventricular myocytes with ultra-fast confocal microscopy using a Zeiss LSM 5 LIVE system that allows sampling rates of up to 60 kHz. Ca(2+ sparks which originated from subsarcolemmal junctional sarcoplasmic reticulum (j-SR release sites in atrial myocytes were anisotropic and elongated in the longitudinal direction of the cell. Ca(2+ sparks in atrial cells originating from non-junctional SR and in ventricular myocytes were symmetrical. Ca(2+ spark recording in line scan mode at 40,000 lines/s uncovered step-like increases of [Ca(2+]i. 2-D imaging of Ca(2+ transients revealed an asynchronous activation of release sites and allowed the sequential recording of Ca(2+ entry through surface membrane Ca(2+ channels and subsequent activation of Ca(2+-induced Ca(2+ release. With a latency of 2.5 ms after application of an electrical stimulus, Ca(2+ entry could be detected that was followed by SR Ca(2+ release after an additional 3 ms delay. Maximum Ca(2+ release was observed 4 ms after the beginning of release. The timing of Ca(2+ entry and release was confirmed by simultaneous [Ca(2+]i and membrane current measurements using the whole cell voltage-clamp technique. In atrial cells activation of discrete individual release sites of the j-SR led to spatially restricted Ca(2+ release events that fused into a peripheral ring of elevated [Ca(2+]i that subsequently propagated in a wave-like fashion towards the center of the cell. In ventricular myocytes asynchronous Ca(2+ release signals from discrete sites with no preferential subcellular location preceded the whole-cell Ca(2+ transient. In summary, ultra-fast confocal imaging allows investigation of Ca(2+ signals with a time resolution similar to patch clamp technique, however in a less invasive fashion.

  12. Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts.

    Science.gov (United States)

    Martin, Tamara P; Lawan, Ahmed; Robinson, Emma; Grieve, David J; Plevin, Robin; Paul, Andrew; Currie, Susan

    2014-02-01

    Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts. PMID:23881186

  13. P2X4 receptor–eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure

    Directory of Open Access Journals (Sweden)

    Ronghua Yang

    2015-01-01

    Full Text Available We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R, a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS. Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP to induce a current (mainly Na+ increased the formation of nitric oxide (NO, as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF.

  14. P2X4 receptor–eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure

    Science.gov (United States)

    Yang, Ronghua; Beqiri, Dardan; Shen, Jian-Bing; Redden, John M.; Dodge-Kafka, Kimberly; Jacobson, Kenneth A.; Liang, Bruce T.

    2014-01-01

    We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na+) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF. PMID:25750695

  15. Measurement of Strain in Cardiac Myocytes at Micrometer Scale Based on Rapid Scanning Confocal Microscopy and Non-Rigid Image Registration.

    Science.gov (United States)

    Lichter, J; Li, Hui; Sachse, Frank B

    2016-10-01

    Measurement of cell shortening is an important technique for assessment of physiology and pathophysiology of cardiac myocytes. Many types of heart disease are associated with decreased myocyte shortening, which is commonly caused by structural and functional remodeling. Here, we present a new approach for local measurement of 2-dimensional strain within cells at high spatial resolution. The approach applies non-rigid image registration to quantify local displacements and Cauchy strain in images of cells undergoing contraction. We extensively evaluated the approach using synthetic cell images and image sequences from rapid scanning confocal microscopy of fluorescently labeled isolated myocytes from the left ventricle of normal and diseased canine heart. Application of the approach yielded a comprehensive description of cellular strain including novel measurements of transverse strain and spatial heterogeneity of strain. Quantitative comparison with manual measurements of strain in image sequences indicated reliability of the developed approach. We suggest that the developed approach provides researchers with a novel tool to investigate contractility of cardiac myocytes at subcellular scale. In contrast to previously introduced methods for measuring cell shorting, the developed approach provides comprehensive information on the spatio-temporal distribution of 2-dimensional strain at micrometer scale.

  16. Inhibitory effect of antisense oligodeoxynucleotide to p44/p42 MAPK on angiotensin II-induced hypertrophic response in cultured neonatal rat cardiac myocyte

    Institute of Scientific and Technical Information of China (English)

    Shi-qinZHANG; BoDING; Zhao-guiGUO; Yun-xiaLI

    2004-01-01

    AIM: To explore the inhibitory effect of antisense oligonucleotide (ODN) to mitogen activated protein kinase(MAPK) on cardiomyocyte hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ). METHODS: A 17-mer phosphorothioate-protected antisense ODN directed against the initiation of translation sites of the p42 and p44 MAPK isoforms byliposomal transfection was applied to inhibit the translation of p44/p42 MAPK mRNA. The sense and random ODNs to p44/p42MAPK were used as sequence controls. Neonatal cardiac myocytes were exposed to Ang Ⅱ (10nmol/L) for 5 min and then harvested in lysis buffer for the measurement of the activity and the phosphorylated protein content of p44/p42MAPK that were tested by P-81 phosphocellulose filter paper method and Western blotting, respectively. The rate of protein synthesis by [3H]leucine incorporation and the diameter of cell were measured after exposure to Ang Ⅱ for 24 h and 72 h, respectively. RESULTS: In cardiac myocyte Ang Ⅱ increased p44/p42MAPK activity and phosphorylated protein content by 140 % and 699 %, and also increased [3H]leucine incorporation and cell diameter by 40 % and 27 %. c-fos and c-myc mRNAs were induced significantly after exposure to Ang Ⅱ. Antisense ODN to p44/p42MAPK (0.2 μmol/L) reduced Ang Ⅱ-induced MAPK activity by 30 %,and phophorylated MAPK protein expression by 59 % in cardiac myocyte, and inhibited c-fos and c-myc mRNA expression induced by Ang Ⅱ by 44 % and 43 %, respectively. The diameter and the rate of protein synthesis of cardiac myocyte induced by Ang Ⅱ were decreased by 16 % and 22 % after pretreatment with antisense ODN to p44/p42MAPK. CONCLUSION: Antisense ODN to p44/p42 MAPK inhibited the increase of rate of protein synthesis,and the augmentation of cell diameter and expression of c-fos and c-myc mRNA induced by Ang Ⅱ in culturedcardiac myocytes, p44/p42 MAPK played a critical role in the hypertrophic response induced by Ang Ⅱ in cultured neonatal rat cardiac myocytes.

  17. Dependence of Na-K pump current on internal Na+ in mammalian cardiac myocytes.

    Science.gov (United States)

    Mogul, D J; Singer, D H; Ten Eick, R E

    1990-08-01

    Na-K pump current (Ipump) is a function of the intracellular Na+ concentration [( Na+]i). We examined the quantitative relationship between Ipump and [Na+]i in isolated guinea pig ventricular myocytes under steady-state conditions. [Na+]i was controlled and "clamped" at several selected concentrations using wide-tipped pipette microelectrodes, and membrane current was measured using the whole cell patch voltage-clamp technique. Ipump generated at a holding potential of -40 mV was determined by measuring the change in steady-state holding current before and during exposure to dihydroouabain (1 mM); Ipump was measured at 11 levels of [Na+]i ranging from 0 to 80 mM (n = 63) with only one measurement per cell and normalized to cell capacitance to account for differences between myocytes in sarcolemmal surface area. Ipump exhibited a nonlinear dependence on [Na+]i; a Hill analysis of the relationship yielded a half-maximal [Na+]i for pump stimulation of 43.2 mM and a Hill coefficient of 1.53. An alternative analysis of the experimental data was performed assuming that occupation of three internal binding sites by Na+ is required for enzyme turnover. Regression analysis gave the best fit when only two different binding affinities (KD) are postulated. The values are KD1 = 1 mM, KD2 = KD3 = 29 mM. From the analysis using the latter model, the level of [Na+]i at which Ipump saturated closely approximated the theoretical saturation level calculated from published estimates of pump turnover rate and density. The maximal sensitivity of the Na-K pump to changes in [Na+]i occurs when internal [Na+] is within the range for the normal resting physiological level. PMID:2167023

  18. A device for rapid and quantitative measurement of cardiac myocyte contractility

    Science.gov (United States)

    Gaitas, Angelo; Malhotra, Ricky; Li, Tao; Herron, Todd; Jalife, José

    2015-03-01

    Cardiac contractility is the hallmark of cardiac function and is a predictor of healthy or diseased cardiac muscle. Despite advancements over the last two decades, the techniques and tools available to cardiovascular scientists are limited in their utility to accurately and reliably measure the amplitude and frequency of cardiomyocyte contractions. Isometric force measurements in the past have entailed cumbersome attachment of isolated and permeabilized cardiomyocytes to a force transducer followed by measurements of sarcomere lengths under conditions of submaximal and maximal Ca2+ activation. These techniques have the inherent disadvantages of being labor intensive and costly. We have engineered a micro-machined cantilever sensor with an embedded deflection-sensing element that, in preliminary experiments, has demonstrated to reliably measure cardiac cell contractions in real-time. Here, we describe this new bioengineering tool with applicability in the cardiovascular research field to effectively and reliably measure cardiac cell contractility in a quantitative manner. We measured contractility in both primary neonatal rat heart cardiomyocyte monolayers that demonstrated a beat frequency of 3 Hz as well as human embryonic stem cell-derived cardiomyocytes with a contractile frequency of about 1 Hz. We also employed the β-adrenergic agonist isoproterenol (100 nmol l-1) and observed that our cantilever demonstrated high sensitivity in detecting subtle changes in both chronotropic and inotropic responses of monolayers. This report describes the utility of our micro-device in both basic cardiovascular research as well as in small molecule drug discovery to monitor cardiac cell contractions.

  19. Variations in Local Calcium Signaling in Adjacent Cardiac Myocytes of the Intact Mouse Heart Detected with Two-Dimensional Confocal Microscopy

    Directory of Open Access Journals (Sweden)

    Karin P Hammer

    2015-01-01

    Full Text Available Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular contractile dysfunction. Differences in Ca kinetics in adjacent cells may also provide a substrate for inefficient contraction and arrhythmias. In a new approach we quantify variation in local Ca transients between adjacent myocytes in the whole heart.Langendorff-perfused mouse hearts were loaded with Fluo-8 AM to detect Ca and Di-4-ANEPPS to visualize cell membranes. A spinning disc confocal microscope with a fast camera allowed us to record Ca signals within an area of 465 µm by 315 µm with an acquisition speed of 55 fps. Images from multiple transients recorded at steady state were registered to their time point in the cardiac cycle to restore averaged local Ca transients with a higher temporal resolution. Local Ca transients within and between adjacent myocytes were compared with regard to amplitude, time to peak and decay at steady state stimulation (250 ms cycle length.Image registration from multiple sequential Ca transients allowed reconstruction of high temporal resolution (2.4 ±1.3ms local CaT in 2D image sets (N= 4 hearts, n= 8 regions. During steady state stimulation, spatial Ca gradients were homogeneous within cells in both directions and independent of distance between measured points. Variation in CaT amplitudes was similar across the short and the long side of neighboring cells. Variations in TAU and TTP were similar in both directions. Isoproterenol enhanced the CaT but not the overall pattern of spatial heterogeneities.Here we detected and analyzed local Ca signals in intact mouse hearts with high temporal and spatial resolution, taking into account 2D arrangement of the cells. We observed significant differences in the variation of CaT amplitude along the long and short axis of cardiac myocytes. Variations of Ca signals between neighboring cells may contribute to the substrate of cardiac remodeling.

  20. Cell volume control in phospholemman (PLM) knockout mice: do cardiac myocytes demonstrate a regulatory volume decrease and is this influenced by deletion of PLM?

    Science.gov (United States)

    Bell, James R; Lloyd, David; Curl, Claire L; Delbridge, Lea M D; Shattock, Michael J

    2009-03-01

    In addition to modulatory actions on Na+-K+-ATPase, phospholemman (PLM) has been proposed to play a role in cell volume regulation. Overexpression of PLM induces ionic conductances, with 'PLM channels' exhibiting selectivity for taurine. Osmotic challenge of host cells overexpressing PLM increases taurine efflux and augments the cellular regulatory volume decrease (RVD) response, though a link between PLM and cell volume regulation has not been studied in the heart. We recently reported a depressed cardiac contractile function in PLM knockout mice in vivo, which was exacerbated in crystalloid-perfused isolated hearts, indicating that these hearts were osmotically challenged. To address this, the present study investigated the role of PLM in osmoregulation in the heart. Isolated PLM wild-type and knockout hearts were perfused with a crystalloid buffer supplemented with mannitol in a bid to prevent perfusate-induced cell swelling and maintain function. Accordingly, and in contrast to wild-type control hearts, contractile function was improved in PLM knockout hearts with 30 mM mannitol. To investigate further, isolated PLM wild-type and knockout cardiomyocytes were subjected to increasing hyposmotic challenges. Initial validation studies showed the IonOptix video edge-detection system to be a simple and accurate 'real-time' method for tracking cell width as a marker of cell size. Myocytes swelled equally in both genotypes, indicating that PLM, when expressed at physiological levels in cardiomyocytes, is not essential to limit water accumulation in response to a hyposmotic challenge. Interestingly, freshly isolated adult cardiomyocytes consistently failed to mount RVDs in response to cell swelling, adding to conflicting reports in the literature. A proposed perturbation of the RVD response as a result of the cell isolation process was not restored, however, with short-term culture in either adult or neonatal cardiomyocytes.

  1. Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

    Science.gov (United States)

    Cuadrado, Irene; Castejon, Borja; Martin, Ana M; Saura, Marta; Reventun-Torralba, Paula; Zamorano, Jose Luis; Zaragoza, Carlos

    2016-01-01

    Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR. PMID:27649573

  2. Angiotensin II Type 1 Receptor-Mediated Electrical Remodeling in Mouse Cardiac Myocytes.

    Directory of Open Access Journals (Sweden)

    Jeremy Kim

    Full Text Available We recently characterized an autocrine renin angiotensin system (RAS in canine heart. Activation of Angiotensin II Type 1 Receptors (AT1Rs induced electrical remodeling, including inhibition of the transient outward potassium current Ito, prolongation of the action potential (AP, increased calcium entry and increased contractility. Electrical properties of the mouse heart are very different from those of dog heart, but if a similar system existed in mouse, it could be uniquely studied through genetic manipulations. To investigate the presence of a RAS in mouse, we measured APs and Ito in isolated myocytes. Application of angiotensin II (A2 for 2 or more hours reduced Ito magnitude, without affecting voltage dependence, and prolonged APs in a dose-dependent manner. Based on dose-inhibition curves, the fast and slow components of Ito (Ito,fast and IK,slow appeared to be coherently regulated by [A2], with 50% inhibition at an A2 concentration of about 400 nM. This very high K0.5 is inconsistent with systemic A2 effects, but is consistent with an autocrine RAS in mouse heart. Pre-application of the microtubule destabilizing agent colchicine eliminated A2 effects on Ito and AP duration, suggesting these effects depend on intracellular trafficking. Application of the biased agonist SII ([Sar1-Ile4-Ile8]A2, which stimulates receptor internalization without G protein activation, caused Ito reduction and AP prolongation similar to A2-induced changes. These data demonstrate AT1R mediated regulation of Ito in mouse heart. Moreover, all measured properties parallel those measured in dog heart, suggesting an autocrine RAS may be a fundamental feedback system that is present across species.

  3. Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix.

    Science.gov (United States)

    Simpson, D G; Terracio, L; Terracio, M; Price, R L; Turner, D C; Borg, T K

    1994-10-01

    Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.

  4. Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies

    Directory of Open Access Journals (Sweden)

    Christina Voulgari

    2010-10-01

    Full Text Available Christina Voulgari, Dimitrios Papadogiannis, Nicholas TentolourisFirst Department of Propaedeutic and Internal Medicine, Athens University Medical School, Laiko General Hospital, Athens, GreeceAbstract: Diabetic cardiomyopathy (DCM, although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies.Keywords: cardiovascular disease, atherosclerosis, cardiac autonomic neuropathy, echocardiography, treatment strategies

  5. Analysis of NAD(P)H fluorescence components in cardiac myocytes from human biopsies: a new tool to improve diagnostics of rejection of transplanted patients

    Science.gov (United States)

    Cheng, Y.; Mateasik, A.; Poirier, N.; Miró, J.; Dahdah, N.; Chorvat, D., Jr.; Chorvatova, A.

    2009-02-01

    Tissue autofluorescence is one of the most versatile non-invasive tools for mapping the metabolic state in living tissues. Increasing interest in the imaging and diagnosis of living cells and tissues, based on their intrinsic fluorescence rather than fluorescence labeling, is closely connected to the latest developments in high-performance spectroscopic and microscopic techniques. We investigate metabolic state of cardiac cells isolated from one additional human biopsy from transplanted pediatric patients presenting either no rejection (R0) or mild rejection (R1). Two different approaches for isolation of human cardiac myocytes are also compared. Spectrally-resolved fluorescence lifetime detection of NAD(P)H fluorescence (excitation by pulsed 375 nm picosecond laser) is tested as a promising new tool for quantitative analysis of intrinsic cellular autofluorescence signals in living cardiomyocytes. This work opens new horizons in the evaluation of cardiac transplant rejection using latest fluorescence imaging approaches.

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

    Science.gov (United States)

    Pilarczyk, Götz; Raulf, Alexandra; Gunkel, Manuel; Fleischmann, Bernd K.; Lemor, Robert; Hausmann, Michael

    2016-01-01

    The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. PMID:26751484

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

    Directory of Open Access Journals (Sweden)

    Götz Pilarczyk

    2016-01-01

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

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

    Science.gov (United States)

    Pilarczyk, Götz; Raulf, Alexandra; Gunkel, Manuel; Fleischmann, Bernd K; Lemor, Robert; Hausmann, Michael

    2016-01-01

    The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. PMID:26751484

  9. Research progress of adult cardiac stem cells

    Directory of Open Access Journals (Sweden)

    Nan ZHENG

    2013-04-01

    Full Text Available The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs. Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on human adult CSCs and epicardium-derived cell (EPDC, as well as the treatment strategies in the field of cardiac regeneration, and the problems and prospect disclosed in the research.

  10. Research progress of adult cardiac stem cells

    OpenAIRE

    Zheng, Nan; Ning-kun ZHANG; Lian-ru GAO

    2013-01-01

    The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs). Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on...

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

    Science.gov (United States)

    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

  12. Activation of extracellular signal-regulated kinase during silibinin-protected, isoproterenol-induced apoptosis in rat cardiac myocytes is tyrosine kinase pathway-mediated and protein kinase C-dependent

    Institute of Scientific and Technical Information of China (English)

    Bei ZHOU; Li-jun WU; Shin-ichi TASHIRO; Satoshi ONODERA; Fumiaki UCHIUMI; Takashi IKEJIMA

    2007-01-01

    Aim: To investigate the mechanism of silibinin-protected isoproterenol-induced apoptosis in rat cardiac myocytes.Methods: The viability of rat cardiac myocytes was measured by MTT method. The apoptotic ratio was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Protein kinase C (PKC) activity assay was carried out according to the instructions of the PepTag non-radioactive protein kinase C assay kit. Western blot analysis was used to evaluate the level of Ras, Raf-1 and mitogen-activated protein kinase (MAPK) expression.Results: The protective effects of silibinin were significantly sup-pressed by inhibitors, including genistein, manumycin A and GW5074 [inhibitors for protein tyrosine kinases (PTK), Ras and Raf- 1, respectively]. The exposure of rat cardiac myocytes to isoproterenol alone caused decreased PKC activity, which was prevented by pretreatment with silibinin dose-dependently. Simultaneously,the increased expression of Ras and Raf-1 activated by silibinin were blocked by the PKC inhibitor, stauroporine. In addition, the extracellularly responsive kinase (ERK) inhibitor, PD98059, suppressed silibinin-protected apoptosis, whereas the p38 MAPK inhibitor, SB203580, protected cardiac myocytes from isoproterenol-induced injury, and the c-Jun N-terminal kinase (JNK) inhibitor, SP600125 had no protective effects. Furthermore, Western blot analysis showed that the expres-sion of phosphorylated ERK was increased by silibinin, the expression of phos-phorylated p38 MAPK was decreased and total ERK, p38, JNK and phosphory-lated JNK MAPK did not change after treatment with both isoproterenol and silibinin. Furthermore, pretreatment of cardiac myocyte with PKC, Ras and Raf inhibitors significantly blocked ERK phosphorylation.Conclusion: Silibinin is suggested to protect isoproterenol-induced rat cardiac myocyte apoptosis by activating the tyrosine kinase pathway, PKC and MAPK pathways.

  13. Pre-Conditioning with CDP-Choline Attenuates Oxidative Stress-Induced Cardiac Myocyte Death in a Hypoxia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Héctor González-Pacheco

    2014-01-01

    Full Text Available Background. CDP-choline is a key intermediate in the biosynthesis of phosphatidylcholine, which is an essential component of cellular membranes, and a cell signalling mediator. CDP-choline has been used for the treatment of cerebral ischaemia, showing beneficial effects. However, its potential benefit for the treatment of myocardial ischaemia has not been explored yet. Aim. In the present work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector in an in vitro model of ischaemia/reperfusion injury. Methods. Neonatal rat cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative stress-induced reperfusion injury, the cells were incubated with H2O2 during reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated using the cell viability MTT assay, and the proportion of apoptotic and necrotic cells was analyzed using the Annexin V determination by flow cytometry. Results. Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant reduction of cells undergoing apoptosis after hypoxia/reperfusion. Preconditioning with CDP-choline attenuated postreperfusion cell death induced by oxidative stress. Conclusion. CDP-choline administration reduces cell apoptosis induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus, it has a potential as cardioprotector in ischaemia/reperfusion-injured cardiomyocytes.

  14. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael;

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane receptor well established to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent pathways. The biological importance of this, however, remains...... obscure. Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2 represents an active signalling component...... that phosphorylates p90 Ribosomal S6 Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction. Moreover, the beta-arrestin2-dependent ERK1/2 signal supports intact proliferation of cardiac myocytes. In contrast to G(q)-activated ERK1/2, and in keeping with its failure to translocate to the nucleus...

  15. 心肌细胞微管图像的灰度特征分析%Gray Characteristic Analysis of Microtubules in Cardiac Myocytes

    Institute of Scientific and Technical Information of China (English)

    姚宇华; 熊江辉; 梁仲刚; 严洪; 李莹辉

    2004-01-01

    目的利用图像灰度的统计特征参数量化微重力条件下大鼠心肌细胞微管图像的形态变化,并研究在不同条件下这种变化的特点.方法 对模拟微重力条件下培养的乳鼠心肌细胞(回转组)和正常条件下培养的心肌细胞(对照组)细胞骨架的微管图像提取灰度统计特征,利用灰度方差、偏度及峰度等参数量化细胞骨架的灰度特征.结果 在对24幅图像进行特征分析后,发现所选的参数对量化微管的灰度特征有不同程度的统计意义.利用灰度方差、偏度和峰度进行多元判决,发现这些参数可以很好地区分模拟微重力条件下培养的心肌细胞图像和正常条件下培养的心肌细胞图像,总的错误判决率达到16.7%.结论 在微重力条件下心肌细胞骨架微管的形态变得弥散,利用灰度特征参数方差、偏度和峰度可以描述这种变化.%Objective To quantify the images of the microtubules in fetal rat cardiac myocytes under simulated microgravity by utilizing the characteristic parameters of image gray, and to study their morphological change. Method Gray characteristic of the microtubules in fetal rat cardiac myocytes was quantified in both simulated mircogravity and control conditions by variance, skewness, and kurtosis. Result From feature analysis of 24 images, the characteristic parameters selected here were proved to be effective. Good result was obtained when discrimination between simulated microgravity group and control group was made by multivariate analysis with these parameters. The total false verdict rate even reached 16.7% when using multivariate analysis with these parameters. Conclusion The morphology of the microtubules in cardiac myocytes cytoskeleton became diffused under simulated microgravity, and the quantitative analysis of gray parameters (variance, skewness, kurtosis) described the variation satisfactorily.

  16. The experimental study of reporter probe 131I-FIAU in neonatal cardiac myocytes after transfer of herpes simplex virus type 1 thymidine kinase reporter gene by different vectors

    International Nuclear Information System (INIS)

    Objective: Reporter gene imaging is a promising approach for noninvasive monitoring of cardiac gene therapy. In the present study, the recombinant plasmid and adenoviral vector carrying reporter gene. herpes simplex virus type 1 thymidine kinase (HSV1-tk), were constructed and transferred into nee-natal cardiac myocytes, and a series of in vitro studies were carried out on the cells transferred to evaluate the uptake of radiolabeled reporter probe and to compare both vectors for cardiac reporter gene imaging. Methods: Neonatal cardiac myocytes were obtained from rat heart by single collagenase digestion. HSVI-tk. chosen as the reporter gene.was inserted into adenovirus vector (Ad5-tk) and plasmid (pDC316-tk), thus it could be transferred into neonatal cardiac myocytes. Recombinant adenovirus containing enhanced green fluorescent protein (Ad5-EGFP) was used as control. Recombinant plasmid was coated with lipofectamine TM 2000 (pDC316-tk/lipoplex). The specific reporter probe of HSV1-tk, 2'-fluoro-2'-deoxy-l-β-D-arabinofuranosyl-uracil (FAU), was labeled with 131I by solid phase oxidation with lodogen. Product wag purified on a reverse. phase Sep-Pak C18 column and the radiochemical purity wag then assessed. The accumulation of it in the transferred cardiac myocytes wag detected as uptake rate. Furthermore, mRNA expression of HSV1-tk was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), while its protein expression wag located by immunocytochemistry. Results: FAU could be labeled with 131I and the labeling efficiency was (53.82 ±2.05)%. The radiochemical purity was (94.85 ± 1.76)% after purification, and it kept stable in vitro for at least 24h. Time-dependent increase of the ac- cumulation of 131I-FIAU was observed in both Ad5-tk group and pDC316-tk/lipoplex group. and the highest uptake rate occurred at 5h, with peak values of (12.55 ± 0.37)% and (2.09 ± 0.34)% respectively. However, it also indicated that greater

  17. Contribution of spontaneous L-type Ca2+ channel activation to the genesis of Ca2+ sparks in resting cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Guangqin; FU; Yu; YANG; Dongmei; HAO; Xuemei; BAI; S

    2004-01-01

    Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sarcoplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the genesis of spontaneous Ca2+ sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca2+ sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCl2 which inhibits spontaneous L-type Ca2+ channel activation, the rate of occurrence of spontaneous Ca2+ sparks was halved from 4.20 to 2.04 events/(100 μm·s), with temporal and spatial properties of individual Ca2+ sparks unchanged. Analysis of the Cd2+-sensitive spark production revealed an open probability of ~10-5 for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type Ca2+ channels in resting heart cells contribute significantly to the production of spontaneous Ca2+ sparks.

  18. Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

    Directory of Open Access Journals (Sweden)

    Jerry Curran

    Full Text Available Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+ leak through ryanodine receptors. Beta-adrenergic (β-AR tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+ waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+ leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+ leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+ leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis

  19. Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

    2015-04-01

    Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

  20. Evidence for angiotensin II type 2 receptor–mediated cardiac myocyte enlargement during in vivo pressure overload

    OpenAIRE

    Senbonmatsu, Takaaki; Ichihara, Sahoko; Price, Edward; Gaffney, F.Andrew; Inagami, Tadashi

    2000-01-01

    The pathophysiological roles of the angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT2 we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT2 is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT2 deletion were independent of activation of embryonic genes for cardiac hypertrophy. ...

  1. Stearoyl-CoA desaturase-1 (SCD1 augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Hiroki Matsui

    Full Text Available Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1 is a rate-limiting enzyme that converts saturated fatty acids (SFAs to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.

  2. Hypoxia and glucose independently regulate the beta-adrenergic receptor-adenylate cyclase system in cardiac myocytes.

    OpenAIRE

    Rocha-Singh, K J; Honbo, N Y; Karliner, J S

    1991-01-01

    We explored the effects of two components of ischemia, hypoxia and glucose deprivation, on the beta-adrenergic receptor (beta AR)-adenylate cyclase system in a model of hypoxic injury in cultured neonatal rat ventricular myocytes. After 2 h of hypoxia in the presence of 5 mM glucose, cell surface beta AR density (3H-CGP-12177) decreased from 54.8 +/- 8.4 to 39 +/- 6.3 (SE) fmol/mg protein (n = 10, P less than 0.025), while cytosolic beta AR density (125I-iodocyanopindolol [ICYP]) increased by...

  3. Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different

    OpenAIRE

    Bell, James R.; Curl, Claire L.; Harding, Tristan W.; Vila Petroff, Martin; Harrap, Stephen B.; Delbridge, Lea M D

    2016-01-01

    Background Cardiac hypertrophy is the most potent cardiovascular risk factor after age, and relative mortality risk linked with cardiac hypertrophy is greater in women. Ischemic heart disease is the most common form of cardiovascular pathology for both men and women, yet significant differences in incidence and outcomes exist between the sexes. Cardiac hypertrophy and ischemia are frequently occurring dual pathologies. Whether the cellular (cardiomyocyte) mechanisms underlying myocardial dama...

  4. Inhibitory Effect of Cinobufagin on L-Type Ca2+ Currents, Contractility, and Ca2+ Homeostasis of Isolated Adult Rat Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Pinya Li

    2014-01-01

    Full Text Available Cinobufagin (CBG, a major bioactive ingredient of the bufanolide steroid compounds of Chan Su, has been widely used to treat coronary heart disease. At present, the effect of CBG on the L-type Ca2+ current (ICa-L of ventricular myocytes remains undefined. The aim of the present study was to characterize the effect of CBG on intracellular Ca2+ ([Ca2+]i handling and cell contractility in rat ventricular myocytes. CBG was investigated by determining its influence on ICa-L, Ca2+ transient, and contractility in rat ventricular myocytes using the whole-cell patch-clamp technique and video-based edge-detection and dual-excitation fluorescence photomultiplier systems. The dose of CBG (10−8 M decreased the maximal inhibition of CBG by 47.93%. CBG reduced ICa-L in a concentration-dependent manner with an IC50 of 4 × 10−10 M, upshifted the current-voltage curve of ICa-L, and shifted the activation and inactivation curves of ICa-L leftward. Moreover, CBG diminished the amplitude of the cell shortening and Ca2+ transients with a decrease in the time to peak (Tp and the time to 50% of the baseline (Tr. CBG inhibited L-type Ca2+ channels, and reduced [Ca2+]i and contractility in adult rat ventricular myocytes. These findings contribute to the understanding of the cardioprotective efficacy of CBG.

  5. Current-Voltage Relationship for Late Na(+) Current in Adult Rat Ventricular Myocytes.

    Science.gov (United States)

    Clark, R B; Giles, W R

    2016-01-01

    It is now well established that the slowly inactivating component of the Na(+) current (INa-L) in the mammalian heart is a significant regulator of the action potential waveform. This insight has led to detailed studies of the role of INa-L in a number of important and challenging pathophysiological settings. These include genetically based ventricular arrhythmias (LQT 1, 2, and 3), ventricular arrhythmias arising from progressive cardiomyopathies (including diabetic), and proarrhythmic abnormalities that develop during local or global ventricular ischemia. Inhibition of INa-L may also be a useful strategy for management of atrial flutter and fibrillation. Many important biophysical parameters that characterize INa-L have been identified; and INa-L as an antiarrhythmia drug target has been studied extensively. However, relatively little information is available regarding (1) the ion transfer or current-voltage relationship for INa-L or (2) the time course of its reactivation at membrane potentials similar to the resting or diastolic membrane potential in mammalian ventricle. This chapter is based on our preliminary findings concerning these two very important physiological/biophysical descriptors for INa-L. Our results were obtained using whole-cell voltage clamp methods applied to enzymatically isolated rat ventricular myocytes. A chemical agent, BDF 9148, which was once considered to be a drug candidate in the Na(+)-dependent inotropic agent category has been used to markedly enhance INa-L current. BDF acts in a potent, selective, and reversible fashion. These BDF 9148 effects are compared and contrasted with the prototypical activator of INa-L, a sea anemone toxin, ATX II. PMID:27586292

  6. Sudden cardiac death in adults: causes, incidence and interventions.

    Science.gov (United States)

    Walker, Wendy Marina

    Many nurses will be familiar with the unexpected death of an adult patient following a sudden, life-threatening cardiac event. It is a situation that demands sensitive nursing care and skilled interventions to provide a foundation for recovery and promote healthy bereavement. This article examines the causes and incidence of sudden cardiac death in adults. Possible reactions of those who are suddenly bereaved are described and immediate care interventions aimed at dealing with the grief process are discussed. The article concludes by identifying ways in which the incidence of sudden cardiac death may be reduced.

  7. β-Adrenergic stimulation increases Cav3.1 activity in cardiac myocytes through protein kinase A.

    Directory of Open Access Journals (Sweden)

    Yingxin Li

    Full Text Available The T-type Ca(2+ channel (TTCC plays important roles in cellular excitability and Ca(2+ regulation. In the heart, TTCC is found in the sinoatrial nodal (SAN and conduction cells. Cav3.1 encodes one of the three types of TTCCs. To date, there is no report regarding the regulation of Cav3.1 by β-adrenergic agonists, which is the topic of this study. Ventricular myocytes (VMs from Cav3.1 double transgenic (TG mice and SAN cells from wild type, Cav3.1 knockout, or Cav3.2 knockout mice were used to study β-adrenergic regulation of overexpressed or native Cav3.1-mediated T-type Ca(2+ current (I(Ca-T(3.1. I(Ca-T(3.1 was not found in control VMs but was robust in all examined TG-VMs. A β-adrenergic agonist (isoproterenol, ISO and a cyclic AMP analog (dibutyryl-cAMP significantly increased I(Ca-T(3.1 as well as I(Ca-L in TG-VMs at both physiological and room temperatures. The ISO effect on I(Ca-L and I(Ca-T in TG myocytes was blocked by H89, a PKA inhibitor. I(Ca-T was detected in control wildtype SAN cells but not in Cav3.1 knockout SAN cells, indicating the identity of I(Ca-T in normal SAN cells is mediated by Cav3.1. Real-time PCR confirmed the presence of Cav3.1 mRNA but not mRNAs of Cav3.2 and Cav3.3 in the SAN. I(Ca-T in SAN cells from wild type or Cav3.2 knockout mice was significantly increased by ISO, suggesting native Cav3.1 channels can be upregulated by the β-adrenergic (β-AR system. In conclusion, β-adrenergic stimulation increases I(Ca-T(3.1 in cardiomyocytes(, which is mediated by the cAMP/PKA pathway. The upregulation of I(Ca-T(3.1 by the β-adrenergic system could play important roles in cellular functions involving Cav3.1.

  8. Fetal myocardium in the kidney capsule: an in vivo model of repopulation of myocytes by bone marrow cells.

    Directory of Open Access Journals (Sweden)

    Eric Y Zhang

    Full Text Available Debate surrounds the question of whether the heart is a post-mitotic organ in part due to the lack of an in vivo model in which myocytes are able to actively regenerate. The current study describes the first such mouse model--a fetal myocardial environment grafted into the adult kidney capsule. Here it is used to test whether cells descended from bone marrow can regenerate cardiac myocytes. One week after receiving the fetal heart grafts, recipients were lethally irradiated and transplanted with marrow from green fluorescent protein (GFP-expressing C57Bl/6J (B6 donors using normal B6 recipients and fetal donors. Levels of myocyte regeneration from GFP marrow within both fetal myocardium and adult hearts of recipients were evaluated histologically. Fetal myocardium transplants had rich neovascularization and beat regularly after 2 weeks, continuing at checkpoints of 1, 2, 4, 6, 8 and12 months after transplantation. At each time point, GFP-expressing rod-shaped myocytes were found in the fetal myocardium, but only a few were found in the adult hearts. The average count of repopulated myocardium with green rod-shaped myocytes was 996.8 cells per gram of fetal myocardial tissue, and 28.7 cells per adult heart tissue, representing a thirty-five fold increase in fetal myocardium compared to the adult heart at 12 months (when numbers of green rod-shaped myocytes were normalized to per gram of myocardial tissue. Thus, bone marrow cells can differentiate to myocytes in the fetal myocardial environment. The novel in vivo model of fetal myocardium in the kidney capsule appears to be valuable for testing repopulating abilities of potential cardiac progenitors.

  9. Differences in the control of basal L-type Ca(2+) current by the cyclic AMP signaling cascade in frog, rat, and human cardiac myocytes.

    Science.gov (United States)

    Treinys, Rimantas; Bogdelis, Andrius; Rimkutė, Lina; Jurevičius, Jonas; Skeberdis, Vytenis Arvydas

    2016-07-01

    β-adrenergic receptors (β-ARs) mediate the positive inotropic effects of catecholamines by cAMP-dependent phosphorylation of the L-type Ca(2+) channels (LTCCs), which provide Ca(2+) for the initiation and regulation of cell contraction. The overall effect of cAMP-modulating agents on cardiac calcium current (I Ca,L) and contraction depends on the basal activity of LTCCs which, in turn, depends on the basal activities of key enzymes involved in the cAMP signaling cascade. Our current work is a comparative study demonstrating the differences in the basal activities of β-ARs, adenylyl cyclase, phosphodiesterases, phosphatases, and LTCCs in the frog and rat ventricular and human atrial myocytes. The main conclusion is that the basal I Ca,L, and consequently the contractile function of the heart, is secured from unnecessary elevation of its activity and energy consumption at the several "checking-points" of cAMP-dependent signaling cascade and the loading of these "checking-points" may vary in different species and tissues. PMID:26676115

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

    Science.gov (United States)

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.

  11. Serum Positive for the Autoantibody against the β1-Adrenoceptor from Chinese Patients with Congestive Heart Failure Decreases Iss in Mouse Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Yuan-yuan Wang

    2011-01-01

    Full Text Available Autoantibodies targeting the β1-adrenergic receptor (AAB-β1 display agonist-like effects, which may have a pathogenic role in the progression of heart failure. Here, we used the electrophysiological recordings to explore the effects of AAB-β1-positive serum from Chinese patients with heart failure on the activity of the peak transient outward potassium current (Ito and the end 50 ms steady-state potassium current (Iss in mouse cardiac myocytes. We found that the AAB-β1-positive serum had no effect on the activity of Ito, but it produced a decrease in the currents of Iss. A low concentration of positive serum (1/100 had a small inhibitory effect on Iss. However, positive serum at 1 : 10, 1 : 20, and 1 : 50 significantly decreased Iss. The concentration-dependence analysis showed that the EC50 of AAB-β1-positive serum was 1/60.24 and its nH was 2.86. It indicated that the AAB-β1 could inhibit Iss in mouse cardiomyocyte in a concentration-dependent manner.

  12. Cardiac arrhythmias in adults with congenital heart disease

    NARCIS (Netherlands)

    Z. Koyak

    2016-01-01

    Arrhythmias are a major cause of hospital admissions and morbidity in adults with congenital heart disease (CHD). Furthermore, the leading cause of death in adults with CHD is sudden cardiac death (SCD) of presumed arrhythmic aetiology. The main objectives of this thesis were to identify risk factor

  13. 趋化因子CXCL10在心肌细胞及巨噬细胞中的表达机制%Mechanism of CXCL10 expression in cardiac myocytes and bone marrow-derived macrophages

    Institute of Scientific and Technical Information of China (English)

    李子南; 翟原; 卢静; 王钜

    2011-01-01

    Objective To investigate the mechanism of CXCL10 expression during myocardial ischemia-reperfusion injury. Methods To stimulate cardiac myocytes,bone marrow-derived macrophages (BMMs) and co-culture system with LPS, H2O2 or calcium ionophore A23187 respectively, and then test the CXCL10, IL-1 β, IL-6, TNF-α levels in the supernant of medium by ELISA. Results ①High dose ( 10 μg/mL) LPS could induce cardiac myocytes to express CXCL10 as well as BMMs to produce IL-1β,IL-6,TNF-α. ②H2O2 ,calcium ionophore A23187 failed to induce CXCL10 expression or IL-1β,IL-6 ,TNF-α expression,either on cardiac myocytes or on BMMs. ③BMMs promote CXCL10 induction of cardiac myocytes,while cardiac myocytes promote IL-6 and TNF-α induction of BMMs. Oppositely,the IL-1 β induction of BMMs was inhibited by cardiac myocytes in this research. Conclusion Cardiac myocytes could be the potential cellular resource during myocardial ischemia-reperfusion injury. It is mainly the activation of TLR4 that cause CXCL10 expression.%目的 探讨心肌缺血-再灌注损伤中趋化因子CXCL10的产生机制.方法 分别用LPS、H2O2、Ca2+载体A23187刺激原代培养的心肌细胞、骨髓来源的巨噬细胞或二者混合培养的共培养系统后,ELISA检测培养基上清中的趋化因子CXCL10和促炎性细胞因子IL-1β、IL-6、TNF-α的含量,观察其表达动力学.结果 ①大剂量(10 μg/mL)的LPS刺激心肌细胞主要产生趋化因子CXCL10;刺激骨髓来源巨噬细胞主要产生促炎性细胞因子IL-1β、IL-6、TNF-α.②H2O2、Ca2+通道激活剂并不能使产生趋化因子CXCL10或IL-1β、IL-6、TNF-α这些促炎性细胞因子.③骨髓来源的巨噬细胞促进心肌细胞表达趋化因子CXCL10;心肌细胞促进骨髓来源的巨噬细胞表达IL-6、TNF-α,但抑制IL-1β的表达.结论 心肌细胞是心肌缺血-再灌注损伤中CXCL10潜在的细胞来源;CXCL10的表达,主要依赖于TLR4的激活.

  14. [Inhibition of oxygen free radicals in potassium channels of cardiac myocytes and the action of salvianolic acid A].

    Science.gov (United States)

    Bao, G

    1993-10-01

    By using the patch clamp technique, the effect of oxygen free radicals on the single potassium channels of cardiac papillary muscle cells were studied, as well as the action of salvianolic acid A. It was found that xanthane-xanthane oxidase generated oxygen free radicals could apparently inhibited the unitary currents of the single potassium channel activity. This inhibition was reversed by salvianolic acid A, which is an effective component extracted from Salvia miltiorrhiza. PMID:8168213

  15. Anandamide reduces intracellular Ca2+ concentration through suppression of Na+/Ca2+ exchanger current in rat cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Qian Li

    Full Text Available PURPOSE: Anandamide, one of the endocannabinoids, has been reported to exhibit cardioprotective properties, particularly in its ability to limit the damage produced by ischemia reperfusion injury. However, the mechanisms underlying the effect are not well known. This study is to investigate whether anandamide alter Na(+/Ca(2+ exchanger and the intracellular free Ca(2+ concentration ([Ca(2+]i. METHODS: Na(+/Ca(2+ exchanger current (I(NCX was recorded and analysed by using whole-cell patch-clamp technique and [Ca(2+]i was measured by loading myocytes with the fluorescent Ca(2+ indicator Fura-2/AM. RESULTS: We found that I(NCX was enhanced significantly after perfusion with simulated ischemic external solution; [Ca(2+]i was also significantly increased by simulated ischemic solution. The reversal potential of I(NCX was shifted to negative potentials in simulated ischemic external solution. Anandamide (1-100 nM failed to affect I(NCX and [Ca(2+]i in normal solution. However, anandamide (1-100 nM suppressed the increase in INCX in simulated ischemic external solution concentration-dependently and normalized INCX reversal potential. Furthermore, anandamide (100 nM significantly attenuated the increase in [Ca(2+]i in simulated ischemic solution. Blocking CB1 receptors with the specific antagonist AM251 (500 nM failed to affect the effects of anandamide on I(NCX and [Ca(2+]i in simulated ischemic solution. CB2 receptor antagonist AM630 (100 nM eliminated the effects of anandamide on I(NCX and [Ca(2+]i in simulated ischemic solution, and CB2 receptor agonist JWH133 (100 nM simulated the effects of anandamide that suppressed the increase in I(NCX and [Ca(2+]i in simulated ischemic solution. In addition, pretreatment with the Gi/o-specific inhibitor pertussis toxin (PTX, 500 ng/ml eliminated the effects of anandamide and JWH133 on I(NCX in simulated ischemic solution. CONCLUSIONS: Collectively, these findings suggest that anandamide suppresses calcium

  16. Activation of KATP channels by Na/K pump in isolated cardiac myocytes and giant membrane patches.

    OpenAIRE

    Kabakov, A Y

    1998-01-01

    Strophanthidin inhibits KATP channels in 2,4-dinitrophenol-poisoned heart cells (). The current study shows that the Na/K pump interacts with KATP current (IK-ATP) via submembrane ATP depletion in isolated giant membrane patches and in nonpoisoned guinea pig cardiac cells in whole-cell configuration. IK-ATP was inhibited by ATP, glibenclamide, or intracellular Cs+. Na/K pump inactivation by substitution of cytoplasmic Na+ for Li+ or N-methylglucamine decreased both IK-ATP by 1/3 (1 mM ATP, ze...

