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Sample records for single ventricular myocytes

  1. Modulation of contraction by intracellular Na+ via Na(+)-Ca2+ exchange in single shark (Squalus acanthias) ventricular myocytes.

    Science.gov (United States)

    Näbauer, M; Morad, M

    1992-01-01

    1. The effect of direct alteration of intracellular Na+ concentration on contractile properties of whole-cell clamped shark ventricular myocytes was studied using an array of 256 photodiodes to monitor the length of the isolated myocytes. 2. In myocytes dialysed with Na(+)-free solution, the voltage dependence of Ca2+ current (ICa) and contraction were similar and bell shaped. Contractions activated at all voltages were completely suppressed by nifedipine (5 microM), and failed to show significant tonic components, suggesting dependence of the contraction on Ca2+ influx through the L-type Ca2+ channel. 3. In myocytes dialysed with 60 mM Na+, a ICa-dependent and a ICa-independent component of contraction could be identified. The Ca2+ current-dependent component was prominent in voltages between -30 to +10 mV. The ICa-independent contractions were maintained for the duration of depolarization, increased with increasing depolarization between +10 to +100 mV, and were insensitive to nifedipine. 4. In such myocytes, repolarization produced slowly decaying inward tail currents closely related to the time course of relaxation and the degree of shortening prior to repolarization. 5. With 60 mM Na+ in the pipette solution, positive clamp potentials activated decaying outward currents which correlated to the size of contraction. These outward currents appeared to be generated by the Na(+)-Ca(2+)-exchanger since they depended on the presence of intracellular Na+, and were neither suppressed by nifedipine nor by K+ channel blockers. 6. The results suggest that in shark (Squalus acanthias) ventricular myocytes, which lack functionally relevant Ca2+ release pools, both Ca2+ channel and the Na(+)-Ca2+ exchanger deliver sufficient Ca2+ to activate contraction, though the effectiveness of the latter mechanism was highly dependent on the [Na+]i. PMID:1338467

  2. Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes

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    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.

  3. Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

    OpenAIRE

    Tuan, Hoang-Trong Minh; Williams, George S. B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

    2011-01-01

    A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

  4. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

    Science.gov (United States)

    Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

    2018-01-01

    We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

  5. Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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    Chen Li

    Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

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

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    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

  7. Dual effect of ethanol on inward rectifier potassium current IK1 in rat ventricular myocytes

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

    2014-01-01

    Roč. 65, č. 4 (2014), s. 497-509 ISSN 0867-5910 Grant - others:GA MZd NT14301 Institutional support: RVO:61388998 Keywords : ethanol * rat ventricular myocyte * rat ventricular action potential model Subject RIV: BO - Biophysics Impact factor: 2.386, year: 2014

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

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    Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

    2012-04-15

    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.

  9. Numerical Analysis of the Effect of T-tubule Location on Calcium Transient in Ventricular Myocytes

    Science.gov (United States)

    George, Uduak Z.; Wang, Jun; Yu, Zeyun

    2013-01-01

    Intracellular calcium (Ca2+) signaling in cardiac myocytes is vital for proper functioning of the heart. Understanding the intracellular Ca2+ dynamics would give an insight into the functions of normal and diseased hearts. In the current study, spatiotemporal Ca2+ dynamics is investigated in ventricular myocytes by considering Ca2+ release and re-uptake via sarcolemma and transverse tubules (T-tubules), Ca2+ diffusion and buffering in the cytosol, and the blockade of Ca2+ activities associated with the sarcoplasmic reticulum. This study is carried out using a three dimensional (3D) geometric model of a branch of T-tubule extracted from the electron microscopy (EM) images of a partial ventricular myocyte. Mathematical modeling is done by using a system of partial differential equations involving Ca2+ , buffers, and membrane channels. Numerical simulation results suggest that a lack of T-tubule structure at the vicinity of the cell surface could increase the peak time of Ca2+ concentration in myocytes. The results also show that T-tubules and mobile buffers play an important role in the regulation of Ca2+ transient in ventricular myocytes. PMID:24212025

  10. Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes

    NARCIS (Netherlands)

    Casini, Simona; Verkerk, Arie O.; van Borren, Marcel M. G. J.; van Ginneken, Antoni C. G.; Veldkamp, Marieke W.; de Bakker, Jacques M. T.; Tan, Hanno L.

    2009-01-01

    AIMS: Cardiac voltage-gated sodium channels control action potential (AP) upstroke and cell excitability. Intracellular calcium (Ca(i)(2+)) regulates AP properties by modulating various ion channels. Whether Ca(i)(2+) modulates sodium channels in ventricular myocytes, is unresolved. We studied

  11. Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes

    DEFF Research Database (Denmark)

    Stengl, Milan; Volders, Paul G A; Thomsen, Morten Bækgaard

    2003-01-01

    In guinea-pig ventricular myocytes, in which the deactivation of slowly activating delayed rectifier potassium current (IKs) is slow, IKs can be increased by rapid pacing as a result of incomplete deactivation and subsequent current accumulation. Whether accumulation of IKs occurs in dogs, in which...

  12. Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

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    Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

    2013-11-01

    Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

  13. BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.

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    Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D; Tilley, Douglas G; Gao, Erhe; Hoffman, Nicholas E; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y

    2016-03-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. Copyright © 2016 Elsevier Ltd. All rights

  14. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    Science.gov (United States)

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y.

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na+-K+-ATPase and L-type Ca2+ channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca2+ channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca2+]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca2+ current (ICa) and sarcoplasmic reticulum (SR) Ca2+ content but not Na+/Ca2+ exchange current (INaCa) or SR Ca2+ uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyrl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca2+ entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca2+ channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. PMID:26796036

  15. 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. ...

  16. Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes.

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    Bryant, Simon; Kimura, Tomomi E; Kong, Cherrie H T; Watson, Judy J; Chase, Anabelle; Suleiman, M Saadeh; James, Andrew F; Orchard, Clive H

    2014-03-01

    L-type Ca channels (LTCC), which play a key role in cardiac excitation-contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC activity. Ventricular myocytes were isolated from male Wistar rats and LTCC current (ICa) recorded using the whole-cell patch-clamp technique. Incubation of myocytes with a membrane-permeable peptide representing the scaffolding domain of Cav-3 (C3SD) reduced basal ICa amplitude in intact, but not detubulated, myocytes, and attenuated the stimulatory effects of the β2-adrenergic agonist zinterol on ICa. The PKA inhibitor H-89 also reduced basal ICa; however, the inhibitory effects of C3SD and H-89 on basal ICa amplitude were not summative. Under control conditions, myocytes stained with antibody against phosphorylated LTCC (pLTCC) displayed a striated pattern, presumably reflecting localization at the t-tubules. Both C3SD and H-89 reduced pLTCC staining at the z-lines but did not affect staining of total LTCC or Cav-3. These data are consistent with the idea that the effects of C3SD and H-89 share a common pathway, which involves PKA and is maximally inhibited by H-89, and suggest that Cav-3 plays an important role in mediating stimulation of ICa at the t-tubules via PKA-induced phosphorylation under basal conditions, and in response to β2-adrenoceptor stimulation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

    Science.gov (United States)

    Ali, Ramez M; Al Kury, Lina T; Yang, Keun-Hang Susan; Qureshi, Anwar; Rajesh, Mohanraj; Galadari, Sehamuddin; Shuba, Yaroslav M; Howarth, Frank Christopher; Oz, Murat

    2015-04-01

    Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1μM) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1μM) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1μM in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    OpenAIRE

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (...

  19. 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.

  20. Model of excitation-contraction coupling of rat neonatal ventricular myocytes.

    Science.gov (United States)

    Korhonen, Topi; Hänninen, Sandra L; Tavi, Pasi

    2009-02-01

    The neonatal rat ventricular myocyte culture is one of the most popular experimental cardiac cell models. To our knowledge, the excitation-contraction coupling (ECC) of these cells, i.e., the process linking the electrical activity to the cytosolic Ca2+ transient and contraction, has not been previously analyzed, nor has it been presented as a complete system in detail. Neonatal cardiomyocytes are in the postnatal developmental stage, and therefore, the features of their ECC differ vastly from those of adult ventricular myocytes. We present the first complete analysis of ECC in these cells by characterizing experimentally the action potential and calcium signaling and developing the first mathematical model of ECC in neonatal cardiomyocytes that we know of. We show that in comparison to adult cardiomyocytes, neonatal cardiomyocytes have long action potentials, heterogeneous cytosolic Ca2+ signals, weaker sarcoplasmic reticulum Ca2+ handling, and stronger sarcolemmal Ca2+ handling, with a significant contribution by the Na+/Ca2+ exchanger. The developed model reproduces faithfully the ECC of rat neonatal cardiomyocytes with a novel description of spatial cytosolic [Ca2+] signals. Simulations also demonstrate how an increase in the cell size (hypertrophy) affects the ECC in neonatal cardiomyocytes. This model of ECC in developing cardiomyocytes provides a platform for developing future models of cardiomyocytes at different developmental stages.

  1. Sustained exposure to catecholamines affects cAMP/PKA compartmentalised signalling in adult rat ventricular myocytes.

    Science.gov (United States)