  17. Sudden cardiac death in young adults

    DEFF Research Database (Denmark)

    Larsen, Maiken K; Nissen, Peter H; Kristensen, Ingrid B;

    2012-01-01

    Familial hypercholesterolemia (FH) is a genetic disorder that may lead to premature coronary heart disease (CHD) and sudden cardiac death (SCD). Mutations in the LDLR or APOB genes cause FH. We have screened the LDLR and the ligand-binding region of APOB genes in 52 cases of SCD. Deceased patients...

  18. Cardioprotective role of Syzygium cumini against glucose-induced oxidative stress in H9C2 cardiac myocytes.

    Science.gov (United States)

    Atale, Neha; Chakraborty, Mainak; Mohanty, Sujata; Bhattacharya, Susinjan; Nigam, Darshika; Sharma, Manish; Rani, Vibha

    2013-09-01

    Diabetic patients are known to have an independent risk of cardiomyopathy. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) that may contribute to diabetic cardiomyopathy. Thus, agents that suppress glucose-induced intracellular ROS levels can have therapeutic potential against diabetic cardiomyopathy. Syzygium cumini is well known for its anti-diabetic potential, but its cardioprotective properties have not been evaluated yet. The aim of the present study is to analyze cardioprotective properties of methanolic seed extract (MSE) of S. cumini in diabetic in vitro conditions. ROS scavenging activity of MSE was studied in glucose-stressed H9C2 cardiac myoblasts after optimizing the safe dose of glucose and MSE by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide. 2',7'-dichlorfluorescein diacetate staining and Fluorescence-activated cell sorting analysis confirmed the suppression of ROS production by MSE in glucose-induced cells. The intracellular NO and H2O2 radical-scavenging activity of MSE was found to be significantly high in glucose-induced cells. Exposure of glucose-stressed H9C2 cells to MSE showed decline in the activity of catalase and superoxide dismutase enzymes and collagen content. 4',6-diamidino-2-phenylindole, propidium iodide and 10-N-nonyl-3,6-bis (dimethylamino) acridine staining revealed that MSE protects myocardial cells from glucose-induced stress. Taken together, our findings revealed that the well-known anti-diabetic S. cumini can also protect the cardiac cells from glucose-induced stress. PMID:23512199

  19. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  20. Cardiac arrhythmias in adult patients with asthma

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Rutten, Frans H; Kors, Jan A;

    2012-01-01

    and electrocardiographic characteristics of arrhythmogenicity (ECG) and to explore the role of β2-mimetics. METHODS: A cross-sectional study was conducted among 158 adult patients with a diagnosis of asthma and 6303 participants without asthma from the cohort of the Utrecht Health Project-an ongoing, longitudinal, primary...... more common (OR: 12.4 [95% CI: 4.7-32.8] and 3.7 [95% CI: 1.3-10.5], respectively). CONCLUSIONS: The adult patients with asthma more commonly show tachycardia and PVCs on the ECG than those without asthma. The patients with asthma received β2-mimetics; the risk of tachycardia and PVCs is even more...

  1. Milrinone for cardiac dysfunction in critically ill adult patients

    DEFF Research Database (Denmark)

    Koster, Geert; Bekema, Hanneke J; Wetterslev, Jørn;

    2016-01-01

    review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias...... analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data. DISCUSSION: The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks...

  2. Primary gastric teratoma on the cardiac orifice in an adult

    Institute of Scientific and Technical Information of China (English)

    Liu Liu; Wen Zhuang; Zhong Chen; Yong Zhou; Xiao-Ran Huang

    2009-01-01

    Gastric teratoma (GT) is a seldom seen congenital abnormality. GT always occurs in children. The greater curvature and posterior wall of the stomach are the most common sites involving GT. We diagnosed a case of GT located on the inferior wall of the cardiac orifice in a 20-year-old man. To the best of our knowledge, this is the first case of GT located on the wall of the cardiac orifice in an adult in the English literature. We report this unusual case as an addition to this rare disease usually found in children. Computed tomography combined with endoscopic ultrasonography can be selected to diagnose GT.

  3. Preoperative cardiac computed tomography for demonstration of congenital cardiac septal defect in adults

    International Nuclear Information System (INIS)

    We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. (orig.)

  4. Preoperative cardiac computed tomography for demonstration of congenital cardiac septal defect in adults

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hye-Joung; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae-Hee; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan [University of Ulsan College of Medicine, Department of Cardiology and Heart Institute, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of); Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won [University of Ulsan College of Medicine, Department of Cardiothoracic surgery, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of)

    2015-06-01

    We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. (orig.)

  5. THE NONLINEAR VISCOELASTIC CONSTITUTIVE MODEL OF CARDIAC MYOCYTE IN SIMULATION OF MICROPIPETTE ASPIRATION EXPERIMENT%心肌细胞大变形黏弹性模型及在实验中的应用

    Institute of Scientific and Technical Information of China (English)

    唐陶; 王世骐; 裘钧; 庄茁

    2009-01-01

    在衡量单个细胞力学行为的研究中,越来越多地采用结合实验的数值模拟方法.在连续介质力学框架下,发展了一种新的心肌细胞本构模型,并与微管吮吸实验结合,探讨了心肌细胞的力学特性.本构模型是对普遍使用的仅能用于小变形分析的标准线性固体模型的一种扩展,它将超弹性性能引入到黏弹性模型中,用以描述细胞的大变形黏弹性效应.基于改进的本构模型,对心肌细胞微管吮吸实验过程进行了有限元模拟,并将计算结果与实验结果以及经典理论解进行了对比.结果显示发展的本构模型适合细胞大变形问题的有限元数值模拟.%Numerical modeling with experimental analysis is increasingly being used to evaluate the mechan-ical properties of living cells in single cell mechanics. In the present study, through the continuum mechanics process, a new constitutive model for cardiac myocyte is developed, and together with the micropipette aspi-ration experiment, the mechanical property of cardiac myocyte is investigated. The commonly used standard linear solid model is extended into a nonlinear viscoelastic constitutive model in which was introduced the hyperelasticity to describe the large deformation of myocytes in response to micropipette aspiration. Based on the constitutive model and experiment data, the experiment process is simulated, and the computational results are compared with the experiment results and classic theoretical solutions. The results show that the new constitutive model suits the computation of large deformation of cells.

  6. Cardiac surgery for adults with mental retardation. Dilemmas in management.

    Science.gov (United States)

    Goldhaber, S Z; Reardon, F E; Goulart, D T; Rubin, I L

    1985-10-01

    In summary, cardiac surgery for adults with mental retardation raises a series of controversial legal, economic, ethical, medical, and nursing dilemmas. During the past 20 years, many improvements have taken place in the care of these patients. However, in the future, judicial and statutory mandates requiring high-quality medical care for persons with mental retardation may conflict increasingly with hospital cost-control legislation and thereby affect clinical decisions. For example, it is conceivable that elective repair of an ostium secundum atrial septal defect in an asymptomatic patient will expend the limited resources necessary to carry out emergency revascularization in a symptomatic patient with impending myocardial infarction. This issue becomes even more delicate when the asymptomatic patient is a mentally retarded ward of the state, and the symptomatic patient is a middle-aged man supporting a wife and several college-age children. There may be no easy solution to this problem, and it will provide the grist for many bioethicists. Fortunately, from a practical point of view, we do not currently have to choose between these patients to receive treatment. Our hope is that health care for mentally retarded patients will not be compromised. We believe that decisions about patient management should be based on enlightened clinical judgment rather than on preconceived notions about this population. In the quest for optimal health care delivery, the special needs of these patients should be considered when cardiac catheterization and possible cardiac surgery are contemplated. Although we have presented an approach to a patient with cardiac disease requiring cardiac surgery, we believe that this approach can be utilized for any retarded patient requiring acute medical care. Currently, because there has not been much training in this area, many physicians and nurses lack first-hand experience in caring for the mentally retarded. This inexperience may lead to

  7. p44/p42 MAPK反义寡脱氧核苷酸对血管紧张素Ⅱ诱导的培养乳鼠心肌细胞肥大反应的抑制作用%Inhibitory effect of antisense oligodeoxynucleotide to p44/p42 MAPK on angiotensin Ⅱ-induced hypertrophic response in cultured neonatal rat cardiac myocyte

    Institute of Scientific and Technical Information of China (English)

    张世勤; 丁波; 郭兆贵; 李云霞

    2004-01-01

    AIM: To explore the inhibitory effect of antisense oligonucleotide (ODN) to mitogen activated protein kinase (MAPK) on cardiomyocyte hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ). METHODS: A 17-mer phosphorothioateprotected antisense ODN directed against the initiation of translation sites of the p42 and p44 MAPK isoforms by liposomal transfection was applied to inhibit the translation of p44/p42 MAPK mRNA. The sense and random ODNs to p44/p42MAPK were used as sequence controls. Neonatal cardiac myocytes were exposed to Ang Ⅱ (10 nmol/L) for 5 min and then harvested in lysis buffer for the measurement of the activity and the phosphorylated protein content of p44/p42MAPK that were tested by P-81 phosphocellulose filter paper method and Western blotting, respectively. The rate of protein synthesis by [3H]leucine incorporation and the diameter of cell were measured after exposure to Ang Ⅱ for 24 h and 72 h, respectively. RESULTS: In cardiac myocyte Ang Ⅱ increased p44/p42MAPK activity and phosphorylated protein content by 140 % and 699 %, and also increased [3H]leucine incorporation and cell diameter by 40 % and 27 %. c-fos and c-myc mRNAs were induced significantly after exposure to Ang Ⅱ. Antisense ODN to p44/p42MAPK (0.2 μmol/L) reduced Ang Ⅱ-induced MAPK activity by 30 %,and phophorylated MAPK protein expression by 59 % in cardiac myocyte, and inhibited c-fos and c-myc mRNA expression induced by Ang Ⅱ by 44 % and 43 %, respectively. The diameter and the rate of protein synthesis of cardiac myocyte induced by Ang Ⅱ were decreased by 16 % and 22 % after pretreatment with antisense ODN to p44/p42MAPK. CONCLUSION: Antisense ODN to p44/p42 MAPK inhibited the increase of rate of protein synthesis,and the augmentation of cell diameter and expression of c-fos and c-nyc mRNA induced by Ang Ⅱ in cultured cardiac myocytes, p44/p42 MAPK played a critical role in the hypertrophic response induced by Ang Ⅱ in cultured neonatal rat cardiac myocytes.

  8. Functional analysis of Na+/K+-ATPase isoform distribution in rat ventricular myocytes.

    Science.gov (United States)

    Despa, Sanda; Bers, Donald M

    2007-07-01

    The Na(+)/K(+)-ATPase (NKA) is the main route for Na(+) extrusion from cardiac myocytes. Different NKA alpha-subunit isoforms are present in the heart. NKA-alpha1 is predominant, although there is a variable amount of NKA-alpha2 in adult ventricular myocytes of most species. It has been proposed that NKA-alpha2 is localized mainly in T-tubules (TT), where it could regulate local Na(+)/Ca(2+) exchange and thus cardiac myocyte Ca(2+). However, there is controversy as to where NKA-alpha1 vs. NKA-alpha2 are localized in ventricular myocytes. Here, we assess the TT vs. external sarcolemma (ESL) distribution functionally using formamide-induced detubulation of rat ventricular myocytes, NKA current (I(Pump)) measurements and the different ouabain sensitivity of NKA-alpha1 (low) and NKA-alpha2 (high) in rat heart. Ouabain-dependent I(Pump) inhibition in control myocytes indicates a high-affinity NKA isoform (NKA-alpha2, K(1/2) = 0.38 +/- 0.16 microM) that accounts for 29.5 +/- 1.3% of I(Pump) and a low-affinity isoform (NKA-alpha1, K(1/2) = 141 +/- 17 microM) that accounts for 70.5% of I(Pump). Detubulation decreased cell capacitance from 164 +/- 6 to 120 +/- 8 pF and reduced I(Pump) density from 1.24 +/- 0.05 to 1.02 +/- 0.05 pA/pF, indicating that the functional density of NKA is significantly higher in TT vs. ESL. In detubulated myocytes, NKA-alpha2 accounted for only 18.2 +/- 1.1% of I(Pump). Thus, approximately 63% of I(Pump) generated by NKA-alpha2 is from the TT (although TT are only 27% of the total sarcolemma), and the NKA-alpha2/NKA-alpha1 ratio in TT is significantly higher than in the ESL. The functional density of NKA-alpha2 is approximately 4.5 times higher in the T-tubules vs. ESL, whereas NKA-alpha1 is almost uniformly distributed between the TT and ESL. PMID:17392375

  9. Enrichment of vital adult cardiac muscle cells by continuous silica sol gradient centrifugation.

    Science.gov (United States)

    Maisch, B

    1981-01-01

    A major improvement in the isolation of vital adult cardiocytes was achieved by isopycnic preformed continuous silica sol gradient centrifugation after perfusion of the heart with collagenase. Vital rat cardiocytes were enriched to 90-95% vital cells reproducibly and constantly by one- or two-step gradient centrifugations. The isolated cardiocytes were tolerant to calcium concentrations up to 0.03 mmol/l, to diluted human serum, and to human complement. Gentamycin (50 microgram/ml) exerted a cytotoxic effect on myocytes, whereas Penicillium and Streptomycin in concentrations of 50 IU/ml did not induce cytolysis of vital cells. Digoxin 15 ng/ml) decreased the natural decay of myocytes of 20% in 25 hours to 8%. Enriched of vital cardiocytes by silica sol gradient centrifugation following their isolation by perfusion with collagenase may be helpful for investigations depending on a high yield of vital myocardial cells. PMID:6277294

  10. Epicardial Lineages and Cardiac Repair

    Directory of Open Access Journals (Sweden)

    Manvendra K. Singh

    2013-08-01

    Full Text Available The death of cardiac myocytes resulting from myocardial infarction is a major cause of heart failure worldwide. Effective therapies for regenerating lost cardiac myocytes are lacking. Recently, the epicardium has been implicated as a source of inflammatory cytokines, growth factors and progenitor cells that modulate the response to myocardial injury. During embryonic development, epicardially-derived cells have the potential to differentiate into multiple cardiac lineages, including fibroblasts, vascular smooth muscle and potentially other cell types. In the healthy adult heart, epicardial cells are thought to be generally quiescent. However, injury of the adult heart results in reactivation of a developmental gene program in the epicardium, which leads to increased epicardial cell proliferation and differentiation of epicardium-derived cells (EPDCs into various cardiac lineages. Recent work suggests that epicardial reactivation after injury is accompanied by, and contributes to, a robust inflammatory response. In this review, we describe the current status of research related to epicardial biology in cardiac development and regeneration, highlighting important recent discoveries and ongoing controversies.

  11. Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review

    Directory of Open Access Journals (Sweden)

    Michael Mazzeffi

    2015-01-01

    Full Text Available Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and amnesia with minimal respiratory and cardiovascular depression. Because of its sympathomimetic properties it would seem to be an excellent choice for patients with depressed ventricular function in cardiac surgery. However, its use has not gained widespread acceptance in adult cardiac surgery patients, perhaps due to its perceived negative psychotropic effects. Despite this limitation, it is receiving renewed interest in the United States as a sedative and analgesic drug for critically ill-patients. In this manuscript, the authors provide an evidence-based clinical review of ketamine use in cardiac surgery patients for intensive care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons. All MEDLINE indexed clinical trials performed during the last 20 years in adult cardiac surgery patients were included in the review.

  12. Knowledge Management in Cardiac Surgery: The Second Tehran Heart Center Adult Cardiac Surgery Database Report

    Directory of Open Access Journals (Sweden)

    Kyomars Abbasi

    2015-10-01

    Full Text Available Background: The Adult Cardiac Surgery Databank (ACSD of Tehran Heart Center was established in 2002 with a view to providing clinical prediction rules for outcomes of cardiac procedures, developing risk score systems, and devising clinical guidelines. This is a general analysis of the collected data.Methods: All the patients referred to Tehran Heart Center for any kind of heart surgery between 2002 and 2008 were included, and their demographic, medical, clinical, operative, and postoperative data were gathered. This report presents general information as well as in-hospital mortality rates regarding all the cardiac procedures performed in the above time period.Results: There were 24959 procedures performed: 19663 (78.8% isolated coronary artery bypass grafting surgeries (CABGs; 1492 (6.0% isolated valve surgeries; 1437 (5.8% CABGs concomitant with other procedures; 832 (3.3% CABGs combined with valve surgeries; 722 (2.9% valve surgeries concomitant with other procedures; 545 (2.2% surgeries other than CABG or valve surgery; and 267 (1.1% CABGs concomitant with valve and other types of surgery. The overall mortality was 205 (1.04%, with the lowest mortality rate (0.47% in the isolated CABGs and the highest (4.49% in the CABGs concomitant with valve surgeries and other types of surgery. Meanwhile, the overall mortality rate was higher in the female patients than in the males (1.90% vs. 0.74%, respectively.Conclusion: Isolated CABG was the most prevalent procedure at our center with the lowest mortality rate. However, the overall mortality was more prevalent in our female patients. This database can serve as a platform for the participation of the other countries in the region in the creation of a regional ACSD.

  13. 26S Proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Samaras, Susan E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); Chen, Billy [Molecular Medicine Program, Department of Medicine, Boston University School of Medicine, Boston, MA (United States); Koch, Stephen R. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); Sawyer, Douglas B.; Lim, Chee Chew [Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (United States); Davidson, Jeffrey M., E-mail: jeff.davidson@vanderbilt.edu [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); Research Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer The 26S proteasome regulates Ankrd1 levels in cardiomyocytes and endothelial cells. Black-Right-Pointing-Pointer Ankrd1 protein degrades 60-fold faster in endothelial cells than cardiomyocytes. Black-Right-Pointing-Pointer Differential degradation appears related to nuclear vs. sarcolemmal localization. Black-Right-Pointing-Pointer Endothelial cell density shows uncoupling of Ankrd1 mRNA and protein levels. -- Abstract: Ankyrin repeat domain 1 protein (Ankrd1), also known as cardiac ankyrin repeat protein (CARP), increases dramatically after tissue injury, and its overexpression improves aspects of wound healing. Reports that Ankrd1/CARP protein stability may affect cardiovascular organization, together with our findings that the protein is crucial to stability of the cardiomyocyte sarcomere and increased in wound healing, led us to compare the contribution of Ankrd1/CARP stability to its abundance. We found that the 26S proteasome is the dominant regulator of Ankrd1/CARP degradation, and that Ankrd1/CARP half-life is significantly longer in cardiomyocytes (h) than endothelial cells (min). In addition, higher endothelial cell density decreased the abundance of the protein without affecting steady state mRNA levels. Taken together, our data and that of others indicate that Ankrd1/CARP is highly regulated at multiple levels of its expression. The striking difference in protein half-life between a muscle and a non-muscle cell type suggests that post-translational proteolysis is correlated with the predominantly structural versus regulatory role of the protein in the two cell types.

  14. Bidirectional reprogramming of fusion cells of pluripotent stem cells/primary cardiac myocytes%诱导多能干细胞/原代心肌细胞的融合细胞表现出双向重建

    Institute of Scientific and Technical Information of China (English)

    熊挺淋; 张晓刚; 赵霞; 马红芬

    2011-01-01

    Objective To construct fusion cells with induced pluripotent stem cells (iPSc) and primary cardiac myocytes in vitro, and to investigate biological features of the fusion cells. Methods Polyethylene glycol (PEG-4000) was used to mediate the cell fusion of iPSc derived from green fluorescent protein (GFP) transgenes (octamer-binding transcription factor-4, Oct-4) mouse and cardiac myocytes from neonatal mouse. Morphological changes of the fusion cells were observed dynamically after alkaline phosphatase (AKP) staining. Specific proteins of stem cells and cardiac myocytes in fusion cells were detected by immunofluores-cence. Chromosome karyotype analysis were performed to determine whether the occurrence of nuclear fusion and degree of integration. Results Fusion cells were constructed successfully by polyethylene glycol mediation. Colony-like cell clusters appeared in 4 d after fusion. The AKP positive rate of iPSc were 0.935 ±0.039, 0.939 ± 0.022, 0.954 ± 0.017, and 0.944 ± 0.027 at the 2nd, 3rd, 4th and 5th days respectively, and that of fusion cells were 0.761 ±0.044, 0.740 ±0.023, 0.681 ±0.034, and 0.748 ±0.045 at the corresponding days respectively. At the same time points, there were significant differences between iPSc AKP-positive rates and those of fusion cells ( P < 0. 05). In the initial stage, fusion cells mainly displayed iPSc characteristics, with Oct-4 positive while cTnT negative. Then the fusion cells began to display both characteristics of iPSc and cardiac myocytes in 7 d after fusion, with positive expression of Oct-4 and cTnT. More than 80% of fusion cells had 76 to 80 chromosomes. Conclusion Fusion cells from diploid iPSc and diploid myocardial cells display the characteristics of the two parental cells and show bidirectional reprogramming.%目的 体外构建诱导多能干细胞(induced pluripotent stem cells,iPSc)与原代心肌细胞的融合细胞,初步探讨融合细胞体外生物学特性.方法

  15. The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael;

    2007-01-01

    The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological...... effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] Ang......II) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains...

  16. Liberación de endotelina-1 por angiotensina ll en miocitos cardíacos aislados Angiotensin II-induced endothelin-1 release in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    María C. Villa-Abrille

    2006-06-01

    Full Text Available Muchos de los efectos de la angiotensina II (Ang II son mediados en realidad por la acción de endotelina (ET endógena liberada y/o producida en respuesta a la Ang II. En este trabajo evaluamos la interacción Ang II/ET-1, sus consecuencias en la contractilidad cardíaca y el papel de las especies reactivas del oxígeno (EROs. Se usaron cardiomiocitos aislados de gato. La Ang II, 1 nM, produjo un efecto inotrópico positivo (EIP de 31.8±3.8% que fue cancelado por inhibición de los receptores AT1, de los receptores de ET, del intercambiador Na+/H+ (NHE, del modo inverso del intercambiador Na+/Ca2+ (NCX o por el secuestro de EROs. La Ang II, 100 nM, produjo un EIP de 70.5±7.6% que fue cancelado por inhibición de los receptores AT1 y bloqueado en parte por inhibición de los receptores de ET, del NHE, del modo inverso del NCX o por el secuestro de EROs. La Ang II, 1 nM, incrementó el ARNm de la preproET-1 lo cual fue anulado por el bloqueo de los receptores AT1. Los resultados permiten concluir que el EIP de la Ang II es debido a la acción de la ET-1 endógena liberada/formada por la Ang II. La ET-1 produce: estimulación del NHE, activación del modo inverso del NCX y un consecuente EIP. Dentro de esta cascada también participarían los EROs.Many of the effects thought to be due to angiotensin II (Ang II are due to the release/formation of endothelin (ET. We tested whether Ang II elicits its positive inotropic effect (PIE by the action of endogenous ET-1 and the role played by the reactive oxygen species (ROS in this mechanism. Experiments were performed in cat isolated ventricular myocytes in which sarcomere shortening (SS was measured to asses contractility after pharmacological interventions and the effect of Ang II on inotropism were analyzed. Ang II 1 nM increased SS by 31.8±3.8% (p<0.05. This PIE was cancelled by AT1 receptor blockade, by ET-1 receptors blockade, by Na+/H+ exchanger (NHE inhibition, by reverse mode Na+/Ca2

  17. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    Science.gov (United States)

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-01-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  18. Down-regulation of microRNA-26b rescued hypoxia-induced apoptosis in cultured neonatal rat cardiac myocytes by regulating PTEN

    OpenAIRE

    Wang, Xiaoyu; Li, Chen; Dai, Qiaoqun

    2015-01-01

    Background: Cardiomyocyte hypoxia causes cardiac hypertrophy and other major myocardial injuries. We investigated the molecular mechanism of microRNA-26b (miR-26b) in regulating hypoxia-induced apoptosis in rat neonatal cardiomyocytes. Methods: Neonatal rat cardiomyocytes was prepared in vitro and hypoxia was induced. Apoptotic cardiomyocytes were examined by TUNEL staining and the expression of miR-26b were monitored by qRT-PCR. The effect of mir-26b downregulation on hypoxia-induced apoptos...

  19. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    Science.gov (United States)

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  20. Provision of Transition Education and Referral Patterns from Pediatric Cardiology to Adult Cardiac Care.

    Science.gov (United States)

    Harbison, Anna L; Grady, Stafford; Chi, Kevin; Fernandes, Susan M

    2016-02-01

    ACC/AHA guidelines recommend a structured preparation for and transfer to adult-oriented cardiac care for adult survivors of pediatric onset heart disease (POHD). Given this, we sought to describe the transition and transfer practices for a cohort of young adults with POHD and to determine factors associated with successful transfer to adult-oriented cardiac care. We performed a single-center, retrospective chart review on patients ≥18 years of age, with POHD likely to require lifelong cardiac care, who were seen in outpatient pediatric cardiology (PC) between 2008 and 2011. Successful transfer was defined as the subsequent attendance at adult cardiology (AC) within 2 years of PC visit. We identified 118 patients who met study criteria. Mean age 22.4 ± 2.0 years, 59 % male, 64 % white and 40 % Hispanic. Mean transition education topics noted was 3.3 ± 1.8 out of 20 and covered the underlying cardiac disease (89 %), follow-up and current medications (56 %) and exercise limitations (34 %). Recommendations for follow-up were AC (57 %) and PC (33 %). Of those told to transfer to AC, 79 % successfully transferred. Characteristics of successful transfer included: prior cardiac surgery (p = 0.008), cardiac medication use (p = 0.006) and frequency of follow-up ≤1 year (p = 0.037). One-quarter of all subjects did not follow-up within at least 2 years. Despite published guidelines, transition education appears lacking and the approach to transfer to adult cardiac care is not consistent. Given the increased risk of morbidity and mortality in this patient population, standardization of transition education and transfer processes appear warranted. PMID:26385471

  1. Effect of hypercholesterolemia on the ionic currents in cardiac ventricular myocytes of rats%高胆固醇血症对大鼠心室肌细胞离子电流的作用

    Institute of Scientific and Technical Information of China (English)

    周宇宏; 王玲; 单宏丽; 张妍; 孙宏丽; 杨宝峰

    2007-01-01

    AIM: To determine whether chronic hypercholesterolemia affects ionic currents on cardiac ventricular myocytes of rats. METHODS: Whole - cell patch - clamp technique was used to record the ionic currents in single cardiac myocytes isolated from normal cholesterolemia and hypercholesterolemia rats. RESULTS: In the hypercholesterol group (group Ⅱ ), serum total - cholesterol level was significantly higher than that of normal group (group Ⅰ) [ (3. 10 ±tricular myocytes of rats, 50% repolarization of action potential duration (APD50) prolonged from (70. 86 ± 8.12) ms (group Ⅰ) to (116.16±6.90)ms (group Ⅱ) (n=10 in each group, P<0.01); APD90 prolonged from (95.10±7. 27)ms (group Ⅰ ) to (144. 04 ± 7.39)ms (group Ⅱ ) (n = 10 in each group, P < 0. 01 ); at the test potential of - 120 mV, Ik1 increased from ( - 16. 98 ±4. 54) pA/pF(group Ⅰ ) to ( - 19.92 ±4.08) pA/pF (group Ⅱ ) (n = 12 in each group, P < 0. 05 ); at the test potential of 0 mV, ICa- L decreased from ( - 8.56 ± 1.29) pA/pF ( group Ⅰ ) to ( -5. 24 ± 0. 90) pA/pF ( group Ⅱ ) ( n = 10 in each group, P < 0. 01 ); at the test potential of + 60 mV, Ito decreased from (13.20±1.97) pA/pF (group Ⅰ) to (10.30±1.97) pA/pF (group Ⅱ) (n=8 in each group, P<0. 05). CON-CLUSION: Hypercholesterolemia affects the ionic currents on cardiomyocytes of rats greatly, which may be the ionic mechanism of cardiac toxicity induced by hypercholesterolemia.%目的:观察高胆固醇血症对大鼠心室肌细胞离子电流的作用.方法:通过全细胞膜片钳技术记录用酶解法分离的正常和高胆固醇饮食的大鼠心室肌细胞离子电流.结果:高胆固醇组(组Ⅱ)血清总胆固醇水平明显高于正常组(组Ⅰ)[(3.10±0.62)mmol·L-1vs(1.18±0.37)mmol·L-1,P<0.01,n=20].组Ⅱ血清甘油三酯也明显高于组Ⅰ[(1.51±0.30)mmol·L-1vs(0.43±0.15)mmol·L-1,P<0.01,n=20].组Ⅱ大鼠心室肌细胞动作电位时程(APD)与组Ⅰ相比明显延长,APD50从(70

  2. Time-resolved fluorescence spectroscopy investigation of the effect of 4-hydroxynonenal on endogenous NAD(P)H in living cardiac myocytes

    Science.gov (United States)

    Chorvatova, Alzbeta; Aneba, Swida; Mateasik, Anton; Chorvat, Dusan; Comte, Blandine

    2013-06-01

    Lipid peroxidation is a major biochemical consequence of the oxidative deterioration of polyunsaturated lipids in cell membranes and causes damage to membrane integrity and loss of protein function. 4-hydroxy-2-nonenal (HNE), one of the most reactive products of n-6 polyunsaturated fatty acid peroxidation of membrane phospholipids, has been shown to be capable of affecting both nicotinamide adenine dinucleotide (phosphate) reduced [NAD(P)H] as well as NADH production. However, the understanding of its effects in living cardiac cells is still lacking. Our goal was to therefore investigate HNE effects on NAD(P)H noninvasively in living cardiomyocytes. Spectrally resolved lifetime detection of endogenous fluorescence, an innovative noninvasive technique, was employed. Individual fluorescence components were resolved by spectral linear unmixing approach. Gathered results revealed that HNE reduced the amplitude of both resolved NAD(P)H components in a concentration-dependent manner. In addition, HNE increased flavoprotein fluorescence and responsiveness of the NAD(P)H component ratio to glutathione reductase (GR) inhibitor. HNE also increased the percentage of oxidized nucleotides and decreased maximal NADH production. Presented data indicate that HNE provoked an important cell oxidation by acting on NAD(P)H regulating systems in cardiomyocytes. Understanding the precise role of oxidative processes and their products in living cells is crucial for finding new noninvasive tools for biomedical diagnostics of pathophysiological states.

  3. Associations between childhood body size, composition, blood pressure and adult cardiac structure: the Fels Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Roy T Sabo

    Full Text Available To determine whether childhood body size, composition and blood pressure are associated with adult cardiac structure by estimating childhood "age of divergence."385 female and 312 male participants in the Fels Longitudinal Study had echocardiographic measurements of left ventricular mass, relative wall thickness, and interventricular septal thickness. Also available were anthropometric measurements of body mass index, waist circumference, percentage body fat, fat free mass, total body fat, and systolic and diastolic blood pressures, taken in both childhood and adulthood. The age of divergence is estimated as the lowest age at which childhood measurements are significantly different between patients with low and high measurements of adult cardiac structure.Childhood body mass index is significantly associated with adult left ventricular mass (indexed by height in men and women (ages of divergence: 7.5 years and 11.5 years, respectively, and with adult interventricular septal thickness in boys (age of divergence: 9 years. Childhood waist circumference indexed by height is associated with left ventricular mass (indexed by height in boys (age of divergence: 8 years. Cardiac structure was in general not associated with childhood body composition and blood pressure.Though results are affected by adult body size, composition and blood pressure, some aspects of adult cardiac structure may have their genesis in childhood body size.

  4. Cardiac Regeneration and Stem Cells.

    Science.gov (United States)

    Zhang, Yiqiang; Mignone, John; MacLellan, W Robb

    2015-10-01

    After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.

  5. Tetrahydroacridine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Wei WANG; Yi-ping WANG; Guo-yuan HU

    2004-01-01

    AIM: To study the effects of tetrahydroacridine (tacrine) on voltage-gated Na+ channels in cardiac tissues.METHODS: Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltagedependent Na+ current was recorded using whole cell voltage-clamp technique. RESULTS: (1) Tacrine reversibly inhibited Na+ current with an IC50 value of 120 μmol/L (95 % confidence range: 108-133 μmol/L). (2) The inhibitory effects of tacrine on Na+ current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 μmol/L caused a negative shift (about 10 mV) in the voltage-dependence of steady-state inactivation of Na+ current, and retarded its recovery from inactivation, but did not affect its activation curve. (4) Intracellular application of tacrine significantly inhibited Na+ current. CONCLUSION: In addition to blocking other voltage-gated ion channels,tacrine blocked Na+ channels in guinea-pig ventricular myocytes. Tactine acted as inactivation stabilizer of Na+channels in cardiac tissues.

  6. Radionuclide angiocardiography in the clinical evaluation of cardiac malpositions in situs solitus in adults.

    Science.gov (United States)

    Guit, G L; Kroon, H M; Chin, J G; Pauwels, E K; van Voorthuisen, A E

    1986-04-01

    A right-sided position of the heart in the chest in situs solitus is an abnormal feature easily discernible from a plain chest radiograph. This cardiac malposition may be due to cardiac displacement (dextroposition), which is usually a feature of lung disease, or a structural abnormality of the heart (dextrocardia). Because each condition has different clinical pathologic implications, it is important to distinguish them. Chest films, however, often provide no conclusive information. We performed radionuclide angiocardiography (RNA) in six adults with a cardiac malposition in situs solitus. It was found that morphologic data obtained from the serial images may distinguish dextroposition from dextrocardia. In addition, these images permitted us to diagnose congenitally corrected transposition, a cardiac anomaly which occurs with increased frequency in situs solitus with dextrocardia. Quantitative shunt detection performed during this procedure is helpful in the differential diagnosis of dextroposition and able to distinguish uncomplicated dextrocardia from dextrocardia associated with other cardiac abnormalities. RNA therefore is a valuable and easily performed method in the analysis of cardiac malpositions in adults.

  7. Microarray profiling to analyse adult cardiac fibroblast identity

    Directory of Open Access Journals (Sweden)

    Milena B. Furtado

    2014-12-01

    We have recently uncovered a unique molecular identity for fibroblasts isolated from the heart [9], expressing a set of cardiogenic transcription factors that have been previously associated with cardiomyocyte ontogenesis. This signature suggests that cardiac fibroblasts may be ideal for use in stem cell replacement therapies, as they may retain the memory of where they derive from embryologically. Our data also revealed that about 90% of fibroblasts from both tail and heart origins share a cell surface signature that has previously been described for mesenchymal stem cells (MSCs, raising the possibility that fibroblasts and MSCs may in fact be the same cell type. Thus, our findings carry profound implications for the field of regenerative medicine. Here, we describe detailed methodology and quality controls related to the gene expression profiling of cardiac fibroblasts, deposited at the Gene Expression Omnibus (GEO under the accession number GSE50531. We also provide the R code to easily reproduce the data quantification and analysis processes.

  8. Stimulation of isolated ventricular myocytes within an open architecture microarray.

    Science.gov (United States)

    Klauke, Norbert; Smith, Godfrey L; Cooper, Jonathan M

    2005-03-01

    prolonged at the higher pacing rate. These studies show the prolonged electrical stimulation of isolated adult cardiac myocytes in microchambers with unimpaired EC coupling as verified on optical records of the action potential, Ca2+ transients and cell shortening. The open architecture provided free (pipetting) access for drug dispensation without cross talk between neighboring microwells, and multiplexed optical detection can be realized to study EC coupling on arrays of cells under both control and experimental conditions.

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

    Science.gov (United States)

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

    2016-04-01

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

  10. Expression profile of microRNAs regulating proliferation and differentiation in mouse adult cardiac stem cells.

    Directory of Open Access Journals (Sweden)

    Luis Brás-Rosário

    Full Text Available The identification of cardiac cells with stem cell properties changed the paradigm of the heart as a post mitotic organ. These cells proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing for cardiac cell homeostasis and regeneration. microRNAs are master switches controlling proliferation and differentiation, in particular regulating stem cell biology and cardiac development. Modulation of microRNAs -regulated gene expression networks holds the potential to control cell fate and proliferation, with predictable biotechnologic and therapeutic applications. To obtain insights into the regulatory networks active in cardiac stem cells, we characterized the expression profile of 95 microRNAs with reported functions in stem cell and tissue differentiation in mouse cardiac stem cells, and compared it to that of mouse embryonic heart and mesenchymal stem cells. The most highly expressed microRNAs identified in cardiac stem cells are known to target key genes involved in the control of cell proliferation and adhesion, vascular function and cardiomyocyte differentiation. We report a subset of differentially expressed microRNAs that are proposed to act as regulators of differentiation and proliferation of adult cardiac stem cells, providing novel insights into active gene expression networks regulating their biological properties.

  11. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    Science.gov (United States)

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

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

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-07-01

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

  14. Reference Values for Cardiac and Aortic Magnetic Resonance Imaging in Healthy, Young Caucasian Adults

    Science.gov (United States)

    Eikendal, Anouk L. M.; Bots, Michiel L.; Haaring, Cees; Saam, Tobias; van der Geest, Rob J.; Westenberg, Jos J. M.; den Ruijter, Hester M.; Hoefer, Imo E.; Leiner, Tim

    2016-01-01

    Background Reference values for morphological and functional parameters of the cardiovascular system in early life are relevant since they may help to identify young adults who fall outside the physiological range of arterial and cardiac ageing. This study provides age and sex specific reference values for aortic wall characteristics, cardiac function parameters and aortic pulse wave velocity (PWV) in a population-based sample of healthy, young adults using magnetic resonance (MR) imaging. Materials and Methods In 131 randomly selected healthy, young adults aged between 25 and 35 years (mean age 31.8 years, 63 men) of the general-population based Atherosclerosis-Monitoring-and-Biomarker-measurements-In-The-YOuNg (AMBITYON) study, descending thoracic aortic dimensions and wall thickness, thoracic aortic PWV and cardiac function parameters were measured using a 3.0T MR-system. Age and sex specific reference values were generated using dedicated software. Differences in reference values between two age groups (25–30 and 30–35 years) and both sexes were tested. Results Aortic diameters and areas were higher in the older age group (all p<0.007). Moreover, aortic dimensions, left ventricular mass, left and right ventricular volumes and cardiac output were lower in women than in men (all p<0.001). For mean and maximum aortic wall thickness, left and right ejection fraction and aortic PWV we did not observe a significant age or sex effect. Conclusion This study provides age and sex specific reference values for cardiovascular MR parameters in healthy, young Caucasian adults. These may aid in MR guided pre-clinical identification of young adults who fall outside the physiological range of arterial and cardiac ageing. PMID:27732640

  15. Anti-Ro/SSA antibodies and cardiac arrhythmias in the adult: facts and hypotheses.

    Science.gov (United States)

    Lazzerini, P E; Capecchi, P L; Laghi-Pasini, F

    2010-09-01

    It is well established that the passive trans-placental passage of anti-Ro/SSA antibodies from mother to foetus is associated with the risk to develop an uncommon syndrome named neonatal lupus (NLE), where the congenital heart block represents the most severe clinical feature. Recent evidence demonstrated that also adult heart, classically considered invulnerable to the anti-Ro/SSA antibodies, may represent a target of the arrhythmogenicity of these autoantibodies. In particular, the prolongation of the QTc interval appears the most frequent abnormality observed in adults with circulating anti-Ro/SSA antibodies, with some data suggesting an association with an increased risk of ventricular arrhythmias, also life threatening. Moreover, even though the association between anti-Ro/SSA antibodies and conduction disturbances is undoubtedly less evident in adults than in infants, from the accurate dissection of the literature data the possibility arises that sometimes also the adult cardiac conduction tissue may be affected by such antibodies. The exact arrhythmogenic mechanisms involved in foetus/newborns and adults, respectively, have not been completely clarified as yet. However, increasing evidence suggests that anti-Ro/SSA antibodies may trigger rhythm disturbances through an inhibiting cross-reaction with several cardiac ionic channels, particularly the calcium channels (L-type and T-type), but also the potassium channel hERG, whose different expression and involvement in the cardiac electrophysiology during lifespan might account for the occurrence of age-related differences.

  16. Characterization and influence of cardiac background sodium current in the atrioventricular node

    OpenAIRE

    Cheng, Hongwei; Li, Jue; James, Andrew F.; Inada, Shin; Choisy, Stéphanie C.M.; Orchard, Clive H.; Zhang, Henggui; Boyett, Mark R.; Hancox, Jules C.

    2016-01-01

    Background inward sodium current (IB,Na) that influences cardiac pacemaking has been comparatively under-investigated. The aim of this study was to determine for the first time the properties and role of IB,Na in cells from the heart's secondary pacemaker, the atrioventricular node (AVN). Myocytes were isolated from the AVN of adult male rabbits and mice using mechanical and enzymatic dispersion. Background current was measured using whole-cell patch clamp and monovalent ion substitution with...

  17. How to formulate membrane potential in a spatially homogeneous myocyte model?

    OpenAIRE

    Tanskanen, A. J.; E. I. Tanskanen; Greenstein, J. L.; Winslow, R L

    2005-01-01

    Membrane potential in a mathematical model of a cardiac myocyte can be formulated in different ways. Assuming a spatially homogeneous myocyte that is strictly charge-conservative and electroneutral as a whole, two methods will be compared: (1) the differential formulation dV/dt=-I/C_m of membrane potential used traditionally; and (2) the capacitor formulation, where membrane potential is defined algebraically by the capacitor equation V=Q/C_m. We examine the relationship between the formulati...