    Fields, Laura A; Koschinski, Andreas; Zaccolo, Manuela

    2016-07-01

    In the heart compartmentalisation of cAMP/protein kinase A (PKA) signalling is necessary to achieve a specific functional outcome in response to different hormonal stimuli. Chronic exposure to catecholamines is known to be detrimental to the heart and disrupted compartmentalisation of cAMP signalling has been associated to heart disease. However, in most cases it remains unclear whether altered local cAMP signalling is an adaptive response, a consequence of the disease or whether it contributes to the pathogenetic process. We have previously demonstrated that isoforms of PKA expressed in cardiac myocytes, PKA-I and PKA-II, localise to different subcellular compartments and are selectively activated by spatially confined pools of cAMP, resulting in phosphorylation of distinct downstream targets. Here we investigate cAMP signalling in an in vitro model of hypertrophy in primary adult rat ventricular myocytes. By using a real time imaging approach and targeted reporters we find that that sustained exposure to catecholamines can directly affect cAMP/PKA compartmentalisation. This appears to involve a complex mechanism including both changes in the subcellular localisation of individual phosphodiesterase (PDE) isoforms as well as the relocalisation of PKA isoforms. As a result, the preferential coupling of PKA subsets with different PDEs is altered resulting in a significant difference in the level of cAMP the kinase is exposed to, with potential impact on phosphorylation of downstream targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes.

    Science.gov (United States)

    Hansen, Peter S; Clarke, Ronald J; Buhagiar, Kerrie A; Hamilton, Elisha; Garcia, Alvaro; White, Caroline; Rasmussen, Helge H

    2007-03-01

    The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for our understanding of heart disease associated with diabetes and design of its treatment. We induced diabetes characterized by hyperglycemia but no other major metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic rabbits and controls were voltage clamped and internally perfused with the whole cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most experiments. There was no effect of diabetes on I(p) recorded when myocytes were perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a significant decrease in I(p) measured when pipette solutions contained 10 mmol/l Na(+). The decrease was independent of membrane voltage but dependent on the intracellular concentration of K(+). There was no effect of diabetes on the sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by restoration of euglycemia or by in vivo angiotensin II receptor blockade with losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump inhibition that can be reversed with pharmacological intervention.

  3. T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

    Science.gov (United States)

    Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

    2015-02-01

    In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Science.gov (United States)

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

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

    Science.gov (United States)

    Nayak, Alok Ranjan; Shajahan, T K; Panfilov, A V; Pandit, Rahul

    2013-01-01

    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 for cardiac

  7. Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes

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    Trine Krogh-Madsen

    2017-12-01

    Full Text Available In silico cardiac myocyte models present powerful tools for drug safety testing and for predicting phenotypical consequences of ion channel mutations, but their accuracy is sometimes limited. For example, several models describing human ventricular electrophysiology perform poorly when simulating effects of long QT mutations. Model optimization represents one way of obtaining models with stronger predictive power. Using a recent human ventricular myocyte model, we demonstrate that model optimization to clinical long QT data, in conjunction with physiologically-based bounds on intracellular calcium and sodium concentrations, better constrains model parameters. To determine if the model optimized to congenital long QT data better predicts risk of drug-induced long QT arrhythmogenesis, in particular Torsades de Pointes risk, we tested the optimized model against a database of known arrhythmogenic and non-arrhythmogenic ion channel blockers. When doing so, the optimized model provided an improved risk assessment. In particular, we demonstrate an elimination of false-positive outcomes generated by the baseline model, in which simulations of non-torsadogenic drugs, in particular verapamil, predict action potential prolongation. Our results underscore the importance of currents beyond those directly impacted by a drug block in determining torsadogenic risk. Our study also highlights the need for rich data in cardiac myocyte model optimization and substantiates such optimization as a method to generate models with higher accuracy of predictions of drug-induced cardiotoxicity.

  8. Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.

    Science.gov (United States)

    Lin, Zhenhao; Xing, Wenlu; Gao, Chuanyu; Wang, Xianpei; Qi, Datun; Dai, Guoyou; Zhao, Wen; Yan, Ganxin

    2018-01-26

    Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (I K ) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters. I K and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (I K s ) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, P =0.001; 12.73±0.34 versus 9.05±1.20, n=5, P =0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, P =0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (I K r ), resting membrane potential, AP amplitude, or maximal velocity of depolarization. VEGF inhibited I K s in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  9. A compartmentalized mathematical model of the β1-adrenergic signaling system in mouse ventricular myocytes.

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    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

  10. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    Science.gov (United States)

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    John Shaw

    Full Text Available 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.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.(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.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 mechanotransduction mechanisms in cardiac

  12. Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

    Science.gov (United States)

    Song, Yejia; Belardinelli, Luiz

    2017-12-14

    Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

  13. Rapid Estrogen Receptor-Mediated Mechanisms Determine the Sexually Dimorphic Sensitivity of Ventricular Myocytes to 17β-Estradiol and the Environmental Endocrine Disruptor Bisphenol A

    Science.gov (United States)

    Belcher, Scott M.; Chen, Yamei; Yan, Sujuan

    2012-01-01

    Previously we showed that 17β-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E2 on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10−12 m, and the most efficacious concentrations for each were at 10−9 m. Sensitivity to E2 and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E2 suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ERβ knockout mouse model showed that ERα and ERβ have opposing actions in myocytes and that the balance between ERβ and ERα signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E2 and BPA is dominated by the stimulatory ERβ-mediated signaling, and the absence of BPA and E2 responsiveness in males is due to a counterbalancing-suppressive action of ERα. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ERα and ERβ signaling. PMID:22166976

  14. Intracellular [Ca2+] and Vo2 after manipulation of the free-energy of the Na+/Ca(2+)-exchanger in isolated rat ventricular myocytes

    NARCIS (Netherlands)

    Fiolet, J. W.; Baartscheer, A.; Schumacher, C. A.

    1995-01-01

    We have investigated whether the Na+/Ca(2+)-exchanger has a functional regulatory role in the control of oxidative metabolism in suspensions of isolated rat ventricular myocytes. Therefore we simultaneously measured intracellular [Ca2+] ([Ca2+]i) with Indo-1 and respiratory rate (Vo2) after abrupt

  15. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    International Nuclear Information System (INIS)

    Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

    2010-01-01

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion–reaction equations presented by Izu et al (2001 Biophys. J. 80 103–20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca 2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca 2+ leak in the form of Ca 2+ quarks, increase the probability of occurrence of spontaneous Ca 2+ waves even with smaller SR Ca 2+ stores, accelerate Ca 2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca 2+ wave model under HF conditions provides a new view of Ca 2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca 2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF

  16. Simulation of the effect of rogue ryanodine receptors on a calcium wave in ventricular myocytes with heart failure

    Science.gov (United States)

    Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping

    2010-06-01

    Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca2+ pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca2+ leak in the form of Ca2+ quarks, increase the probability of occurrence of spontaneous Ca2+ waves even with smaller SR Ca2+ stores, accelerate Ca2+ wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca2+ wave model under HF conditions provides a new view of Ca2+ dynamics that could not be mimicked by adjusting traditional parameters involved in Ca2+ release units and other ion channels, and contributes to understanding the underlying mechanism of HF.

  17. Block of the delayed rectifier current (IK) by the 5-HT3 antagonists ondansetron and granisetron in feline ventricular myocytes.

    Science.gov (United States)

    de Lorenzi, F G; Bridal, T R; Spinelli, W

    1994-01-01

    1. We investigated the effects of two 5-HT3 antagonists, ondansetron and granisetron, on the action potential duration (APD) and the delayed rectifier current (IK) of feline isolated ventricular myocytes. Whole-cell current and action potential recordings were performed at 37 degrees C with the patch clamp technique. 2. Ondansetron and granisetron blocked IK with a KD of 1.7 +/- 1.0 and 4.3 +/- 1.7 microM, respectively. At a higher concentration (30 microM), both drugs blocked the inward rectifier (IKl). 3. The block of IK was dependent on channel activation. Both drugs slowed the decay of IK tail currents and produced a crossover with the pre-drug current trace. These results are consistent with block and unblock from the open state of the channel. 4. Granisetron showed an intrinsic voltage-dependence as the block increased with depolarization. The equivalent voltage-dependency of block (delta) was 0.10 +/- 0.04, suggesting that granisetron blocks from the intracellular side at a binding site located 10% across the transmembrane electrical field. 5. Ondansetron (1 microM) and granisetron (3 microM) prolonged APD by about 30% at 0.5 Hz. The prolongation of APD by ondansetron was abolished at faster frequencies (3 Hz) showing reverse rate dependence. 6. In conclusion, the 5-HT3 antagonists, ondansetron and granisetron, are open state blockers of the ventricular delayed rectifier and show a clear class III action. PMID:7834204

  18. Quantitative analysis of the Ca2+ -dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes.

    Science.gov (United States)

    Bartos, Daniel C; Morotti, Stefano; Ginsburg, Kenneth S; Grandi, Eleonora; Bers, Donald M

    2017-04-01

    [Ca 2+ ] i enhanced rabbit ventricular slowly activating delayed rectifier K + current (I Ks ) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K + current (I Kr ) amplitude and voltage dependence were unaffected by high [Ca 2+ ] i . When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca 2+ transient or when [Ca 2+ ] i was buffered to 500 nm. The slowly activating delayed rectifier K + current (I Ks ) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca 2+ ([Ca 2+ ] i ) and β-adrenergic receptor (β-AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca 2+ ] i dependence of I Ks in steady-state conditions and with dynamically changing membrane potential and [Ca 2+ ] i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca 2+ ] i , we found that raising [Ca 2+ ] i from 100 to 600 nm produced similar increases in I Ks as did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca 2+ ] i increased maximally activated tail I Ks , negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, I Ks recorded during a normal physiological Ca 2+ transient was similar to I Ks measured with [Ca 2+ ] i clamped at 500-600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca 2+ ] i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca 2+ ] i , in the submembrane or

  19. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    Carneiro-Júnior, M.A.; Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R.; Amadeu, M.A.; Oliveira, E.M.; Felix, L.B.; Cruz, J.S.; Mill, J.G.; Natali, A.J.; Prímola-Gomes, T.N.