  18. Cardiac adaptation to endurance training in young adult

    Directory of Open Access Journals (Sweden)

    Sandip Meghnad Hulke

    2011-01-01

    Full Text Available Context: Regular physical exercise is known to cause improvement of the cardiovascular function. This adaptation is studied here with the help of non-invasive methods. Aims: To evaluate morphological changes in heart by echocardiography, to see the effect of exercise on autonomic function, on aerobic power and to assess the sequence of changes. Settings and Design: Study comprises of 12-week duration and was done on the students of physical education. Materials and Methods: This study was a longitudinal study in which 100 subjects (51 male, 20.18 yrs±1.147, 49 female, 19.91 yrs±1.89 were assessed using electrocardiography, echocardiography and Queen′s College Step test (for VO 2max within 7 days of admission to their college and re-examined after 12 weeks. Statistical Analysis: Paired t-test using Graph pad prism5 software. Results: Electrocardiographic evaluation was suggestive of significant decrease in heart rate, significant increase in RR interval and t-wave amplitude in cardiac leads in males and similar but not significant result in females. No significant change was found in left ventricular morphology and ejection fraction after exercise program. Conclusions: The results of this study suggest that the exercise training over a period of 3 months does not influence cardiovascular morphology, but causes changes in parasympathetic and sympathetic tone and improves aerobic power.

  19. Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.

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    Wei-Chang Huang

    Full Text Available Myocardial injury, such as myocardial infarction (MI, can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.

  20. High sugar intake exacerbates cardiac reperfusion injury in perinatal taurine depleted adult rats

    OpenAIRE

    Kulthinee Supaporn; Wyss J Michael; Jirakulsomchok Dusit; Roysommuti Sanya

    2010-01-01

    Abstract Perinatal taurine depletion and high sugar diets blunted baroreflex function and heightens sympathetic nerve activity in adult rats. Cardiac ischemia/reperfusion also produces these disorders and taurine treatment appears to improve these effects. This study tests the hypothesis that perinatal taurine exposure predisposes recovery from reperfusion injury in rats on either a basal or high sugar diet. Female Sprague-Dawley rats were fed normal rat chow with 3% beta-alanine (taurine dep...

  1. Mechanical analysis of single myocyte contraction in a 3-D elastic matrix.

    Directory of Open Access Journals (Sweden)

    John Shaw

    Full Text Available BACKGROUND: Cardiac myocytes experience mechanical stress during each heartbeat. Excessive mechanical stresses under pathological conditions cause functional and structural remodeling that lead to heart diseases, yet the precise mechanisms are still incompletely understood. To study the cellular and molecular level mechanotransduction mechanisms, we developed a new 'cell-in-gel' experimental system to exert multiaxial (3-D stresses on a single myocyte during active contraction. METHODS: Isolated myocytes are embedded in an elastic hydrogel to simulate the mechanical environment in myocardium (afterload. When electrically stimulated, the in-gel myocyte contracts while the matrix resists shortening and broadening of the cell, exerting normal and shear stresses on the cell. Here we provide a mechanical analysis, based on the Eshelby inclusion problem, of the 3-D strain and stress inside and outside the single myocyte during contraction in an elastic matrix. RESULTS: (1 The fractional shortening of the myocyte depends on the cell's geometric dimensions and the relative stiffness of the cell to the gel. A slender or softer cell has less fractional shortening. A myocyte of typical dimensions embedded in a gel of similar elastic stiffness can contract only 20% of its load-free value. (2 The longitudinal stress inside the cell is about 15 times the transverse stress level. (3 The traction on the cell surface is highly non-uniform, with a maximum near its ends, showing 'hot spots' at the location of intercalated disks. (4 The mechanical energy expenditure of the myocyte increases with the matrix stiffness in a monotonic and nonlinear manner. CONCLUSION: Our mechanical analyses provide analytic solutions that readily lend themselves to parametric studies. The resulting 3-D mapping of the strain and stress states serve to analyze and interpret ongoing cell-in-gel experiments, and the mathematical model provides an essential tool to decipher and quantify

  2. THE EFFECT OF EXERCISE PRECONDITION INDUCED MIR-21 AND BAX GENE EXPRESSIONS ON RATS' CARDIAC MYOCYTE AFTER EXHAUSTIVE EXERCISES%运动预适应对力竭运动后心肌mir-21和bax基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    黄雅雯

    2011-01-01

    [目的]探讨运动预适应(excerise preconditioning,EP)对大鼠一次性力竭运动后心肌mir-21和bax基因表达的影响.[方法]健康雄性SD大鼠36只,随机分为对照组(C组)、一次性力竭运动组(E组)、运动预适应+一次性力竭运动组(EP组).力竭运动后即刻和24 h取各组心肌采用real-time PCR检测各心肌内mir-21和bax基因表达情况.[结果]EP可以显著抑制一次性力竭运动后心肌内mir-21基因的下调表达(P<0.05)和bax基因的上调表达(P<0.05).[结论]EP可以通过抑制mir-21基因下调从而抑制bax基因的上调来发挥保护作用.%[ Objective] To explore the effect of exercise preconditioning induced mir-21 and bax gene expressions on rats' cardiac myocyte after exhaustive exercises. [Methods] 36 healthy male SD rats were randomly divided into control group (C group) , exhaustive exercises (E group) , exercise preconditioning+ exhaustive exercises (EP group) .Used real-time PCR to detect expressions of mir-21 and bax after exhaustive exercises and 24h. [Results] The results of real-time PCR suggested that in EP group, down-regulation of mir-21 and up-regulation of bax cardiac myocyte were obviously inhibited by exhaustive exercises. [Conclusion] EP could inhibit the down-regulation of bax gene through inhibiting up-regulation of mir-21 gene.

  3. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: lushaj@surgery.wisc.edu [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)

    2012-06-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  4. Minimally invasive cardiac surgery in the adult: surgical instruments, equipment, and techniques.

    Science.gov (United States)

    Kitamura, M; Uwabe, K; Hirota, J; Kawai, A; Endo, M; Koyanagi, H

    1998-09-01

    To clarify the special instruments and equipment used for minimally invasive cardiac surgery (MICS), we examined the initial experiences with MICS operations with ministernotomy or minithoracotomy at our institution. Fifty adult patients with congenital, valvular, and/or ischemic heart diseases underwent MICS operations, and all surgical procedures were completed without conversion to full sternotomy. The length of the skin incision was about 10 cm or less in all patients. Postoperative recovery was favorable, and the majority of the patients were discharged from the hospital around the end of the second postoperative week. In this series of patients, an oscillating bone saw, lifting type retractor, 2 blade spreader, cannula with a balloon, and right-angled aortic clamp among other items, were very useful for successfully performing various operations with MICS approaches and techniques. The associated results suggest that MICS with ministernotomy or minithoracotomy was feasible using special instruments and equipment and could be encouraged for adult patients with various cardiovascular diseases.

  5. Coronary artery calcification is associated with atherogenic lipid changes, cardiac dysfunction and morphologic abnormalities in HIV-1 infected black adults

    Institute of Scientific and Technical Information of China (English)

    MENG Qing-yi; DU Jie-fu; LAI Hong; LAI Sheng-han

    2005-01-01

    @@ The heart is an organ frequently affected in the acquired immunodeficiency syndrome.1 But there is little information as to whether the coronary artery calcification can identify asymptomatic individuals at high risk for having cardiac morphological and functional abnormalities and cardiac risk factors in human immunodeficiency virus (HIV)-infected persons. Accordingly, the purpose of this study was to determine whether coronary artery calcification was associated with cardiac morphological and functional abnormalities, atherogenic lipid and C-reactive protein (CRP) changes in a black adult population with HIV-1 infection.

  6. Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult.

    Science.gov (United States)

    Silva, A C; Rodrigues, S C; Caldeira, J; Nunes, A M; Sampaio-Pinto, V; Resende, T P; Oliveira, M J; Barbosa, M A; Thorsteinsdóttir, S; Nascimento, D S; Pinto-do-Ó, P

    2016-10-01

    A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on β1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair. PMID:27424216

  7. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  8. High Density Sphere Culture of Adult Cardiac Cells Increases the Levels of Cardiac and Progenitor Markers and Shows Signs of Vasculogenesis

    Directory of Open Access Journals (Sweden)

    Kristina Vukusic

    2013-01-01

    Full Text Available 3D environment and high cell density play an important role in restoring and supporting the phenotypes of cells represented in cardiac tissues. The aim of this study was therefore to investigate the suitability of high density sphere (HDS cultures for studies of cardiomyocyte-, endothelial-, and stem-cell biology. Primary adult cardiac cells from nine human biopsies were cultured using different media for up to 9 weeks. The possibilities to favor a certain cell phenotype and induce production of extra cellular matrix (ECM were studied by histology, immunohistochemistry, and quantitative real-time PCR. Defined media gave significant increase in both cardiac- and progenitor-specific markers and also an intraluminal position of endothelial cells over time. Cardiac media showed indication of differentiation and maturity of HDS considering the ECM production and activities within NOTCH regulation but no additional cardiac differentiation. Endothelial media gave no positive effects on endothelial phenotype but increased proliferation without fibroblast overgrowth. In addition, indications for early vasculogenesis were found. It was also possible to affect the Wnt signaling in HDS by addition of a glycogen synthase kinase 3 (GSK3 inhibitor. In conclusion, these findings show the suitability of HDS as in vitro model for studies of cardiomyocyte-, endothelial-, and stem-cell biology.

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

    Science.gov (United States)

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

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

  10. shRNA沉默芳香烃受体表达对心肌细胞分化过程中WNT信号通路的影响%Effect of shRNA silenced aromatic hydrocarbon receptor on WNT signaling pathway during the differentiation of cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    范志刚; 朱春; 余章斌; 胡晓山; 李萌萌; 朱金改; 朱莎莎; 韩树萍

    2013-01-01

      目的观察芳香烃受体(AHR)基因沉默后对P19细胞向心肌分化进程中WNT信号通路的影响。方法根据小鼠AHR基因序列设计并构建AHR基因的shRNA真核表达载体,将AHR干扰质粒转染至P19细胞,通过G418筛选出稳定的AHR基因沉默表达的阳性细胞株,应用实时荧光定量RT-PCR技术检测P19细胞分化过程中WNT信号通路中关键基因GSK3β、β-catenin mRNA的表达水平。结果构建的AHR-shRNA表达质粒能显著抑制AHR基因的表达;随着P19细胞向心肌细胞分化,实验组β-catenin基因的相对表达量低于对照组,而GSK3β基因的相对表达量则高于对照组,差异均有统计学意义(P均<0.01)。结论干扰AHR基因表达对心脏发育过程中WNT信号通路产生调节作用。%Objective To explore the effect of shRNA silenced aromatic hydrocarbon receptor (AHR) on WNT signaling path-way during the differentiation of P19 cells into cardiac myocytes. Methods The eukaryotic expression vector of mouse AHR gene was designed and constructed. The interference plasmid was transfected into P19 cell and the positive stains to AHR gene silencing were screened by G418. The mRNA expression of important genes GSK3βandβ-catenin were evaluated by real-time fluorescent quantita-tive PCR during the differentiation of P19 cells. Results The constructed AHR-shRNA plasmid significantly inhibited the expression of AHR gene. Along with the differentiation of P19 cell into cardiac myocytes, in the interference group the expression ofβ-catenin gene was lower whereas the expression of GSK3βgene was elevated than those of control group with significant differences (all P<0.01). Conclusions The interference of AHR gene expression can regulate WNT signaling pathway in the development of heart.

  11. Ionic Remodeling and Direct Effects of Valsartan on Ionic Currentsin Human Atrial Myocytes with Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    Xue Yumei; Wu Shulin; Deng Chunyu; Qian Weimin; Chen Chunbo

    2004-01-01

    Objectives Previous studies demonstrated that angiotensin receptor antagonists had effects on some potassium channels in guinea pig myocytes and cloned channels that expressed in human cardiac myocytes. This study determined the direct effects of Valsartan on I caL, INa, IKur, IK1 and Ito1 in isolated human atrial myocytes. Methods and Results Specimens of right atrial appendage tissue were obtained from 39 patients with coronary artery and valvular heart diseases during cardiopulmonary bypass procedure. Pre- operation cardiac rhythm was sinus (SR)in 19 patients and was atrial fibrillation (AF) in the others. Single atrial myocyte was isolated by enzymatic dissociation with the chunk method. The ionic currents were recorded using the whole cell coffiguration of the voltage clamp technique. ICaL and Ito1 densities in AF patients were significantly lower than those in SR patients by 74% and 60%, respectively, while IK1density was significantly higher by 34% at command potential of - 120 mV. With 10 μmol/L Valsartan, INa density was significantly decreased by 59% in SR patients and by 66% in AF patients. IKur and IKl density were significantly decreased in only AF patients by 31% and23%, respectively. Conclusions Conclusions Decreased IcaL and Itol and increased IKl at hyperpolarizing potentials in AF patients' atrial myocytes may result from the electrophysiological remodeling by AF. Valsartan significantly decreases INa, IK1 and IKur current densities in AF patients' myocyte, but decreases only INa in SR patients' myocyte, suggesting that Valsartan may be beneficial to the recovering of remolded atria.

  12. 神经介素 B 对大鼠心室肌细胞 L 型钙离子通道调节及机制研究%Modulation of L-type Ca2 + channels by neuromedin B in adult rat ventricular myocytes and the underlying mechanisms

    Institute of Scientific and Technical Information of China (English)

    应娇茜; 张园; 孙玉芳; 张国强; 常志刚

    2016-01-01

    Objective Toinvestigagte the effects of neuromedin B (NeuroB) on L-type Ca2 +channel currents ( IL ) and clarify the relevant signal pathway in adult rat ventricular myocytes.Methods RT-PCR and western blotting analysis were used todetect the expression ofNeuroB receptors in adult rat ventricular myocytes. The content of cAM P was detected by ELISA. The whole-cell patch clamp recording was used to investigate the effect of NeuroB on IL in adult rat ventricular myocytes. Further transduction pathway was studied by pharmacological methods.Results The NeuroB receptorwas endogenouly expressed in adult rat ventricular myocytes. NeuroB enhanced IL in a concentration-dependent manner. NeuroB-mediated increasement of IL was blocked by phosphokinase A ( PKA ) antagonist KT-5720 ,while the antagonist of phosphokinase C (PKC ) GF109203X elicited no such effects. NeuroB induced significant increase of cAM P level in adult rat ventricular myocytes.Conclusions NeuroB enhanced IL in adult rat ventricular myocytes through a NeuroB receptor-denpendent PKA signalling pathway ,whereas PKC was not involved.%目的:研究神经介素 B(NeuroB)对成年大鼠心室肌细胞 L 型钙离子通道的调节及信号转导机制。方法应用 RT-PCR 及 Western blot 方法研究 NeuroB 受体 mRNA 及蛋白在成年大鼠心室肌细胞中的表达。应用 ELISA 方法检测 NeuroB 对心室肌细胞中 cAMP 含量的影响。应用全细胞膜片钳技术研究 NeuroB 对成年大鼠心室肌细胞 L 型钙离子通道电流(IL )的作用,并应用药理学方法阐明其信号转导机制。结果 NeuroB 受体在成年大鼠心室肌细胞中呈高表达。 NeuroB 对大鼠心室肌细胞 IL 具有量效依赖性的增加作用。蛋白激酶 A(PKA)阻断剂 KT-5720能够抑制 NeuroB对该 IL 的增强作用,但蛋白激酶 C(PKC)阻断剂 GF109203X 却无任何效应。 NeuroB 可浓度依赖性增加心室肌细胞中 cAMP 含量水平。结论 NeuroB

  13. Conventional hemofiltration during cardiopulmonary bypass increases the serum lactate level in adult cardiac surgery

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    Rabie Soliman

    2016-01-01

    Full Text Available Objective: To evaluate the effect of hemofiltration during cardiopulmonary bypass on lactate level in adult patients who underwent cardiac surgery. Design: An observational study. Setting: Prince Sultan cardiac center, Riyadh, Saudi Arabia. Participants: The study included 283 patients classified into two groups: Hemofiltration group (n=138, hemofiltration was done during CPB. Control group (n = 145, patients without hemofiltration. Interventions: Hemofiltration during cardiopulmonary bypass. Measurements and Main Results: Monitors included hematocrit, lactate levels, mixed venous oxygen saturation, amount of fluid removal during hemofiltration and urine output. The lactate elevated in group H than group C (P < 0.05, and the PH showed metabolic acidosis in group H (P < 0.05. The mixed venous oxygen saturation decreased in group H than group C (P < 0.05. The number of transfused packed red blood cells was lower in group H than group C (P < 0.05. The hematocrit was higher in group H than group C (P < 0.05. The urine output was lower in group H than group C (P < 0.05. Conclusions: Hemofiltration during cardiopulmonary bypass leads to hemoconcentration, elevated lactate level and increased inotropic support. There are some recommendations for hemofiltration: First; Hemofiltration should be limited for patients with impaired renal function, positive fluid balance, reduced response to diuretics or prolonged bypass time more than 2 hours. Second; Minimal amount of fluids should be administered to maintain adequate cardiac output and reduction of priming volumes is preferable to maintain controlled hemodilution. Third; it should be done before weaning of or after cardiopulmonary bypass and not during the whole time of cardiopulmonary bypass.

  14. Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac contractility

    Institute of Scientific and Technical Information of China (English)

    Ming ZHENG; Rong HOU; Rui-ping XIAO

    2004-01-01

    AIM: To determine the possible role of pH in mediating activation of p38 mitogen-activated protein kinase (MAPK) and the consequent function of activated p38 MAPK in regulating cardiac contractility. METHODS: Adult rat cardiomyocytes were isolated and cultured. Low pH media was used to induce intracellular acidosis and contraction of single cardiomyocyte was measured. RESULTS: Phosphorylation of p38 MAPK was increased during ischemia, and pHi was decreased. Intracellular acidosis activated p38 MAPK to a similar level as ischemia. Inhibition of p38 MAPK activation by SB203580, a specific inhibitor of p38 MAPK, reversed acidosis-mediated reduction of myocyte contractility. CONCLUSION: In adult rat cardiomyocytes, intracellular acidification activated p38 MAPK and decreased cardiac contractility. Pretreatment of cardiomyocytes with SB203580 completely blocked p38 MAPK activation and partially reversed acidosis-mediated decline of cardiac contractility.

  15. Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells

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    Piera D’Elia

    2013-01-01

    Full Text Available IGF-binding proteins (IGFBPs and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology.

  16. Dynamic Measurement of Hemodynamic Parameters and Cardiac Preload in Adults with Dengue: A Prospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Vipa Thanachartwet

    Full Text Available Few previous studies have monitored hemodynamic parameters to determine the physiological process of dengue or examined inferior vena cava (IVC parameters to assess cardiac preload during the clinical phase of dengue. From January 2013 to July 2015, we prospectively studied 162 hospitalized adults with confirmed dengue viral infection using non-invasive cardiac output monitoring and bedside ultrasonography to determine changes in hemodynamic and IVC parameters and identify the types of circulatory shock that occur in patients with dengue. Of 162 patients with dengue, 17 (10.5% experienced dengue shock and 145 (89.5% did not. In patients with shock, the mean arterial pressure was significantly lower on day 6 after fever onset (P = 0.045 and the pulse pressure was significantly lower between days 4 and 7 (P50% between days 4 and 5 (P<0.05. Hypovolemic shock was observed in 9 (52.9% patients and cardiogenic shock in 8 (47.1%, with a median (interquartile range time to shock onset of 6.0 (5.0-6.5 days after fever onset, which was the median day of defervescence. Intravascular hypovolemia occurred before defervescence, whereas myocardial dysfunction occurred on the day of defervescence until 2 weeks after fever onset. Hypovolemic shock and cardiogenic shock each occurred in approximately half of the patients with dengue shock. Therefore, dynamic measures to estimate changes in hemodynamic parameters and preload should be monitored to ensure adequate fluid therapy among patients with dengue, particularly patients with dengue shock.

  17. Transfection of hypertrophic cardiac myocytes in vitro with 99Tcm-labeled antisense miR208b oligonucleotide%99Tcm标记反义miR208b寡核苷酸及其转染离体肥大心肌细胞的实验研究

    Institute of Scientific and Technical Information of China (English)

    王静; 冯会娟; 欧阳伟; 孙云钢; 吴菊清; 陈盼

    2015-01-01

    Objective To test the efficiency of transfecting 9 Tcm-labeled anti-miR208b oligonucleotide into early hypertrophic cardiac myocytes in vitro. Methods The anti-oligonucleotide targeting miR208b (AMO) was synthesized and modified with LNA followed by conjugation with N-hydroxysuccinimidyl S-acetyl-meraptoacetyl triglycine (NHS-MAG3) and radiolabeling with 9 Tcm. NHS-MAG3-LNA-AMO and labeled AMO were purified with Sep-Pak C18 column chromatography, and the former was examined for UV absorption at the 260 nm using Gene Quant DNA/RNA calculator. The labeling efficiency, radiochemical purity, stability and molecular hybridization activity were analyzed. An angiotensin II-induced cell model of hypertrophic cardiac myocytes was transfected with 9 Tcm-NHS-MAG3-LNA-AMO via liposome, and the relative expression of miRNA208b and retention ratio of the labeled AMO in early hypertrophic cells were determined. Results The labeling efficiency and radiochemical purity of the labeled AMO after purification exceeded 84% and 86%, respectively. The radio-chemical purities of the labeled AMO incubated in serum and normal saline for 12 h were both higher than 80%, and the labeled AMO showed a capacity to hybridize with the target gene. In the hypertrophic model of cardiac myocytes, the retention ratio of labeled AMO at 6 h was higher than 20%. Conclusion The 9 Tcm-labeled antisense probe can be efficiently transfected into hypertrophic cardiac myocytes in vitro, which provides an experimental basis for subsequent radionuclide imaging studies.%目的:探索用放射性核素99Tcm标记反义miR208b寡核苷酸,并转染离体早期肥大心肌细胞的实验过程及方法。方法合成针对miR208b的反义miR寡核苷酸(AMO),LNA(带锁核酸)修饰AMO,将双功能螯合剂NHS-MAG3(N-羟基琥珀酰亚胺-巯基乙酰基三甘氨酸)与LNA-AMO偶联后,用99Tcm标记,然后用Sep-Pak C18反相层析法对NHS-MAG3-LNA-AMO及其标记物进行洗

  18. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  19. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    Directory of Open Access Journals (Sweden)

    Daniela L Buscariollo

    Full Text Available Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg or vehicle (0.09% NaCl i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  20. Beating and insulting children as a risk for adult cancer, cardiac disease and asthma.

    Science.gov (United States)

    Hyland, Michael E; Alkhalaf, Ahmed M; Whalley, Ben

    2013-12-01

    The use of physical punishment for children is associated with poor psychological and behavioral outcomes, but the causal pathway is controversial, and the effects on later physical health unknown. We conducted a cross-sectional survey of asthma, cancer, and cardiac patients (150 in each category, 75 male) recruited from outpatient clinics and 250 healthy controls (125 male). All participants were 40-60 years old and citizens of Saudi Arabia, where the use of beating and insults is an acceptable parenting style. Demographic data and recalled frequency of beatings and insults as a child were assessed on an 8-point scale. Beating and insults were highly correlated (ρ = 0.846). Propensity score matching was used to control for demographic differences between the disease and healthy groups. After controlling for differences, more frequent beating (once or more per month) and insults were associated with a significantly increased risk for cancer (RR = 1.7), cardiac disease (RR = 1.3) and asthma (RR = 1.6), with evidence of increased risk for cancer and asthma with beating frequency of once every 6 months or more. Our results show that a threatening parenting style of beating and insults is associated with increased risk for somatic disease, possibly because this form of parenting induces stress. Our findings are consistent with previous research showing that child abuse and other early life stressors adversely affect adult somatic health, but provide evidence that the pathogenic effects occur also with chronic minor stress. A stress-inducing parenting style, even when normative, has long term adverse health consequences. PMID:23054177

  1. Excitation-Contraction Coupling between Human Atrial Myocytes with Fibroblasts and Stretch Activated Channel Current: A Simulation Study

    Directory of Open Access Journals (Sweden)

    Heqing Zhan

    2013-01-01

    Full Text Available Myocytes have been regarded as the main objectives in most cardiac modeling studies and attracted a lot of attention. Connective tissue cells, such as fibroblasts (Fbs, also play crucial role in cardiac function. This study proposed an integrated myocyte-Isac-Fb electromechanical model to investigate the effect of Fbs and stretch activated ion channel current (Isac on cardiac electrical excitation conduction and mechanical contraction. At the cellular level, an active Fb model was coupled with a human atrial myocyte electrophysiological model (including Isac and a mechanical model. At the tissue level, electrical excitation conduction was coupled with an elastic mechanical model, in which finite difference method (FDM was used to solve the electrical excitation equations, while finite element method (FEM was used for the mechanics equations. The simulation results showed that Fbs and Isac coupling caused diverse effects on action potential morphology during repolarization, depolarized the resting membrane potential of the human atrial myocyte, slowed down wave propagation, and decreased strains in fibrotic tissue. This preliminary simulation study indicates that Fbs and Isac have important implications for modulating cardiac electromechanical behavior and should be considered in future cardiac modeling studies.

  2. Human embryonic and fetal mesenchymal stem cells differentiate toward three different cardiac lineages in contrast to their adult counterparts.

    Science.gov (United States)

    Ramkisoensing, Arti A; Pijnappels, Daniël A; Askar, Saïd F A; Passier, Robert; Swildens, Jim; Goumans, Marie José; Schutte, Cindy I; de Vries, Antoine A F; Scherjon, Sicco; Mummery, Christine L; Schalij, Martin J; Atsma, Douwe E

    2011-01-01

    Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.

  3. Does Parsonnet scoring model predict mortality following adult cardiac surgery in India?

    Directory of Open Access Journals (Sweden)

    Moningi Srilata

    2015-01-01

    Full Text Available Aims and Objectives: To validate the Parsonnet scoring model to predict mortality following adult cardiac surgery in Indian scenario. Materials and Methods: A total of 889 consecutive patients undergoing adult cardiac surgery between January 2010 and April 2011 were included in the study. The Parsonnet score was determined for each patient and its predictive ability for in-hospital mortality was evaluated. The validation of Parsonnet score was performed for the total data and separately for the sub-groups coronary artery bypass grafting (CABG, valve surgery and combined procedures (CABG with valve surgery. The model calibration was performed using Hosmer-Lemeshow goodness of fit test and receiver operating characteristics (ROC analysis for discrimination. Independent predictors of mortality were assessed from the variables used in the Parsonnet score by multivariate regression analysis. Results: The overall mortality was 6.3% (56 patients, 7.1% (34 patients for CABG, 4.3% (16 patients for valve surgery and 16.2% (6 patients for combined procedures. The Hosmer-Lemeshow statistic was <0.05 for the total data and also within the sub-groups suggesting that the predicted outcome using Parsonnet score did not match the observed outcome. The area under the ROC curve for the total data was 0.699 (95% confidence interval 0.62-0.77 and when tested separately, it was 0.73 (0.64-0.81 for CABG, 0.79 (0.63-0.92 for valve surgery (good discriminatory ability and only 0.55 (0.26-0.83 for combined procedures. The independent predictors of mortality determined for the total data were low ejection fraction (odds ratio [OR] - 1.7, preoperative intra-aortic balloon pump (OR - 10.7, combined procedures (OR - 5.1, dialysis dependency (OR - 23.4, and re-operation (OR - 9.4. Conclusions: The Parsonnet score yielded a good predictive value for valve surgeries, moderate predictive value for the total data and for CABG and poor predictive value for combined procedures.

  4. Transcatheter Closure of Atrial Septal Defects Improves Cardiac Remodeling and Function of Adult Patients with Permanent Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    Liang Chen; Yuan Bai; Fei-Yu Wang; Zhi-Gang Zhang; Xing-Hua Shan; Tao Chen; Xian-Xian Zhao

    2015-01-01

    Background:Permanent atrial fibrillation (AF) is the most common form of dysrhythmia associated with atrial septal defects (ASDs) in patients older than 40 years.However,little is known about cardiac remodeling after transcatheter closure in patients with permanent AF.This study was designed to compare cardiac events and remodeling effects after transcatheter closure in such patients.Methods:Clinical data of 289 adult patients older than 40 years who underwent ASD closure at our center were analyzed retrospectively.Of them,63 patients with permanent AF were assigned to the case group,and the other 226 patients without permanent AF were assigned to the control group.Cardiac events and changes in left and right cardiac cavity dimensions before the procedure and 6 months after the procedure were compared between the two groups.Results:Patients in the case group were significantly older than those in the control group.The right ventricular (RV) volume and right atrial (RA) volume were decreased significantly in both the groups during a median follow-up period of 6 months after closure (P < 0.001).The left atrial dimensions,left ventricular end-systolic dimensions,left ventricular end-diastolic dimensions and left ventricular ejection fraction showed no significant change before and after the procedure in both the groups.Changes of the RV volume and RA volume in the case group were significantly smaller than those in the control group (P =0.005 and P < 0.001).The New York Heart Association cardiac function was improved in both the groups during the 6 months follow-up period.Conclusions:The transcatheter closure of ASD can improve the cardiac remodeling and cardiac function in patients with or without AF.

  5. Transcatheter Closure of Atrial Septal Defects Improves Cardiac Remodeling and Function of Adult Patients with Permanent Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Liang Chen

    2015-01-01

    Full Text Available Background: Permanent atrial fibrillation (AF is the most common form of dysrhythmia associated with atrial septal defects (ASDs in patients older than 40 years. However, little is known about cardiac remodeling after transcatheter closure in patients with permanent AF. This study was designed to compare cardiac events and remodeling effects after transcatheter closure in such patients. Methods: Clinical data of 289 adult patients older than 40 years who underwent ASD closure at our center were analyzed retrospectively. Of them, 63 patients with permanent AF were assigned to the case group, and the other 226 patients without permanent AF were assigned to the control group. Cardiac events and changes in left and right cardiac cavity dimensions before the procedure and 6 months after the procedure were compared between the two groups. Results: Patients in the case group were significantly older than those in the control group. The right ventricular (RV volume and right atrial (RA volume were decreased significantly in both the groups during a median follow-up period of 6 months after closure (P < 0.001. The left atrial dimensions, left ventricular end-systolic dimensions, left ventricular end-diastolic dimensions and left ventricular ejection fraction showed no significant change before and after the procedure in both the groups. Changes of the RV volume and RA volume in the case group were significantly smaller than those in the control group (P = 0.005 and P < 0.001. The New York Heart Association cardiac function was improved in both the groups during the 6 months follow-up period. Conclusions: The transcatheter closure of ASD can improve the cardiac remodeling and cardiac function in patients with or without AF.

  6. Inhibition of ref-1 stimulates the production of reactive oxygen species and induces differentiation in adult cardiac stem cells.

    Science.gov (United States)

    Gurusamy, Narasimman; Mukherjee, Subhendu; Lekli, Istvan; Bearzi, Claudia; Bardelli, Silvana; Das, Dipak K

    2009-03-01

    Redox effector protein-1 (Ref-1) plays an essential role in DNA repair and redox regulation of several transcription factors. In the present study, we examined the role of Ref-1 in maintaining the redox status and survivability of adult cardiac stem cells challenged with a subtoxic level of H2O2 under inhibition of Ref-1 by RNA interference. Treatment of cardiac stem cells with a low concentration of H2O2 induced Ref-1-mediated survival signaling through phosphorylation of Akt. However, Ref-1 inhibition followed by H2O2 treatment extensively induced the level of intracellular reactive oxygen species (ROS) through activation of the components of NADPH oxidase, like p22( phox ), p47( phox ), and Nox4. Cardiac differentiation markers (Nkx2.5, MEF2C, and GATA4), and cell death by apoptosis were significantly elevated in Ref-1 siRNA followed by H2O2-treated stem cells. Further, inhibition of Ref-1 increased the level of p53 but decreased the phosphorylation of Akt, a molecule involved in survival signaling. Treatment with ROS scavenger N-acetyl-L-cysteine attenuated Ref-1 siRNA-mediated activation of NADPH oxidase and cardiac differentiation. Taken together, these results indicate that Ref-1 plays an important role in maintaining the redox status of cardiac stem cells and protects them from oxidative injury-mediated cell death and differentiation.

  7. Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Claudia O Rodrigues

    Full Text Available RATIONALE: The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types. OBJECTIVE: To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations. METHODS AND RESULTS: c-kit+, sca-1+ CPCs obtained from adult mouse left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and were self-renewing, pluripotent and clonogenic. Detailed single cell clonal analysis of 17 clones revealed that most (14/17 exhibited trilineage differentiation potential. However, striking morphological differences were observed among clones that were heritable and stable in long-term culture. 3 major groups were identified: round (7/17, flat or spindle-shaped (5/17 and stellate (5/17. Stellate morphology was predictive of vasculogenic differentiation in Matrigel. Genome-wide expression studies and bioinformatic analysis revealed clonally stable, heritable differences in stromal cell-derived factor-1 (SDF-1 expression that correlated strongly with stellate morphology and vasculogenic capacity. Endogenous SDF-1 production contributed directly to vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100, an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4, reduced tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non-vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel dermal implants in vivo, while CPCs with low SDF-1 production were not. CONCLUSIONS: Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene expression patterns and differentiation potential. Clone-specific levels of SDF-1 expression both predict and promote development of a vasculogenic phenotype via a previously unreported autocrine

  8. PERK signal pathway is involved in hypoxia-induced endoplasmic reti culum stress and apoptosis in cultured cardiac myocytes%PERK通路参与了缺氧心肌细胞的内质网应激及凋亡

    Institute of Scientific and Technical Information of China (English)

    刘春蕾; 李鑫; 李蕊君; 何云云; 何昆仑; 王莉莉

    2012-01-01

    AIM: To invesligale the role of endoplasmic reliculum (ER) slress in the process of hypoxia — induced neonalal ral myocardial injury through PERK signal pathway. METHODS: Neonalal rat cardiac myocyles were randomly divided into conlrol group and hypoxia 1 h, 4 h, 8 h, 12 h and 24 h groups. Cell viability was evaluated by delermi-ning the inlracellular conlenl of ATP. Apoptosis was measured by high — conlenl analysis ( HCA) cell imaging syslem. The prolein levels of GRP78, calreliculin, p — PERK, p — eIF2α, ATF4 and CHOP were delecled by Weslern blolling at differ-ent Lime poinls. The primary cullured neonalal ral cardiac myocyles were Irealed with an agonisl of PERK palhway salu-brinal and the cell apoplosis was observed under hypoxia. RESULTS: In the early phase, hypoxia induced an increase in the expression of calreliculin and GPR78. In the middle phase of hypoxia, the levels of p — PERK, p — eIF2α and ATF4 were increased. In the later phase of hypoxia, increased CHOP level was also observed. Salubrinal effectively prolecled the cardiac myocyles from hypoxic injury. CONCLUSION: Hypoxia aclivales ER slress in cardiac myocyles and also aclivales PERK signal palhway. PERK signaling prolecls cardiac myocyles from hypoxic damage in the early stage and triggers apoplosis of the cells in the laler phase.%目的:观察缺氧对原代培养的Wistar乳鼠心肌细胞的损伤,探讨内质网应激在缺氧心肌损伤发生发展过程中起的作用及PERK通路是否参与其信号转导过程.方法:将原代培养的乳鼠心肌细胞随机分为正常对照组和缺氧1 h、4 h、8 h、12 h、24 h组,通过测定细胞ATP含量反映细胞活力;高内涵分析细胞成像系统检测多参数凋亡;采用免疫细胞化学和蛋白印迹方法检测以内质网为靶点的分子伴侣(GRP78和钙网蛋白)的表达,PERK通路(PERK和eIF2α)的磷酸化水平,以及其下游分子(ATF4和CHOP)在缺氧不同时点蛋白的表达变化特征.采用PERK

  9. Quality of Life in Young Adult Patients with a Cardiogenetic Condition Receiving an ICD for Primary Prevention of Sudden Cardiac Death

    NARCIS (Netherlands)

    Verkerk, Agnes J.; Vermeer, Alexa M.; Smets, Ellen M.; Dekker, Lukas R.; Wilde, Arthur A.; Van Langen, Irene M.; Christiaans, Imke; Nieuwkerk, Pythia T.

    2015-01-01

    BackgroundProphylactic implantable cardioverter defibrillator (ICD) therapy prevents sudden cardiac death (SCD) among young adults with cardiogenetic conditions, but might reduce quality of life (QoL) due to potential device complications, ongoing medical appointments, and lifestyle restrictions. We

  10. Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

    OpenAIRE

    Shengqiong Deng; Qian Zhao; Xianjin Zhou; Lin Zhang; Luer Bao; Lixiao Zhen; Yuzhen Zhang; Huimin Fan; Zhongmin Liu; Zuoren Yu

    2016-01-01

    Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been pro...

  11. Expression Profile of microRNAs Regulating Proliferation and Differentiation in Mouse Adult Cardiac Stem Cells

    OpenAIRE

    Brás-Rosário, Luis; Matsuda, Alex; Pinheiro, Ana Isabel; Gardner, Rui; Lopes, Telma; Amaral, Andreia; Gama-Carvalho, Margarida

    2013-01-01

    The identification of cardiac cells with stem cell properties changed the paradigm of the heart as a post mitotic organ. These cells proliferate and differentiate into cardiomyocytes, endothelial and vascular smooth muscle cells, providing for cardiac cell homeostasis and regeneration. microRNAs are master switches controlling proliferation and differentiation, in particular regulating stem cell biology and cardiac development. Modulation of microRNAs -regulated gene expression networks holds...

  12. Neonatal Heart-Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats

    Directory of Open Access Journals (Sweden)

    Shengqiong Deng

    2016-06-01

    Full Text Available Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem/progenitor cells. Reactivation of cardiac stem/progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been proven in adult humans. A lower level of miR-708 in c-kit(+ stem/progenitor cells was detected compared to non-progenitors. Overexpression of miR-708 induced cardiomyocyte differentiation of cardiac stem/progenitor cells. This finding strengthened the potential of applying miRNAs in the regeneration of injured hearts, and this indicates that miR-708 could be a novel candidate for treatment of heart diseases.

  13. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

    Institute of Scientific and Technical Information of China (English)

    Qiangzhe Zhang; Li Chen; Tian Tian; Xin Wang; Pu Li; Jurgen Hescheler; Guangju Ji; Yue Ma; Junjie Jiang; Pengcheng Han; Qi Yuan; Jing Zhang; Xiaoqian Zhang; Yanyan Xu; Henghua Cao; Qingzhang Meng

    2011-01-01

    Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs)are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs. We found that both Noggin and the panretinoic acid receptor antagonist BMS-189453 (RAi) significantly increased the cardiac differentiation efficiency of hESCs. To investigate retinoid functions, we compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results showed that the expression levels of the ventricular-specific gene IRX-4 were radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular-specific marker, was expressed in the majority of the cardiomyocytes in Noggin+RAi-treated cultures, hut not in the cardiomyocytes of Noggin+RA-treated cultures. Flow cytometry analysis and electrophysiologicai studies indicated that with 64.7 ± 0.88% (mean ± s.e.m) cardiac differentiation efficiency, 83% of the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like action potentials (APs). With 50.7 ± 1.76% cardiac differentiation efficiency, 94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like APs. These results were further confirmed by imaging studies that assessed the patterns and properties of the Ca2+ sparks of the cardiomyocytes from the two cultures. These findings demonstrate that retinoid signaling specifies the atrial versus ventricular differentiation of hESCs. This study also shows that relatively homogeneous embryonic atrial- and ventricular-like myocyte populations can be efficiently derived from hESCs by specifically regulating Noggin

  14. Nongenomic steroid action: Inhibiting effects on cell-to-cell communication between rat ventricular myocytes

    OpenAIRE

    Verrecchia, Franck; Sarrouilhe, Denis; Hervé, Jean-Claude

    2001-01-01

    Numerous steroids are now believed to possess rapid membrane effects independent of the classical gene activation pathways and are potent modulators of membrane proteins, including voltage-and ligand-operated channels. The effects of steroids on the functional state of the intercellular channels clustered in gap junctions were compared by estimation of either the permeability for a fluorescent dye or the electrical conductance in cardiac myocytes of newborn rat. At 25 μM, the esters of 17β-es...

  15. Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

    OpenAIRE

    Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E.; Zhong, Ju-ming

    2015-01-01

    Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- a...

  16. Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes.

    OpenAIRE

    Ibarra, J; Morley, G E; Delmar, M

    1991-01-01

    The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

  17. Cardiac abnormalities in adult patients with polymyositis or dermatomyositis as assessed by non-invasive modatities

    DEFF Research Database (Denmark)

    Christensen, Anne Friesgaard

    2016-01-01

    Objectives Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies (IIM). The study objective was in a controlled setting to describe cardiac abnormalities by non-invasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM......) and to identify predictors for cardiac dysfunction. Methods In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HC) were assessed by serum levels of cardiac troponin-I (TnI), electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging (TDI) and quantitative...... cardiac (99m) technetium pyrophosphate ((99m) Tc-PYP) scintigraphy. Results Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% vs. 0%, P = 0.02) and longer QRS and QTc intervals (P = 0.007 and P 

  18. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults

    DEFF Research Database (Denmark)

    Straus, Sabine M J M; Kors, Jan A; De Bruin, Marie L;

    2006-01-01

    OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation...... of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study......). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men...

  19. Does grid-controlled fluoroscopy lower patient doses during adult cardiac procedures ?

    International Nuclear Information System (INIS)

    Purpose: Commercial companies advertise grid-controlled fluoroscopy as a tool that significantly lowers patient and consequently staff doses. In the haemodynamic unit of Athens General Hospital, a Philips Allura FP10 digital flat panel system equipped with a grid-controlled X-ray tube has been installed in 2004. Twenty months later, the grid ceased to function and the question arose whether the X-ray tube should be replaced. Since the cost of grid-controlled X-ray tube is very high, it was decided that the laboratory should continue working as long as the X-ray tube would function. Material and Method: Since interventional procedures are known to be associated with high radiation doses, patient doses are routinely recorded. The data include fluoroscopy time, number of images acquired, as well as the total and fluoroscopic Dose-Area-Product (DAP) dose delivered to patient. From our dose records patient doses collected during Coronary Angiography (CA) and Percutaneous Transluminal Coronary Angioplasty (PTCA) with and without the grid-controlled fluoroscopy present were compared on a total sample of 998 patients. Results: The analysis of the results showed that (a) no statistically significant patient dose increase was noticed with grid not in use, (b) the difference in fluoroscopy time was not statistically significant for CA procedures, while it was statistically significant for PTCA procedures and (c) for both kinds of procedures the difference in number of frames, with and without the grid in use, was statistically significant (more frames when grid not in use). Conclusion: The results of this study suggest that hospital administrators may question the costly investment on grid-controlled X-ray tubes, with the deficient function of which -during adult cardiac diagnostic and therapeutic interventions-, patient dose does not increase, even when more frames are recorded. (author)

  20. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia.