    2014-01-01

    In cardiomyocytes, calcium (Ca 2+ ) release units comprise clusters of intracellular Ca 2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca 2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca 2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F 0 ), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca 2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F 0 , full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes

  20. Effect of exercise training on Ca{sup 2+} release units of left ventricular myocytes of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro-Júnior, M.A. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil); Amadeu, M.A.; Oliveira, E.M. [Universidade de São Paulo, Laboratório de Bioquímica e Biologia Molecular do Exercício, Escola de Educação Física e Esportes, São Paulo, SP (Brazil); Felix, L.B. [Universidade Federal de Viçosa, Departamento de Engenharia Elétrica, Viçosa, MG (Brazil); Cruz, J.S. [Universidade Federal de Minas Gerais, Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Belo Horizonte, MG (Brazil); Mill, J.G. [Universidade Federal do Espírito Santo, Departamento de Ciências Fisiológicas, Vitória, ES (Brazil); Natali, A.J.; Prímola-Gomes, T.N. [Universidade Federal de Viçosa, Laboratório de Biologia do Exercício, Departamento de Educação Física, Viçosa, MG (Brazil)

    2014-08-29

    In cardiomyocytes, calcium (Ca{sup 2+}) release units comprise clusters of intracellular Ca{sup 2+} release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca{sup 2+} sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca{sup 2+} sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F{sub 0}), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca{sup 2+} sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F{sub 0}, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of

  1. Effect of exercise training on Ca²⁺ release units of left ventricular myocytes of spontaneously hypertensive rats.

    Science.gov (United States)

    Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

    2014-11-01

    In cardiomyocytes, calcium (Ca²⁺) release units comprise clusters of intracellular Ca²⁺ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca²⁺ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca²⁺ sparks (HC=7.61 ± 0.26 vs NC=4.79 ± 0.19 per 100 µm/s) and decreased its amplitude (HC=0.260 ± 0.08 vs NC=0.324 ± 0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05 ± 0.08 vs NC=1.26 ± 0.01 µm), total duration (HC=11.51 ± 0.12 vs NC=14.97 ± 0.24 ms), time to peak (HC=4.84 ± 0.06 vs NC=6.31 ± 0.14 ms), and time constant of decay (HC=8.68 ± 0.12 vs NC=10.21 ± 0.22 ms). These changes were partially reversed in HT rats (frequency of Ca²⁺ sparks=6.26 ± 0.19 µm/s, amplitude=0.282 ± 0.10 ΔF/F0, full width at half-maximum amplitude=1.14 ± 0.01 µm, total duration=13.34 ± 0.17 ms, time to peak=5.43 ± 0.08 ms, and time constant of decay=9.43 ± 0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release

  2. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    M.A. Carneiro-Júnior

    2014-11-01

    Full Text Available In cardiomyocytes, calcium (Ca2+ release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age were divided into 4 groups: normotensive (NC and hypertensive control (HC, and normotensive (NT and hypertensive trained (HT animals (7 rats per group. NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2 and FK506 binding protein (FKBP12.6 increased (270% and decreased (88%, respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230% and normalizing FKBP12.6 gene expression (112%. Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0, full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm, total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms, time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms, and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms. These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms. Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

  3. Compartmentalized cAMP Signaling Associated With Lipid Raft and Non-raft Membrane Domains in Adult Ventricular Myocytes.

    Science.gov (United States)

    Agarwal, Shailesh R; Gratwohl, Jackson; Cozad, Mia; Yang, Pei-Chi; Clancy, Colleen E; Harvey, Robert D

    2018-01-01

    Aim: Confining cAMP production to discrete subcellular locations makes it possible for this ubiquitous second messenger to elicit unique functional responses. Yet, factors that determine how and where the production of this diffusible signaling molecule occurs are incompletely understood. The fluid mosaic model originally proposed that signal transduction occurs through random interactions between proteins diffusing freely throughout the plasma membrane. However, it is now known that the movement of membrane proteins is restricted, suggesting that the plasma membrane is segregated into distinct microdomains where different signaling proteins can be concentrated. In this study, we examined what role lipid raft and non-raft membrane domains play in compartmentation of cAMP signaling in adult ventricular myocytes. Methods and Results: The freely diffusible fluorescence resonance energy transfer-based biosensor Epac2-camps was used to measure global cytosolic cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. We found that β-adrenergic receptors, which are expressed in lipid raft and non-raft domains, produce cAMP responses near the plasma membrane that are distinctly different from those produced by E-type prostaglandin receptors, which are expressed exclusively in non-raft domains. We also found that there are differences in basal cAMP levels associated with lipid raft and non-raft domains, and that this can be explained by differences in basal adenylyl cyclase activity associated with each of these membrane environments. In addition, we found evidence that phosphodiesterases 2, 3, and 4 work together in regulating cAMP activity associated with both lipid raft and non-raft domains, while phosphodiesterase 3 plays a more prominent role in the bulk cytoplasmic compartment. Conclusion: These results suggest that different membrane

  4. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats.