    Science.gov (United States)

    Reyes, Laura M; Kirschenman, Raven; Quon, Anita; Morton, Jude S; Shah, Amin; Davidge, Sandra T

    2015-09-01

    Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P ≤ 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID:26157059

  1. Comparison of cardiac magnetic resonance imaging features of isolated left ventricular non-compaction in adults versus dilated cardiomyopathy in adults

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, H. [Department of Radiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, S., E-mail: cjrzhaoshihua2009@163.com [Department of Radiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Jiang, S.; Lu, M.; Yan, C.; Ling, J.; Zhang, Y.; Liu, Q.; Ma, N.; Yin, G.; Wan, J. [Department of Radiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Yang, Y. [Department of Cardiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Li, L. [Department of Pathology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Jerecic, R. [MR Research and Development, Siemens Medical Solutions, Chicago, IL (United States); He, Z. [Department of Nuclear Medicine, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China)

    2011-09-15

    Aim: To compare cardiac magnetic resonance imaging (MRI) features between isolated left ventricular non-compaction (IVNC) and dilated cardiomyopathy (DCM) in adults. Materials and methods: A consecutive series of 50 patients with IVNC from a single institution were reviewed. During the same period, 50 patients with DCM who had prominent trabeculations, who were matched for age, gender, and body surface area, were prospectively included. Left ventricular (LV) morphology and function were assessed using cardiac MRI. Results: Compared with patients with DCM, patients with IVNC had a significantly lower LV sphericity index and end-diastolic volume index (LVEDVI) and a greater LV ejection fraction (LVEF), number of trabeculated segments, and ratio of non-compacted to compacted myocardium (NC/C ratio). There were no significant differences in stroke volume index, cardiac output, and cardiac index between the two patient groups. In patients with IVNC, the number of trabeculated segments and the NC/C ratio correlated positively with LVEDVI (r = 0.626 and r = 0.559, respectively) and negatively with LVEF (r = -0.647 and r = -0.521, respectively, p < 0.001 for all). In patients with DCM, the number of non-compacted segments and the NC/C ratio had no correlation with either the LVEDVI (r = -0.082 and r = -0.135, respectively) or the LVEF (r = 0.097 and r = 0.205, respectively). Conclusion: There are demonstrable morphological and functional differences between IVNC and DCM at LV assessment using cardiac MRI. The occurrence of trabeculated myocardium might be due to a different pathophysiological mechanism.

  2. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation

    NARCIS (Netherlands)

    Kamphuis, M.; Zwinderman, K.A.H.; Vogels, T.; Vliegen, H.W.; Kamphuis, R.P.; Ottenkamp, J.; Verloove-Vanhorick, S.P.; Bruil, J.

    2004-01-01

    This study represents the development and validation of a cardiac-specific module of the generic health-related quality of life (HRQoL) instrument, the TAAQOL (TNO/AZL Adult Quality Of Life), for young adults with congenital heart disease (CHD). Items were selected based on literature, an explorativ

  3. Plasma high sensitivity troponin T levels in adult survivors of childhood leukaemias: determinants and associations with cardiac function.

    Directory of Open Access Journals (Sweden)

    Yiu-fai Cheung

    Full Text Available BACKGROUND: We sought to quantify plasma high sensitivity cardiac troponin (hs-cTnT levels, their determinants, and their associations with left ventricular (LV myocardial deformation in adult survivors of childhood acute leukaemias. METHODS AND RESULTS: One hundred adult survivors (57 males of childhood acute leukaemias, aged 24.1 ± 4.2 years, and 42 age-matched controls (26 males were studied. Plasma cTnT was determined using a highly sensitive assay. Genotyping of NAD(PH oxidase and multidrug resistance protein polymorphisms was performed. Left ventricular function was assessed by conventional, three-dimensional, and speckle tracking echocardiography. The medians (interquartile range of hs-cTnT in male and female survivors were 4.9 (4.2 to 7.2 ng/L and 1.0 (1.0 to 3.5 ng/L, respectively. Nineteen survivors (13 males, 6 females (19% had elevated hs-cTnT (>95(th centile of controls. Compared to those without elevated hs-TnT levels, these subjects had received larger cumulative anthracycline dose and were more likely to have leukaemic relapse, stem cell transplant, and cardiac irradiation. Their LV systolic and early diastolic myocardial velocities, isovolumic acceleration, and systolic longitudinal strain rate were significantly lower. Survivors having CT/TT at CYBA rs4673 had higher hs-cTnT levels than those with CC genotype. Functionally, increased hs-cTnT levels were associated with worse LV longitudinal systolic strain and systolic and diastolic strain rates. CONCLUSIONS: Increased hs-cTnT levels occur in a significant proportion of adult survivors of childhood acute leukaemias and are associated with larger cumulative anthracycline dose received, history of leukaemic relapse, stem cell transplant, and cardiac irradiation, genetic variants in free radical metabolism, and worse LV myocardial deformation.

  4. Cardiac and non-cardiac causes of T-wave inversion in the precordial leads in adult subjects: A Dutch case series and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Salah; AM; Said; Rene; Bloo; Ramon; de; Nooijer; Andries; Slootweg

    2015-01-01

    AIM: To describe the electrocardiographic(ECG) phenomena characterized by T-wave inversion in the precordial leads in adults and to highlight its differential diagnosis. METHODS: A retrospective chart review of 8 adult patients who were admitted with ECG T-wave inversion in the anterior chest leads with or without prolongation of corrected QT(QTc) interval. They had different clinical conditions. Each patient underwent appropriate clinical assessment including investigation for myocardial involvement. Single and multimodality noninvasive, semi-invasive and invasive diagnostic approach were used to ascertain the diagnosis. The diagnostic assessment included biochemical investigation, cardiac and abdominal ultrasound, cerebral and chest computed tomography, nuclear medicine and coronary angiography.RESULTS: Eight adult subjects(5 females) with a mean age of 66 years(range 51 to 82) are analyzed. The etiology of T-wave inversion in the precordial leads were diverse. On admission, all patients had normal blood pressure and the ECG showed sinus rhythm. Five patients showed marked prolongation of the QTc interval. The longest QTc interval(639 ms) was found in the patient with pheochromocytoma. Giant T-wave inversion(≥ 10 mm) was found in pheochromocytoma followed by electroconvulsive therapy and finally ischemic heart disease. The deepest T-wave was measured in lead V3(5 ×). In 3 patients presented with mild T-wave inversion(patients 1, 5 and 4 mm), the QTc interval was not prolonged(432, 409 and 424 msec), respectively.CONCLUSION: T-wave inversion associated with or without QTc prolongation requires meticulous history taking, physical examination and tailored diagnostic modalities to reach rapid and correct diagnosis to establish appropriate therapeutic intervention.

  5. Centrifugal pump and roller pump in adult cardiac surgery: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Saczkowski, Richard; Maklin, Michelle; Mesana, Thierry; Boodhwani, Munir; Ruel, Marc

    2012-08-01

    Centrifugal pump (CP) and roller pump (RP) designs are the dominant main arterial pumps used in cardiopulmonary bypass (CPB). Trials reporting clinical outcome measures comparing CP and RP are controversial. Therefore, a meta-analysis was undertaken to evaluate clinical variables from randomized controlled trials (RCTs). Keyword searches were performed on Medline (1966-2011), EmBase (1980-2011), and CINAHL (1981-2011) for studies comparing RP and CP as the main arterial pump in adult CPB. Pooled fixed-effects estimates for dichotomous and continuous data were calculated as an odds ratio and weighted-mean difference, respectively. The P value was utilized to assess statistical significance (P pump-related malfunction or mishap. The meta-analysis of RCTs comparing CP and RP in adult cardiac surgery suggests no significant difference for hematological variables, postoperative blood loss, transfusions, neurological outcomes, or mortality.

  6. Pro: early extubation in the operating room following cardiac surgery in adults.

    Science.gov (United States)

    Singh, Karen E; Baum, Victor C

    2012-12-01

    There is growing evidence that the general current approach in many centers of continued mechanical ventilation following cardiac surgery has evolved through historical experience rather than having a strong physiological basis in current practice. There is evidence going back several decades supporting very early (in the operating room [OR]) extubation in pediatric cardiac anesthesia. The authors provide evidence from numerous sources showing that extubation in the OR or shortly after arrival in the ICU is safe and cost-effective and is not prevented by the type of cardiac surgery or the use of cardiopulmonary bypass. They query if the paradigm should not be reversed and very early extubation be the routine unless contraindicated. Like any anesthetic technique, appropriate patient selection is called for, but this technique is widely appropriate. PMID:22798230

  7. Evaluation of the influence of pulmonary hypertension in ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio da Silva

    2015-08-01

    Full Text Available Abstract Objective: To evaluate the influence of pulmonary hypertension in the ultra-fast-track anesthesia technique in adult cardiac surgery. Methods: A retrospective study. They were included 40 patients divided into two groups: GI (without pulmonary hypertension and GII (with pulmonary hypertension. Based on data obtained by transthoracic echocardiography. We considered as the absence of pulmonary hypertension: a pulmonary artery systolic pressure (sPAP 40 mmHg associated with additional echocardiographic signs of PH. It was established as influence of pulmonary hypertension: the impossibility of extubation in the operating room, the increase in the time interval for extubation and reintubation the first 24 hours postoperatively. Univariate and multivariate analyzes were performed when necessary. Considered significant a P value <0.05. Results: The GI was composed of 21 patients and GII for 19. All patients (100% were extubated in the operating room in a medium time interval of 17.58±8.06 min with a median of 18 min in GII and 17 min in GI. PH did not increase the time interval for extubation (P=0.397. It required reintubation of 2 patients in GII (5% of the total, without statistically significant as compared to GI (P=0.488. Conclusion: In this study, pulmonary hypertension did not influence on ultra-fast-track anesthesia in adult cardiac surgery.

  8. Calcium handling by vascular myocytes in hypertension

    Directory of Open Access Journals (Sweden)

    R.C.A. Tostes

    1997-03-01

    Full Text Available Calcium ions (Ca2+ trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1 the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2 Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3 intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4 using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

  9. Association of renal function with cardiac calcifications in older adults : the cardiovascular health study

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Mozaffarian, Dariush; Katz, Ronit; Kestenbaum, Bryan; Fried, Linda F.; Gottdiener, John S.; Shlipak, Michael G.; Siscovick, David S.

    2009-01-01

    Background. Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are highly prevalent in patients with end-stage renal disease. It is less well established whether milder kidney disease is associated with cardiac calcifications. We evaluated the relationships between renal function an

  10. RSK3 – A Regulator of Pathological Cardiac Remodeling

    Science.gov (United States)

    Martinez, Eliana C.; Passariello, Catherine L.; Li, Jinliang; Matheson, Christopher J.; Dodge-Kafka, Kimberly; Reigan, Philip; Kapiloff, Michael S.

    2015-01-01

    Summary The family of p90 ribosomal S6 kinases (RSK) are pleiotropic effectors for extracellular signal-regulated kinase (ERK) signaling pathways. Recently, RSK3 was shown to be important for pathological remodeling of the heart. While cardiac myocyte hypertrophy can be compensatory for increased wall stress, in chronic heart diseases this non-mitotic cell growth is usually associated with interstitial fibrosis, increased cell death, and decreased cardiac function. Although RSK3 is less abundant in the cardiac myocyte than other RSK family members, RSK3 appears to serve a unique role in cardiac myocyte stress responses. A potential mechanism conferring RSK3’s unique function in the heart is anchoring by the scaffold protein muscle A-kinase Anchoring Protein β (mAKAPβ). Recent findings suggest that RSK3 should be considered as a therapeutic target for the prevention of heart failure, a clinical syndrome of major public health significance. PMID:25988524

  11. Cardiac MRI in a Patient with Coincident Left Ventricular Non-Compaction and Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Zahra Alizadeh-Sani

    2011-12-01

    Full Text Available Left ventricular non-compaction cardiomyopathy is a rare congenital cardiomyopathy that affects both children and adults. Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular non-compaction and establish prognostic factors. We report a 47-year-old woman with a history of dilated cardiomyopathy with unknown etiology. Echocardiography showed mild left ventricular enlargement with severe systolic dysfunction (EF = 20-25%. According to cardiac magnetic resonance imaging findings non-compaction left ventricle with hypertrophic cardiomyopathy was considered, and right ventricular septal biopsy was recommended. Right ventricular endomyocardial biopsy showed moderate hypertrophy of cardiac myocytes with foci of myocytolysis and moderate interstitial fibrosis. No evidence of infiltrative deposition was seen.

  12. Effects of acupuncture at the acupoints of 12 meridians on gastrointestinal and cardiac electricity in healthy adults.

    Science.gov (United States)

    Chang, Xiao-Rong; Yan, Jie; Shen, Jing; Liu, Mi; Wang, Xiao-Juan

    2010-09-01

    The effect of acupuncture at the acupoints of 12 meridians on gastrointestinal and cardiac electricity in healthy adults was studied. Specific regulation between meridian points and viscera was also investigated. An electrogastrogram (EGG), electrointestinogram (EIG), carotid pulse graph, phonocardiogram and electrocardiogram were obtained in 30 healthy adults before and after acupuncture at various acupoints of 12 meridians. The effects of acupuncture on the amplitude and frequency of the EGG, EIG, pre-ejection period and the left ventricular ejection time were then analyzed. Acupuncture revealed that LR3 decreased the amplitude of the EGG while LI11 (Quchi), SJ5 (Waiguan), ST36 (Zusanli), SP9 (Yinlingquan) and SI6 (Yanglao) increased the amplitude. Multiple comparisons among the latter five acupoints indicated that there were significant differences between SP9, LI11, SJ5 and ST36 (p < 0.01, p < 0.01, p < 0.05) and SI6, LI11 and SJ5 (p < 0.01, p < 0.05). SP9 effected EGG amplitude the most, followed by SI6, ST36, SJ5 and LI11. Four acupoints increased the amplitude of the EIG (p < 0.05), including HT5 (Tongli), GB34 (Yanglingquan), SP9 and SI6. No significant differences were observed between these acupoints, but SI6 showed the most obvious effect on EIG amplitude, followed by GB34, SP9 and HT5. No significant effects on the frequency of the gastrointestinal slow wave or on cardiac function indexes were observed. Effects were observed, however, on pre-ejection period and left ventricular ejection time. Routine acupuncture had no detrimental effects on the stomach, intestine and heart in healthy adults, but instead regulated physiological function within a normal range. These findings demonstrate the existence of specific connections between the meridian points and the viscera. The results suggest that multiple meridians control the same viscus, and the same meridian can regulate the functions of multiple viscera. PMID:20869017

  13. Direct reprogramming of fibroblasts into myocytes to reverse fibrosis.

    Science.gov (United States)

    Muraoka, Naoto; Ieda, Masaki

    2014-01-01

    Heart disease is a major cause of morbidity and mortality worldwide. The low regenerative capacity of adult human hearts has thus far limited the available therapeutic approaches for heart failure. Therefore, new therapies that can regenerate damaged myocardium and improve heart function are urgently needed. Although cell transplantation-based therapies may hold great potential, direct reprogramming of endogenous cardiac fibroblasts, which represent more than half of the cells in the heart, into functional cardiomyocytes in situ may be an alternative strategy by which to regenerate the heart. We and others demonstrated that functional cardiomyocytes can be directly generated from fibroblasts by using several combinations of cardiac-enriched factors in mouse and human. In vivo gene delivery of cardiac reprogramming factors generates new cardiac muscle and improved heart function after myocardial infarction in mouse. This article reviews recent progress in cardiac reprogramming research and discusses the perspectives and challenges of this new technology for future regenerative therapy. PMID:24079415

  14. The Cardiac Conduction System: Generation and Conduction of the Cardiac Impulse.

    Science.gov (United States)

    Kennedy, Alan; Finlay, Dewar D; Guldenring, Daniel; Bond, Raymond; Moran, Kieran; McLaughlin, James

    2016-09-01

    In this article, the authors outline the key components behind the automated generation of the cardiac impulses and the effect these impulses have on cardiac myocytes. Also, a description of the key components of the normal cardiac conduction system is provided, including the sinoatrial node, the atrioventricular node, the His bundle, the bundle branches, and the Purkinje network. Finally, an outline of how each stage of the cardiac conduction system is represented on the electrocardiogram is described, allowing the reader of the electrocardiogram to translate background information about the normal cardiac conduction system to everyday clinical practice. PMID:27484656

  15. Bursting calcium rotors in cultured cardiac myocyte monolayers

    OpenAIRE

    Bub, Gil; Glass, Leon; Publicover, Nelson G.; Shrier, Alvin

    1998-01-01

    Rotating waves (rotors) of cellular activity were observed in nonconfluent cultures of embryonic chick heart cells by using a macroscopic imaging system that detected fluorescence from intracellular Ca2+. Unlike previous observations of rotors or spiral waves in other systems, the rotors did not persist but exhibited a repetitive pattern of spontaneous onset and offset leading to a bursting rhythm. Similar dynamics were observed in a cellular automaton model of excitable media that incorporat...

  16. Care for the adult family members of victims of unexpected cardiac death.

    Science.gov (United States)

    Zalenski, Robert; Gillum, Richard F; Quest, Tammie E; Griffith, James L

    2006-12-01

    More than 300,000 sudden coronary deaths occur annually in the United States, despite declining cardiovascular death rates. In 2000, deaths from heart disease left an estimated 190,156 new widows and 68,493 new widowers. A major unanswered question for emergency providers is whether the immediate care of the loved ones left behind by the deceased should be a therapeutic task for the staff of the emergency department in the aftermath of a fatal cardiac arrest. Based on a review of the literature, the authors suggest that more research is needed to answer this question, to assess the current immediate needs and care of survivors, and to find ways to improve care of the surviving family of unexpected cardiac death victims. This would include improving quality of death disclosure, improving care for relatives during cardiopulmonary resuscitation of their family member, and improved methods of referral for services for prevention of psychological and cardiovascular morbidity during bereavement. PMID:16946285

  17. A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery.

    Science.gov (United States)

    Butterworth, J F; Hines, R L; Royster, R L; James, R L

    1995-10-01

    Milrinone can reverse acute postischemic myocardial dysfunction after cardiopulmonary bypass, although neither the appropriate bolus dose nor its pharmacokinetics has been established for cardiac surgical patients. Consenting patients undergoing cardiac surgery received milrinone (25, 50, or 75 micrograms/kg) in an open-label, dose-escalating study if their cardiac index was plasma concentrations and pharmacokinetic analysis. Twenty-nine of 60 consenting patients had cardiac indices 15%. The 75-micrograms/kg dose was associated with a case of ventricular tachycardia. The three-compartment model better described milrinone drug disposition than the two-compartment model by both visual inspection and Schwartz-Bayesian criterion. There was only limited evidence of dose-dependence, so data from all three doses are reported together (and normalized to the 50-micrograms/kg dose). Data from one patient was discarded (samples mislabeled). Using mixed-effects nonlinear regression (for n = 28), the following volumes were determined for the three compartments: V1 = 11.1 L, V2 = 16.9 L, and V3 = 363 L. Similarly, the following clearances were estimated for the three compartments: Cl1 = 0.067 L/min, Cl2 = 1.05 L/min, and Cl3 = 0.31 L/min. The 50-micrograms/kg loading dose appeared more potent than the 25-micrograms/kg dose, and, as potent, but with possibly fewer side-effects than the 75-micrograms/kg dose. The short context-sensitive half-times of 6.7 or 10.2 min after 1- or 10-min bolus infusions underscore the need for prompt institution of a maintenance infusion when milrinone concentrations must be maintained.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7574011

  18. Effects of cardiac resynchronization therapy on health-related quality of life in older adults with heart failure

    Directory of Open Access Journals (Sweden)

    Karin F Hoth

    2008-10-01

    Full Text Available Karin F Hoth1,2, Justin Nash3, Athena Poppas4, Kristin E Ellison4, Robert H Paul5, Ronald A Cohen31Division of Psychosocial Medicine, National Jewish Medical and Research Center, Denver, CO, USA; 2Department of Psychiatry, University of Colorado, Denver, CO, USA; 3Department of Psychiatry and Human Behavior; 4Department of Cardiology, Warren Alpert Medical School of Brown University, Providence, RI, USA; 5Department of Psychology, Division of Behavioral Neuroscience, University of Missouri St. Louis, St. Louis, MO, USAAbstract: The aim of the study was to examine changes in health-related quality of life among older adults undergoing cardiac resynchronization therapy (CRT, a pacemaker based intervention for heart failure. Twenty-one patients (mean age = 68; SD = 8 completed measures of cardiovascular health and quality of life prior to and 3-months post-CRT. Following the intervention, patients reported improvements in their perception of their physical functioning (t = 2.8, p < 0.01 and feelings of vitality (t = 2.9, p < 0.01 on the MOS SF-36 Health Survey. Patients improved on objective clinical measures of exercise capacity, cardiac ejection fraction, and ventricular dyssynchrony. Younger patients reported greater improvements in physical functioning and decreases in pain. Higher baseline body mass index was associated with less improvement in physical functioning. Finally, patients with nonischemic heart failure reported greater improvements on multiple subscales of the SF-36 than patients with ischemic heart failure. This preliminary study documented improvements in health-related quality of life following CRT. The findings highlight that specific patient characteristics may be associated with quality of life changes. Future studies will benefit from including quality of life measures that assess multiple health-related domains.Keywords: cardiac resynchronization therapy, heart failure, quality of life

  19. Cardiac mechanics in patients with human immunodeficiency virus: a study of systolic myocardial deformation in children and young adults.

    Science.gov (United States)

    Al-Naami, Ghassan; Kiblawi, Fuad; Kest, Helen; Hamdan, Ayman; Myridakis, Dorothy

    2014-08-01

    Human immunodeficiency virus (HIV) infection causes dysfunction of different organ systems. Myocardial diastolic dysfunction has been reported previously in an adult HIV population. Our aim was to study myocardial strain in children and young adults infected by HIV who have apparently normal ejection fraction. Forty HIV-infected patients (mean age 20.6 ± 1.5 years) with normal ejection fraction and 55 matched normal controls (mean age 17 ± 1.5 years) were studied by two-dimensional echocardiogram. The images were stored then exported to velocity vector imaging software for analysis. Measures considered were left-ventricular peak global systolic strain (LV S) and strain rate (LV SR) as well as right-ventricular peak global systolic strain (RV S) and strain rate (RV SR). Circumferential measures of the left ventricle included the following: LV circumferential peak global systolic strain (LV circ S), strain rate (LV circ SR), radial velocity (LV rad vel), and rotational velocity (LV rot vel) at the level of the mitral valve. Statistical significance was set at p strain and strain rate in children and young adults. Normal ejection fraction might be attributed to preserved circumferential myocardial deformation. Strain and strain rate may help identify HIV patients at high risk for cardiac dysfunction and allow early detection of silent myocardial depression.

  20. Validation of an in vitro contractility assay using canine ventricular myocytes

    International Nuclear Information System (INIS)

    Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

  1. Research progress of adult cardiac stem cells%成体心肌干细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    郑楠; 张宁坤; 高连如

    2013-01-01

    传统观点认为心脏是一个终末分化器官,然而随着成体心肌干细胞(CSCs)的发现,这种观点已受到广泛质疑.由于CSCs具有高度的自我更新能力和特异性心肌分化潜能,目前被认为是最有希望应用于缺血性心脏病及其他终末期心脏病替代治疗的干细胞类型.本文综述了目前关于人源CSCs、心外膜源细胞(EPDC)的研究概况,及其应用于心脏再生领域的治疗策略和研究中存在的问题.%The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs). Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on human adult CSCs and epicardium-derived cell (EPDC), as well as the treatment strategies in the field of cardiac regeneration, and the problems and prospect disclosed in the research.

  2. Congenital left ventricular wall abnormalities in adults detected by gated cardiac multidetector computed tomography: Clefts, aneurysms, diverticula and terminology problems

    Energy Technology Data Exchange (ETDEWEB)

    Erol, Cengiz, E-mail: drcengizerol@yahoo.com [Selcuk University, Selcuklu Faculty of Medicine, Department of Radiology, Alaeddin Keykubat Central Campus, Selcuklu, 42250 Konya (Turkey); Koplay, Mustafa, E-mail: koplaymustafa@hotmail.com [Selcuk University, Selcuklu Faculty of Medicine, Department of Radiology, Alaeddin Keykubat Central Campus, Selcuklu, 42250 Konya (Turkey); Olcay, Ayhan, E-mail: drayhanolcay@gmail.com [29 May Hospital, Department of Cardiology, Vatan Street, Fatih, 34150 Istanbul (Turkey); Kivrak, Ali Sami, E-mail: alisamikivrak@hotmail.com [Selcuk University, Selcuklu Faculty of Medicine, Department of Radiology, Alaeddin Keykubat Central Campus, Selcuklu, 42250 Konya (Turkey); Ozbek, Seda, E-mail: dsadr@hotmail.com [Selcuk University, Selcuklu Faculty of Medicine, Department of Radiology, Alaeddin Keykubat Central Campus, Selcuklu, 42250 Konya (Turkey); Seker, Mehmet, E-mail: hikmet.irfan@hotmail.com [29 May Hospital, Department of Radiology, Vatan Street, Fatih, 34150 Istanbul (Turkey); Paksoy, Yahya, E-mail: yahyapaksoy@yahoo.com [Selcuk University, Selcuklu Faculty of Medicine, Department of Radiology, Alaeddin Keykubat Central Campus, Selcuklu, 42250 Konya (Turkey)

    2012-11-15

    Objectives: Our aim was to evaluate congenital left ventricular wall abnormalities (clefts, aneurysms and diverticula), describe and illustrate imaging features, discuss terminology problems and determine their prevalence detected by cardiac CT in a single center. Materials and methods: Coronary CT angiography images of 2093 adult patients were evaluated retrospectively in order to determine congenital left ventricular wall abnormalities. Results: The incidence of left ventricular clefts (LVC) was 6.7% (141 patients) and statistically significant difference was not detected between the sexes regarding LVC (P = 0.5). LVCs were single in 65.2% and multiple in 34.8% of patients. They were located at the basal to mid inferoseptal segment of the left ventricle in 55.4%, the basal to mid anteroseptal segment in 24.1%, basal to mid inferior segment in 17% and septal-apical septal segment in 3.5% of cases. The cleft length ranged from 5 to 22 mm (mean 10.5 mm) and they had a narrow connection with the left ventricle (mean 2.5 mm). They were contractile with the left ventricle and obliterated during systole. Congenital left ventricular septal aneurysm that was located just under the aortic valve was detected in two patients (0.1%). No case of congenital left ventricular diverticulum was detected. Conclusion: Cardiac CT allows us to recognize congenital left ventricular wall abnormalities which have been previously overlooked in adults. LVC is a congenital structural variant of the myocardium, is seen more frequently than previously reported and should be differentiated from aneurysm and diverticulum for possible catastrophic complications of the latter two.

  3. A Meta-Analysis of Renal Function After Adult Cardiac Surgery With Pulsatile Perfusion.

    Science.gov (United States)

    Nam, Myung Ji; Lim, Choon Hak; Kim, Hyun-Jung; Kim, Yong Hwi; Choi, Hyuk; Son, Ho Sung; Lim, Hae Ja; Sun, Kyung

    2015-09-01

    The aim of this meta-analysis was to determine whether pulsatile perfusion during cardiac surgery has a lesser effect on renal dysfunction than nonpulsatile perfusion after cardiac surgery in randomized controlled trials. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were used to identify available articles published before April 25, 2014. Meta-analysis was conducted to determine the effects of pulsatile perfusion on postoperative renal functions, as determined by creatinine clearance (CrCl), serum creatinine (Cr), urinary neutrophil gelatinase-associated lipocalin (NGAL), and the incidences of acute renal insufficiency (ARI) and acute renal failure (ARF). Nine studies involving 674 patients that received pulsatile perfusion and 698 patients that received nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the meta-analysis. Stratified analysis was performed according to effective pulsatility or unclear pulsatility of the pulsatile perfusion method in the presence of heterogeneity. NGAL levels were not significantly different between the pulsatile and nonpulsatile groups. However, patients in the pulsatile group had a significantly higher CrCl and lower Cr levels when the analysis was restricted to studies on effective pulsatile flow (P < 0.00001, respectively). The incidence of ARI was significantly lower in the pulsatile group (P < 0.00001), but incidences of ARF were similar. In conclusion, the meta-analysis suggests that the use of pulsatile flow during CPB results in better postoperative renal function.

  4. Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts.

    Directory of Open Access Journals (Sweden)

    Alok Ranjan Nayak

    Full Text Available Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a single myocyte-fibroblast (MF units and (b two-dimensional (2D arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a both homogeneous and inhomogeneous distributions of fibroblasts, (b various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models

  5. A multistep procedure to prepare pre-vascularized cardiac tissue constructs using adult stem sells, dynamic cell cultures, and porous scaffolds.

    Science.gov (United States)

    Pagliari, Stefania; Tirella, Annalisa; Ahluwalia, Arti; Duim, Sjoerd; Goumans, Marie-Josè; Aoyagi, Takao; Forte, Giancarlo

    2014-01-01

    The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs) are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs) are stimulated in vitro to obtain their commitment toward the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment.

  6. A Multistep Procedure To Prepare Pre-Vascularized Cardiac Tissue Constructs Using Adult Stem Sells, Dynamic Cell Cultures And Porous Scaffolds

    Directory of Open Access Journals (Sweden)

    Stefania ePagliari

    2014-06-01

    Full Text Available The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs are stimulated in vitro to obtain their commitment towards the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment.

  7. Purinergic facilitation of ATP-sensitive potassium current in rat ventricular myocytes

    OpenAIRE

    Babenko, Andrey P.; Vassort, Guy

    1997-01-01

    The effects of different purinergic agonists on the cardiac adenosine 5′-triphosphate (ATP)-sensitive potassium current (IK(ATP)), appearing during dialysis of rat isolated ventricular myocytes with a low-ATP (100 μM) internal solution under whole-cell patch-clamp conditions, were examined in the presence of a P1 purinoceptor antagonist.The extracellular application of ATP in the micromolar range induced, besides known inward currents through cationic and chloride channels, the facilitation o...

  8. Intracellular Ca2+ Modulation during Short Exposure to Ischemia-Mimetic Factors in Isolated Rat Ventricular Myocytes

    OpenAIRE

    Danijel, Pravdic; Nikolina, Vladic; Zeljko, Bosnjak J

    2009-01-01

    We investigated the effects of different ischemia-mimetic factors on intracellular Ca2+ concentration ([Ca2+]i). Ventricular myocytes were isolated from adult Wistar rats, and [Ca2+]i was measured using fluorescent indicator fluo-4 AM by confocal microscopy. Intracellular pH was measured using c5-(and-6)-carboxy SNARF-1 AM, a dual emission pH-sensitive ionophore. Myocytes were exposed to hypoxia, extracellular acidosis (pHo 6.8), Na-lactate (10 mM), or to combination of those factors for 25 m...

  9. Norepinephrine transporter (NET) is expressed in cardiac sympathetic ganglia of adult rat

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.

  10. Anatomic correction of ALCAPA in an adult presenting with sudden cardiac death

    Science.gov (United States)

    Simry, Walid; Afifi, Ahmed; Hosny, Hatem; Elguindy, Ahmed; Yacoub, Magdi

    2015-01-01

    We report on a young adult with ALCAPA, who was successfully resuscitated after collapsing in ventricular fibrillation while playing football. This was followed by anatomical correction of the anomaly with a smooth recovery and return to his daily activities. The advantages of this approach are discussed in this brief report. PMID:26779521

  11. Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin

    NARCIS (Netherlands)

    Chong, James J. H.; Chandrakanthan, Vashe; Xaymardan, Munira; Asli, Naisana S.; Li, Joan; Ahmed, Ishtiaq; Heffernan, Corey; Menon, Mary K.; Scarlett, Christopher J.; Rashidianfar, Amirsalar; Biben, Christine; Zoellner, Hans; Colvin, Emily K.; Pimanda, John E.; Biankin, Andrew V.; Zhou, Bin; Pu, William T.; Prall, Owen W. J.; Harvey, Richard P.

    2011-01-01

    Colony-forming units fibroblast (CFU-Fs), analogous to those giving rise to bone marrow (BM) mesenchymal stem cells (MSCs), are present in many organs, although the relationship between BM and organ-specific CFU-Fs in homeostasis and tissue repair is unknown. Here we describe a population of adult c

  12. Clinical features and risk assessment for cardiac surgery in adult congenital heart disease: Three years at a single Japanese center

    Directory of Open Access Journals (Sweden)

    Satoshi Kurokawa

    2014-04-01

    Conclusion: Cardiac surgery could be safely performed in most ACHD cases. Exercise tolerance testing can be useful in identifying patients at high risk of mortality or major complications. BNP can be valuable in predicting poor outcomes after cardiac surgery.

  13. Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes

    Directory of Open Access Journals (Sweden)

    Arie O. Verkerk

    2012-05-01

    Full Text Available The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh and noradrenalin (NA as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signalling proteins (RGS proteins suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 µM ACh and 1 µM NA on the intrinsic action potentials of sinotrial (SA nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1,000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA or a combination of both and may thus guide further experiments with RGS proteins.

  14. Primary Prevention of Sudden Cardiac Death in Adults with Transposition of the Great Arteries: A Review of Implantable Cardioverter-Defibrillator Placement.

    Science.gov (United States)

    Sodhi, Sandeep S; Cedars, Ari M

    2015-08-01

    Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question of whether implantable cardioverter-defibrillators should be placed in this cohort as a preventive measure to abort sudden death has largely gone unanswered. Therefore, we review the available literature surrounding this issue. PMID:26413012

  15. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    Science.gov (United States)

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  16. ALCAPA Presents in an Adult with Exercise Intolerance but Preserved Cardiac Function

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2012-01-01

    Full Text Available Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA is a rare congenital anomaly that usually manifests as severe left-sided heart failure and mitral valve insufficiency during the first one to two months of life. The majority of these cases die in infancy if not corrected early upon presentation. Adulthood presentation is rare and most of the untreated patients who reach adulthood present with left ventricular dysfunction, severe mitral regurgitation, and sometimes myocardial infarction. Here we report a case of a 20-year-old woman with a history of exercise intolerance since childhood that was misinterpreted as asthma until a 2D-Echo revealed ALCAPA with RCA collaterals to the left anterior descending artery, preserved LV ejection fraction, and absence of apparent mitral valve abnormality. One month after the ALCAPA diagnosis, she successfully underwent surgical reconstruction of left main and pulmonary artery without any major complications. She had normal left ventricular function without apparent ischemic cardiac symptoms eighteen months after procedure.

  17. Ordered Assembly of the Adhesive and Electrochemical Connections within Newly Formed Intercalated Disks in Primary Cultures of Adult Rat Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Sarah B. Geisler

    2010-01-01

    Full Text Available The intercalated disk (ID is a complex structure that electromechanically couples adjoining cardiac myocytes into a functional syncitium. The integrity of the disk is essential for normal cardiac function, but how the diverse elements are assembled into a fully integrated structure is not well understood. In this study, we examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remodeling. As cells make contact with their neighbors, transmembrane adhesion proteins localize along the line of apposition, concentrating at the sites of membrane attachment of the terminal sarcomeres. Cx43 gap junctions and ankyrin-G, an essential cytoskeletal component of voltage gated sodium channel complexes, were secondarily recruited to membrane domains involved in cell-cell contacts. The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk. Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture.

  18. Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Steve O Winitsky

    2005-04-01

    Full Text Available It has long been held as scientific fact that soon after birth, cardiomyocytes cease dividing, thus explaining the limited restoration of cardiac function after a heart attack. Recent demonstrations of cardiac myocyte differentiation observed in vitro or after in vivo transplantation of adult stem cells from blood, fat, skeletal muscle, or heart have challenged this view. Analysis of these studies has been complicated by the large disparity in the magnitude of effects seen by different groups and obscured by the recently appreciated process of in vivo stem-cell fusion. We now show a novel population of nonsatellite cells in adult murine skeletal muscle that progress under standard primary cell-culture conditions to autonomously beating cardiomyocytes. Their differentiation into beating cardiomyocytes is characterized here by video microscopy, confocal-detected calcium transients, electron microscopy, immunofluorescent cardiac-specific markers, and single-cell patch recordings of cardiac action potentials. Within 2 d after tail-vein injection of these marked cells into a mouse model of acute infarction, the marked cells are visible in the heart. By 6 d they begin to differentiate without fusing to recipient cardiac cells. Three months later, the tagged cells are visible as striated heart muscle restricted to the region of the cardiac infarct.

  19. Cardiac Rehabilitation is Associated with Lasting Improvements in Cognitive Function in Older Adults with Heart Failure

    Science.gov (United States)

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Objective Heart failure (HF) is a known risk factor for cognitive impairment. Cardiac rehabilitation (CR) may attenuate poor neurocognitive outcomes in HF via improved physical fitness—a significant promoter of cognitive function. However, no study has examined the possible acute and lasting benefits of CR on cognitive function in persons with HF. Methods and Results 52 patients with HF completed a 12-week Phase II CR program. All participants were administered neuropsychological testing and completed a brief physical fitness assessment at baseline, completion of CR (i.e. 12-weeks), and 12-month follow-up. Repeated measures analyses showed a significant time effect for both attention/executive function and memory (p performance increased from baseline to 12-weeks and these gains remained up to 12-months; memory was unchanged from baseline to 12-weeks, but then improved between the 12-week and 12-month time points. Physical fitness improved from baseline to 12-weeks and these benefits were maintained 12-months later. Changes in physical fitness and cognitive function over time did not reach a statistically significant association, though poorer physical fitness was associated with decreased cognitive performance at the baseline and 12-month time points. Conclusions CR is associated with both acute and lasting cognitive benefits in patients with HF. Prospective studies with extended follow-ups are needed to clarify the mechanisms that underpin cognitive improvements following CR (e.g., improved cerebral perfusion) and whether CR can ultimately reduce risk for cognitive decline and conditions like Alzheimer’s disease in HF. PMID:25181916

  20. Cardiac magnetic resonance imaging in dilated cardiomyopathy in adults - towards identification of myocardial inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, Antje; Beling, Mark; Stangl, Karl [Charite-Universitaetsmedizin Berlin, Department of Cardiology, Campus Mitte, Berlin (Germany); Elgeti, Thomas; Durmus, Tahir; Idiz, Merve Ece; Schilling, Rene; Taupitz, Matthias; Wagner, Moritz [Charite-Universitaetsmedizin Berlin, Department of Radiology, Campus Mitte, Berlin (Germany); Butler, Craig [University of Alberta, Mazankowski Alberta Heart Institute, Edmonton (Canada); Klingel, Karin; Kandolf, Reinhard [University Hospital, Department of Molecular Pathology, Tuebingen (Germany); Kivelitz, Dietmar [Asklepios Klinik St. Georg, Department of Radiology, Hamburg (Germany)

    2011-05-15

    To assess active myocardial inflammation by cardiovascular magnetic resonance (CMR) and endomyocardial biopsy (EMB) amongst adult patients with dilated cardiomyopathy (DCM). We evaluated 23 adults with chronic DCM, who had successfully undergone both CMR and EMB within 3.5 {+-} 2.6 days. EMB was considered the gold standard. CMR assessment of myocardial inflammation used the following parameters as recommended by the recently published ''Lake Louise Criteria'': global myocardial oedema, global relative enhancement (RE), and late gadolinium enhancement (LGE). According to ''Lake Louise Criteria'', myocardial inflammation was diagnosed if two or more of the three above-mentioned parameters were positive. Myocardial inflammation was confirmed by immunohistology in 12 patients (52.2%). Sensitivity, specificity, and diagnostic accuracy of CMR to detect immunohistologically confirmed myocardial inflammation were 75.0%, 72.7%, and 73.9%, respectively. Sensitivity, specificity, and diagnostic accuracy of the individual CMR parameters to detect myocardial inflammation were as follows: global myocardial oedema, 91.7%, 81.8%, and 87.0%, respectively; global RE, 58.3%, 63.6%, and 60.9%, respectively; LGE, 58.3%, 45.4%, and 52.2%, respectively. Global myocardial oedema was identified as a promising CMR parameter for assessment of myocardial inflammation in patients with DCM. In these patients, global myocardial oedema yielded superior diagnostic performance compared to ''Lake Louise Criteria''. (orig.)

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

    Science.gov (United States)

    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.

  2. Radiographic evaluation of the cardiac silluet using the VHS method (Vertebral Heart Size) in young and adults coatis (Nasua nasua, Linneaus 1766) living in captivity

    OpenAIRE

    Andresa de Cássia Martini; Yara Silva Meireles; Samuel Monzem; Luiz Paulo Vasconcelos; Nívea Clarice Monteiro Rocha Turbino; Magyda Arabia Araji Dahroug; Daniela Farias; Pedro Brandini Néspoli; Gentil Ferreira Gonçalves; Roberto Lopes de Souza; Luciana Dambrósio Guimarães

    2014-01-01

    Radiographic examination of the toracic cavity is an usefull noninvasive method for assessment, monitoring the progress of heart disease, suggesting prognosis and guiding the treatment. The aim of this study was to evaluate the cardiac silhouette of young and adults coatis and evaluate its relationship to the number of thoracic vertebrae (VHS), the method proposed by Buchanam and Buchele (1995) for small animals. We evaluated a group of 20 coatis, divided by age: I (GI) and 8 animals aged bet...

  3. A multistep procedure to prepare pre-vascularized cardiac tissue constructs using adult stem sells, dynamic cell cultures, and porous scaffolds

    OpenAIRE

    Stefania ePagliari; Annalisa eTirella; Arti eAhluwalia; Sjoerd eDuim; Marie-Josè eGoumans; Takao eAoyagi; Giancarlo eForte

    2014-01-01

    The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult ste...

  4. Sexual hormones: effects on cardiac and mitochondrial activity after ischemia-reperfusion in adult rats. Gender difference.

    Science.gov (United States)

    Pavón, Natalia; Martínez-Abundis, Eduardo; Hernández, Luz; Gallardo-Pérez, Juan Carlos; Alvarez-Delgado, Carolina; Cerbón, Marco; Pérez-Torres, Israel; Aranda, Alberto; Chávez, Edmundo

    2012-10-01

    In this work we studied the influence of sex hormones on heart and mitochondrial functions, from adult castrated female and male, and intact rats. Castration was performed at their third week of life and on the fourth month animals were subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure recordings were made, cytokines levels were measured, histopathological studies were performed and thiobarbituric acid reactive species were determined. At the mitochondrial level respiratory control, transmembranal potential and calcium management were determined; Western blot of some mitochondrial components was also performed. Alterations in cardiac function were worst in intact males and castrated females as compared with those found in intact females and castrated males, cytokine levels were modulated also by hormonal status. Regarding mitochondria, in those obtained from hearts from castrated females without ischemia-reperfusion, all evaluated parameters were similar to those observed in mitochondria after ischemia-reperfusion. The results show hormonal influences on the heart at functional and mitochondrial levels. PMID:22609314

  5. The influence of patient size on dose conversion coefficients: a hybrid phantom study for adult cardiac catheterization

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Perry; Lee, Choonsik [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL 32611 (United States); Johnson, Kevin [Department of Radiology, University of Florida, Jacksonville, FL 32209 (United States); Siragusa, Daniel [Department of Radiology, Division of Vascular Interventional Radiology, University of Florida, Jacksonville, FL 32209 (United States); Bolch, Wesley E [Departments of Nuclear and Radiological and Biomedical Engineering, University of Florida, Gainesville, FL 32611 (United States)], E-mail: wbolch@ufl.edu

    2009-06-21

    In this study, the influence of patient size on organ and effective dose conversion coefficients (DCCs) was investigated for a representative interventional fluoroscopic procedure-cardiac catheterization. The study was performed using hybrid phantoms representing an underweight, average and overweight American adult male. Reference body sizes were determined using the NHANES III database and parameterized based on standing height and total body mass. Organ and effective dose conversion coefficients were calculated for anterior-posterior, posterior-anterior, left anterior oblique and right anterior oblique projections using the Monte Carlo code MCNPX 2.5.0 with the metric dose area product being used as the normalization factor. Results show body size to have a clear influence on DCCs which increased noticeably when body size decreased. It was also shown that if patient size is neglected when choosing a DCC, the organ and effective dose will be underestimated to an underweight patient and will be overestimated to an underweight patient, with errors as large as 113% for certain projections. Results were further compared with those published for a KTMAN-2 Korean patient-specific tomographic phantom. The published DCCs aligned best with the hybrid phantom which most closely matched in overall body size. These results highlighted the need for and the advantages of phantom-patient matching, and it is recommended that hybrid phantoms be used to create a more diverse library of patient-dependent anthropomorphic phantoms for medical dose reconstruction.

  6. Heart regeneration in adult MRL mice

    OpenAIRE

    Leferovich, John M.; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang-Ming; Zwas, Donna; Lankford, Edward B.; Heber-Katz, Ellen

    2001-01-01

    The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary ...

  7. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review.

    Directory of Open Access Journals (Sweden)

    Marnie L Elizaga

    Full Text Available BACKGROUND: Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines. METHODS: Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. 'Routine cardiac investigations' (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls, and 'Symptom-driven cardiac investigations' are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine. RESULTS: Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12% had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine. CONCLUSIONS: Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603

  8. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    Directory of Open Access Journals (Sweden)

    Palade Philip T

    2010-11-01

    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  9. Effects of Angiotensin Ⅱ on Expression of the Gap Junction Channel Protein Connexin 43 in Neonatal Rat Ventricular Myocytes

    Institute of Scientific and Technical Information of China (English)

    Jun Yang; Wei Wu

    2007-01-01

    To study the effects of angiotensin Ⅱ,as a mediator of cardiac hypertrophy,on expression of connexin 43 (Cx43) in cultured neonatal rat ventricular myocytes and correlation of expression of Cx43 and cardiomyocyte hypertrophy.Methods Cardiomyocytes were isolated from newborn SD rats.Angiotensin Ⅱ was added into the media to induce myocyte hypertrophy.Cultures were exposed to 10 ~6 mol/L angiotensin Ⅱ for 72 h,Cx43 expression was characterized by RT-PCR and Immunofluorescence methods.Results Immunofluorescence analysis revealed decreased Cx43 immunoreactivity in cells treated for 72 h with angiotensin Ⅱ.RT-PCR analysis demonstrated there was an obvious decrease of Cx43 mRNA level in cells exposed to angiotensin Ⅱ for 72 h.The changes of expression of connexin 43 were related to its entrance into S phase of the cell cycle.Cultured neonatal rat cardiomyocytes were exposed for 72 h to increase concentrations of angiotensin Ⅱ ( 1.0 × 10-9 ~ 1.0 × 10-6mol/L),resulting in significantly decreased Cx43 expression.Conclusions Angiotensin Ⅱ leads to a concentration-dependent decrease in Cx43 protein in cultured neonatal rat ventricular myocytes by decreasing Cx43 mRNA synthesis.Signal transduction pathways activated by angiotensin Ⅱ under pathophysiologic conditions of cardiac hypertrophy could initiate remodeling of gap junctions.

  10. Immunoreactive atrial natriuretic peptide and dopamine beta-hydroxylase in myocytes and chromaffin cells of the heart of the African lungfish, Protopterus aethiopicus.

    Science.gov (United States)

    Larsen, T H; Helle, K B; Saetersdal, T

    1994-07-01

    The heart of the African lungfish, Protopterus aethiopicus, was examined for immunoreactive atrial natriuretic peptide (ANP) and dopamine beta-hydroxylase (D beta H) as markers for hormone secreting myocytes and chromaffin cells, respectively. Specific antibodies raised against rat alpha-ANP and rat D beta H were used for immunofluorescence microscopy and immunogold electron microscopy. D beta H-immunoreactive cells were restricted to subendocardial areas of the atrium whereas ANP immunoreactivity occurred throughout both the atrial and the ventricular myocardium, showing particularly strong staining intensity in the atrial myocytes. The granular ANP immunostaining in the atrial myocytes was frequently accumulated in the sarcoplasm. In the ventricular myocytes ANP immunoreactivity occurred as scattered granular staining throughout the sarcoplasm. ANP and D beta H immunofluorescence staining coincided with the presence of immunoreactive specific granules and secretory vesicles in the cardiac myocytes and chromaffin cells, respectively, as revealed by electron microscopy. The number of ANP-containing specific granules was generally high in the atrial myocytes, and they were frequently observed in clusters in subsarcolemmal areas. Granular frequency was considerably lower and the mean granular diameter was smaller (0.142 +/- 0.045 micron versus 0.213 +/- 0.049 micron) in the ventricular than in the atrial myocytes. The present results indicate that ANP and D beta H are phylogenetically highly conserved proteins from the dipnoi to the rat. The large amounts of ANP and of specific granules are consistent with an endocrine myocardium in the Protopterus heart. The presence of D beta H and secretory vesicles in the subendocardial chromaffin cells of the atrium suggests a local production of catecholamines from dopamine in the heart of this dipnoan. PMID:7926645

  11. Assessment of DNA synthesis in Islet-1+ cells in the adult murine heart

    International Nuclear Information System (INIS)

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1+) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1+ cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine (3H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of 3H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1+ cells. Whereas Islet− non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1+ cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes

  12. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de; Nicol, Philipp, E-mail: Philipp.Nicol@gmx.de; Eschenhagen, Thomas, E-mail: t.eschenhagen@uke.de

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  13. Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

    Science.gov (United States)

    Bondanelli, Marta; Bonadonna, Stefania; Ambrosio, Maria Rosaria; Doga, Mauro; Gola, Monica; Onofri, Alessandro; Zatelli, Maria Chiara; Giustina, Andrea; degli Uberti, Ettore C

    2005-09-01

    Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (Pgigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocitygigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (Pgigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a

  14. Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

    Science.gov (United States)

    Bondanelli, Marta; Bonadonna, Stefania; Ambrosio, Maria Rosaria; Doga, Mauro; Gola, Monica; Onofri, Alessandro; Zatelli, Maria Chiara; Giustina, Andrea; degli Uberti, Ettore C

    2005-09-01

    Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (Pgigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocitygigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (Pgigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a

  15. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  16. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    Science.gov (United States)

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (Pfitness, ejection fraction, and insulin resistance. PMID:27346646

  17. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    Science.gov (United States)

    Leitgeb, N.; Niedermayr, F.; Neubauer, R.; Loos, G.

    2010-10-01

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m-2. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  18. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    International Nuclear Information System (INIS)

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m-2. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  19. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    Energy Technology Data Exchange (ETDEWEB)

    Leitgeb, N; Niedermayr, F; Neubauer, R; Loos, G, E-mail: norbert.leitgeb@tugraz.a [Institute of Clinical Engineering with European Notified Body of Medical Devices, Graz University of Technology, Inffeldgasse 18, A-8010 Graz (Austria)

    2010-10-21

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m{sup -2}. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  20. c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling.

    Directory of Open Access Journals (Sweden)

    Nanako Kawaguchi

    Full Text Available BACKGROUND: Resident c-kit positive (c-kitpos cardiac stem cells (CSCs could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential. METHODOLOGY/PRINCIPAL FINDINGS: We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs. CONCLUSION/SIGNIFICANCE: c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

  1. Activation of cardiac chloride conductance by the tyrosine kinase inhibitor, genistein.

    OpenAIRE

    Shuba, L. M.; Asai, T.; Pelzer, S.; McDonald, T. F.

    1996-01-01

    1. Genistein (GST), an inhibitor of protein tyrosine kinase (PTK), Na3VO4 (VO4), an inhibitor of phosphotyrosine phosphatase (PTPase), and forskolin (FSK), an activator of the cyclic AMP-dependent, cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, were applied to guinea-pig ventricular myocytes to probe for a possible role of tyrosine phosphorylation in the regulation of cardiac Cl- channels. 2. Myocytes in the standard whole-cell configuration were pulsed to various pot...

  2. Influence of skeletal muscle satellite cells implanted into infarcted myocardium on remnant myocyte volumes

    Institute of Scientific and Technical Information of China (English)

    钟竑; 朱洪生; 卫洪超; 张臻

    2003-01-01

    Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes.Methods Thirty-six adult mongrel canines were divided randomly into implantation group and control group. In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4', 6-diamidino-2-phenylindone (DAPI) in vitro. In both groups, a model of acute myocardial infarction was established in every dog. In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells. The dogs in the control group received M199 solution without skeletal muscle satellite cells. The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time). Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope. Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS. A P<0.05 was considered significant.Results A portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs. Cross-sectional area and cell volume were increased in normal myocardium. Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross-sectional area, cell area and cell volume differed significantly from those of the control group (P< 0.05). Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged. Conclusion Skeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium.

  3. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation.

    Science.gov (United States)

    Kamphuis, M; Zwinderman, K H; Vogels, T; Vliegen, H W; Kamphuis, R P; Ottenkamp, J; Verloove-Vanhorick, S P; Bruil, J

    2004-05-01

    This study represents the development and validation of a cardiac-specific module of the generic health-related quality of life (HRQoL) instrument, the TAAQOL (TNO/AZL Adult Quality Of Life), for young adults with congenital heart disease (CHD). Items were selected based on literature, an explorative previous study in CHD patients, interviews with patients, and the advice of experts. The newly developed Congenital Heart Disease-TNO/AZL Adult Quality of Life (CHD-TAAQOL) was tested in 156 patients with mild or complex CHD and consisted of three hypothesised subject scales: 'Symptoms' (9 items), 'Impact Cardiac Surveillance' (7 items), and 'Worries' (10 items). Cronbach's alpha for the three scales were 0.77, 0.78, and 0.82, respectively. Scale structure was confirmed by Principal Component Analysis, corrected item-scale and interscale correlations. Overall, 55% of reported health status problems were associated with negative emotions, which is an argument for assessing HRQoL as a concept distinct from health status. Convergent validity with validated generic instruments (TAAQOL and Short Form-36, SF-36) showed satisfactory coefficients. Discriminant validity was proven by significantly higher scores for mild CHD patients compared with those with complex CHD. In conclusion, the CHD-TAAQOL module together with the generic TAAQOL can be used to assess group differences for cardiac-specific HRQoL in young adults with CHD. Testing psychometric properties of the CHD-TAAQOL shows satisfactory results. However, to detect changes in HRQoL over time, further research is needed.

  4. Cardiac mitochondria exhibit dynamic functional clustering

    Directory of Open Access Journals (Sweden)

    Felix Tobias Kurz

    2014-09-01

    Full Text Available Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010. Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös-Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N=9 versus 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks (Aon et al., 2008.

  5. Voluntary exercise-induced changes in beta2-adrenoceptor signalling in rat ventricular myocytes.

    Science.gov (United States)

    Stones, Rachel; Natali, Antonio; Billeter, Rudolf; Harrison, Simon; White, Ed

    2008-09-01

    Regular exercise is beneficial to cardiovascular health. We tested whether mild voluntary exercise training modifies key myocardial parameters [ventricular mass, intracellular calcium ([Ca2+]i) handling and the response to beta-adrenoceptor (beta-AR) stimulation] in a manner distinct from that reported for beneficial, intensive training and pathological hypertrophic stimuli. Female rats performed voluntary wheel-running exercise for 6-7 weeks. The mRNA expression of target proteins was measured in left ventricular tissue using real-time reverse transcriptase-polymerase chain reaction. Simultaneous measurement of cell shortening and [Ca2+]i transients were made in single left ventricular myocytes and the inotropic response to beta1- and beta2-AR stimulation was measured. Voluntary exercise training resulted in cardiac hypertrophy, the heart weight to body weight ratio being significantly greater in trained compared with sedentary animals. However, voluntary exercise caused no significant alteration in the size or time course of myocyte shortening and [Ca2+]i transients or in the mRNA levels of key proteins that regulate Ca2+ handling. The positive inotropic response to beta1-AR stimulation and the level of beta1-AR mRNA were unaltered by voluntary exercise but both mRNA levels and inotropic response to beta2-AR stimulation were significantly reduced in trained animals. The beta2-AR inotropic response was restored by exposure to pertussis toxin. We propose that in contrast to pathological stimuli and to beneficial, intense exercise training, modulation of Ca2+ handling is not a major adaptive mechanism in the response to mild voluntary exercise. In addition, and in a reversal of the situation seen in heart failure, voluntary exercise training maintains the beta1-AR response but reduces the beta2-AR response. Therefore, although voluntary exercise induces cardiac hypertrophy, there are distinct differences between its effects on key myocardial regulatory mechanisms

  6. Laminar arrangement of ventricular myocytes influences electrical behavior of the heart.

    Science.gov (United States)

    Hooks, Darren A; Trew, Mark L; Caldwell, Bryan J; Sands, Gregory B; LeGrice, Ian J; Smaill, Bruce H

    2007-11-01

    The response of the heart to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. A long-held view of cardiac electrical anisotropy is that electrical conductivity is greatest along the myocyte axis allowing most rapid propagation of electrical activation in this direction, and that conductivity is isotropic transverse to the myocyte axis supporting a slower uniform spread of activation in this plane. In this context, knowledge of conductivity in two directions, parallel and transverse to the myofiber axis, is sufficient to characterize the electrical action of the heart. Here we present new experimental data that challenge this view. We have used a novel combination of intramural electrical mapping, and experiment-specific computer modeling, to demonstrate that left ventricular myocardium has unique bulk conductivities associated with three microstructurally-defined axes. We show that voltage fields induced by intramural current injection are influenced by not only myofiber direction, but also the transmural arrangement of muscle layers or myolaminae. Computer models of these experiments, in which measured 3D tissue structure was reconstructed in-silico, best matched recorded voltages with conductivities in the myofiber direction, and parallel and normal to myolaminae, set in the ratio 4:2:1, respectively. These findings redefine cardiac tissue as an electrically orthotropic substrate and enhance our understanding of how external shocks may act to successfully reset the fibrillating heart into a uniform electrical state. More generally, the mechanisms governing the destabilization of coordinated electrical propagation into ventricular arrhythmia need to be evaluated in the light of this discovery.

  7. Cardiac troponin T mutations in Chinese patients with hypertrophic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    吴恒芳; 杨笛; 万文辉; 卞智萍; 徐晋丹; 马文珠; 张寄南

    2004-01-01

    @@ Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by unexplained ventricular hypertrophy and myofibrillar disarray, with a prevalence of about 0.2% in general population. HCM is associated with gene abnormalities. Nearly 200 mutations have been described in ten genes in patients with HCM.1 Cardiac troponin T (cTnT) is an essential component of the troponin complex and plays a central role in the calcium regulation of contractions in cardiac myocytes

  8. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

    OpenAIRE

    Harris, Brett S.; Zhang, Yuhua; Card, Lauren; Rivera, Lee B.; Brekken, Rolf A.; Bradshaw, Amy D.

    2011-01-01

    Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associa...

  9. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Cédric eBOULARAN; Céline eGALES

    2015-01-01

    Cyclic adenosine 3’,5’-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  10. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  11. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  12. Characteristics of the inward-rectifying potassium current in mouse ventricular myocytes and its relation to early after-depolarization

    Institute of Scientific and Technical Information of China (English)

    周盈颖; 郝雪梅; 范劲松; 刘泰(木逢)

    1996-01-01

    The properties of the inward-rectifying potassium current (IK1) were studied in the single myocytes isolated from adult mouse ventricles by the whole-cell patch-damp technique for the first time. Most of the properties of IK1 including channel conductances, activation, inactivation, rectification and external K+ sensitivity in mouse ventricular myocyte were similar to those in other species, but the current-voltage (1-V) curve of mouse ventricular myocyte showed no negative slope, i.e the slope in the range of membrane potential 50 mV positive to the reversal potential (VRev) was virtually flat and remained at a low current level ((59±39) pA). Under the superfusion of Tyrode’s solution with 3mmol/L K+ and 3mmol/L Cs+, IK1 in the above region nearly decreased to zero, and then the early after-depolarization (EAD) occurred. The results suggest that this distinctive characteristic of IK1 in mouse ventricular myocyte may relate to the high susceptibility to EA0 in mouse myocardium. The inhibition of IK1 se

  13. TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min [Core Laboratory, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2013-02-01

    The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function.

  14. Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Lu-feng CHENG; Dong YAN; Subat TURDI; Parhat KERRAM

    2007-01-01

    Aim: To study the effects of haloperidol on sodium currents (INa) in guinea pig ventricular myocytes. Method: Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on INa, in individual ventricular myocytes.Results: Haloperidol (0.1-3 μmol/L) inhibited INa in a concentration-dependent manner with an IC50 of 0.253±0.015 μmol/L. The inhibition rate of haloperidol (0.3 μmol/L) on INa was 22.14%±0.02%, and the maximum conductance was reduced.Haloperidol significantly reduced the midpoints for the activation and inactiva-tion of INa by 2.09 and 4.09 mV, respectively. The time constant of recovery was increased. The increase in time intervals could only recover by 90.14%±1.4% (n=6); however, haloperidol at 0.03 μmol/L enhanced INa conductance. The mid-points for the activation and inactivation of INa were shifted by 1.38 and 5.69 mV,respectively, at this concentration of haloperidol.Conclusion: Haloperidol dis-played a biphasic effect on INa in guinea pig cardiac myocytes. High concentra-tions of haloperidol inhibited INa, while lower concentrations of haloperidol shifted the activation and inactivation curve to the left. Full recovery of recovery curve was not achieved after 0.3 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.

  15. Effects of the venom of the spider Ornithoctonus hainana on neonatal rat ventricular myocytes cellular and ionic electrophysiology.

    Science.gov (United States)

    Zhang, Yiya; Liu, Jinyan; Liu, Zhonghua; Wang, Meichi; Wang, Jing; Lu, Shanshan; Zhu, Li; Zeng, Xiongzhi; Liang, Songping

    2014-09-01

    Cardiac ion channels are membrane-spanning proteins that allow the passive movement of ions across the cell membrane along its electrochemical gradient, which regulates the resting membrane potential as well as the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters, hormones and drugs of cardiac diseases. Spider venoms contain high abundant of toxins that target diverse ion channels and have been considered as a potential resource of new constituents with specific pharmacological properties. However, few peptides from spider venoms were detected as cardiac channel antagonists. In order to explore the effects of the venom of Ornithoctonus hainana on the action potential and ionic currents of neonatal rat ventricular myocytes (NRVMs), whole cell patch clamp technique was used to record action potential duration (APD), sodium current (INa), L calcium current (ICaL), rapidly activating and inactivating transient outward currents (Ito1), rapid (IKr) and slow (IKs) components of the delayed rectifier currents and the inward rectifier currents (IK1). Our results showed that 100 μg/mL venom obviously prolonged APDs. Significantly, the venom could inhibit INa and ICaL effectively, while no evident inhibitory effects on cardiac K(+) channels (Ito1, Iks, Ikr and Ik1) were observed, suggesting that the venom represented a multifaceted pharmacological profile. The effect of venom on Na(+) and Ca(2+) currents of ventricular myocytes revealed that the hainan venom as a rich resource of cardiac channel antagonists might be valuable tools for the investigation of both channels and drug development.

  16. Effects of temperature and intracellular sodium, ATP and pH on Na+-Ca2+ exchange currents of intact guinea-pig myocytes

    Institute of Scientific and Technical Information of China (English)

    Hong-yiZHOU; Chong-yangHAN; Xiao-liangWANG

    2004-01-01

    AIM: The Na+-Ca2+ exchange is a major pathway for removal of cytosolic Ca2+ in cardiac myocytes. There have been many re-searches reporting about the effects of temperature, intracellular sodium, ATE and pH on Na+-Ca2+ exchange currents. But most of these researches were made with giant-patch voltage-clamp technique or with Ca2+ flux studies in sarcolemmal vesicles. During

  17. Comparison of fractal dimension and Shannon entropy in myocytes from rats treated with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate

    OpenAIRE

    de Oliveira, Marcos Aurélio Barboza; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseni; Cortez, José Luís Lasso; de Godoy, Moacir Fernandes; Braile, Domingo Marcolino

    2014-01-01

    Introduction Solutions that cause elective cardiac arrest are constantly evolving, but the ideal compound has not yet been found. The authors compare a new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat heart. Objective To quantify the fractal dimension and Shannon entropy in rat myocytes subjected to cardioplegia solution using histidine-tryptophan with glutamate in an experimental...

  18. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    Science.gov (United States)

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance.

  19. Ultraviolet photoalteration of late Na+ current in guinea-pig ventricular myocytes.

    Science.gov (United States)

    La, C; You, Y; Zhabyeyev, P; Pelzer, D J; McDonald, T F

    2006-03-01

    UV irradiation has multiple effects on mammalian cells, including modification of ion channel function. The present study was undertaken to investigate the response of membrane currents in guinea-pig ventricular myocytes to the type A (355, 380 nm) irradiation commonly used in Ca(2+) imaging studies. Myocytes configured for whole-cell voltage clamp were generally held at -80 mV, dialyzed with K(+)-, Na(+)-free pipette solution, and bathed with K(+)-free Tyrode's solution at 22 degrees C. During experiments that lasted for approximately 35 min, UVA irradiation caused a progressive increase in slowly-inactivating inward current elicited by 200-ms depolarizations from -80 to -40 mV, but had little effect on background current or on L-type Ca(2+) current. Trials with depolarized holding potential, Ca(2+) channel blockers, and tetrodotoxin (TTX) established that the current induced by irradiation was late (slowly-inactivating) Na(+) current (I(Na)). The amplitude of the late inward current sensitive to 100 microM: TTX was increased by 3.5-fold after 20-30 min of irradiation. UVA modulation of late I(Na) may (i) interfere with imaging studies, and (ii) provide a paradigm for investigation of intracellular factors likely to influence slow inactivation of cardiac I(Na). PMID:16783617

  20. Patterns of evolution of myocyte damage after human heart transplantation detected by indium-111 monoclonal antimyosin

    International Nuclear Information System (INIS)

    The indium-111 labeled Fab fragment of antimyosin monoclonal antibody was used to study cardiac rejection and the time course of myocyte damage after transplantation. Fifty-three studies were performed in 21 patients, 17 men and 4 women, aged 19 to 54 years (mean 37 +/- 8), from 7 to 40 months after transplantation. Repeat studies were available in 8, and 10 were studied after the first year of transplantation. A heart-to-lung ratio was used for quantitation of uptake (normal 1.46 +/- 0.04). Differences between absent (1.69 +/- 0.29) and moderate (1.90 +/- 0.36) rejection were significant (p less than 0.03). Antimyosin ratio at 1 to 3 months (1.89 +/- 0.35) differed from that at greater than 12 months (1.65 +/- 0.2) (p less than 0.01). Repeat studies revealed a decrease in antimyosin ratio in 5 patients with uneventful clinical course; 2 had persistent activity after transplantation and suffered heart failure from rejection. After 1 year of transplantation uptake was within normal limits in 7 of 10 patients, and high uptake was associated with vascular rejection in 1. Because they can define evolving patterns of myocardial lesion activity, antimyosin studies could be useful both in patient management and in concentrating resources for those patients who most require them. The heart-to-lung ratio is suggested to monitor sequentially the degree of myocyte damage after transplantation

  1. Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Michael eNivala

    2012-05-01

    Full Text Available Intracellular calcium (Ca cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR, mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 L-type Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a varient of Gillespie’s method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5x5x5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100x20x10 CRUs, a one-second heart time simulation takes about 10 minutes of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown.

  2. Mesenchymal stem cells improve cardiac conduction by upregulation of connexin 43 through paracrine signaling

    OpenAIRE

    Mureli, Shwetha; Gans, Christopher P.; Bare, Dan J; Geenen, David L.; Kumar, Nalin M.; Banach, Kathrin

    2012-01-01

    Mesenchymal stem cells (MSCs) were shown to improve cell survival and alleviate cardiac arrhythmias when transplanted into cardiac tissue; however, little is known about the mechanism by which MSCs modify the electrophysiological properties of cardiac tissue. We aimed to distinguish the influence of cell-cell coupling between myocytes and MSCs from that of MSC-derived paracrine factors on the spontaneous activity and conduction velocity (θ) of multicellular cardiomyocyte preparations. HL-1 ce...

  3. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1

    Science.gov (United States)

    Musaro, A.; McCullagh, K. J.; Naya, F. J.; Olson, E. N.; Rosenthal, N.

    1999-01-01

    Localized synthesis of insulin-like growth factors (IGFs) has been broadly implicated in skeletal muscle growth, hypertrophy and regeneration. Virally delivered IGF-1 genes induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy, restoring and improving muscle mass and strength in mice. Here we show that the molecular pathways underlying the hypertrophic action of IGF-1 in skeletal muscle are similar to those responsible for cardiac hypertrophy. Transfected IGF-1 gene expression in postmitotic skeletal myocytes activates calcineurin-mediated calcium signalling by inducing calcineurin transcripts and nuclear localization of calcineurin protein. Expression of activated calcineurin mimics the effects of IGF-1, whereas expression of a dominant-negative calcineurin mutant or addition of cyclosporin, a calcineurin inhibitor, represses myocyte differentiation and hypertrophy. Either IGF-1 or activated calcineurin induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs.

  4. Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy: A Cross-Sectional Study from the St. Jude Lifetime Cohort

    Science.gov (United States)

    Mulrooney, Daniel A.; Armstrong, Gregory T.; Huang, Sujuan; Ness, Kirsten K.; Ehrhardt, Matthew J.; Joshi, Vijaya M.; Plana, Juan Carlos; Soliman, Elsayed Z.; Green, Daniel M.; Srivastava, Deokumar; Santucci, Aimee; Krasin, Matthew J.; Robison, Leslie L.; Hudson, Melissa M.

    2016-01-01

    Background Studies of cardiac disease among adult survivors of childhood cancer have generally relied upon self-reported or registry-based data. Objective Systematically assess cardiac outcomes among childhood cancer survivors Design Cross-sectional Setting St. Jude Children's Research Hospital Patients 1,853 adult survivors of childhood cancer, ≥18 years old, and ≥10 years from treatment with cardiotoxic therapy for childhood cancer. Measurements History/physical examination, fasting metabolic and lipid panels, echocardiogram, electrocardiogram (ECG), 6-minute walk test (6MWT) all collected at baseline evaluation. Results Half (52.3%) of the survivors were male, median age 8.0 years (range: 0-24) at cancer diagnosis, 31.0 years (18-60) at evaluation. Cardiomyopathy was present in 7.4% (newly identified at the time of evaluation in 4.7%), coronary artery disease (CAD) in 3.8% (newly identified in 2.2%), valvular regurgitation/stenosis in 28.0% (newly identified in 24.8%), and conduction/rhythm abnormalities in 4.6% (newly identified in 1.4%). Nearly all (99.7%) were asymptomatic. The prevalences of cardiac conditions increased with age at evaluation, ranging from 3-24% among those 30-39 years to 10-37% among those ≥40 years. On multivariable analysis, anthracycline exposure ≥250 mg/m2 increased the odds of cardiomyopathy (odds ratio [OR] 2.7, 95% CI 1.1-6.9) compared to anthracycline unexposed survivors. Radiation to the heart increased the odds of cardiomyopathy (OR 1.9 95% CI 1.1-3.7) compared to radiation unexposed survivors. Radiation >1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. Limitations 61% participation rate of survivors exposed to cardiotoxic therapies, which were limited to anthracyclines and cardiac-directed radiation. A comparison group and longitudinal assessments are not available. Conclusions Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood

  5. The impairment of ILK related angiogenesis involved in cardiac maladaptation after infarction.

    Directory of Open Access Journals (Sweden)

    Jun Xie

    Full Text Available BACKGROUND: Integrin linked kinase (ILK, as an important component of mechanical stretch sensor, can initiate cellular signaling response in the heart when cardiac preload increases. Previous work demonstrated increased ILK expression could induce angiogenesis to improved heart function after MI. However the patholo-physiological role of ILK in cardiac remodeling after MI is not clear. METHOD AND RESULTS: Hearts were induced to cardiac remodeling by infarction and studied in Sprague-Dawley rats. Until 4 weeks after infarction, ILK expression was increased in non-ischemic tissue in parallel with myocytes hypertrophy and compensatory cardiac function. 8 weeks later, when decompensation of heart function occurred, ILK level returned to baseline. Followed ILK alternation, vascular endothelial growth factor (VEGF expression and phosphorylation of endothelial nitric oxide synthase (eNOS was significantly decreased 8 weeks after MI. Histology study also showed significantly microvessel decreased and myocytes loss 8 weeks paralleled with ILK down-regulation. While ILK expression was maintained by gene delivery, tissue angiogenesis and cardiac function was preserved during cardiac remodeling. CONCLUSION: Temporally up-regulation of ILK level in non-ischemic myocytes by increased external load is associated with beneficial angiogenesis to maintain infarction-induced cardiac hypertrophy. When ILK expression returns to normal, this cardiac adaptive response for infarction is weaken. Understanding the ILK related mechanism of cardiac maladaptation leads to a new strategy for treatment of heart failure after infarction.

  6. Relationship between left ventricular mass and coronary artery disease in young adults: a single-center study using cardiac computed tomography.

    Science.gov (United States)

    Cho, Jae Yong; Sun, Joo Sung; Sur, Young Keun; Park, Jin Sun; Kang, Doo Kyoung

    2015-12-01

    We evaluated the relationship between coronary artery disease (CAD) and left ventricular mass (LVM) as measured by cardiac computed tomography (CT) in young adults ≤40 years of age. We retrospectively enrolled 490 consecutive individuals (383 males; mean age, 35.2 ± 4.4 years) who underwent cardiac CT. CAD was defined by the presence of any plaque detected by coronary CT angiography. Left ventricular (LV) function, including LVM, was automatically measured by a dedicated workstation. LVM and LVM index (LVMi) in patients with CT-detected CAD were compared to those of patients without CT-detected CAD. Logistic regression analysis was used to evaluate the relationship between cardiovascular risk factors and CAD. Fifty-five individuals had CT-detected CAD (11.2 %, 53 males). LVM measured by cardiac CT was 126.9 ± 30.0 g for males and 93.6 ± 20.9 g for females. LVM was higher (117.8 ± 30.8 vs. 133.6 ± 33.1 g, P Obesity, hypertension, smoking, hypercholesterolemia, LVM and LVMi were predictors of CT-detected CAD. Body mass index (r = 0.237, P < 0.001) and systolic blood pressure (r = 0.281, P < 0.001) were positively correlated with LVM. In the multivariate analysis, LVM [odds ratio (OR) = 1.016] and LVMi (OR = 1.026) remained independent predictors of CAD. LVM and LVMi in patients with CT-detected CAD were higher than that of patients without CT-detected CAD. LVM and LVMi measured by cardiac CT were independent predictors of CAD.

  7. Ca(2+)-activated chloride channel activity during Ca(2+) alternans in ventricular myocytes.

    Science.gov (United States)

    Kanaporis, Giedrius; Blatter, Lothar A

    2016-11-01

    Cardiac alternans, defined beat-to-beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias. We investigated mechanisms of cardiac alternans in single rabbit ventricular myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. A strong correlation between beat-to-beat alternations of AP morphology and CaT alternans was observed. During CaT alternans application of voltage clamp protocols in form of pre-recorded APs revealed a prominent Ca(2+)-dependent membrane current consisting of a large outward component coinciding with AP phases 1 and 2, followed by an inward current during AP repolarization. Approximately 85% of the initial outward current was blocked by Cl(-) channel blocker DIDS or lowering external Cl(-) concentration identifying it as a Ca(2+)-activated Cl(-) current (ICaCC). The data suggest that ICaCC plays a critical role in shaping beat-to-beat alternations in AP morphology during alternans.

  8. Inhibition of p53 by pifithrin-alpha reduces myocyte apoptosis and leukocyte transmigration in aged rat hearts following 24 hours of reperfusion.

    Science.gov (United States)

    Liu, Peitan; Xu, Baohuan; Cavalieri, Thomas A; Hock, Carl E

    2008-11-01

    Ischemic heart disease is a common age-related disease. Apoptotic cell death and inflammation are the major contributors to I/R injury. The mechanisms that trigger myocyte apoptosis and inflammation during myocardial I/R (MI/R) remain to be elucidated. Published data from our laboratory demonstrated that pretreatment of MI/R rats with pifithrin-alpha (PFT), a specific p53 inhibitor, reduced myocyte apoptosis and improved cardiac function compared with MI/R rats pretreated with saline at 4 h of reperfusion. In the present study, we investigated the effects of PFT on the occurrence of myocyte apoptosis and leukocyte transmigration in the later period of reperfusion. Aged (20-month-old) male F344 rats were subjected to 30 min of myocardial ischemia via ligature of the LCA, followed by 24 h of reperfusion. Pifithrin-alpha (2.2 mg/kg, intraperitoneally) or saline was administered to rats before ischemia. The results indicate that pretreatment of MI/R rats with PFT significantly decreased the percentage of infarct area to ischemic area (33 +/- 8 vs. 54 +/- 9, P ischemic area of the heart (339 +/- 37 vs. 498 +/- 75 cells/10 high-power fields, P < 0.05). These data suggest that inhibition of p53 transcriptional function by PFT attenuates myocyte apoptosis and alleviates leukocyte transmigration at 24 h of reperfusion. The mechanisms by which p53 modulates leukocyte transmigration require further investigation. PMID:18317410

  9. Nesfatin-1 Suppresses Cardiac L-type Ca2+ Channels Through Melanocortin Type 4 Receptor and the Novel Protein Kinase C Theta Isoform Pathway

    Directory of Open Access Journals (Sweden)

    Jiaoqian Ying

    2015-05-01

    Full Text Available Background/Aims: Nesfatin-1 (NF-1, an anorexic nucleobindin-2 (NUCB2-derived hypothalamic peptide, acts as a peripheral cardiac modulator and it can induce negative inotropic effects. However, the mechanisms underlying these effects in cardiomyocytes remain unclear. Methods: Using patch clamp, protein kinase assays, and western blot analysis, we studied the effect of NF-1 on L-type Ca2+ currents (ICa,L and to explore the regulatory mechanisms of this effect in adult ventricular myocytes. Results: NF-1 reversibly decreased ICa,L in a dose-dependent manner. This effect was mediated by melanocortin 4 receptor (MC4-R and was associated with a hyperpolarizing shift in the voltage-dependence of inactivation. Dialysis of cells with GDP-β-S or anti-Gβ antibody as well as pertussis toxin pretreatment abolished the inhibitory effects of NF-1 on ICa,L. Protein kinase C (PKC antagonists abolished NF-1-induced responses, whereas inhibition of PKA activity or intracellular application of the fast Ca2+-chelator BAPTA elicited no such effects. Application of NF-1 increased membrane abundance of PKC theta isoform (PKCθ, and PKCθ inhibition abolished the decrease in ICa,L induced by NF-1. Conclusion: These data suggest that NF-1 suppresses L-type Ca2+ channels via the MC4-R that couples sequentially to the βγ subunits of Gi/o-protein and the novel PKCθ isoform in adult ventricular myocytes.

  10. Biological determinants of aldosterone-induced cardiac fibrosis in rats.

    Science.gov (United States)

    Robert, V; Silvestre, J S; Charlemagne, D; Sabri, A; Trouvé, P; Wassef, M; Swynghedauw, B; Delcayre, C

    1995-12-01

    To determine the events leading to cardiac fibrosis in aldosterone-salt hypertensive rats, we studied protein and mRNA accumulation of procollagens I and III for 60 days. After 3 and 7 days of treatment systolic pressure was normal, and no histological or biochemical changes were seen in rat hearts. At day 15 arterial pressure was raised (+40%) and left ventricular hypertrophy was +15%. Cardiac examination after hemalun-eosin staining and immunolabeling with anticollagen I and III antibodies showed no structural alterations, but an 83% increase in right ventricular type III procollagen mRNA levels was found. At 30 and 60 days we found progressive cardiac fibrosis, with inflammatory cells, myocyte necrosis, and elevation of both types I and III procollagen mRNA levels in both ventricles. To determine whether aldosterone had effects on Na,K-ATPase that might lead to ionic disturbances and induce myocyte necrosis, we studied the major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase alpha 1- and beta 1-subunit mRNA levels were elevated in kidney at day 1, neither of these cardiac transcripts nor the specific alpha 2 isoform was altered between 1 and 15 days. These results show that accumulation of procollagen mRNAs occurs before collagen deposition. Cardiac alterations are late and not preceded by changes in Na,K-ATPase cardiac gene expression, precluding a direct modulation of cardiac collagen synthesis and Na,K-ATPase by aldosterone. PMID:7490157

  11. Myomaker mediates fusion of fast myocytes in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Landemaine, Aurélie; Rescan, Pierre-Yves; Gabillard, Jean-Charles, E-mail: Jean-charles.gabillard@rennes.inra.fr

    2014-09-05

    Highlights: • Myomaker is transiently expressed in fast myocytes during embryonic myogenesis. • Myomaker is essential for fast myocyte fusion in zebrafish. • The function of myomaker is conserved among Teleostomi. - Abstract: Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation. Confocal observations showed a marked phenotype characterized by the persistence of mononucleated muscle cells in the fast myotome at developmental stages where these cells normally fuse to form multinucleated myotubes. This indicates that myomaker is essential for myocyte fusion in zebrafish. Thus, there is an evolutionary conservation of myomaker expression and function among Teleostomi.

  12. Illuminating Myocyte-Fibroblast Homotypic and Heterotypic Gap Junction Dynamics Using Dynamic Clamp.

    Science.gov (United States)

    Brown, Tashalee R; Krogh-Madsen, Trine; Christini, David J

    2016-08-23

    Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however, the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa that slow propagation, cause zig-zag conduction paths, and decouple cardiomyocytes, resulting in a substrate for cardiac arrhythmia. An emerging mechanism suggests that fibroblasts promote arrhythmogenesis through direct electrical interactions with cardiomyocytes via gap junction (GJ) channels. In the heart, three major connexin (Cx) isoforms, Cx40, Cx43, and Cx45, form GJ channels in cell-type-specific combinations. Because each Cx is characterized by a unique time- and transjunctional voltage-dependent profile, we investigated whether the electrophysiological contributions of fibroblasts would vary with the specific composition of the myocyte-fibroblast (M-F) GJ channel. Due to the challenges of systematically modifying Cxs in vitro, we coupled native cardiomyocytes with in silico fibroblast and GJ channel electrophysiology models using the dynamic-clamp technique. We found that there is a reduction in the early peak of the junctional current during the upstroke of the action potential (AP) due to GJ channel gating. However, effects on the cardiomyocyte AP morphology were similar regardless of the specific type of GJ channel (homotypic Cx43 and Cx45, and heterotypic Cx43/Cx45 and Cx45/Cx43). To illuminate effects at the tissue level, we performed multiscale simulations of M-F coupling. First, we developed a cell-specific model of our dynamic-clamp experiments and investigated changes in the underlying membrane currents during M-F coupling. Second, we performed two-dimensional tissue sheet simulations of cardiac fibrosis and incorporated GJ channels in a cell type-specific manner. We determined that although GJ channel gating reduces junctional current, it does not

  13. Cardiac cAMP: production, hydrolysis, modulation and detection.

    Science.gov (United States)

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability. PMID:26483685

  14. STIM1 enhances SR Ca2+ content through binding phospholamban in rat ventricular myocytes.

    Science.gov (United States)

    Zhao, Guiling; Li, Tianyu; Brochet, Didier X P; Rosenberg, Paul B; Lederer, W J

    2015-08-25

    In ventricular myocytes, the physiological function of stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum (ER/SR) Ca(2+) sensor, is unclear with respect to its cellular localization, its Ca(2+)-dependent mobilization, and its action on Ca(2+) signaling. Confocal microscopy was used to measure Ca(2+) signaling and to track the cellular movement of STIM1 with mCherry and immunofluorescence in freshly isolated adult rat ventricular myocytes and those in short-term primary culture. We found that endogenous STIM1 was expressed at low but measureable levels along the Z-disk, in a pattern of puncta and linear segments consistent with the STIM1 localizing to the junctional SR (jSR). Depleting SR Ca(2+) using thapsigargin (2-10 µM) changed neither the STIM1 distribution pattern nor its mobilization rate, evaluated by diffusion coefficient measurements using fluorescence recovery after photobleaching. Two-dimensional blue native polyacrylamide gel electrophoresis and coimmunoprecipitation showed that STIM1 in the heart exists mainly as a large protein complex, possibly a multimer, which is not altered by SR Ca(2+) depletion. Additionally, we found no store-operated Ca(2+) entry in control or STIM1 overexpressing ventricular myocytes. Nevertheless, STIM1 overexpressing cells show increased SR Ca(2+) content and increased SR Ca(2+) leak. These changes in Ca(2+) signaling in the SR appear to be due to STIM1 binding to phospholamban and thereby indirectly activating SERCA2a (Sarco/endoplasmic reticulum Ca(2+) ATPase). We conclude that STIM1 binding to phospholamban contributes to the regulation of SERCA2a activity in the steady state and rate of SR Ca(2+) leak and that these actions are independent of store-operated Ca(2+) entry, a process that is absent in normal heart cells. PMID:26261328

  15. Stroke and cardiac cell death: Two peas in a pod.

    Science.gov (United States)

    Gonzales-Portillo, Chiara; Ishikawa, Hiroto; Shinozuka, Kazutaka; Tajiri, Naoki; Kaneko, Yuji; Borlongan, Cesar V

    2016-03-01

    A close pathological link between stroke brain and heart failure may exist. Here, we discuss relevant laboratory and clinical reports demonstrating neural and cardiac myocyte cell death following ischemic stroke. Although various overlapping risk factors exist between cerebrovascular incidents and cardiac incidents, stroke therapy has largely neglected the cardiac pathological consequences. Recent preclinical stroke studies have implicated an indirect cell death pathway, involving toxic molecules, that originates from the stroke brain and produces cardiac cell death. In concert, previous laboratory reports have revealed a reverse cell death cascade, in that cardiac arrest leads to ischemic cell death in the brain. A deeper understanding of the crosstalk of cell death pathways between stroke and cardiac failure will facilitate the development of novel treatments designed to arrest the global pathology of both diseases thereby improving the clinical outcomes of patients diagnosed with stroke and heart failure.

  16. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Directory of Open Access Journals (Sweden)

    A. Medeiros

    2004-12-01

    Full Text Available The effect of swimming training (ST on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12 and trained (T, N = 12 male Wistar rats (200-220 g. ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm. RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm, since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13% and myocyte dimension (21% were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  17. Radiographic evaluation of the cardiac silluet using the VHS method (Vertebral Heart Size in young and adults coatis (Nasua nasua, Linneaus 1766 living in captivity

    Directory of Open Access Journals (Sweden)

    Andresa Cássia Martini

    2014-02-01

    Full Text Available Radiographic examination of the toracic cavity is an usefull noninvasive method for assessment, monitoring the progress of heart disease, suggesting prognosis and guiding the treatment. The aim of this study was to evaluate the cardiac silhouette of young and adults coatis and evaluate its relationship to the number of thoracic vertebrae (VHS, the method proposed by Buchanam and Buchele (1995 for small animals. We evaluated a group of 20 coatis, divided by age: I (GI and 8 animals aged between 4 and 5 months and group II (GII with 12 animals over 12 months old. Based in chest radiographs and VD laterolateral right projections for determining the major axis (L and short axis (Y being the sum of L and S is the value obtained by ESR, the relative depth/width (D / L chest were obtained and the results determined the type of conformation of the thorax, which results greater than 1.25 cm denote chest type deep, 0.75 to 1.25 cm chest intermediate and inferior results will 0.75cm wide chest. It was observed that the heart is alocated between the fourth and seventh pair of ribs, VHS average coatis healthy adults was 9.36 ± 0.75 and 8.06 ± 0 youth, 595 units thoracic vertebrae and the predominant conformation found was of intermediate type when compared to dogs. The mean values in this study serve as a basis for interpretation of the VHS type, however, a larger number may be required animals to determine the physiological limits of the cardiac silhouette in coati.