    Science.gov (United States)

    Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

    2014-08-29

    In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

  5. TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

    Science.gov (United States)

    Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

    2008-09-01

    We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

  6. Comparison of the effects of caffeine and other methylxanthines on [Ca2+]i in rat ventricular myocytes.

    Science.gov (United States)

    Donoso, P.; O'Neill, S. C.; Dilly, K. W.; Negretti, N.; Eisner, D. A.

    1994-01-01

    1. The effects of caffeine and other methylxanthines were investigated on intracellular calcium concentration ([Ca2+]i) and contraction in rat isolated ventricular myocytes. The use of the fluorescent indicator, Indo-1, allowed simultaneous measurement of [Ca2+]i and the intracellular concentration of the methylxanthines. 2. Rapid application of caffeine (10 mM) produced a transient rise of [Ca2+]i which decayed to resting levels. This was accompanied by a transient contraction which decayed to a level above baseline. The addition of theophylline also produced a transient increase of [Ca2+]i. However, following the initial transient, contraction decayed before redeveloping to a maintained level. 3. Direct measurements showed that [caffeine]i rose more quickly than did [theophylline]i. The slower rise of [theophylline]i was associated with a delay in the increase of [Ca2+]i. At lower concentrations of the methylxanthines, theophylline was less effective than caffeine at initiating Ca release. The rate of entry of theobromine was similar to that of theophylline. 4. Isocaffeine did not produce a rise of [Ca2+]i. The rate of rise of [isocaffeine]i was much slower than that of either caffeine or theophylline. 5. Measurements of the oil:water partition coefficient showed that the order of relative partitioning into oil was: caffeine > theophylline > theobromine > isocaffeine. This is similar to the order of rate of entry into the cell. 6. We conclude that many of the differences in the effects of these methylxanthines can be attributed to differences in membrane permeability due to differences in oil:water partition. PMID:8004389

  7. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Yu-luan; He, Li [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiao, Jun [Department of Cardiology, Chongqing Emergency Medical Center, Chongqing (China); Xia, Shuang; Deng, Song-bai [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China); Xiu, Yun [Institute of Life Science, Chongqing Medical University, Chongqing (China); She, Qiang [Department of Cardiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2012-02-17

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I{sub to}) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg{sup −1}·day{sup −1}). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I{sub to} was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I{sub to} reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I{sub to} of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

  8. Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

    International Nuclear Information System (INIS)

    Xiang, Yu-luan; He, Li; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

    2012-01-01

    Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I to ) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg −1 ·day −1 ). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I to was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I to reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I to of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM

  9. Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes.

    Science.gov (United States)

    Feng, Li; Gong, Jing; Jin, Zhen-yi; Li, Ning; Sun, Li-ping; Wu, Yi-ling; Pu, Jie-lin

    2009-07-05

    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. 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). 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 APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change. 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.

  10. Quantitative analysis of the Ca2+‐dependent regulation of delayed rectifier K+ current I Ks in rabbit ventricular myocytes

    Science.gov (United States)

    Bartos, Daniel C.; Morotti, Stefano; Ginsburg, Kenneth S.; Grandi, Eleonora

    2017-01-01

    Key points [Ca2+]i enhanced rabbit ventricular slowly activating delayed rectifier K+ current (I Ks) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol.Rabbit ventricular rapidly activating delayed rectifier K+ current (I Kr) amplitude and voltage dependence were unaffected by high [Ca2+]i.When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca2+ transient or when [Ca2+]i was buffered to 500 nm. Abstract The slowly activating delayed rectifier K+ current (I Ks) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+ ([Ca2+]i) and β‐adrenergic receptor (β‐AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca2+]i dependence of I Ks in steady‐state conditions and with dynamically changing membrane potential and [Ca2+]i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole‐cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]i from 100 to 600 nm produced similar increases in I Ks as did β‐AR activation, and the effects appeared additive. Both β‐AR activation and high [Ca2+]i increased maximally activated tail I Ks, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well‐established mathematical model of the rabbit myocyte. In both AP‐clamp experiments and simulations, I Ks recorded during a normal physiological Ca2+ transient was similar to I Ks measured with [Ca2+]i clamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft

  11. Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte

    Science.gov (United States)

    Michailova, A.; McCulloch, A.

    2001-01-01

    We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

  12. Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

    Science.gov (United States)

    Morisawa, T; Hasegawa, J; Hama, R; Kitano, M; Kishimoto, Y; Kawasaki, H

    1999-01-01

    The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.

  13. Calpain inhibition reduces amplitude and accelerates decay of the late sodium current in ventricular myocytes from dogs with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Albertas Undrovinas

    Full Text Available Calpain is an intracellular Ca²⁺-activated protease that is involved in numerous Ca²⁺ dependent regulation of protein function in many cell types. This paper tests a hypothesis that calpains are involved in Ca²⁺-dependent increase of the late sodium current (INaL in failing heart. Chronic heart failure (HF was induced in 2 dogs by multiple coronary artery embolization. Using a conventional patch-clamp technique, the whole-cell INaL was recorded in enzymatically isolated ventricular cardiomyocytes (VCMs in which INaL was activated by the presence of a higher (1 μM intracellular [Ca²⁺] in the patch pipette. Cell suspensions were exposed to a cell- permeant calpain inhibitor MDL-28170 for 1-2 h before INaL recordings. The numerical excitation-contraction coupling (ECC model was used to evaluate electrophysiological effects of calpain inhibition in silico. MDL caused acceleration of INaL decay evaluated by the two-exponential fit (τ₁ = 42±3.0 ms τ₂ = 435±27 ms, n = 6, in MDL vs. τ₁ = 52±2.1 ms τ₂ = 605±26 control no vehicle, n = 11, and vs. τ₁ = 52±2.8 ms τ₂ = 583±37 ms n = 7, control with vehicle, P<0.05 ANOVA. MDL significantly reduced INaL density recorded at -30 mV (0.488±0.03, n = 12, in control no vehicle, 0.4502±0.0210, n = 9 in vehicle vs. 0.166±0.05pA/pF, n = 5, in MDL. Our measurements of current-voltage relationships demonstrated that the INaL density was decreased by MDL in a wide range of potentials, including that for the action potential plateau. At the same time the membrane potential dependency of the steady-state activation and inactivation remained unchanged in the MDL-treated VCMs. Our ECC model predicted that calpain inhibition greatly improves myocyte function by reducing the action potential duration and intracellular diastolic Ca²⁺ accumulation in the pulse train.Calpain inhibition reverses INaL changes in failing dog ventricular

  14. Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and Purkinje fibers.

    Science.gov (United States)

    Nayak, Alok Ranjan; Panfilov, A V; Pandit, Rahul

    2017-02-01

    We present systematic numerical studies of the possible effects of the coupling of human endocardial and Purkinje cells at cellular and two-dimensional tissue levels. We find that the autorhythmic-activity frequency of the Purkinje cell in a composite decreases with an increase in the coupling strength; this can even eliminate the autorhythmicity. We observe a delay between the beginning of the action potentials of endocardial and Purkinje cells in a composite; such a delay increases as we decrease the diffusive coupling, and eventually a failure of transmission occurs. An increase in the diffusive coupling decreases the slope of the action-potential-duration-restitution curve of an endocardial cell in a composite. By using a minimal model for the Purkinje network, in which we have a two-dimensional, bilayer tissue, with a layer of Purkinje cells on top of a layer of endocardial cells, we can stabilize spiral-wave turbulence; however, for a sparse distribution of Purkinje-ventricular junctions, at which these two layers are coupled, we can also obtain additional focal activity and many complex transient regimes. We also present additional effects resulting from the coupling of Purkinje and endocardial layers and discuss the relation of our results to the studies performed in anatomically accurate models of the Purkinje network.

  15. Right ventricular function assessment in single LAD lesion patients ...

    African Journals Online (AJOL)

    Rania Gaber

    2015-10-09

    Oct 9, 2015 ... Doppler method in patients with single LAD lesion. Methods: The patient group was ... Results: The right ventricular tissue Doppler parameters (Sm, E, A, E/A ratio, IVA, E/E00) of the patients group were significantly .... cardial interaction effect of tethered LV anterior myocardium. Mittal et al. reported that Left ...

  16. 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

  17. Effect of Ca2+ Efflux Pathway Distribution and Exogenous Ca2+ Buffers on Intracellular Ca2+ Dynamics in the Rat Ventricular Myocyte: A Simulation Study

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Orchard, C.

    2014-01-01

    Roč. 2014, č. 2014 (2014), s. 920208 ISSN 2314-6133 Grant - others:GA MZd NT14301 Institutional support: RVO:61388998 Keywords : calcium efflux * calcium buffers * cardiac myocyte * computer model Subject RIV: BO - Biophysics Impact factor: 1.579, year: 2014

  18. Studies of left ventricular volume estimation from single photon emission computed tomography

    International Nuclear Information System (INIS)

    Hiraki, Yoshio; Shimizu, Mitsuharu; Joja, Ikuo; Aono, Kaname; Yanagi, Hidekiyo; Indo, Haruaki; Seno, Yoshimasa; Teramoto, Shigeru; Nagaya, Isao.

    1988-01-01

    We studied the comparative accuracy of 99m Tc cardiac blood pool Single Photon Emission Computed Tomography (SPECT) for the measurement of left ventricular volume in 20 patients undergoing SPECT and single plane contrast left ventriculography (LVG). Left ventricular volume was calculated based on the total number of voxels in left ventricle. End-diastolic left ventricular volume (EDV) and end-systolic left ventricular volume (ESV) calculated from SPECT were compared with those from LVG. SPECT volume values showed a high degree of correlation with those by LVG (r = 0.923 for EDV, r = 0.903 for ESV). We appreciated the usefulness and accuracy of SPECT in measuring left ventricular volume because of its three-dimensional information. (author)

  19. Mechanisms of isoform-specific Na/K pump regulation by short- and long-term adrenergic activation in rat ventricular myocytes.