  18. Cardiac metabolism and arrhythmias

    OpenAIRE

    Barth, Andreas S.; Tomaselli, Gordon F.

    2009-01-01

    Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all deaths in the U.S.1, 2 The major causes of sudden cardiac death in adults age 35 and older are coronary artery disease (70–80%) and dilated cardiomyopathy (10–15%).3 At the molecular level, a wide variety of mechanisms contribute to arrhythmias that cause sudden cardiac death, ranging from genetic predisposition (rare mutations and common polymorphisms in ion channels and structural...

  19. Effects of remifentanil on intracellular Ca2+ and its transients induced by electrical stimulation and caffeine in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ye; Michael G. Irwin; LI Rui; CHEN Zhiwu; Tak-Ming Wong

    2009-01-01

    Background Preconditioning with remifentanil confers cardioprotection. Since Ca2+ overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca2+ ([Ca2+]I) and its transients induced by electrical stimulation and caffeine, which reflects Ca2+ handling by Ca2+ handling proteins, in rat ventricular myocytes. Methods Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca]I was determined by spectrofluorometry. Remifentanil at 0.1-1000 μg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca2+]I, and the amplitude, time resting and 50% decay (t50) of both transients induced by electrical stimulation (E[Ca2+]I) and caffeine (C[Ca2+]I) were determined.Results Remifentanil (0.1-1000.0 μg/L) decreased the [Ca2+]I in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t50 of both transients dose-dependently.Conclusion Remifentanil reduced the [Ca2+]I and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

  20. Executive functions improvement following a 5-month aquaerobics program in older adults: Role of cardiac vagal control in inhibition performance.

    Science.gov (United States)

    Albinet, Cédric T; Abou-Dest, Amira; André, Nathalie; Audiffren, Michel

    2016-03-01

    The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (heart rate variability) and psychological variables. Thirty-six sedentary seniors aged 60-75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration. PMID:26812613

  1. Executive functions improvement following a 5-month aquaerobics program in older adults: Role of cardiac vagal control in inhibition performance.

    Science.gov (United States)

    Albinet, Cédric T; Abou-Dest, Amira; André, Nathalie; Audiffren, Michel

    2016-03-01

    The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (heart rate variability) and psychological variables. Thirty-six sedentary seniors aged 60-75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration.

  2. The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

    Science.gov (United States)

    Xu, Hao; Zhao, Manxi; Liang, Shenghui; Huang, Quanshu; Xiao, Yunchuan; Ye, Liang; Wang, Qinyi; He, Longmei; Ma, Lanxiang; Zhang, Hua; Zhang, Li; Jiang, Hui; Ke, Xiao; Gu, Yuchun

    2016-01-01

    Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases. PMID:27762288

  3. Differences of promethazine and terfenadine on ion channels in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    LI Xue-wen; NIU Shuan-cheng; ZHANG Xuan-ping; L(U) Ji-yuan; BAI Feng; ZHANG Ling; WU Bo-wei

    2006-01-01

    @@ Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias1 and experimental arrhythmias.2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes (TdP) like ventricular arrhythmia.3 This may be due to the blockage on rectifier postassium current (Ik) of terfenadine, resulting in the prolongation of the action potential duration (APD) and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the Ik and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.

  4. Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

    Directory of Open Access Journals (Sweden)

    Megan A Cummins

    2014-03-01

    Full Text Available Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP. The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz and fast (2 Hz rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of

  5. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis

    Directory of Open Access Journals (Sweden)

    Kain Vasundhara

    2011-11-01

    Full Text Available Abstract Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB, Azelnidipine (AZL on contractile dysfunction, intracellular calcium (Ca2+ cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP injection of streptozotocin (STZ. Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS, time-to-PS (TPS, time-to-relengthening (TR90, maximal velocity of shortening/relengthening (± dL/dt and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD, calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property.

  6. Hyperlactatemia in patients undergoing adult cardiac surgery under cardiopulmonary bypass: Causative factors and its effect on surgical outcome

    Science.gov (United States)

    Naik, Rakesh; George, Gladdy; Karuppiah, Sathappan; Philip, Madhu Andrew

    2016-01-01

    Objectives of the Study: To identify the factors causing high lactate levels in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) and to assess the association between high blood lactate levels and postoperative morbidity and mortality. Methods: A retrospective observational study including 370 patients who underwent cardiac surgeries under cardiopulmonary bypass. The patients were divided into 2 groups based on serum lactate levels; those with serum lactate levels greater than or equal to 4 mmol/L considered as hyperlactatemia and those with serum lactate levels less than 4 mmol/L. Blood lactate samples were collected intraoperatively and postoperatively in the ICU. Preoperative and intraoperative risk factors for hyperlactatemia were identified using the highest intraoperative value of lactate. The postoperative morbidity and mortality associated with hyperlactatemia was studied using the overall (intraoperative and postoperative values) peak lactate levels. Preoperative clinical data, perioperative events and postoperative morbidity and mortality were recorded. Results: Intraoperative peak blood lactate levels of 4.0 mmol/L or more were present in 158 patients (42.7%). Females had higher peak intra operative lactate levels (P = 0.011). There was significant correlation between CPB time (Pearson correlation coefficient r = 0.024; P = 0.003) and aortic cross clamp time (r = 0.02, P = 0.007) with peak intraoperative blood lactate levels. Patients with hyperlactatemia had significantly higher rate of postoperative morbidity like atrial fibrillation (19.9% vs. 5.3%; P = 0.004), prolonged requirement of inotropes (34% vs. 11.8%; P = 0.001), longer stay in the ICU (P = 0.013) and hospital (P = 0.001). Conclusions: Hyperlactatemia had significant association with post-operative morbidity. Detection of hyperlactatemia in the perioperative period should be considered as an indicator of inadequate tissue oxygen delivery and must be aggressively

  7. High-sensitivity cardiac troponin T is associated with cognitive decline in older adults at high cardiovascular risk

    DEFF Research Database (Denmark)

    Wijsman, Liselotte W; de Craen, Anton Jm; Trompet, Stella;

    2016-01-01

    diseases risk factors or Apolipoprotein E genotype. Further adjusting for NT-proBNP levels revealed the same results. CONCLUSIONS: Higher levels of hs-cTnT associate with worse cognitive function and steeper cognitive decline in older adults independent of cardiovascular diseases, risk factors and NT-proBNP....

  8. Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

    OpenAIRE

    Zhao, Mingming; Fajardo, Giovanni; Urashima, Takashi; Spin, Joshua M; Poorfarahani, Sara; Rajagopalan, Viswanathan; Huynh, Diem; Connolly, Andrew; Quertermous, Thomas; Bernstein, Daniel

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

  9. Simulation methods and validation criteria for modeling cardiac ventricular electrophysiology

    OpenAIRE

    Shankarjee Krishnamoorthi; Luigi E Perotti; Nils P Borgstrom; Ajijola, Olujimi A.; Anna Frid; Ponnaluri, Aditya V.; Weiss, James N.; Zhilin Qu; Klug, William S.; Ennis, Daniel B.; Alan Garfinkel

    2014-01-01

    © 2014 Krishnamoorthi et al. We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transm...

  10. The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis.

    Science.gov (United States)

    Lehman, John J; Boudina, Sihem; Banke, Natasha Hausler; Sambandam, Nandakumar; Han, Xianlin; Young, Deanna M; Leone, Teresa C; Gross, Richard W; Lewandowski, E Douglas; Abel, E Dale; Kelly, Daniel P

    2008-07-01

    High-capacity mitochondrial ATP production is essential for normal function of the adult heart, and evidence is emerging that mitochondrial derangements occur in common myocardial diseases. Previous overexpression studies have shown that the inducible transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is capable of activating postnatal cardiac myocyte mitochondrial biogenesis. Recently, we generated mice deficient in PGC-1alpha (PGC-1alpha(-/-) mice), which survive with modestly blunted postnatal cardiac growth. To determine if PGC-1alpha is essential for normal cardiac energy metabolic capacity, mitochondrial function experiments were performed on saponin-permeabilized myocardial fibers from PGC-1alpha(-/-) mice. These experiments demonstrated reduced maximal (state 3) palmitoyl-l-carnitine respiration and increased maximal (state 3) pyruvate respiration in PGC-1alpha(-/-) mice compared with PGC-1alpha(+/+) controls. ATP synthesis rates obtained during maximal (state 3) respiration in permeabilized myocardial fibers were reduced for PGC-1alpha(-/-) mice, whereas ATP produced per oxygen consumed (ATP/O), a measure of metabolic efficiency, was decreased by 58% for PGC-1alpha(-/-) fibers. Ex vivo isolated working heart experiments demonstrated that PGC-1alpha(-/-) mice exhibited lower cardiac power, reduced palmitate oxidation, and increased reliance on glucose oxidation, with the latter likely a compensatory response. (13)C NMR revealed that hearts from PGC-1alpha(-/-) mice exhibited a limited capacity to recruit triglyceride as a source for lipid oxidation during beta-adrenergic challenge. Consistent with reduced mitochondrial fatty acid oxidative enzyme gene expression, the total triglyceride content was greater in hearts of PGC-1alpha(-/-) mice relative to PGC-1alpha(+/+) following a fast. Overall, these results demonstrate that PGC-1alpha is essential for the maintenance of maximal, efficient cardiac

  11. Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio to Acute and Chronic Temperature Change Using High-Resolution Echocardiography.

    Directory of Open Access Journals (Sweden)

    Ling Lee

    Full Text Available The zebrafish (Danio rerio is an important organism as a model for understanding vertebrate cardiovascular development. However, little is known about adult ZF cardiac function and how contractile function changes to cope with fluctuations in ambient temperature. The goals of this study were to: 1 determine if high resolution echocardiography (HRE in the presence of reduced cardiodepressant anesthetics could be used to accurately investigate the structural and functional properties of the ZF heart and 2 if the effect of ambient temperature changes both acutely and chronically could be determined non-invasively using HRE in vivo. Heart rate (HR appears to be the critical factor in modifying cardiac output (CO with ambient temperature fluctuation as it increases from 78 ± 5.9 bpm at 18°C to 162 ± 9.7 bpm at 28°C regardless of acclimation state (cold acclimated CA- 18°C; warm acclimated WA- 28°C. Stroke volume (SV is highest when the ambient temperature matches the acclimation temperature, though this difference did not constitute a significant effect (CA 1.17 ± 0.15 μL at 18°C vs 1.06 ± 0.14 μl at 28°C; WA 1.10 ± 0.13 μL at 18°C vs 1.12 ± 0.12 μl at 28°C. The isovolumetric contraction time (IVCT was significantly shorter in CA fish at 18°C. The CA group showed improved systolic function at 18°C in comparison to the WA group with significant increases in both ejection fraction and fractional shortening and decreases in IVCT. The decreased early peak (E velocity and early peak velocity / atrial peak velocity (E/A ratio in the CA group are likely associated with increased reliance on atrial contraction for ventricular filling.

  12. Dissociation enzyme effects on the biophysical properties of calcium current in acutely isolated rat ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Julio Álvarez

    2013-04-01

    Full Text Available Proteolytic enzymes such as collagenase, trypsin and pronase E are widely used to acutely dissociate adult cardiomyocytes. There is some evidence that enzyme treatment can alter ionic channels. The aim of the present investigation was to compare the characteristics of the L-type Ca2+ current (ICaL of rat ventricular cardiomyocytes dissociated with two enzyme combinations: collagenase + trypsin (C+T and collagenase + pronase E (C+P. ICaL density (pA/pF was significantly lower (~ 2 pA/pF in myocytes isolated with the C+P combination. However, its inactivation time course was barely affected. As well, the voltage dependency of ICaL kinetics was not affected by the C+P treatment. Our results suggest that, compared to the C+T, treatment with the C+P enzyme combination could decrease the number of functional (expressed channels in the sarcolemma.

  13. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-01

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation.

  14. "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results.

    Science.gov (United States)

    Keith, Matthew C L; Bolli, Roberto

    2015-03-27

    Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kit(pos) cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have (facetiously) dubbed this conceptual construct "string theory" of c-kit(pos) cardiac cells because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kit(pos) cells derived from the first heart field exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kit(pos) cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype (resembling bone marrow mesenchymal stem/stromal cells), and are capable of contributing significantly only to nonmyocytic lineages (fibroblasts, smooth muscle cells, and endothelial cells). If these 2 populations (first heart field and proepicardium) express different levels of c-kit, the cardiomyogenic potential of first heart field progenitors might be reconciled with recent results of c-kit(pos) cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, noncardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c

  15. "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results.

    Science.gov (United States)

    Keith, Matthew C L; Bolli, Roberto

    2015-03-27

    Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kit(pos) cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have (facetiously) dubbed this conceptual construct "string theory" of c-kit(pos) cardiac cells because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kit(pos) cells derived from the first heart field exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kit(pos) cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype (resembling bone marrow mesenchymal stem/stromal cells), and are capable of contributing significantly only to nonmyocytic lineages (fibroblasts, smooth muscle cells, and endothelial cells). If these 2 populations (first heart field and proepicardium) express different levels of c-kit, the cardiomyogenic potential of first heart field progenitors might be reconciled with recent results of c-kit(pos) cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, noncardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c

  16. Identification of caveolar resident proteins in ventricular myocytes using a quantitative proteomic approach: dynamic changes in caveolar composition following adrenoceptor activation.

    Science.gov (United States)

    Wypijewski, Krzysztof J; Tinti, Michele; Chen, Wenzhang; Lamont, Douglas; Ashford, Michael L J; Calaghan, Sarah C; Fuller, William

    2015-03-01

    The lipid raft concept proposes that membrane environments enriched in cholesterol and sphingolipids cluster certain proteins and form platforms to integrate cell signaling. In cardiac muscle, caveolae concentrate signaling molecules and ion transporters, and play a vital role in adrenergic regulation of excitation-contraction coupling, and consequently cardiac contractility. Proteomic analysis of cardiac caveolae is hampered by the presence of contaminants that have sometimes, erroneously, been proposed to be resident in these domains. Here we present the first unbiased analysis of the proteome of cardiac caveolae, and investigate dynamic changes in their protein constituents following adrenoreceptor (AR) stimulation. Rat ventricular myocytes were treated with methyl-β-cyclodextrin (MβCD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from MβCD-treated and control cell lysates using a standard discontinuous sucrose gradient. BCEMs were harvested, pelleted, and resolubilized, then alkylated, digested, and labeled with iTRAQ reagents, and proteins identified by LC-MS/MS on a LTQ Orbitrap Velos Pro. Proteins were defined as BCEM resident if they were consistently depleted from the BCEM fraction following MβCD treatment. Selective activation of α-, β1-, and β2-AR prior to preparation of BCEMs was achieved by application of agonist/antagonist pairs for 10 min in populations of field-stimulated myocytes. We typically identified 600-850 proteins per experiment, of which, 249 were defined as high-confidence BCEM residents. Functional annotation clustering indicates cardiac BCEMs are enriched in integrin signaling, guanine nucleotide binding, ion transport, and insulin signaling clusters. Proteins possessing a caveolin binding motif were poorly enriched in BCEMs, suggesting this is not the only mechanism that targets proteins to caveolae. With the notable exception of the cavin family, very few proteins show

  17. Identification of Caveolar Resident Proteins in Ventricular Myocytes Using a Quantitative Proteomic Approach: Dynamic Changes in Caveolar Composition Following Adrenoceptor Activation*

    Science.gov (United States)

    Wypijewski, Krzysztof J.; Tinti, Michele; Chen, Wenzhang; Lamont, Douglas; Ashford, Michael L. J.; Calaghan, Sarah C.; Fuller, William

    2015-01-01

    The lipid raft concept proposes that membrane environments enriched in cholesterol and sphingolipids cluster certain proteins and form platforms to integrate cell signaling. In cardiac muscle, caveolae concentrate signaling molecules and ion transporters, and play a vital role in adrenergic regulation of excitation–contraction coupling, and consequently cardiac contractility. Proteomic analysis of cardiac caveolae is hampered by the presence of contaminants that have sometimes, erroneously, been proposed to be resident in these domains. Here we present the first unbiased analysis of the proteome of cardiac caveolae, and investigate dynamic changes in their protein constituents following adrenoreceptor (AR) stimulation. Rat ventricular myocytes were treated with methyl-β-cyclodextrin (MβCD) to deplete cholesterol and disrupt caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from MβCD-treated and control cell lysates using a standard discontinuous sucrose gradient. BCEMs were harvested, pelleted, and resolubilized, then alkylated, digested, and labeled with iTRAQ reagents, and proteins identified by LC-MS/MS on a LTQ Orbitrap Velos Pro. Proteins were defined as BCEM resident if they were consistently depleted from the BCEM fraction following MβCD treatment. Selective activation of α-, β1-, and β2-AR prior to preparation of BCEMs was achieved by application of agonist/antagonist pairs for 10 min in populations of field-stimulated myocytes. We typically identified 600–850 proteins per experiment, of which, 249 were defined as high-confidence BCEM residents. Functional annotation clustering indicates cardiac BCEMs are enriched in integrin signaling, guanine nucleotide binding, ion transport, and insulin signaling clusters. Proteins possessing a caveolin binding motif were poorly enriched in BCEMs, suggesting this is not the only mechanism that targets proteins to caveolae. With the notable exception of the cavin family, very few proteins

  18. Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    FENG Li; GONG Jing; JIN Zhen-yi; LI Ning; SUN Li-ping; WU Yi-ling; PU Jie-lin

    2009-01-01

    Background Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. Methods The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n=8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). Results SSYX treatment accelerated the HR from (141.8±36.0) beats per minute to (163.0±38.0) beats per minute (P=0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD30, APD50 and APDgo were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD3o and APD9o did not significantly change.Conclusions The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

  19. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  20. Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Amanda L. Vega

    2011-01-01

    sarcoplasmic reticulum (SR and the sarcolemma where Ca2+ release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca2+] during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes.

  1. Relation of fragmented QRS complex to right ventricular fibrosis detected by late gadolinium enhancement cardiac magnetic resonance in adults with repaired tetralogy of fallot.

    Science.gov (United States)

    Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Seung Woo; Yang, Ji-Hyuk; Jun, Tae-Gook; Kang, I-Seok; Lee, Heung Jae; Choe, Yeon Hyeon; Huh, June

    2012-01-01

    Fragmented QRS (fQRS) on 12-lead electrocardiography reflects conduction delay caused by myocardial fibrosis and dysfunction. Ventricular fibrosis detected by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is reportedly correlated with worse clinical outcomes in adults with repaired tetralogy of Fallot (TOF). The aim of this study was to assess whether the presence of fQRS is associated with right ventricular (RV) fibrosis or dysfunction in this patient group. In 37 consecutive patients (median age 30 years, median age at repair 6.6 years), the number of leads showing fQRS, defined as the presence of >2 notches on the R/S wave in ≥2 contiguous leads, was counted. RV systolic function, dilatation, and LGE score were measured using LGE CMR. Ventricular LGE was observed mainly at the previous surgical sites: the RV outflow tract (33 of 37), ventricular septal defect patch region (15 of 37), and RV anterior wall (11 of 37). Fragmented QRS was found mostly in the right and mid precordial leads. The fQRS group (n = 20) demonstrated higher RV LGE scores (p <0.001) and lower RV ejection fractions (p = 0.02) and a trend toward larger RV end-diastolic and end-systolic volumes (p = 0.12 and p = 0.06, respectively) compared to the non-fQRS group (n = 17). The number of electrocardiographic leads showing fQRS was positively correlated with RV LGE score (r = 0.75, p <0.001). The presence of fQRS remained independently associated with the presence of supramedian RV LGE score, even after adjusting for relevant parameters. In conclusion, fQRS was closely associated with more extensive RV fibrosis and dysfunction in adults with repaired tetralogy of Fallot.

  2. Does Pre-hospital Endotracheal Intubation Improve Survival in Adults with Non-traumatic Out-of-hospital Cardiac Arrest? A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ling Tiah

    2014-11-01

    Full Text Available Introduction: Endotracheal intubation (ETI is currently considered superior to supraglottic airway devices (SGA for survival and other outcomes among adults with non-traumatic out-of-hospital cardiac arrest (OHCA. We aimed to determine if the research supports this conclusion by conducting a systematic review. Methods: We searched the MEDLINE, Scopus and CINAHL databases for studies published between January 1, 1980, and 30 April 30, 2013, which compared pre-hospital use of ETI with SGA for outcomes of return of spontaneous circulation (ROSC; survival to hospital admission; survival to hospital discharge; and favorable neurological or functional status. We selected studies using pre-specified criteria. Included studies were independently screened for quality using the Newcastle-Ottawa scale. We did not pool results because of study variability. Study outcomes were extracted and results presented as summed odds ratios with 95% CI. Results: We identified five eligible studies: one quasi-randomized controlled trial and four cohort studies, involving 303,348 patients in total. Only three of the five studies reported a higher proportion of ROSC with ETI versus SGA with no difference reported in the remaining two. None found significant differences between ETI and SGA for survival to hospital admission or discharge. One study reported better functional status at discharge for ETI versus SGA. Two studies reported no significant difference for favorable neurological status between ETI and SGA. Conclusion: Current evidence does not conclusively support the superiority of ETI over SGA for multiple outcomes among adults with OHCA. [West J Emerg Med. 2014;15(7:-0.

  3. Coagulation Parameter Thresholds Associated with Non-Bleeding in the Eighth Hour of Adult Cardiac Surgical Post-Cardiotomy Extracorporeal Membrane Oxygenation.

    Science.gov (United States)

    Riley, Jeffrey B; Schears, Gregory J; Nuttall, Gregory A; Oliver, William C; Ereth, Mark H; Dearani, Joseph A

    2016-06-01

    Excessive bleeding and allogeneic transfusion during adult post-cardiotomy venoarterial extracorporeal membrane oxygenation (ECMO) are potentially harmful and expensive. Balancing the inhibition of clotting and distinguishing surgical from non-surgical bleeding in post-operative period is difficult. The sensitivity of coagulation tests including Thromboelastography(®) (TEG) to predict chest tube drainage in the early hours of ECMO was examined with the use of receiver-operating characteristics (ROC). The results are useful to incorporate in clinical evidence-based algorithms to guide management decisions. In the eighth hour of ECMO, 26 of the 53 adult patients (49%) studied were identified as non-bleeders (less than 2.0 mL/kg/h). All had experienced various types of cardiac surgical procedures. Fifty-two percent were female and the group was 54 ± 19 (mean ± 1 SD) years old. The coagulation parameter threshold with the maximum sensitivity and specificity to predict non-bleeding at 8 hours on ECMO was the kaolin plus heparinase TEG maximum amplitude (KH-TEG MA) at a significant ROC threshold (t) > 50 mm. The activated partial thromboplastin time (aPTT) t 51°, and the kaolin activated clotting time (ACT) t < 148 seconds were sensitive predictors of non-bleeders. The whole-blood KH-TEG MA was superior to the plasma-based aPTT or International Normalization Ratio (INR) to predict bleeding in the eighth hour of ECMO. Using coagulation laboratory thresholds that predict non-bleeding can begin a process of identifying patients earlier that are likely to bleed. Awareness of these parameter thresholds may improve care through patient protection from unnecessary transfusion and prolonging the life of the ECMO circuit. An algorithm incorporating the ROC thresholds was created to help recognize surgical bleeding to minimize unnecessary transfusions. PMID:27578897

  4. A unified theory of calcium alternans in ventricular myocytes

    Science.gov (United States)

    Qu, Zhilin; Liu, Michael B.; Nivala, Michael

    2016-01-01

    Intracellular calcium (Ca2+) alternans is a dynamical phenomenon in ventricular myocytes, which is linked to the genesis of lethal arrhythmias. Iterated map models of intracellular Ca2+ cycling dynamics in ventricular myocytes under periodic pacing have been developed to study the mechanisms of Ca2+ alternans. Two mechanisms of Ca2+ alternans have been demonstrated in these models: one relies mainly on fractional sarcoplasmic reticulum Ca2+ release and uptake, and the other on refractoriness and other properties of Ca2+ sparks. Each of the two mechanisms can partially explain the experimental observations, but both have their inconsistencies with the experimental results. Here we developed an iterated map model that is composed of two coupled iterated maps, which unifies the two mechanisms into a single cohesive mathematical framework. The unified theory can consistently explain the seemingly contradictory experimental observations and shows that the two mechanisms work synergistically to promote Ca2+ alternans. Predictions of the theory were examined in a physiologically-detailed spatial Ca2+ cycling model of ventricular myocytes. PMID:27762397

  5. Transitions of protein traffic from cardiac ER to junctional SR

    OpenAIRE

    Sleiman, Naama H.; McFarland, Timothy P.; Jones, Larry R.; Cala, Steven E.

    2015-01-01

    The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca2+ release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appe...

  6. Prevalence of coronary artery ectasia in older adults and the relationship with epicardial fat volume by cardiac computed tomography angiography

    Institute of Scientific and Technical Information of China (English)

    Jun-Jie Yang; Xia Yang; Zhi-Ye Chen; Qi Wang; Bai He; Luo-Shan Du; Yun-Dai Chen

    2013-01-01

    Objective Coronary artery ectasia (CAE) refers to abnormal dilation of coronary artery segments to 1.5 times of adjacent normal ones. Epicardial fat is associated with cardiovascular risk factors. The relationship between CAE and epicardial fat has not yet been investigated. This study aimed to assess the relationship between CAE and epicardial fat volume (EFV) in older people by dual-source computed tomography coronary angiography (CTCA). Methods We prospectively enrolled 1400 older adults who were scheduled for dual-source CTCA. Under reconstruction protocols, patients with abnormal segments 1.5 times larger than the adjacent segments were accepted as CAE. EFV was measured by semi-automated software. Traditional risk factors in CAE patients, as well as the extent of EFV, were analyzed and compared to non-CAE group. Results A total of 885 male and 515 female older patients were enrolled. CAE was identified by univariable analysis in 131 patients and significantly correlated to hypertension, smoking, hyperlipidemia, prior percutaneous coronary intervention and ascending aorta aneurysm. EFV was shown to be significantly higher in CAE patients than patients without ectasia. In multivariable analyses, EFV (P = 0.018), hypertension (P < 0.001) and hyperlipidemia (P < 0.001) were significantly correlated to CAE. There was a significant negative correlation between EFV and Markis classification. Conclusions CAE can be reliably recognized by dual-source CTCA. Epicardial fat might play a role in etiopathogenesis and progression of CAE, providing a new target for treating ectasia.

  7. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.

    Science.gov (United States)

    Lombardo, Daniel M; Fenton, Flavio H; Narayan, Sanjiv M; Rappel, Wouter-Jan

    2016-08-01

    Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy. PMID:27494252

  8. Inibição da corrente de cálcio tipo L por tramadol e enantiômeros em miócitos cardíacos de ratos Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats

    Directory of Open Access Journals (Sweden)

    Emiliano Medei

    2011-10-01

    -L, in which the peak amplitude was reduced by 64.4 ± 2.8% and 68.9 ± 5.8%, respectively at 0 mV (p > 0.05. Tramadol, (+- and (--tramadol shifted the steady-state inactivation of I Ca-L to more negative membrane potentials. Also, tramadol and (+-tramadol markedly shifted the time-dependent recovery curve of I Ca-L to the right and slowed down the recovery of I Ca-L from inactivation. The time constant was increased from 175.6 ± 18.6 to 305.0 ± 32.9 ms (p < 0.01 for tramadol and from 248.1 ± 28.1 ms to 359.0 ± 23.8 ms (p < 0.05 for (+-tramadol. The agonist of µ-opioid receptor DAMGO had no effect on the I Ca-L. CONCLUSION: The inhibition of I Ca-L induced by tramadol and its enantiomers was unrelated to the activation of opioid receptors and could explain, at least in part, their negative cardiac inotropic effect.

  9. Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy.

    Science.gov (United States)

    Seo, Kinya; Rainer, Peter P; Shalkey Hahn, Virginia; Lee, Dong-Ik; Jo, Su-Hyun; Andersen, Asger; Liu, Ting; Xu, Xiaoping; Willette, Robert N; Lepore, John J; Marino, Joseph P; Birnbaumer, Lutz; Schnackenberg, Christine G; Kass, David A

    2014-01-28

    Chronic neurohormonal and mechanical stresses are central features of heart disease. Increasing evidence supports a role for the transient receptor potential canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression for both is normally very low but is increased by cardiac disease, and genetic gain- or loss-of-function studies support contributions to hypertrophy and dysfunction. Selective small-molecule inhibitors remain scarce, and none target both channels, which may be useful given the high homology among them and evidence of redundant signaling. Here we tested selective TRPC3/6 antagonists (GSK2332255B and GSK2833503A; IC50, 3-21 nM against TRPC3 and TRPC6) and found dose-dependent blockade of cell hypertrophy signaling triggered by angiotensin II or endothelin-1 in HEK293T cells as well as in neonatal and adult cardiac myocytes. In vivo efficacy in mice and rats was greatly limited by rapid metabolism and high protein binding, although antifibrotic effects with pressure overload were observed. Intriguingly, although gene deletion of TRPC3 or TRPC6 alone did not protect against hypertrophy or dysfunction from pressure overload, combined deletion was protective, supporting the value of dual inhibition. Further development of this pharmaceutical class may yield a useful therapeutic agent for heart disease management.

  10. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.

    Directory of Open Access Journals (Sweden)

    Viswanathan Rajagopalan

    Full Text Available A large body of evidence suggests that thyroid hormones (THs are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3 treatment in myocardial infarction (MI rats increased left ventricular (LV contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day was available in drinking water ad libitum immediately following MI and continuing for 2 month(s (mo. Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

  11. Interplay between cardiac function and heart development.

    Science.gov (United States)

    Andrés-Delgado, Laura; Mercader, Nadia

    2016-07-01

    Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease. This requires cardiomyocytes to be mechanically durable and able to mount coordinated responses to a variety of environmental signals on different time scales, including cardiac pressure loading and electrical and hemodynamic forces. During physiological growth, myocytes, endocardial and epicardial cells have to adaptively remodel to these mechanical forces. Here we review some of the recent advances in the understanding of how mechanical forces influence cardiac development, with a focus on fluid flow forces. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  12. Changes in myocardial lactate, pyruvate and lactate-pyruvate ratio during cardiopulmonary bypass for elective adult cardiac surgery: Early indicator of morbidity

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    P M Kapoor

    2011-01-01

    Full Text Available Background: Myocardial lactate assays have been established as a standard method to compare various myocardial protection strategies. This study was designed to test whether coronary sinus (CS lactates, pyruvate and lactate-pyruvate (LP ratio correlates with myocardial dysfunction and predict postoperative outcomes. Materials and Methods: This prospective observational study was conducted on 40 adult patients undergoing elective cardiac surgery with the aid of cardiopulmonary bypass (CPB. CS blood sampling was done for estimation of myocardial lactate (ML, pyruvate (MP and lactate-pyruvate ratio (MLPR namely: pre-CPB (T 1 , after removal of aortic cross clamp (T 2 and 30 minutes post-CPB (T 3 . Results: Baseline myocardial LPR strongly correlated with Troponin-I at T1 (s: 0.6. Patients were sub grouped according to the median value of myocardial lactate (2.9 at baseline T1 into low myocardial lactate (LML group, mean (2.39±0.4 mmol/l, n=19 and a high myocardial lactate (HML group, mean (3.65±0.9 mmol/l, n=21. A significant increase in PL, ML, MLPR and TropI occurred in both groups as compared to baseline. Patients in HML group had significant longer period of ICU stay. Patients with higher inotrope score had significantly higher ML (T2, T3. ML with a baseline value of 2.9 mmol/l had 70.83% sensitivity and 62.5% specificity (ROC area: 0.7109 Std error: 0.09 while myocardial pyruvate with a baseline value of 0.07 mmol/l has 79.17% sensitivity and 68.75% specificity (ROC area: 0.7852, Std error: 0.0765 for predicting inotrope requirement after CPB. Conclusion: CS lactate, pyruvate and LP ratio correlate with myocardial function and can predict postoperative outcome.

  13. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  14. Implementation of Contraction to Electrophysiological Ventricular Myocyte Models, and Their Quantitative Characterization via Post-Extrasystolic Potentiation.

    Directory of Open Access Journals (Sweden)

    Yanyan Claire Ji

    Full Text Available Heart failure (HF affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT and cardiac contractility modulation (CCM have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF.

  15. Implementation of Contraction to Electrophysiological Ventricular Myocyte Models, and Their Quantitative Characterization via Post-Extrasystolic Potentiation.

    Science.gov (United States)

    Ji, Yanyan Claire; Gray, Richard A; Fenton, Flavio H

    2015-01-01

    Heart failure (HF) affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM) have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement) as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF. PMID:26317204

  16. Omega-3 Fatty Acid Supplementation Appears to Attenuate Particulate Air Pollution-induced Cardiac Effects and Lipid Changes in Healthy Middle-aged Adults.

    Science.gov (United States)

    Context: Air pollution exposure has been associated with adverse cardiovascular effects. A recent epidemiologic study reported that omega-3 fatty acid (fish oil) supplementation blunted the cardiac responses to air pollution exposure. Objective: To evaluate in a randomized contro...

  17. Influence of Thromboxane A2 on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

    Science.gov (United States)

    Jeong, In Seok; Cho, Hwa Jin; Cho, Jeong Gwan; Kim, Sang Hyung; Na, Kook Joo

    2016-01-01

    Background and Objectives Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. Subjects and Methods Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. Results In the excised inside-out patches, the thromboxane A2 analog, U46619, decreased the KATP channel activity in a dose-dependent manner; however, the thromboxane A2 receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced KATP channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced KATP channel activity. Conclusion Thromboxane A2 may inhibit KATP channel activity, and may have a harmful effect on ischemic myocardium. PMID:27482267

  18. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium

    OpenAIRE

    Frantz, Stefan; Kobzik, Lester; Kim, Young-Dae; Fukazawa, Ryuji; Medzhitov, Ruslan; Lee, Richard T.; Kelly, Ralph A.

    1999-01-01

    Expression of innate immune response proteins, including IL-1β, TNF, and the cytokine-inducible isoform of nitric oxide synthase (iNOS), have been documented in the hearts of humans and experimental animals with heart failure regardless of etiology, although the proximal events leading to their expression are unknown. Noting that expression of a human homologue of Drosophila Toll, a proximal innate immunity transmembrane signaling protein in the fly, now termed human Toll-like receptor 4 (hTL...

  19. Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

    Directory of Open Access Journals (Sweden)

    Nicoline Willemijn Smit

    2014-10-01

    Full Text Available Stem cell therapy has been suggested to be a promising option for regeneration of injured myocardium, for example following a myocardial infarction. For clinical use cell-based therapies have to be safe and applicable and are aimed to renovate the architecture of the heart. Yet for functional and coordinated activity synchronized with the host myocardium stem cells have to be capable of forming electrical connections with resident cardiomyocytes. In this paper we discuss whether stem cells are capable of establishing functional electrotonic connections with cardiomyocytes and whether these may generate a risk for arrhythmias. Application of stem cells in the clinical setting with outcomes concerning arrhythmogenic safety and future perspectives will also briefly be touched upon.

  20. Calcium and IP3 dynamics in cardiac myocytes: Experimental and computational perspectives and approaches

    Directory of Open Access Journals (Sweden)

    Felix eHohendanner

    2014-03-01

    Full Text Available Calcium plays a crucial role in excitation-contraction coupling (ECC, but it is also a pivotal second messenger activating Ca2+-dependent transcription factors in a process termed excitation-transcription coupling (ETC. Evidence accumulated over the past decade indicates a pivotal role of inositol 1,4,5-trisphosphate receptor (IP3R-mediated Ca2+ release in the regulation of cytosolic and nuclear Ca2+ signals. IP3 is generated by stimulation of plasma membrane receptors that couple to phospholipase C (PLC, liberating IP3 from phosphatidylinositol 4,5-bisphosphate (PIP2. An intriguing aspect of IP3 signaling is the presence of the entire PIP2-PLC-IP3 signaling cascade as well as the presence of IP3Rs at the inner and outer membranes of the nuclear envelope (NE which functions as a Ca2+ store. The observation that the nucleus is surrounded by its own putative Ca2+ store raises the possibility that nuclear IP3-dependent Ca2+ release plays a critical role in ETC. This provides a potential mechanism of regulation that acts locally and autonomously from the global cytosolic Ca2+ signal underlying ECC. Moreover, there is evidence that: (i the sarcoplasmic reticulum (SR and NE are a single contiguous Ca2+ store; (ii the nuclear pore complex is the major gateway for Ca2+ and macromolecules to pass between the cytosol and the nucleoplasm; (iii the inner membrane of the NE hosts key Ca2+ handling proteins including the Na+/Ca2+ exchanger (NCX/GM1 complex, ryanodine receptors (RyRs, nicotinic acid adenine dinucleotide phosphate receptors (NAADPRs, Na+/K+ ATPase and Na+/H+ exchanger. Thus, it appears that the nucleus represents a Ca2+ signaling domain equipped with its own ion channels and transporters that allow for complex local Ca2+ signals. Many experimental and modeling approaches have been used for the study of intracellular Ca2+ signaling but the key to understanding of the dual role of Ca2+ mediating ECC and ECT lays in quantitative differences of local [Ca2+

  1. Nuclear translocation of the cardiac L-type calcium channel C-terminus is regulated by sex and 17β-estradiol.

    Science.gov (United States)

    Mahmoodzadeh, S; Haase, H; Sporbert, A; Rharass, T; Panáková, D; Morano, I

    2016-08-01

    The cardiac voltage gated l-type Ca(2+) channel (Cav1.2) constitutes the main entrance gate for Ca(2+) that triggers cardiac contraction. Several studies showed that the distal C-terminus fragment of Cav1.2 α1C subunit (α1C-dCT) is proteolytically cleaved and shuttles between the plasma membrane and the nucleus, which is regulated both developmentally and by Ca(2+). However, the effects of sex and sex hormone 17β-estradiol (E2, estrogen) on α1C-dCT nuclear translocation are still unexplored. To investigate the sexual disparity in the α1C-dCT nuclear translocation, we first generated an antibody directed against a synthetic peptide (GRRASFHLE) located in α1C-dCT, and used it to probe ventricular myocytes from adult female and male mice. Immunocytochemistry of isolated mouse primary adult ventricular myocytes revealed both nuclear staining and cytosolic punctuate staining around the T-tubules. The ratio of nuclear to cytosolic intensity (Inuc/Icyt) was significantly higher in isolated female cardiomyocytes (1.42±0.05) compared to male cardiomyocytes (1.05±0.02). Western blot analysis of nuclear fraction confirmed these data. Furthermore, we found a significant decrease in nuclear staining intensity of α1C-dCT in both female and male cardiomyocytes upon serum withdrawal for 18h (Inuc/Icyt 1.05±0.02 and 0.89±0.02, respectively). Interestingly, subsequent E2 treatment (10(-8)M) for 8h normalized the intracellular distribution of α1C-dCT in male cardiomyocytes (Inuc/Icyt 1.04±0.02), but not in female cardiomyocytes. Acute treatment of male cardiomyocytes with E2 for 45min revealed a similar effect. This effect of E2 was revised by ICI indicating the involvement of ER in this signaling pathway. Taken together, our results showed that the shuttling of α1C-CT in cardiomyocytes is regulated in a sex-dependent manner, and E2-activated ER may play a role in the nuclear shuttling of α1C-dCT in male cardiomyocytes. This may explain, at least partly, the observed

  2. Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes

    International Nuclear Information System (INIS)

    Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca2+ stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca2+ imaging, we found that the depletion of ER/SR Ca2+ stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca2+ ([Ca2+]i), followed by sustained increase depending on extracellular Ca2+. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na+/Ca2+ exchanger inhibitors, inhibited [Ca2+]i relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl3) or by an increased extracellular Ca2+([Ca2+]o) increased the concentration of intracelluar Ca2+, whereas, the sustained elevation of [Ca2+]i was reduced in the presence of SKF96365. Similarly, the duration of [Ca2+]i increase was also shortened in the absence of extracellular Ca2+. Western blot analysis showed that GdCl3 increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl3. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca2+-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis.

  3. Assembly of a functional 3D primary cardiac construct using magnetic levitation

    Directory of Open Access Journals (Sweden)

    Glauco Souza

    2016-07-01

    Full Text Available Easily assembled organotypic co-cultures have long been sought in medical research. In vitro tissue constructs with faithful representation of in vivo tissue characteristics are highly desirable for screening and characteristic assessment of a variety of tissue types. Cardiac tissue analogs are particularly sought after due to the phenotypic degradation and difficulty of culture of primary cardiac myocytes. This study utilized magnetic nanoparticles and primary cardiac myocytes in order to levitate and culture multicellular cardiac aggregates (MCAs. Cells were isolated from 2 day old Sprague Dawley rat hearts and subsequently two groups were incubated with either C1: 33 µL nanoshell/million cells or C2: 50 µL nanoshell/million cells. Varying numbers of cells for each concentration were cultured in a magnetic field in a 24 well plate and observed over a period of 12 days. Constructs generally formed spherical structures. Masson’s trichrome staining of a construct shows the presence of extracellular matrix protein, indicating the presence of functional fibroblasts. Many constructs exhibited noticeable contraction after 4 days of culture and continued contracting noticeably past day 9 of culture. Noticeable contractility indicates the presence of functional primary cardiac myocytes in culture. Phenotypic conservation of cardiac cells was ascertained using IHC staining by α-actinin and collagen. CD31 and fibrinogen were probed in order to assess localization of fibroblasts and endothelial cells. The study verifies a protocol for the use of magnetic levitation in order to rapidly assemble 3D cardiac like tissue with phenotypic and functional stability.

  4. mAKAP – A Master Scaffold for Cardiac Remodeling

    Science.gov (United States)

    Passariello, Catherine L.; Li, Jinliang; Dodge-Kafka, Kimberly; Kapiloff, Michael S.

    2014-01-01

    Cardiac remodeling is regulated by an extensive intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cellular adaptation. In the last few years, it has become apparent that multimolecular signaling complexes or ‘signalosomes’ are important for fidelity in intracellular signaling and for mediating crosstalk between the different signaling pathways. These complexes integrate upstream signals and control downstream effectors. In the cardiac myocyte, the protein mAKAPβ serves as a scaffold for a large signalosome that is responsive to cAMP, calcium, hypoxia, and mitogen-activated protein kinase signaling. The main function of mAKAPβ signalosomes is to modulate stress-related gene expression regulated by the transcription factors NFATc, MEF2 and HIF-1α and type II histone deacetylases that control pathological cardiac hypertrophy. PMID:25551320

  5. Cardiac cAMP: production, hydrolysis, modulation and detection

    Directory of Open Access Journals (Sweden)

    Cédric eBOULARAN

    2015-10-01

    Full Text Available Cyclic adenosine 3’,5’-monophosphate (cAMP modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.

  6. Assessment of antibody mediated cytolysis of adult cardiocytes isolated by centrifugation in a continuous gradient of Percoll in patients with acute myocarditis.

    Science.gov (United States)

    Maisch, B; Trostel-Soeder, R; Berg, P A; Kochsiek, K

    1981-01-01

    Principal objections to conventional cytotoxicity assays in cardiac disease with myocytes as target cells are the use of fetal or neonatal myocardium, the cell-membrane of which does not express all antigenic determinants, and the use of trypsin as enzyme for isolation of the cells, since this alters the myolemmal membrane considerably. An improved and rapid procedure for the isolation of intact adult cardiocytes with collaggenase was developed. by means of a performed continuous self-generating silica sol and gradient centrifugation average enrichment of 81% vital myocytes was achieved by a single isopycnic procedure. The yield was improved to 94 +/- 3% vital cells by identical second centrifugation. Cardiocytes isolated by this method were used as target cells in an assay measuring the cytolytic activity of antibodies in the presence of complement: sera of patients suffering from acute viral myocarditis (Coxsackie B- and influenza-virus) with complement fixing antisacrolemmal antibodies (ASA) of the IgG- and IgM-type showed significant cardiocytolysis. ASA are postulated to play a role in the pathogenesis of acute Coxsackie B- and influenza-virus myocarditis. PMID:6268709

  7. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  8. The Effect of U50488 on the Cardiac Rhythm and Intracellular Calcium in the Rat Heart.

    Institute of Scientific and Technical Information of China (English)

    Zhang Weimin; Xin Dalin; Wong Takming

    2000-01-01

    The effect of U50488, a selective k-opioid receptor agonist, on cardiac rhythm in the isolated perfused rat heart and intracellular calcium ([Ca2+] i) in the single ventricular myocyte were studied. The results showed that U50488 can induce arrhythmias dose-dependently in the isolated perfused rat heart and increase [Ca2+] i in the single ventricular myocyte. The effect of U50488 can be blocked by a selectivek-receptor antagonist, nor-binaltorphimine.The arrhythmogenic effects and the increase of [ Ca2 + ] i induced by U50488 were blocked by U73122, neomycin and streptomycin, which are selective phospolipase C inhibitors, but not by U73433, the inactive structural analog of U73122. These results demonstrated that the arrhythmogenic effect of cardiac k-receptor is due to activation of phosphoinositol/Ca2+ pathway.

  9. The H{sub 1}–H{sub 2} domain of the α{sub 1} isoform of Na{sup +}–K{sup +}–ATPase is involved in ouabain toxicity in rat ventricular myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Chen; Li, Jun-xia; Guo, Hui-cai; Zhang, Li-nan; Guo, Wei; Meng, Jing; Wang, Yong-li, E-mail: wangyongli@gmail.com

    2012-07-01

    The composition of different isoforms of Na{sup +}-K{sup +}-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H{sub 1}–H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α{sub 1} or α{sub 2} isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca{sup 2+}]{sub i}), attenuated mitochondrial Ca{sup 2+} overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 μM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca{sup 2+}]{sub i} and the contractility induced by 1 μM but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease. -- Highlights: ► We prepared two antibodies against the H{sub 1}-H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA. ► The H{sub 1}-H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity. ► The H{sub 1}-H{sub 2

  10. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Zhen-lun GU; Mei-lin XIE; Wen-xuan ZHOU; Ci-yi GUO

    2007-01-01

    Aim: To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Methods: Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. Results: In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Inthe Western blot analysis, EGCG significantly inhibited pressure overload-inducedp53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. Conclusion: EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload in-duced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

  11. A compartmentalized mathematical model of the β1-adrenergic signaling system in mouse ventricular myocytes.

    Directory of Open Access Journals (Sweden)

    Vladimir E Bondarenko

    Full Text Available The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca(2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol. The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca(2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca(2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca(2+]i transients; changes in intracellular and transmembrane Ca(2+ fluxes; and [Na(+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca(2+]i transients. In particular, the model includes two subpopulations of the L-type Ca(2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca(2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of

  12. Indirect three-dimensional printing: A method for fabricating polyurethane-urea based cardiac scaffolds.

    Science.gov (United States)

    Hernández-Córdova, R; Mathew, D A; Balint, R; Carrillo-Escalante, H J; Cervantes-Uc, J M; Hidalgo-Bastida, L A; Hernández-Sánchez, F

    2016-08-01

    Biomaterial scaffolds are a key part of cardiac tissue engineering therapies. The group has recently synthesized a novel polycaprolactone based polyurethane-urea copolymer that showed improved mechanical properties compared with its previously published counterparts. The aim of this study was to explore whether indirect three-dimensional (3D) printing could provide a means to fabricate this novel, biodegradable polymer into a scaffold suitable for cardiac tissue engineering. Indirect 3D printing was carried out through printing water dissolvable poly(vinyl alcohol) porogens in three different sizes based on a wood-stack model, into which a polyurethane-urea solution was pressure injected. The porogens were removed, leading to soft polyurethane-urea scaffolds with regular tubular pores. The scaffolds were characterized for their compressive and tensile mechanical behavior; and their degradation was monitored for 12 months under simulated physiological conditions. Their compatibility with cardiac myocytes and performance in novel cardiac engineering-related techniques, such as aggregate seeding and bi-directional perfusion, was also assessed. The scaffolds were found to have mechanical properties similar to cardiac tissue, and good biocompatibility with cardiac myocytes. Furthermore, the incorporated cells preserved their phenotype with no signs of de-differentiation. The constructs worked well in perfusion experiments, showing enhanced seeding efficiency. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1912-1921, 2016. PMID:26991636

  13. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    Institute of Scientific and Technical Information of China (English)

    胡琴; 李隆贵

    2003-01-01

    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  14. Nonequilibrium arrhythmic states and transitions in a mathematical model for diffuse fibrosis in human cardiac tissue.

    Directory of Open Access Journals (Sweden)

    Rupamanjari Majumder

    Full Text Available We present a comprehensive numerical study of spiral- and scroll-wave dynamics in a state-of-the-art mathematical model for human ventricular tissue with fiber rotation, transmural heterogeneity, myocytes, and fibroblasts. Our mathematical model introduces fibroblasts randomly, to mimic diffuse fibrosis, in the ten Tusscher-Noble-Noble-Panfilov (TNNP model for human ventricular tissue; the passive fibroblasts in our model do not exhibit an action potential in the absence of coupling with myocytes; and we allow for a coupling between nearby myocytes and fibroblasts. Our study of a single myocyte-fibroblast (MF composite, with a single myocyte coupled to N(f fibroblasts via a gap-junctional conductance G(gap, reveals five qualitatively different responses for this composite. Our investigations of two-dimensional domains with a random distribution of fibroblasts in a myocyte background reveal that, as the percentage P(f of fibroblasts increases, the conduction velocity of a plane wave decreases until there is conduction failure. If we consider spiral-wave dynamics in such a medium we find, in two dimensions, a variety of nonequilibrium states, temporally periodic, quasiperiodic, chaotic, and quiescent, and an intricate sequence of transitions between them; we also study the analogous sequence of transitions for three-dimensional scroll waves in a three-dimensional version of our mathematical model that includes both fiber rotation and transmural heterogeneity. We thus elucidate random-fibrosis-induced nonequilibrium transitions, which lead to conduction block for spiral waves in two dimensions and scroll waves in three dimensions. We explore possible experimental implications of our mathematical and numerical studies for plane-, spiral-, and scroll-wave dynamics in cardiac tissue with fibrosis.

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

    Science.gov (United States)

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

    2012-08-01

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

  16. Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias.

    Science.gov (United States)

    Chopra, Nagesh; Yang, Tao; Asghari, Parisa; Moore, Edwin D; Huke, Sabine; Akin, Brandy; Cattolica, Robert A; Perez, Claudio F; Hlaing, Thinn; Knollmann-Ritschel, Barbara E C; Jones, Larry R; Pessah, Isaac N; Allen, Paul D; Franzini-Armstrong, Clara; Knollmann, Björn C

    2009-05-01

    Heart muscle excitation-contraction (E-C) coupling is governed by Ca(2+) release units (CRUs) whereby Ca(2+) influx via L-type Ca(2+) channels (Cav1.2) triggers Ca(2+) release from juxtaposed Ca(2+) release channels (RyR2) located in junctional sarcoplasmic reticulum (jSR). Although studies suggest that the jSR protein triadin anchors cardiac calsequestrin (Casq2) to RyR2, its contribution to E-C coupling remains unclear. Here, we identify the role of triadin using mice with ablation of the Trdn gene (Trdn(-/-)). The structure and protein composition of the cardiac CRU is significantly altered in Trdn(-/-) hearts. jSR proteins (RyR2, Casq2, junctin, and junctophilin 1 and 2) are significantly reduced in Trdn(-/-) hearts, whereas Cav1.2 and SERCA2a remain unchanged. Electron microscopy shows fragmentation and an overall 50% reduction in the contacts between jSR and T-tubules. Immunolabeling experiments show reduced colocalization of Cav1.2 with RyR2 and substantial Casq2 labeling outside of the jSR in Trdn(-/-) myocytes. CRU function is impaired in Trdn(-/-) myocytes, with reduced SR Ca(2+) release and impaired negative feedback of SR Ca(2+) release on Cav1.2 Ca(2+) currents (I(Ca)). Uninhibited Ca(2+) influx via I(Ca) likely contributes to Ca(2+) overload and results in spontaneous SR Ca(2+) releases upon beta-adrenergic receptor stimulation with isoproterenol in Trdn(-/-) myocytes, and ventricular arrhythmias in Trdn(-/-) mice. We conclude that triadin is critically important for maintaining the structural and functional integrity of the cardiac CRU; triadin loss and the resulting alterations in CRU structure and protein composition impairs E-C coupling and renders hearts susceptible to ventricular arrhythmias. PMID:19383796

  17. Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

    DEFF Research Database (Denmark)

    Molina, C.E.; Gesser, Hans; Llach, A.;

    2007-01-01

    mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from -78 ± 3 to -84 ± 3 mV, and stabilized the resting membrane potential at -92 ± 4 mV. ACh also shortened the action potential...... hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at -120...... of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential. teleost heart; IK,ACh; cholinergic modulation; action potential...

  18. Changes in human atrial myocyte dimension among different ages%不同年龄人心房肌细胞的形态观察

    Institute of Scientific and Technical Information of China (English)

    孙秀梅; 胡小琴; 苏俊武; 潘世伟; 刘迎龙

    2001-01-01

    AIM: To observe the changes in right atrial myocyte dimensionswith myocardial development. METHODS: Cell length, width, length/width and cross-sectional area were measured in right atrial myocytes isolated from 12 weaning [ages 0.4-5 years, (1.8±1.3) years, n=103 cells], 10 young [6-11 years, (9.3±1.8) years, n=104 cells], 13 adult [30-56 years, (43.7±11.5) years, n=110 cells] human hearts. RESULTS: Cell length, width, length/width and cross-sectional area, at weanling group were (70.2±1.3) μm, (8.0±0.2) μm, (9.0±0.2) and (50.9±2.6) μm2, respectively, at young group were (93.5±1.6) μm, (11.7±0.3) μm, 8.1±0.2, (109.7±5.8) μm2, and (100.9±2.2) μm, (12.1±0.3) μm, 8.5±0.2, (119.0±5.5) μm2 for adult group. Clearly, young myocyte lenght, width, cross-sectional area were greater than that of myocytes at weanling group(P<0.01) but adult myocytes length/width and cross-sectional area increase slightly compared with young group. The length/width ratio has no significant change through myocyte maturity, which is between 8-9. CONCLUSIONS: Our data suggest that myocyte dimensions expect length/width ratio have increased progressively with maturity, the length/width ratio is preserved in atrial myocyte during the period of normal myocyte growth from weanling to adulthood, and these changes in myocyte dimensions are similar with ventricular myocytes changes from other mammalian species.%的:观察不同年龄人心房肌细胞的形态变化。方法:取右心房组织块进行酶解,得到单个细胞。分别观察小儿组(12例0.4-5岁,平均1.8岁±1.3岁,n=103个细胞)、儿童组(10例6-11岁,平均9.3岁±1.8岁,n=104)、成年组(13例30-56岁,平均43.7岁±11.5岁,n=110)病人心房肌细胞的长、宽(直径)、长/宽比和细胞横截面积(±s)。结果:细胞长(μm)小儿组为70.2±1.3,儿童组为93.5±1.6,成年组为100.8±2.2,细胞宽(μm)分别为8.0±0.2、11.7±0.3、12.0±0.3

  19. Leptin modulates electrophysiological characteristics and isoproterenol-induced arrhythmogenesis in atrial myocytes

    OpenAIRE

    Lin, Yung-Kuo; Chen, Yao-Chang; Huang, Jen-Hung; Lin, Yenn-Jiang; Huang, Shiang-Suo; Chen, Shih-Ann; Chen, Yi-Jen

    2013-01-01

    Background Obesity is an important risk factor for atrial fibrillation (AF). Leptin is an important adipokine. However, it is not clear whether leptin directly modulates the electrophysiological characteristics of atrial myocytes. Results Whole cell patch clamp and indo-1 fluorescence were used to record the action potentials (APs) and ionic currents in isolated rabbit left atrial (LA) myocytes incubated with and without (control) leptin (100 nM) for 1 h to investigate the role of leptin on a...

  20. Raloxifene acutely suppresses ventricular myocyte contractility through inhibition of the L-type calcium current

    OpenAIRE

    Liew, Reginald; Stagg, Mark A; MacLeod, Kenneth T; Collins, Peter

    2004-01-01

    The selective oestrogen (ER) receptor modulator, raloxifene, is widely used in the treatment of postmenopausal osteoporosis, but may also possess cardioprotective properties. We investigated whether it directly suppresses myocyte contractility through Ca2+ channel antagonism in a similar way to 17β-oestradiol.Cell shortening and Ca2+ transients were measured in single guinea-pig ventricular myocytes field-stimulated (1 Hz, 37°C) in a superfusion chamber. Electrophysiological recordings were p...

  1. Enhanced expression of ROCK in left atrial myocytes of mitral regurgitation: a potential mechanism of myolysis

    OpenAIRE

    Chen, Huang-Chung; Chang, Jen-Ping; Chang, Tzu-Hao; Lin, Yu-Sheng; Huang, Yao-Kuang; Pan, Kuo-Li; Fang, Chih-Yuan; Chen, Chien-Jen; Ho, Wan-Chun; Chen, Mien-Cheng

    2015-01-01

    Background Severe mitral regurgitation (MR) may cause myolysis in the left atrial myocytes. Myolysis may contribute to atrial enlargement. However, the relationship between Rho-associated kinase (ROCK) and myolysis in the left atrial myocytes of MR patients remain unclear. Methods This study comprised 22 patients with severe MR [12 with atrial fibrillation (AF) and ten in sinus rhythm]. Left atrial appendage tissues were obtained during surgery. Normal left atrial tissues were purchased. Immu...

  2. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  3. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  4. Exercise, Nrf2 and Antioxidant Signaling in Cardiac Aging.

    Science.gov (United States)

    Narasimhan, Madhusudhanan; Rajasekaran, Namakkal S

    2016-01-01

    Aging is represented by a progressive decline in cellular functions. The age-related deformities in cardiac behaviors are the loss of cardiac myocytes through apoptosis or programmed cell death. Oxidative stress (OS) and its deleterious consequence contribute to age-related mechanical remodeling, reduced regenerative capacity, and apoptosis in cardiac tissue. The pathogenesis of OS in the elderly can predispose the heart to other cardiac complications such as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and so on. At the molecular level, oxidant-induced activation of Nrf2 (Nuclear erythroid-2-p45-related factor-2), a transcription factor, regulates several genes containing AREs (Antioxidant Response Element) and bring the respective translates to counteract the reactive radicals and establish homeostasis. Myriad of Nrf2 gene knockout studies in various organs such as lung, liver, kidney, brain, etc. have shown that dysregulation of Nrf2 severely affects the oxidant/ROS sensitivity and predispose the system to several pathological changes with aberrant cellular lesions. On the other hand, its gain of function chemical interventions exhibited oxidant stress resistance and cytoprotection. However, thus far, only a few investigations have shown the potential role of Nrf2 and its non-pharmacological induction in cardiac aging. Therefore, here we review the involvement of Nrf2 signaling along with its responses and ramifications on the cascade of OS under acute exercise stress (AES), moderate exercise training (MET), and endurance exercise stress (EES) conditions in the aging heart. PMID:27378947

  5. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  6. [Stem cells and cardiac regeneration].

    Science.gov (United States)

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  7. Effect of osmotic stress on spontaneous calcium sparks in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Hong XIE; Pei-hong ZHU

    2006-01-01

    Aim: To study whether the volume of cardiomyocytes and their functions would change under severe pathological conditions or osmotic stress. To clarify the role of ryanodine receptors/calcium release channels (RyRs) in the functional change, the effect of osmotic stress on spontaneous Ca2+ sparks in rat ventricular myocytes was investigated. Methods: A laser scanning confocal microscope was used to detect spontaneous Ca2+ sparks of intact or saponin permeabilized myocytes loaded with Fluo-4. High and low tonicity was obtained by adding sucrose and reducing NaCl concentration in the external medium, respectively. Results: In intact myocytes the frequency of Ca2+ sparks was increased and decreased by hyperosmotic (1.5 T) and hyposmotic (0.6 T) exposure, respectively. In addition, hyperosmotic exposure increased the temporal parameters and decreased the spatial parameter of Ca2+ sparks, while opposite changes occurred with hyposmotic exposure. The spatio-temporal properties of Ca2+ sparks were slightly affected by altering [K+]i (50-200 mmol/L) in saponin permeabilized myocytes in the presence of 8% dextran. It was observed that the spatio-temporal parameters of the Ca2+ sparks in permeabilized myocytes were dose-dependently altered by dextran. The propagating velocity of Ca2+ waves in intact and permeabilized myocyte was also affected by osmotic pressure or dextran. Conclusion: The effect of osmotic stress on the frequency of spontaneous Ca2+ sparks might be ascribed to the change of myoplasmic Ca2+ and Ca2+ content in the sarcoplasmic reticulum, while the effect on the spatio-temporal properties is caused by the alteration of Ca2+ diffusion mainly resulting from the morphological change of the myocytes.

  8. Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis

    Directory of Open Access Journals (Sweden)

    Burchfield Jana S

    2008-10-01

    Full Text Available Abstract A new era has begun in the treatment of ischemic disease and heart failure. With the discovery that stem cells from diverse organs and tissues, including bone marrow, adipose tissue, umbilical cord blood, and vessel wall, have the potential to improve cardiac function beyond that of conventional pharmacological therapy comes a new field of research aiming at understanding the precise mechanisms of stem cell-mediated cardiac repair. Not only will it be important to determine the most efficacious cell population for cardiac repair, but also whether overlapping, common mechanisms exist. Increasing evidence suggests that one mechanism of action by which cells provide tissue protection and repair may involve paracrine factors, including cytokines and growth factors, released from transplanted stem cells into the surrounding tissue. These paracrine factors have the potential to directly modify the healing process in the heart, including neovascularization, cardiac myocyte apoptosis, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair.

  9. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  10. [Advanced resuscitation of adults

    DEFF Research Database (Denmark)

    Lippert, F.K.; Lauritsen, T.L.; Torp-Pedersen, C.

    2008-01-01

    International and European Resuscitation Council (ERC) Guidelines for Resuscitation 2005 implicate major changes in resuscitation, including new universal treatment algorithms. This brief summary of Guidelines 2005 for advanced resuscitation of adult cardiac arrest victims is based upon the ERC...

  11. Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration.

    Science.gov (United States)

    Zeng, Bin; Tong, Suiyang; Ren, Xiaofeng; Xia, Hao

    2016-08-01

    Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were co-localized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2'-deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury. PMID:25480318

  12. Computational analysis of the regulation of Ca2+ dynamics in rat ventricular myocytes

    Science.gov (United States)

    Bugenhagen, Scott M.; Beard, Daniel A.

    2015-10-01

    Force-frequency relationships of isolated cardiac myocytes show complex behaviors that are thought to be specific to both the species and the conditions associated with the experimental preparation. Ca2+ signaling plays an important role in shaping the force-frequency relationship, and understanding the properties of the force-frequency relationship in vivo requires an understanding of Ca2+ dynamics under physiologically relevant conditions. Ca2+ signaling is itself a complicated process that is best understood on a quantitative level via biophysically based computational simulation. Although a large number of models are available in the literature, the models are often a conglomeration of components parameterized to data of incompatible species and/or experimental conditions. In addition, few models account for modulation of Ca2+ dynamics via β-adrenergic and calmodulin-dependent protein kinase II (CaMKII) signaling pathways even though they are hypothesized to play an important regulatory role in vivo. Both protein-kinase-A and CaMKII are known to phosphorylate a variety of targets known to be involved in Ca2+ signaling, but the effects of these pathways on the frequency- and inotrope-dependence of Ca2+ dynamics are not currently well understood. In order to better understand Ca2+ dynamics under physiological conditions relevant to rat, a previous computational model is adapted and re-parameterized to a self-consistent dataset obtained under physiological temperature and pacing frequency and updated to include β-adrenergic and CaMKII regulatory pathways. The necessity of specific effector mechanisms of these pathways in capturing inotrope- and frequency-dependence of the data is tested by attempting to fit the data while including and/or excluding those effector components. We find that: (1) β-adrenergic-mediated phosphorylation of the L-type calcium channel (LCC) (and not of phospholamban (PLB)) is sufficient to explain the inotrope-dependence; and (2) that

  13. Elevated NF-κB activation is conserved in human myocytes cultured from obese type 2 diabetic patients and attenuated by AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Green, Charlotte Jane; Pedersen, Maria; Pedersen, Bente K;

    2011-01-01

    To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes....

  14. Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current

    Directory of Open Access Journals (Sweden)

    Jaakko Haverinen

    2011-11-01

    Full Text Available Evolutionary origin and physiological significance of the tetrodotoxin (TTX resistance of the vertebrate cardiac Na+ current (INa is still unresolved. To this end, TTX sensitivity of the cardiac INa was examined in cardiac myocytes of a cyclostome (lamprey, three teleost fishes (crucian carp, burbot and rainbow trout, a clawed frog, a snake (viper and a bird (quail. In lamprey, teleost fishes, frog and bird the cardiac INa was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol·L−1. In the snake heart, about 80% of the INa was TTX-resistant with EC50 value of 0.65 μmol·L−1, the rest being TTX-sensitive (EC50 = 0.5 nmol·L−1. Although TTX-resistance of the cardiac INa appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na+ channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.

  15. Cardiac sympathetic nerve terminal function in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Chang-seng LIANG

    2007-01-01

    Increased cardiac release of norepinephrine (NE) and depleted cardiac stores of NE are two salient features of the human failing heart. Researches from my labo-ratory have shown that these changes are accompanied by a functional defect of NE uptake in the cardiac sympathetic nerve terminals. Our studies have shown that the decrease of NE uptake is caused by reduction of NE transporter density in the sympathetic nerve endings, and this change is responsible, at least in part, for the increased myocardial interstitial NE, decreased myocardial adrenoceptor density, and increased myocyte apoptosis in experimental cardiomyopathies. We have also provided evidence in both intact animals and cultured PC12 cells that the decrease of NE transporter is induced by the actions of oxidative metabolites of exogenous NE, involving endoplasmic reticulum stress and impaired N-glycosylation of the NE transporter. This change in the cardiac sympathetic NE uptake function, as demonstrated by [123I] metaiodobenzylguanidine in human studies, may not only serve as an important prognostic variable in patients with congestive heart failure, but also be used as a surrogate for the efficacies of various therapeutic interventions for heart failure. Finally, increasing evidence suggests and further studies are needed to show that the cardiac sympathetic nerve terminal function may be a direct target for pharmacologic treatment of congestive heart failure.

  16. Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction.

    Science.gov (United States)

    Bers, Donald M

    2014-01-01

    Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as smaller events not detectable as Ca sparks). Much, but not all, of the SR Ca leak occurs via ryanodine receptors and can be exacerbated in pathological states such as heart failure. The extent of SR Ca leak is important because it can (a) reduce SR Ca available for release, causing systolic dysfunction; (b) elevate diastolic [Ca]i, contributing to diastolic dysfunction; (c) cause triggered arrhythmias; and (d) be energetically costly because of extra ATP used to repump Ca. This review addresses quantitative aspects and manifestations of SR Ca leak and its measurement, and how leak is modulated by Ca, associated proteins, and posttranslational modifications in health and disease. PMID:24245942

  17. Study of transmembrane La3+ movement in rat ventricular myocytes by the patch-clamp technique

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    We have studied transmembrane La3+ movement in rat ventricular myocytes for the first time by using the whole-cell patch-clamp recording mode. La3+ (0.01-5.0 mmol/L) could not bring out inward currents through the L-type calcium channel in rat ventricular myocytes, while it could enter the cells by the same way carried by 1μmol/L ionomycin. When the outward Na+ concentration gradient is formed, La3+ can enter the cells via Na-Ca exchange, and the exchange currentsincrease with the increase of external La3+ concentrations. But compared with Na-Ca exchange currents in the same concentration, the former is only 14%-38% of the latter. The patch-clamp experiment indicates that La3+ normally can not enter ventricular myocytes through L-type calcium channel, but it can enter the cells via Na-Ca exchange.

  18. Signaling Pathways Involved in Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Tao Zewei; Li Longgui

    2006-01-01

    Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress.Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy (normal growth) and physiological hypertrophy (growth induced by physical conditioning), and maladaptive hypertrophy, including pathologic or reactive hypertrophy (growth induced by pathologic stimuli) and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response,including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt (PI3Ks/Akt),G protein-coupled receptors, small G proteins,MAPK, PKCs, Gp130/STAT'3, Na+/H+ exchanger,peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

  19. Cardiac carcinoid: tricuspid delayed hyperenhancement on cardiac 64-slice multidetector CT and magnetic resonance imaging.

    LENUS (Irish Health Repository)

    Martos, R

    2012-02-01

    INTRODUCTION: Carcinoid heart disease is a rare condition in adults. Its diagnosis can be easily missed in a patient presenting to a primary care setting. We revised the advantages of using coronary multidetector computed tomography (MDCT) and cardiac magnetic resonance imaging (MRI) in diagnosing this condition. MATERIALS AND METHODS: We studied a 65-year-old patient with carcinoid heart disease and right heart failure using transthoracic Doppler-echocardiogram, cardiac MDCT and MRI. Cardiac echocardiogram revealed marked thickening and retraction of the tricuspid leaflets with dilated right atrium and ventricle. Cardiac MDCT and MRI demonstrated fixation and retraction of the tricuspid leaflets with delayed contrast hyperenhancement of the tricuspid annulus. CONCLUSION: This case demonstrates fascinating imaging findings of cardiac carcinoid disease and highlights the increasing utility of contrast-enhanced MRI and cardiac MDCT in the diagnosis of this interesting condition.

  20. Docosahexaenoic acid has influence on action potentials and transient outward potassium currents of ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Yu

    2010-04-01

    Full Text Available Abstract Background There are many reports about the anti-arrhythmic effects of ω-3 polyunsaturated fatty acids, however, the mechanisms are still not completely delineated. The purpose of this study was to investigate the characteristics of action potentials and transient outward potassium currents (Ito of Sprague-Dawley rat ventricular myocytes and the effects of docosahexaenoic acid (DHA on action potentials and Ito. Methods The calcium-tolerant rat ventricular myocytes were isolated by enzyme digestion. Action potentials and Ito of epicardial, mid-cardial and endocardial ventricular myocytes were recorded by whole-cell patch clamp technique. Results 1. Action potential durations (APDs were prolonged from epicardial to endocardial ventricular myocytes (P 2. Ito current densities were decreased from epicardial to endocardial ventricular myocytes, which were 59.50 ± 15.99 pA/pF, 29.15 ± 5.53 pA/pF, and 12.29 ± 3.62 pA/pF, respectively at +70 mV test potential (P 3. APDs were gradually prolonged with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 μmol/L to 1 μmol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, and its half-inhibited concentration was 5.3 μmol/L. The results showed that there were regional differences in the distribution of action potentials and Ito in rat epicardial, mid-cardial and endocardial ventricular myocytes. APDs were prolonged and Ito current densities were gradually reduced with the increase of DHA concentrations. Conclusion The anti-arrhythmia mechanisms of DHA are complex, however, the effects of DHA on action potentials and Ito may be one of the important causes.

  1. Developmental origin and lineage plasticity of endogenous cardiac stem cells.

    Science.gov (United States)

    Santini, Maria Paola; Forte, Elvira; Harvey, Richard P; Kovacic, Jason C

    2016-04-15

    Over the past two decades, several populations of cardiac stem cells have been described in the adult mammalian heart. For the most part, however, their lineage origins and in vivo functions remain largely unexplored. This Review summarizes what is known about different populations of embryonic and adult cardiac stem cells, including KIT(+), PDGFRα(+), ISL1(+)and SCA1(+)cells, side population cells, cardiospheres and epicardial cells. We discuss their developmental origins and defining characteristics, and consider their possible contribution to heart organogenesis and regeneration. We also summarize the origin and plasticity of cardiac fibroblasts and circulating endothelial progenitor cells, and consider what role these cells have in contributing to cardiac repair.

  2. Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression

    Institute of Scientific and Technical Information of China (English)

    Bing-yan GUO; Yong-jun LI; Rui HAN; Shao-1ing YANG; Ying-hui SHI; De-rong HAN; Hong ZHOU; Mei WANG

    2011-01-01

    Aim:To investigate whether telmisartan(Telm)pretreatment attenuates isoproterenol(Iso)-induced postinfarction remodeling(PIR)in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin.Methods:PIR was induced in male Wistar rats with two consecutive injections of Iso(80 mg/kg,sc)at an interval of 24 h.Primary Culture of ventricular myocytes from neonatal rats was prepared.Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase(LDH)activity.Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis.Results:In the rats with PIR.Telm(10 mg·kg-1·d-1,po for 65 d)suppressed lso-induced increases in gravimetric parameters.cardiomyocyte diameter and collagen volume fraction,but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis.The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin.In cultured cardiomyocytes,Telm (5-20 μmol/L)inhibited the celI death and LDH release induced by lSO(10 μmol/L).and reversed Iso-induced reduction in adiponectinprotein expression.In cardiomyocytes exposed to Iso(20 μmol/L).GW9662(30 μmol/L),a selective antagonist of PPAR-v,blocked the effects of Telm Dretreatment on adiponectin protein expression,as well as the protective effects of Telm on Iso-induced celI injUry.Conclusion:Telm attenuates Iso-induced cardiac remodeling and cell injury,which is associated with induction of cardiac adiponectin expression.

  3. A neonatal blueprint for cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Enzo R. Porrello

    2014-11-01

    Full Text Available Adult mammals undergo minimal regeneration following cardiac injury, which severely compromises cardiac function and contributes to the ongoing burden of heart failure. In contrast, the mammalian heart retains a transient capacity for cardiac regeneration during fetal and early neonatal life. Recent studies have established the importance of several evolutionarily conserved mechanisms for heart regeneration in lower vertebrates and neonatal mammals including induction of cardiomyocyte proliferation, epicardial cell activation, angiogenesis, extracellular matrix deposition and immune cell infiltration. In this review, we provide an up-to-date account of the molecular and cellular basis for cardiac regeneration in lower vertebrates and neonatal mammals. The historical context for these recent findings and their ramifications for the future development of cardiac regenerative therapies are also discussed.

  4. Vitamin D and Cardiac Differentiation.

    Science.gov (United States)

    Kim, Irene M; Norris, Keith C; Artaza, Jorge N

    2016-01-01

    Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID:26827957

  5. Knowledge-based 3D reconstruction of the right ventricle : comparison with cardiac magnetic resonance in adults with congenital heart disease

    NARCIS (Netherlands)

    Trzebiatowska-Krzynska, Aleksandra; Driessen, Mieke; Sieswerda, GT; Wallby, Lars; Swahn, Eva; Meijboom, Folkert

    2015-01-01

    AIM: Assessment of right ventricular (RV) function is a challenge, especially in patients with congenital heart disease (CHD). The aim of the present study is to assess whether knowledge-based RV reconstruction, used in the everyday practice of an echo-lab for adult CHD in a tertiary referral center

  6. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-α-mediated transcription of fatty acid metabolic genes

    International Nuclear Information System (INIS)

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-α plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-α activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-α mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-α-mediated FA metabolic gene transcription

  7. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

    Science.gov (United States)

    Kanani, S.; Pumir, A.; Krinsky, V.

    2008-01-01

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  8. Magnesium gating of cardiac gap junction channels.

    Science.gov (United States)

    Matsuda, Hiroyuki; Kurata, Yasutaka; Oka, Chiaki; Matsuoka, Satoshi; Noma, Akinori

    2010-09-01

    We aimed to study kinetics of modulation by intracellular Mg(2+) of cardiac gap junction (Mg(2+) gate). Paired myocytes of guinea-pig ventricle were superfused with solutions containing various concentrations of Mg(2+). In order to rapidly apply Mg(2+) to one aspect of the gap junction, the non-junctional membrane of one of the pair was perforated at nearly the connecting site by pulses of nitrogen laser beam. The gap junction conductance (G(j)) was measured by clamping the membrane potential of the other cell using two-electrode voltage clamp method. The laser perforation immediately increased G(j), followed by slow G(j) change with time constant of 3.5 s at 10 mM Mg(2+). Mg(2+) more than 1.0 mM attenuated dose-dependently the gap junction conductance and lower Mg(2+) (0.6 mM) increased G(j) with a Hill coefficient of 3.4 and a half-maximum effective concentration of 0.6 mM. The time course of G(j) changes was fitted by single exponential function, and the relationship between the reciprocal of time constant and Mg(2+) concentration was almost linear. Based on the experimental data, a mathematical model of Mg(2+) gate with one open state and three closed states well reproduced experimental results. One-dimensional cable model of thirty ventricular myocytes connected to the Mg(2+) gate model suggested a pivotal role of the Mg(2+) gate of gap junction under pathological conditions. PMID:20553744

  9. Instability of spiral and scroll waves in the presence of a gradient in the fibroblast density: the effects of fibroblast-myocyte coupling

    CERN Document Server

    Zimik, Soling

    2016-01-01

    Fibroblast-myocyte coupling can modulate electrical-wave dynamics in cardiac tissue. In diseased hearts, the distribution of fibroblasts is heterogeneous, so there can be gradients in the fibroblast density (henceforth we call this GFD) especially from highly injured regions, like infarcted or ischemic zones, to less-wounded regions of the tissue. Fibrotic hearts are known to be prone to arrhythmias, so it is important to understand the effects of GFD in the formation and sustenance of arrhythmic re- entrant waves, like spiral or scroll waves. Therefore, we investigate the effects of GFD on the stability of spiral and scroll waves of electrical activation in a state-of-the- art mathematical model for cardiac tissue in which we also include fibroblasts. By introducing GFD in controlled ways, we show that spiral and scroll waves can be unstable in the presence of GFDs because of regions with varying spiral or scroll-wave frequency {\\omega}, induced by the GFD. We examine the effects of the resting membrane pote...

  10. Dosimetry of electromagnetic field exposure of an active armlet and its electromagnetic interference to the cardiac pacemakers using adult, child and infant models.

    Science.gov (United States)

    Yang, Hu; Wang, Yuduo; Yang, Jiangang; Wu, Tongning

    2016-01-01

    Wearable devices have been popularly used with people from different age groups. As a consequence, the concerns of their electromagnetic field (EMF) exposure to the human body and their electromagnetic interference (EMI) to the implanted medical devices have attracted many studies. The aim of this study was to evaluate the human exposure to the EMF of an active radiofrequency identification (RFID) armlet as well as its EMI to the cardiac pacemaker (CP). Different human models from various age groups were applied to assess the result variability. The scalar potential finite element method was utilized in the simulation. Local EMF exposure and the exposure to the central nerve system tissues were evaluated using different metrics. EMI to the CP was assessed in terms of the conducted voltage to the CP. The results from all the models revealed that the studied RFID armlet would not produce the EMF exposure exceeding the safety limits. The calculated interference voltage was highly dependent on the distance between the RFID armlet and the CP (i.e. the physical dimension of the individual model). The results proposed to evaluate the appropriateness of the current EMI measurement protocol for this kind of devices used by the infants. PMID:25568953

  11. Interventional cardiac catheterization.

    Science.gov (United States)

    Pihkala, J; Nykanen, D; Freedom, R M; Benson, L N

    1999-04-01

    Over the past decade, transcatheter interventions have become increasingly important in the treatment of patients with congenital heart lesions. These procedures may be broadly grouped as dilations (e.g., septostomy, valvuloplasty, angioplasty, and endovascular stenting) or as closures (e.g., vascular embolization and device closure of defects). Balloon valvuloplasty has become the treatment of choice for patients in all age groups with simple valvar pulmonic stenosis and, although not curative, seems at least comparable to surgery for congenital aortic stenosis in newborns to young adults. Balloon angioplasty is successfully applied to a wide range of aortic, pulmonary artery, and venous stenoses. Stents are useful in dilating lesions of which the intrinsic elasticity results in vessel recoil after balloon dilation alone. Catheter-delivered coils are used to embolize a wide range of arterial, venous, and prosthetic vascular connections. Although some devices remain investigational, they have been successfully used for closure of many arterial ducts and atrial and ventricular septal defects. In the therapy for patients with complex CHD, best results may be achieved by combining cardiac surgery with interventional catheterization. The cooperation among interventional cardiologists and cardiac surgeons was highlighted in a report of an algorithm to manage patients with tetralogy of Fallot or pulmonary atresia with diminutive pulmonary arteries, involving balloon dilation, coil embolization of collaterals, and intraoperative stent placement. In this setting, well-planned catheterization procedures have an important role in reducing the overall number of procedures that patients may require over a lifetime, with improved outcomes.

  12. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  13. Calcium homeostasis in a local/global whole cell model of permeabilized ventricular myocytes with a Langevin description of stochastic calcium release.

    Science.gov (United States)

    Wang, Xiao; Weinberg, Seth H; Hao, Yan; Sobie, Eric A; Smith, Gregory D

    2015-03-01

    Population density approaches to modeling local control of Ca(2+)-induced Ca(2+) release in cardiac myocytes can be used to construct minimal whole cell models that accurately represent heterogeneous local Ca(2+) signals. Unfortunately, the computational complexity of such "local/global" whole cell models scales with the number of Ca(2+) release unit (CaRU) states, which is a rapidly increasing function of the number of ryanodine receptors (RyRs) per CaRU. Here we present an alternative approach based on a Langevin description of the collective gating of RyRs coupled by local Ca(2+) concentration ([Ca(2+)]). The computational efficiency of this approach no longer depends on the number of RyRs per CaRU. When the RyR model is minimal, Langevin equations may be replaced by a single Fokker-Planck equation, yielding an extremely compact and efficient local/global whole cell model that reproduces and helps interpret recent experiments that investigate Ca(2+) homeostasis in permeabilized ventricular myocytes. Our calculations show that elevated myoplasmic [Ca(2+)] promotes elevated network sarcoplasmic reticulum (SR) [Ca(2+)] via SR Ca(2+)-ATPase-mediated Ca(2+) uptake. However, elevated myoplasmic [Ca(2+)] may also activate RyRs and promote stochastic SR Ca(2+) release, which can in turn decrease SR [Ca(2+)]. Increasing myoplasmic [Ca(2+)] results in an exponential increase in spark-mediated release and a linear increase in nonspark-mediated release, consistent with recent experiments. The model exhibits two steady-state release fluxes for the same network SR [Ca(2+)] depending on whether myoplasmic [Ca(2+)] is low or high. In the later case, spontaneous release decreases SR [Ca(2+)] in a manner that maintains robust Ca(2+) sparks. PMID:25485896

  14. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts

    Science.gov (United States)

    Liu, Yu; Chen, Li; Diaz, Andrea Diaz; Benham, Ashley; Xu, Xueping; Wijaya, Cori S.; Fa’ak, Faisal; Luo, Weijia; Soibam, Benjamin; Azares, Alon; Yu, Wei; Lyu, Qiongying; Stewart, M. David; Gunaratne, Preethi; Cooney, Austin; McConnell, Bradley K.; Schwartz, Robert J.

    2016-01-01

    Mesp1 directs multipotential cardiovascular cell fates, even though it’s transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1’s transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1Cre/+; Rosa26EYFP/+ ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells. PMID:27538477

  15. Effect of pre-cardiac and adult stages of Dirofilaria immitis in pulmonary disease of cats: CBC, bronchial lavage cytology, serology, radiographs, CT images, bronchial reactivity, and histopathology.

    Science.gov (United States)

    Ray Dillon, A; Tillson, D M; Wooldridge, A; Cattley, R; Hathcock, J; Brawner, W R; Cole, R; Welles, B; Christopherson, P W; Lee-Fowler, T; Bordelon, S; Barney, S; Sermersheim, M; Garbarino, R; Wells, S Z; Diffie, E B; Schachner, E R

    2014-11-15

    A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement

  16. Safe and easy method with little modification in technique is useful for successful internal jugular vein cannulation on the same side even after intra-arterial puncture without using ultrasound guidance in adult cardiac patients

    Directory of Open Access Journals (Sweden)

    Rajesh Thosani

    2016-01-01

    Full Text Available Background: The modification in technique is useful for successful right-sided internal jugular vein (IJV cannulation on the same side even after intra-arterial puncture without using ultrasound guidance in adult patients. Materials and Methods: This study was carried out in total 160 adult patient from American Society of Anesthesiologists Grade II to III patients male (n = 95 and female (n = 65 who underwent cardiac surgery where cannulation was done on right sided by triple lumen catheter (7 French using Seldinger technique. Results: Majority of patients were cannulated successfully by Seldinger technique with single or double attempt except for five patients in which arterial puncture occurred. All five patients were cannulated successfully on the same side with this modified technique without any significant major complications. They were managed by application of blocker at the end of arterial needle puncture without removing it. In our routine practice, we were used to removing this needle and applying compression for few minutes to prevent hematoma formation after an arterial puncture. In this study, cannula was used as a marker or guideline for the relocation of IJV on the same side and recannulation was performed by changing the direction of needle on same side lateral to the previous one and without going towards the same direction to prevent the arterial puncture again. Conclusion: Most simple and useful modified technique for institutes where the complications are most common with trainee doctors and in hospitals where there is no advanced facility like ultrasound-guided cannulation available. By this modification, it will be time saving, very comfortable, and user-friendly technique with high success rate.

  17. [Cardiac output monitoring by impedance cardiography in cardiac surgery].

    Science.gov (United States)

    Shimizu, H; Seki, S; Mizuguchi, A; Tsuchida, H; Watanabe, H; Namiki, A

    1990-04-01

    The cardiac output monitoring by impedance cardiography, NCCOM3, was evaluated in adult patients (n = 12) who were subjected to coronary artery bypass grafting. Values of cardiac output measured by impedance cardiography were compared to those by the thermodilution method. Changes of base impedance level used as an index of thoracic fluid volume were also investigated before and after cardiopulmonary bypass (CPB). Correlation coefficient (r) of the values obtained by thermodilution with impedance cardiography was 0.79 and the mean difference was 1.29 +/- 16.9 (SD)% during induction of anesthesia. During the operation, r was 0.83 and the mean difference was -14.6 +/- 18.7%. The measurement by impedance cardiography could be carried out through the operation except when electro-cautery was used. Base impedance level before CPB was significantly lower as compared with that after CPB. There was a negative correlation between the base impedance level and central venous pressure (CVP). No patients showed any signs suggesting lung edema and all the values of CVP, pulmonary artery pressure and blood gas analysis were within normal ranges. From the result of this study, it was concluded that cardiac output monitoring by impedance cardiography was useful in cardiac surgery, but further detailed examinations will be necessary on the relationship between the numerical values of base impedance and the clinical state of the patients. PMID:2362347

  18. Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells

    Directory of Open Access Journals (Sweden)

    Giacomo Palazzolo

    2016-01-01

    Full Text Available The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs. We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C, known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis.

  19. Conservative Management of Cardiac Hemangioma for 11 Years.

    Science.gov (United States)

    Gribaa, Rym; Slim, Mehdi; Neffati, Elyes; Boughzela, Essia

    2015-10-01

    Cardiac hemangiomas are benign tumors with an unpredictable natural history. Surgical resection is the treatment of choice; however, conservative management can be an alternative in some patients. We report a case of a left-sided cardiac hemangioma that we managed conservatively for 11 years without obvious major complications in the patient, an adult woman. PMID:26504439

  20. Relationship between coronary atherosclerosis and 'sudden cardiac death'

    International Nuclear Information System (INIS)

    Coronary arteriosclerosis in mini-pigs was produced by combination of hypercholesterolemia and twofold X irradiation of the cardiac region. 15-21 weeks following irradiation 40% of the adult animals and 58% of the juvenils died of 'sudden cardiac death'. The mortality rate decreased significantly after application of the calcium-channel blocking agent nifedipine

  1. Effects of Kaempferia parviflora Wall. Ex. Baker and sildenafil citrate on cGMP level, cardiac function, and intracellular Ca2+ regulation in rat hearts.

    Science.gov (United States)

    Weerateerangkul, Punate; Palee, Siripong; Chinda, Kroekkiat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2012-09-01

    Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes. PMID:22691878

  2. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects. PMID:27107944

  3. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

  4. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  5. Health in adults with congenital heart disease.

    Science.gov (United States)

    Cuypers, Judith A A E; Utens, Elisabeth M W J; Roos-Hesselink, Jolien W

    2016-09-01

    Since the introduction of cardiac surgery, the prospects for children born with a cardiac defect have improved spectacularly. Many reach adulthood and the population of adults with congenital heart disease is increasing and ageing. However, repair of congenital heart disease does not mean cure. Many adults with congenital heart disease encounter late complications. Late morbidity can be related to the congenital heart defect itself, but may also be the consequence of the surgical or medical treatment or longstanding alterations in hemodynamics, neurodevelopment and psychosocial development. This narrative review describes the cardiac and non-cardiac long-term morbidity in the adult population with congenital heart disease. PMID:27451323

  6. Cardiac assessment of African hedgehogs (Atelerix albiventris).

    Science.gov (United States)

    Black, Peter A; Marshall, Cecilia; Seyfried, Alice W; Bartin, Anne M

    2011-03-01

    Cardiomyopathy is a common finding in captive African hedgehogs (Atelerix albiventris) at postmortem exam. To date, treatment attempts have been mostly empirical and unrewarding. The objective of this study was to determine reference cardiac values for captive African hedgehogs based on echocardiogram, electrocardiogram (ECG), and radiographs. Adult African hedgehogs with no clinical signs of cardiac disease (n = 13) were selected. Each animal was anesthetized with isoflurane via facemask and an echocardiogram, ECG, and radiographs were performed. Standard measurements were taken and the descriptive statistics performed. Values were comparable to limited data available in other hedgehog species and other similar-sized exotic species. Two animals were removed from consideration of reference values due to valvular defects that were considered significant. These data are the first establishing cardiac parameters in normal African hedgehogs using radiographic cardiac measurement, echocardiogram, and ECG. Evaluating animals with possible cardiomyopathy may allow for earlier diagnosis and more successful treatment. PMID:22946370

  7. Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes

    Directory of Open Access Journals (Sweden)

    Higashi Richard M

    2008-10-01

    Full Text Available Abstract Background The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30 and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis. Results The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells. Conclusion The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells

  8. Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish.

    Science.gov (United States)

    Saera-Vila, Alfonso; Kish, Phillip E; Kahana, Alon

    2016-09-01

    Fibroblast growth factors (Fgfs) regulate critical biological processes such as embryonic development, tissue homeostasis, wound healing, and tissue regeneration. In zebrafish, Fgf signaling plays an important role in the regeneration of the spinal cord, liver, heart, fin, and photoreceptors, although its exact mechanism of action is not fully understood. Utilizing an adult zebrafish extraocular muscle (EOM) regeneration model, we demonstrate that blocking Fgf receptor function using either a chemical inhibitor (SU5402) or a dominant-negative transgenic construct (dnFGFR1a:EGFP) impairs muscle regeneration. Adult zebrafish EOMs regenerate through a myocyte dedifferentiation process, which involves a muscle-to-mesenchyme transition and cell cycle reentry by differentiated myocytes. Blocking Fgf signaling reduced cell proliferation and active caspase 3 levels in the regenerating muscle with no detectable levels of apoptosis, supporting the hypothesis that Fgf signaling is involved in the early steps of dedifferentiation. Fgf signaling in regenerating myocytes involves the MAPK/ERK pathway: inhibition of MEK activity with U0126 mimicked the phenotype of the Fgf receptor inhibition on both muscle regeneration and cell proliferation, and activated ERK (p-ERK) was detected in injured muscles by immunofluorescence and western blot. Interestingly, following injury, ERK2 expression is specifically induced and activated by phosphorylation, suggesting a key role in muscle regeneration. We conclude that the critical early steps of myocyte dedifferentiation in EOM regeneration are dependent on Fgf signaling. PMID:27267062

  9. Cardiac Rehabilitation: Improving Function and Reducing Risk.

    Science.gov (United States)

    Servey, Jessica T; Stephens, Mark

    2016-07-01

    Cardiac rehabilitation is a comprehensive multidisciplinary program individually tailored to the needs of patients with cardiovascular disease. The overall goals focus on improving daily function and reducing cardiovascular risk factors. Cardiac rehabilitation includes interventions aimed at lowering blood pressure and improving lipid and diabetes mellitus control, with tobacco cessation, behavioral counseling, and graded physical activity. The physical activity component typically involves 36 sessions over 12 weeks, during which patients participate in supervised exercise under cardiac monitoring. There are also intensive programs that include up to 72 sessions lasting up to 18 weeks, although these programs are not widely available. Additional components of cardiac rehabilitation include counseling on nutrition, screening for and managing depression, and assuring up-to-date immunizations. Cardiac rehabilitation is covered by Medicare and recommended for patients following myocardial infarction, bypass surgery, and stent placement, and for patients with heart failure, stable angina, and several other conditions. Despite proven benefits in mortality rates, depression, functional capacity, and medication adherence, rates of referral for cardiac rehabilitation are suboptimal. Groups less likely to be referred are older adults, women, patients who do not speak English, and persons living in areas where cardiac rehabilitation is not locally available. Additionally, primary care physicians refer patients less often than cardiologists and cardiothoracic surgeons. PMID:27386722

  10. Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process.

    Science.gov (United States)

    Avitabile, Daniele; Crespi, Alessia; Brioschi, Chiara; Parente, Valeria; Toietta, Gabriele; Devanna, Paolo; Baruscotti, Mirko; Truffa, Silvia; Scavone, Angela; Rusconi, Francesca; Biondi, Andrea; D'Alessandra, Yuri; Vigna, Elisa; Difrancesco, Dario; Pesce, Maurizio; Capogrossi, Maurizio C; Barbuti, Andrea

    2011-05-01

    The efficacy of cardiac repair by stem cell administration relies on a successful functional integration of injected cells into the host myocardium. Safety concerns have been raised about the possibility that stem cells may induce foci of arrhythmia in the ischemic myocardium. In a previous work (36), we showed that human cord blood CD34(+) cells, when cocultured on neonatal mouse cardiomyocytes, exhibit excitation-contraction coupling features similar to those of cardiomyocytes, even though no human genes were upregulated. The aims of the present work are to investigate whether human CD34(+) cells, isolated after 1 wk of coculture with neonatal ventricular myocytes, possess molecular and functional properties of cardiomyocytes and to discriminate, using a reporter gene system, whether cardiac differentiation derives from a (trans)differentiation or a cell fusion process. Umbilical cord blood CD34(+) cells were isolated by a magnetic cell sorting method, transduced with a lentiviral vector carrying the enhanced green fluorescent protein (EGFP) gene, and seeded onto primary cultures of spontaneously beating rat neonatal cardiomyocytes. Cocultured EGFP(+)/CD34(+)-derived cells were analyzed for their electrophysiological features at different time points. After 1 wk in coculture, EGFP(+) cells, in contact with cardiomyocytes, were spontaneously contracting and had a maximum diastolic potential (MDP) of -53.1 mV, while those that remained isolated from the surrounding myocytes did not contract and had a depolarized resting potential of -11.4 mV. Cells were then resuspended and cultured at low density to identify EGFP(+) progenitor cell derivatives. Under these conditions, we observed single EGFP(+) beating cells that had acquired an hyperpolarization-activated current typical of neonatal cardiomyocytes (EGFP(+) cells, -2.24 ± 0.89 pA/pF; myocytes, -1.99 ± 0.63 pA/pF, at -125 mV). To discriminate between cell autonomous differentiation and fusion, EGFP(+)/CD34

  11. Nitric oxide regulates cardiac intracellular Na⁺ and Ca²⁺ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.

    Science.gov (United States)

    Pavlovic, Davor; Hall, Andrew R; Kennington, Erika J; Aughton, Karen; Boguslavskyi, Andrii; Fuller, William; Despa, Sanda; Bers, Donald M; Shattock, Michael J

    2013-08-01

    In the heart, Na/K-ATPase regulates intracellular Na(+) and Ca(2+) (via NCX), thereby preventing Na(+) and Ca(2+) overload and arrhythmias. Here, we test the hypothesis that nitric oxide (NO) regulates cardiac intracellular Na(+) and Ca(2+) and investigate mechanisms and physiological consequences involved. Effects of both exogenous NO (via NO-donors) and endogenously synthesized NO (via field-stimulation of ventricular myocytes) were assessed in this study. Field stimulation of rat ventricular myocytes significantly increased endogenous NO (18 ± 2 μM), PKCε activation (82 ± 12%), phospholemman phosphorylation (at Ser-63 and Ser-68) and Na/K-ATPase activity (measured by DAF-FM dye, western-blotting and biochemical assay, respectively; pPLM(WT) but not PLM(KO) or PLM(3SA) myocytes (where phospholemman cannot be phosphorylated) as measured by whole-cell perforated-patch clamp. Field-stimulation with l-NAME or PKC-inhibitor (2 μM Bis) resulted in elevated intracellular Na(+) (22 ± 1.5 and 24 ± 2 respectively, vs. 14 ± 0.6mM in controls) in SBFI-AM-loaded rat myocytes. Arrhythmia incidence was significantly increased in rat hearts paced in the presence of l-NAME (and this was reversed by l-arginine), as well as in PLM(3SA) mouse hearts but not PLM(WT) and PLM(KO). We provide physiological and biochemical evidence for a novel regulatory pathway whereby NO activates Na/K-ATPase via phospholemman phosphorylation and thereby limits Na(+) and Ca(2+) overload and arrhythmias. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".

  12. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  13. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  14. ROLE OF ALPHA-ADRENERGIC BLOCKING AGENT IN HYPERTROPHY OF CARDIAC MYOCYTE CARDIAC MYOCYTE%α受体阻滞剂对心肌细胞肥大的作用

    Institute of Scientific and Technical Information of China (English)

    谢协驹; 吉丽敏; 符史干

    2001-01-01

    objective:The present study was to investigate the role of alphal-adrenergic receptor blocking agent(phentolamine) in the hypertrophy of cardiaomyocyte induced by adrenaline.Methods:The measurement of cell surface area and[3H]-Leucine incorporation judged the hypertrophy of cardiaomyocyte in cultured neonatal rat myocardal cells,Results:The results showed that adrenaline could significantly increase cell.surface area promote[3H]-Leucine incorporation.Alphal-adrenergic blocking agent could markedly block effects of adrenaline increasing cell surface area and promoting [3H]-Leucine incorporation, Conclusions:These results suggest that alpha-adrenergic blocking agent can prevent the hypertrophy of cardiomyocytes induced by adrenaline in cultured neontal rat myocardal cells.%目的:观察α受体阻滞剂酚妥拉明对肾上腺素诱导的心肌细胞肥大的作用。方法:在培养新生大鼠心肌细胞上。通过测量心肌细胞表面积和[3H]-Leu的掺入量来判断心肌细胞肥大。结果:肾上腺素要明显增加心肌细胞表面和[3H]-亮氨酸([3H-Leu]的掺入量,α受体阻滞剂酚妥拉明能阻断肾上腺素增加心肌细胞表面积和[3H]-Leu掺入量的作用。结论:α受体阻滞有减轻肾上腺素诱导心肌细胞肥大的作用。

  15. Activation and propagation of Ca(2+) release during excitation-contraction coupling in atrial myocytes.

    OpenAIRE

    Kockskämper, J; Sheehan, K A; Bare, D.J.; Lipsius, S. L.; Mignery, G A; Blatter, L A

    2001-01-01

    Fast two-dimensional confocal microscopy and the Ca(2+) indicator fluo-4 were used to study excitation-contraction (E-C) coupling in cat atrial myocytes which lack transverse tubules and contain both subsarcolemmal junctional (j-SR) and central nonjunctional (nj-SR) sarcoplasmic reticulum. Action potentials elicited by field stimulation induced transient increases of intracellular Ca(2+) concentration ([Ca(2+)](i)) that were highly inhomogeneous. Increases started at distinct subsarcolemmal r...

  16. Platelet-derived growth factor receptor-β in myocyte was upregulated by angiotensin II

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    To observe the regulation of platelet-derived growth factor (PDGF) receptor-βin myocyte stimulated by angiotensin II (AngII) at both integrated and cellular levels and reveal the signal transduction mechanism in cell, two kidneys, one clip (2K1C) renal hypertension were performed by placing a sliver clip around the left renal artery. Blood pressure and the ratio of left ventricular weight to body weight were measured at 4 and 8 weeks after operation. The content of AngII in heart was detected by radioimmunology assay; the protein level of PDGF receptor-βin heart was measured by Western blot analysis. The alteration of PDGF receptor-βstimulated by AngII and several inhibitors was observed on cultured neonatal rat ventricular myocyte (NRVM). The content of AngII in heart of 2K1C renal hypertensive rat at 4 and 8 weeks after operation was increased. Compared with sham group, 4 and 8 weeks after operation, PDGF receptor-βin heart of 2K1C group was upregulated by 100.3% and 127.1% (P < 0.05), respectively. This upregulation could be inhibited by captopril. For cultured myocyte, PDGF receptor-βwas increased by 47.1% after being stimulated by AngII and this upregulation could be inhibited by losartan which was an inhibitor of AT1 receptor. PLC inhibitor (U73122) and MEK inhibitor (PD98059) could partly inhibit PDGF receptor-βupregulation induced by AngII. These results suggested that AngII could upregulate PDGF receptor-βin myocyte by its AT1 receptor and this effect was at least partly dependent on PLC and extracellular signal-regulated kinase (ERK).

  17. Heuristic problems in defining the three-dimensional arrangement of the ventricular myocytes.

    Science.gov (United States)

    Anderson, Robert H; Ho, Siew Yen; Sanchez-Quintana, Damian; Redmann, Klaus; Lunkenheimer, Paul P

    2006-06-01

    There is lack of consensus concerning the three-dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a "unique myocardial band," or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three-dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three-dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces.

  18. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    A.S. Amin; A. Asghari-Roodsari; H.L. Tan

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  19. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  20. Evidence for selective regulation of the phosphorylation of myocyte proteins by isoproterenol and prostaglandin E1.

    Science.gov (United States)

    Hayes, J S; Bowling, N; King, K L; Boder, G B

    1982-01-12

    Both isoproterenol and prostaglandin E1 increased the activation state of cyclic AMP-dependent protein kinase in cultured myocytes; however, only isoproterenol enhanced phosphorylase activity and contractile state. Following the incubation of intact myocytes with 32PO3-(4), 32 phosphoproteins were resolved from total cellular proteins by electrophoresis in sodium dodecyl sulfate polyacrylamide gels followed by autoradiography. Isoproterenol stimulated 32PO3-(4) incorporation into 16 proteins, including 2 phosphoproteins not observed under control conditions. By contrast, prostaglandin E1 neither caused a measurable change in the protein phosphorylation pattern nor interfered with isoproterenol's capacity to do so. Isoproterenol stimulated myocyte protein phosphorylation in either the presence or absence of extracellular Ca2+. The results suggest that the regulation of protein phosphorylation following adenylate cyclase stimulation is: (1) an agonist-specific process and not due solely to a random accumulation of intracellular cycle AMP and activation of protein kinase; (2) the Ca2+ mobilization component of beta-receptor activation does not account for the paradoxical effects of isoproterenol and prostaglandin E1; (3) activation of cyclic AMP-dependent protein kinase does not always result in an enhancement of protein phosphorylation.

  1. Comparative study of myocytes from normal and mdx mice iPS cells.

    Science.gov (United States)

    Chen, Fei; Cao, Jiqing; Liu, Qiang; Qin, Jie; Kong, Jie; Wang, Yanyun; Li, Yaqin; Geng, Jia; Li, Qiuling; Yang, Liqing; Xiang, Andy Peng; Zhang, Cheng

    2012-02-01

    Recently, induced pluripotent stem cells (iPS cells) have been derived from various techniques and show great potential for therapy of human diseases. Furthermore, the iPS technique can be used to provide cell models to explore pathological mechanisms of many human diseases in vitro, such as Duchenne muscular dystrophy (DMD), which is a severe recessive X-linked form of muscular dystrophy without effective treatment. In this study, we try to determine whether there are different characteristics of myocytes from mdx iPS cells and C57BL/10 iPS cells. Our results showed that both of mdx and C57BL/10 cells could be induced into iPS cells in vitro, whereas colony-forming ability of mdx iPS cells was much weaker than that of C57BL/10 iPS cells. Meanwhile, mdx iPS cells could be induced to differentiate into myocytes, whereas their differentiation efficiency was much lower than that of C57BL/10 iPS cells. And, the number of apoptotic cells in differentiated myocytes from mdx iPS cells was significantly higher than that from C57BL/10 iPS cells. More importantly, treatment of a pan-caspase inhibitor (Z-VAD) produced a significant decrease in apoptotic cells. This study might add some insight to the biology study of dystrophin gene. PMID:21976068

  2. Improvement of cardiac function in mouse myocardial infarction after transplantation of epigenetically-modified bone marrow progenitor cells.

    Directory of Open Access Journals (Sweden)

    Johnson Rajasingh

    Full Text Available OBJECTIVE: To study usefulness of bone marrow progenitor cells (BPCs epigenetically altered by chromatin modifying agents in mediating heart repair after myocardial infarction in mice. METHODS AND RESULTS: We tested the therapeutic efficacy of bone marrow progenitor cells treated with the clinically-used chromatin modifying agents Trichostatin A (TSA, histone deacetylase inhibitor and 5Aza-2-deoxycytidine (Aza, DNA methylation inhibitor in a mouse model of acute myocardial infarction (AMI. Treatment of BPCs with Aza and TSA induced expression of pluripotent genes Oct4, Nanog, Sox2, and thereafter culturing these cells in defined cardiac myocyte-conditioned medium resulted in their differentiation into cardiomyocyte progenitors and subsequently into cardiac myocytes. Their transition was deduced by expression of repertoire of markers: Nkx2.5, GATA4, cardiotroponin T, cardiotroponin I, α-sarcomeric actinin, Mef2c and MHC-α. We observed that the modified BPCs had greater AceH3K9 expression and reduced histone deacetylase1 (HDAC1 and lysine-specific demethylase1 (LSD1 expression compared to untreated BPCs, characteristic of epigenetic changes. Intra-myocardial injection of modified BPCs after AMI in mice significantly improved left ventricular function. These changes were ascribed to differentiation of the injected cells into cardiomyocytes and endothelial cells. CONCLUSION: Treatment of BPCs with Aza and TSA converts BPCs into multipotent cells, which can then be differentiated into myocyte progenitors. Transplantation of these modified progenitor cells into infarcted mouse hearts improved left ventricular function secondary to differentiation of cells in the niche into myocytes and endothelial cells.

  3. Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication

    Directory of Open Access Journals (Sweden)

    Diana Lindner

    2014-01-01

    Full Text Available Myocarditis is an inflammatory disease caused by viral infection. Different subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac inflammation associated with myocyte loss and remodeling. Here, we study possible cell sources for viral replication using three compartments of the heart: fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j mice with Coxsackievirus B3 (CVB3 and detected increased gene expression of anti-inflammatory and antiviral cytokines in the heart. Subsequently, we infected cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due to viral infection, the expression of TNF-α, IL-6, MCP-1, and IFN-β was significantly increased in cardiac fibroblasts compared to cardiomyocytes or macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts were infected by CVB3 and displayed a higher virus replication (132-fold increase compared to cardiomyocytes (14-fold increase between 6 and 24 hours after infection. At higher virus concentrations, macrophages are able to reduce the viral copy number. At low virus concentration a persistent virus infection was determined. Therefore, we suggest that cardiac fibroblasts play an important role in the pathology of CVB3-induced myocarditis and are another important contributor of virus replication aggravating myocarditis.

  4. Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Madonna, Rosalinda [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Shelat, Harnath; Xue, Qun; Willerson, James T. [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States); De Caterina, Raffaele [Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Geng, Yong-Jian, E-mail: yong-jian.geng@uth.tmc.edu [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States)

    2009-10-15

    Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury. The growth factor, erythropoietin (Epo), ameliorates the inflammatory response of the myocardium to ischemic injury. This study was designed to assess the role of Epo in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-{alpha}. Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of myocardin A, a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-{alpha}. Compared to untreated cells, the Epo-treated cardiac myoblasts exhibited better morphology and viability. Immunoblotting revealed lower levels of active caspase-3 and reductions in iNOS expression and NO production in Epo-treated cells. Furthermore, Epo pretreatment reduced nuclear translocation of NF-{kappa}B and inhibited phosphorylation of inhibitor of kappa B (I{kappa}B) in TNF-{alpha}-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-{alpha} by inhibiting NF-{kappa}B-mediated iNOS expression and NO production and by preventing caspase-3 activation.

  5. Influence of the cardiac myosin hinge region on contractile activity.

    Science.gov (United States)

    Margossian, S S; Krueger, J W; Sellers, J R; Cuda, G; Caulfield, J B; Norton, P; Slayter, H S

    1991-06-01

    The participation of cardiac myosin hinge in contractility was investigated by in vitro motility and ATPase assays and by measurements of sarcomere shortening. The effect on contractile activity was analyzed using an antibody directed against a 20-amino acid peptide within the hinge region of myosin. This antibody bound specifically at the hinge at a distance of 55 nm from the S1/S2 junction, was specific to human, dog, and rat cardiac myosins, did not crossreact with gizzard or skeletal myosin, and had no effect on ATPase activity of purified S1 and myofibrils. However, it completely suppressed the movement of actin filaments in in vitro motility assays and reduced active shortening of sarcomeres of skinned cardiac myocytes by half. Suppression of motion by the anti-hinge antibody may reflect a mechanical constraint imposed by the antibody upon the mobility of the S2 region of myosin. The results suggest that the steps in the mechanochemical energy transduction can be separately influenced through S2.

  6. Aerobic interval training partly reverse contractile dysfunction and impaired Ca2+ handling in atrial myocytes from rats with post infarction heart failure

    OpenAIRE

    Johnsen, Anne Berit; Høydal, Morten Andre; Røsbjørgen, Ragnhild; Stølen, Tomas; Wisløff, Ulrik

    2013-01-01

    Background: There is limited knowledge about atrial myocyte Ca2+ handling in the failing hearts. The aim of this study was to examine atrial myocyte contractile function and Ca2+ handling in rats with post-infarction heart failure (HF) and to examine whether aerobic interval training could reverse a potential dysfunction. Methods and results: Post-infarction HF was induced in Sprague Dawley rats by ligation of the left descending coronary artery. Atrial myocyte shortening was depressed (p

  7. Aerobic Interval Training Partly Reverse Contractile Dysfunction and Impaired Ca2+ Handling in Atrial Myocytes from Rats with Post Infarction Heart Failure

    OpenAIRE

    Johnsen, Anne Berit; Høydal, Morten; Røsbjørgen, Ragnhild; Stølen, Tomas; Wisløff, Ulrik

    2013-01-01

    Background There is limited knowledge about atrial myocyte Ca2+ handling in the failing hearts. The aim of this study was to examine atrial myocyte contractile function and Ca2+ handling in rats with post-infarction heart failure (HF) and to examine whether aerobic interval training could reverse a potential dysfunction. Methods and results Post-infarction HF was induced in Sprague Dawley rats by ligation of the left descending coronary artery. Atrial myocyte shortening was depressed (p

  8. Global intracoronary infusion of allogeneic cardiosphere-derived cells improves ventricular function and stimulates endogenous myocyte regeneration throughout the heart in swine with hibernating myocardium.

    Directory of Open Access Journals (Sweden)

    Gen Suzuki

    Full Text Available Cardiosphere-derived cells (CDCs improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the "stop-flow" technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation.Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25. CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼ 33 × 10(6 icCDCs. Global icCDC infusion was safe and while ∼ 3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23 ± 6 to 51 ± 5% (p<0.01. In diseased hearts, myocyte proliferation (phospho-histone-H3 increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs.Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair.

  9. Anthracycline-induced cardiac injury using a cardiac cell line: potential for gene therapy studies.

    Science.gov (United States)

    L'Ecuyer, T; Horenstein, M S; Thomas, R; Vander Heide, R

    2001-11-01

    Anthracyclines are effective antitumor agents whose chief limitation has been cardiotoxicity directly related to free radical production. Therefore, strategies designed to selectively overexpress antioxidant proteins in the heart could protect against drug-induced toxicity and allow higher doses of chemotherapy. However, to date an adequate cardiac model system that is susceptible to anthracycline injury and can express foreign genes in a controlled fashion has been lacking. Developing a cardiac model system would permit examination of the relationship between the expression level of a potentially protective foreign gene and the degree of protection from injury. In this study we have examined the potential of the H9C2 rat cardiac myocyte cell line in this regard. H9C2 cells differentiate in a reproducible fashion, as shown by progressive increases in muscle tropomyosin-expressing cells, the organization of this thin filament protein, and the percentage of muscle cells contained within myotubes. Exposure of this cell line to the anthracycline doxorubicin produces cell injury as indicated by release of the intracellular enzyme lactate dehydrogenase into the culture medium. This injury is preceded by generation of reactive oxygen species, indicated by fluorescence after loading with carboxy-dichlorodihydrofluorescein diacetate. Stable transfection of H9C2 cells with a plasmid producing a tetracycline transactivator protein allows foreign genes to be expressed at a level tightly controlled by the concentration of tetracycline in the culture medium. Since H9C2 cells differentiate, can be injured by anthracycline exposure, and can express foreign genes at controllable levels, this is a suitable system in which to design genetic approaches to prevent this important clinical problem. PMID:11708868

  10. Effects of rHu-EPO on Myocyte Apoptosis and Cardiac Function Follow-ing Acute Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    YE Liang; DU Xinling; XIA Jiahong; JIANG Ping

    2005-01-01

    The mechanisms of rHu-EPO attenuating the apoptosis after myocardial infarction in rats were studied. Thirty-two rats were divided into three groups: sham operation group (Sham), acute myocardial infarction group (MI) and rHu-EPO-treated group (MI+ EPO). Acute myocardial infarction model was made by ligating the anterior descending coronary artery. rHu-EPO was administered i. p. in MI+EPO group at the dose of 5 000 IU/kg body weight immediately after the ligation. Each rat in MI+EPO group received the same dose of rHu-EPO daily the next 6 days. On the 14th day all rats underwent hemodynamic measurements and then killed. The samples were examined with HE stain, immunohistochemistry technique (bcl-2, bax) and TUNEL dyeing. The results showed that hemodynamic function in MI+ EPO group was much better than in MI group.The number of the cells positive for bax and TUNEL in MI+EPO group was less than that in MI group. The number of the cells positive for bcl-2 in MI+EPO group was more than that in MI group. These findings suggested that rHu-EPO could treat myocardial infarction by preventing apoptosis and attenuating post-infarction deterioration in hemodynamic function.

  11. Thymbra capitata essential oil prevents cell death induced by 4-hydroxy-2-nonenal in neonatal rat cardiac myocytes.

    Science.gov (United States)

    Hortigón-Vinagre, María P; Blanco, José; Ruiz, Trinidad; Henao, Fernando

    2014-10-01

    An interdisciplinary experimental investigation on the antioxidant activity of Thymbra capitata essential oil was made. This plant is a Mediterranean culinary herb, whose essential oil antioxidant power has recently been demonstrated in vitro as one of the highest in nature. We tested if this in vitro antioxidant capacity was reproducible on biological systems using as model system primary cultures of neonatal rat cardiomyocytes treated with the lipid peroxidation product 4-hydroxy-2-nonenal. The composition and the in vitro antioxidant activity of the T. capitata essential oil were also assessed. Cell viability, mitochondrial membrane potential, and reactive oxygen species level were measured in cells treated with pathophysiologic doses of 4-hydroxy-2-nonenal (capitata essential oil, and the ability of small doses (capitata essential oil. PMID:25203731

  12. Effects of Glucose on Transmembrane Ionic Current of Ventricular Myocytes in Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    AIJing; JIAOJun-dong; WANGHe; DUZhi-min; YANGBao-feng

    2004-01-01

    Aim To determine the effects of glucose oi1APD, IK1, IK, ICa-L of ventricular myocytes in guinea pigs. Methods Whole-cell patch-clamp technique was used to record the changed action potential ionic current induced by glucose of single cell in guinea pig ventricular myocytes, to compare the action of 0, 10 and 20 mmol·L-1 glucoses on transmembrane ionic current. Results (1) Compared with 10 mmol·L-1 glucose concentrations, 0 and 20 mmol·L-1 glucose both shortened APD of ventricular myocytes (P<0.05). (2) The inward components of IK1 density were maximal when the glucose concentration was at 10 mmol·L-1. Normalized 1-V relationships showed that both 0 and 20 mmol·L-1 glucose produced a left-shift of I-V curve. The reverse potential changed from-72.4 mV to-64.6 mV. (3) Compared with 10 mmol·L-1, both 0 and 20 mmol·L-1 glucose markedly increased the ICa-L amplitude and density. The ICa-L current density was (-8.0350.82) pA/pF (n=8) at a test potential of 10 mV when the glucose concentration was 10 mmol·L-1. But its current density decreased to (-5.45±0.67) pA/pF and (-6.50±0.56) pA/pF when glucose concentrations were 0 and 20 mmol·L-1, respectively. (4) The current densities of IK were (18.96±2.86) pA/pF, (8.66±1.87) pA/pF, and(15.32:1:3.12) pA/pF, at ±70mV for 0, 10 and 20 mmol·L-1 glucoses, respectively. Conclusion Glucose in different concentrations has different effects on APD, IK1, IK, and ICa-L of single ventricular myocyte in guinea pigs. There are similar actions of 0 and 20 mmol·L-1 glucoses on the transmembrane ionic current of ventricular myocytes in guinea pigs.

  13. YB-1 gene expression is kept constant during myocyte differentiation through replacement of different transcription factors and then falls gradually under the control of neural activity.

    Science.gov (United States)

    Kobayashi, Shunsuke; Tanaka, Toru; Moue, Masamitsu; Ohashi, Sachiyo; Nishikawa, Taishi

    2015-11-01

    We have previously reported that translation of acetylcholine receptor α-subunit (AChR α) mRNA in skeletal muscle cells is regulated by Y-box binding protein 1 (YB-1) in response to neural activity, and that in the postnatal mouse developmental changes in the amount of YB-1 mRNA are similar to those of AChR α mRNA, which is known to be regulated by myogenic transcription factors. Here, we examined transcriptional regulation of the YB-1 gene in mouse skeletal muscle and differentiating C2C12 myocytes. Although neither YB-1 nor AChR α was detected at either the mRNA or protein level in adult hind limb muscle, YB-1 expression was transiently activated in response to denervation of the sciatic nerve and completely paralleled that of AChR α, suggesting that these genes are regulated by the same transcription factors. However, during differentiation of C2C12 cells to myotubes, the level of YB-1 remained constant even though the level of AChR α increased markedly. Reporter gene, gel mobility shift and ChIP assays revealed that in the initial stage of myocyte differentiation, transcription of the YB-1 gene was regulated by E2F1 and Sp1, and was then gradually replaced under the control of both MyoD and myogenin through an E-box sequence in the proximal region of the YB-1 gene promoter. These results suggest that transcription factors for the YB-1 gene are exchanged during skeletal muscle cell differentiation, perhaps playing a role in translational control of mRNAs by YB-1 in both myotube formation and the response of skeletal muscle tissues to neural stimulation.

  14. Cardiac hypertrophy and failure--a disease of adaptation. Modifications in membrane proteins provide a molecular basis for arrhythmogenicity.

    Science.gov (United States)

    Moalic, J M; Charlemagne, D; Mansier, P; Chevalier, B; Swynghedauw, B

    1993-05-01

    Cardiac hypertrophy is the physiological adaptation of the heart to chronic mechanical overload. Cardiac failure indicates the limits of the process. Cardiac hypertrophy is only one example of biological adaptation and results from the induction of several changes in gene expression, mostly of the fetal type, including those coding for the myosin heavy chain or the alpha-subunit of the Na+,K(+)-ATPase. From a thermodynamic point of view, the decrease in Vmax allows the heart to produce a normal tension at a lower cost. This process results from changes both in the sarcomere and in the expression of certain membrane proteins. The decrease in calcium transient is determined by several changes in membrane proteins that result in a rather fragile equilibrium in terms of calcium homeostasis. Any abnormal input in calcium will have exaggerated detrimental consequences on a hypertrophied myocyte and may cause automaticity and arrhythmias or an exaggerated response to anoxia in terms of compliance. PMID:8485830

  15. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  16. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

  17. Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture.

    Science.gov (United States)

    Maruyama, Sonomi; Nakamura, Kazuto; Papanicolaou, Kyriakos N; Sano, Soichi; Shimizu, Ippei; Asaumi, Yasuhide; van den Hoff, Maurice J; Ouchi, Noriyuki; Recchia, Fabio A; Walsh, Kenneth

    2016-01-01

    Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4-expressing fibroblast lineage cells (Fstl1-cfKO mice) led to a reduction in injury-induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1-cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1. PMID:27234440

  18. Ca2+ paradox injury mediated through TRPC channels in mouse ventricular myocytes.

    Science.gov (United States)

    Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

    2010-12-01

    BACKGROUND AND PURPOSE The Ca(2+) paradox is an important phenomenon associated with Ca(2+) overload-mediated cellular injury in myocardium. The present study was undertaken to elucidate molecular and cellular mechanisms for the development of the Ca(2+) paradox. EXPERIMENTAL APPROACH Fluorescence imaging was performed on fluo-3 loaded quiescent mouse ventricular myocytes using confocal laser scanning microscope. KEY RESULTS The Ca(2+) paradox was readily evoked by restoration of the extracellular Ca(2+) following 10-20 min of nominally Ca(2+)-free superfusion. The Ca(2+) paradox was significantly reduced by blockers of transient receptor potential canonical (TRPC) channels (2-aminoethoxydiphenyl borate, Gd(3+), La(3+)) and anti-TRPC1 antibody. The sarcoplasmic reticulum (SR) Ca(2+) content, assessed by caffeine application, gradually declined during Ca(2+)-free superfusion, which was further accelerated by metabolic inhibition. Block of SR Ca(2+) leak by tetracaine prevented Ca(2+) paradox. The Na(+) /Ca(2+) exchange (NCX) blocker KB-R7943 significantly inhibited Ca(2+) paradox when applied throughout superfusion period, but had little effect when added for a period of 3 min before and during Ca(2+) restoration. The SR Ca(2+) content was better preserved during Ca(2+) depletion by KB-R7943. Immunocytochemistry confirmed the expression of TRPC1, in addition to TRPC3 and TRPC4, in mouse ventricular myocytes. CONCLUSIONS AND IMPLICATIONS These results provide evidence that (i) the Ca(2+) paradox is primarily mediated by Ca(2+) entry through TRPC (probably TRPC1) channels that are presumably activated by SR Ca(2+) depletion; and (ii) reverse mode NCX contributes little to the Ca(2+) paradox, whereas inhibition of NCX during Ca(2+) depletion improves SR Ca(2+) loading, and is associated with reduced incidence of Ca(2+) paradox in mouse ventricular myocytes.

  19. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  20. Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177

    Science.gov (United States)

    Walther, Stefanie; Pluteanu, Florentina; Renz, Susanne; Nikonova, Yulia; Maxwell, Joshua T.; Yang, Li-Zhen; Schmidt, Kurt; Edwards, Joshua N.; Wakula, Paulina; Groschner, Klaus; Maier, Lars S.; Spiess, Joachim; Blatter, Lothar A.; Pieske, Burkert

    2014-01-01

    Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca2+-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. PMID:25015964

  1. Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    He, Ben; Zhao, Yi-Chao; Gao, Ling-Chen; Ying, Xiao-Ying; Xu, Long-Wei; Su, Yuan-Yuan; Ji, Qing-Qi; Lin, Nan; Pu, Jun

    2016-06-01

    Dysregulation of the ubiquitin proteasome system components ubiquitin ligases and proteasome plays an important role in the pathogenesis of cardiac hypertrophy. However, little is known about the role of another ubiquitin proteasome system component, the deubiquitinating enzymes, in cardiac hypertrophy. Here, we revealed a crucial role of ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme prominently expressed in the heart, in attenuating pathological cardiac hypertrophy and dysfunction. USP4 levels were consistently decreased in human failing hearts and in murine hypertrophied hearts. Adenovirus-mediated gain- and loss-of-function approaches indicated that deficiency of endogenous USP4 promoted myocyte hypertrophy induced by angiotensin II in vitro, whereas restoration of USP4 significantly attenuated the prohypertrophic effect of angiotensin II. To corroborate the role of USP4 in vivo, we generated USP4 global knockout mice and mice with cardiac-specific overexpression of USP4. Consistent with the in vitro study, USP4 depletion exacerbated the hypertrophic phenotype and cardiac dysfunction in mice subjected to pressure overload, whereas USP4 transgenic mice presented ameliorated pathological cardiac hypertrophy compared with their control littermates. Molecular analysis revealed that USP4 deficiency augmented the activation of the transforming growth factor β-activated kinase 1 (TAK1)-(JNK1/2)/P38 signaling in response to hypertrophic stress, and blockage of TAK1 activation abolished the pathological effects of USP4 deficiency in vivo. These findings provide the first evidence for the involvement of USP4 in cardiac hypertrophy, and shed light on the therapeutic potential of targeting USP4 in the treatment of cardiac hypertrophy.

  2. Effects of oleic acid on the high threshold barium current in seabass Dicentrarchus labrax ventricular myocytes

    OpenAIRE

    Chatelier, Aurelien; Imbert, Nathalie; Zambonino, Jose-luis; McKenzie, David; Bois, P.

    2006-01-01

    The present study employed a patch clamp technique in isolated seabass ventricular myocytes to investigate the hypothesis that oleic acid (OA), a mono-unsaturated fatty acid, can exert direct effects upon whole-cell barium currents. Acute application of free OA caused a dose-dependent depression of the whole-cell barium current that was evoked by a voltage step to 0 mV from a holding potential of -80 mV. The derived 50% inhibitory concentration (IC50) was 12.49 +/- 0.27 mu mol l(-1). At a con...

  3. Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Leonardo Bocchi

    Full Text Available Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI, lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60 or vehicle (V, n = 55, or sham operated (n = 18. In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration

  4. Coupling primary and stem cell-derived cardiomyocytes in an in vitro model of cardiac cell therapy.

    Science.gov (United States)

    Aratyn-Schaus, Yvonne; Pasqualini, Francesco S; Yuan, Hongyan; McCain, Megan L; Ye, George J C; Sheehy, Sean P; Campbell, Patrick H; Parker, Kevin Kit

    2016-02-15

    The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell-derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell-cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell-cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes. PMID:26858266

  5. Biomimetic material strategies for cardiac tissue engineering

    International Nuclear Information System (INIS)

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

  6. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-08

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

  7. The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat

    International Nuclear Information System (INIS)

    Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD50 (14 μg MC-LReq kg-1 body weight) and 1LD50 (87 μg MC-LReq kg-1 body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD50 dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD50 not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil

  8. Comparison of tapentadol with tramadol for analgesia after cardiac surgery

    OpenAIRE

    Srinivas Kalyanaraman Iyer; Gokulakrishnan Mohan; Sivakumar Ramakrishnan; Sanjay Theodore

    2015-01-01

    Background: Tapentadol is a relatively new analgesic. We decided to compare it with tramadol for their various effects after cardiac surgery. Setting: A study in a tertiary care hospital. Materials and Methods: Sixty adults undergoing cardiac surgery were divided into 2 groups of 30 each by computerized random allotment (Group X = tapentadol 50 mg oral and Group Y = tramadol 100 mg oral). Informed Consent and Institutional Ethics Committee approval were obtained. The patients were given eithe...

  9. Fast tracking in paediatric cardiac anaesthesia : an update.

    OpenAIRE

    Lake Carol

    2002-01-01

    A care plan in which cardiac surgical patients progress quickly through the perioperative course to hospital discharge is often referred to as a Fast Track. Such care plans have been used extensively in adult cardiac patients but are also applicable to paediatric patients. Although no randomised controlled trials are available to document a reduction in hospital costs and avoidance of iatrogenic complications with paediatric fast tracks, many healthcare administrators encourage their use. Fas...

  10. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  11. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  12. Ectopic automaticity induced in ventricular myocytes by transgenic overexpression of HCN2.

    Science.gov (United States)

    Oshita, Kensuke; Itoh, Masayuki; Hirashima, Shingo; Kuwabara, Yoshihiro; Ishihara, Keiko; Kuwahara, Koichiro; Nakao, Kazuwa; Kimura, Takeshi; Nakamura, Kei-Ichiro; Ushijima, Kazuo; Takano, Makoto

    2015-03-01

    Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed in the ventricles of fetal hearts but are normally down-regulated as development progresses. In the hypertrophied heart, however, these channels are re-expressed and generate a hyperpolarization-activated, nonselective cation current (Ih), which evidence suggests may increase susceptibility to arrhythmia. To test this hypothesis, we generated and analyzed transgenic mice overexpressing HCN2 specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg mice exhibited no discernible abnormalities. After the application of isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed intermittent atrioventricular dissociation followed by idioventricular rhythm. Consistent with this observation, 0.3 μmol/L ISO-induced spontaneous action potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%, ISO significantly depolarized the resting membrane potential (RMP), and the late repolarization phase of evoked action potentials (APs) was significantly longer than in WT myocytes. Analysis of membrane currents revealed that these differences are attributable to the Ih tail current. These findings suggest HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive β-adrenergic stimulation. PMID:25562801

  13. Effects of Aconitine on [Ca2+] Oscillation in Cultured Myocytes of Neonatal Rats

    Institute of Scientific and Technical Information of China (English)

    Yah LIU; Shiwei ZHANG; Man LIANG; Qian LIU; Liang LIU

    2008-01-01

    Summary: In order to investigate the effects of aconitine on [Ca2+] oscillation patterns in cultured myocytes of neonatal rats, fluorescent Ca2+ indicator Fluo-4 NW and laser scanning confocal microscope (LSCM) were used to detect the real-time changes