    Science.gov (United States)

    Yin, Jian; Guo, Hui-Cai; Yu, Ding; Wang, Hui-Ci; Li, Jun-Xia; Wang, Yong-Li

    2014-01-01

    Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH) and low-affinity current (IPL), α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane. © 2014 S. Karger AG, Basel.

  20. Mechanisms of Isoform-Specific Na/K Pump Regulation by Short- and Long-Term Adrenergic Activation in Rat Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Jian Yin

    2014-05-01

    Full Text Available Background: Many stressful conditions, including cardiovascular diseases, induce long-term elevations in circulating catecholamines, thereby leading to changes of the Na/K pump and thus affecting myocardial functions. However, only short-term adrenergic regulation of the Na/K pump has been reported. The present study is the first investigation of long-term adrenergic regulation of the Na/K pump and the potential mechanism. Methods: After acutely isolated Sprague-Dawley rat myocytes were incubated with noradrenaline or isoprenaline for 24 h, Na/K pump high- (IPH and low-affinity current (IPL, α-isoform mRNA, and α-isoform protein were examined using patch-clamp, RT-PCR, and Western blotting techniques, respectively. Results: After the short-term incubation, isoprenaline reduced the IPL through a PKA-dependent pathway that involves α1-isoform translocation from the membrane to early endosomes, and noradrenaline increased the IPH through a PKC-dependent pathway that involves α2-isoform translocation from late endosomes to the membrane. After long-term incubation, isoprenaline increased the IPL, α1-isoform mRNA, and α1-isoform protein, and noradrenaline reduced the IPH, α2-isoform mRNA, and α1-isoform protein through a PKA-or PKC-dependent pathway, respectively. Conclusions: These results suggest that long-term adrenergic Na/K pump regulation is isoform-specific and negatively feeds back on the short-term response. Furthermore, long-term regulation involves transcription and translation of the respective α-isoform, whereas short-term regulation involves the translocation of the available α-isoform to the plasma membrane.

  1. Effect of epinephrine on inhibition of sodium current induced by bupivacaine in ventricular myocytes of rats%肾上腺素对布比卡因抑制大鼠心室肌细胞钠电流的影响

    Institute of Scientific and Technical Information of China (English)

    陈鸿飞; 刘付丽; 吴一泉; 徐旭仲

    2016-01-01

    目的:研究肾上腺素对较低浓度布比卡因所抑制的大鼠心室肌细胞钠电流(INa)的影响。方法:采用急性酶解分离法获得Sprague-Dawley雄性大鼠心室肌细胞,随机分为2组(n=5),以全细胞膜片钳技术记录INa,观察0.15μg/mL肾上腺素对40μmol/L布比卡因和50μmol/L布比卡因所抑制的INa的影响。结果:40μmol/L和50μmol/L布比卡因对大鼠心室肌细胞INa抑制率分别为(50.2%±5.8%)和(62.7%±7.7%),差异有统计学意义(P<0.05)。当加入0.15μg/mL肾上腺素后,40μmol/L布比卡因组抑制率变到(33.7%±10.2%),差异有统计学意义(P<0.05);50μmol/L布比卡因组抑制率变为(62.1%±7.3%),差异无统计学意义(P>0.05),肾上腺素对I-V曲线无明显影响。结论:肾上腺素可以部分恢复较低浓度布比卡因所抑制的心室肌细胞INa,但其作用在较高浓度布比卡因中受到限制。%Objective: To determine the effect of epinephrine on inhibition of sodium current (INa) induced by bupivacaine inventricular myocytes of rats.Methods: The ventricular myocytes isolated from Sprague-Dawley rats by acute enzymatic dissociation were randomly divided into two groups (n=5). The whole-cell patch clamp technique was used to record INa in single ventricular myocytes and the effect of 0.15 ug/mL epinephrine inhibi-tion of INa on induced by 40 or 50 μmol/L bupivacaine were observed.Results:The inhibition rates of 40 μmol/L bupivacaine or 50 μmol/L bupivacaine on INa was 50.2%±5.8 % or 62.7%±7.7 % (P0.05) in the 50 μmol/L bupivacaine group. Epinephrine did not shift the I-V curve.Conclusion: Epinephrine can reverse inhibition of INa induced by low-concentration bupivacaine. This effect of epinephrine will be limited to a higher level concentration of bupivacaine.

  2. Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

    Science.gov (United States)

    Gulothungan, G.; Malathi, R.

    2018-04-01

    Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet

  3. Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

    Science.gov (United States)

    Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

    2014-01-01

    We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

  4. Assessment of right ventricular function using gated blood pool single photon emission computed tomography in inferior myocardial infarction with or without hemodynamically significant right ventricular infarction

    International Nuclear Information System (INIS)

    Takahashi, Masaharu

    1992-01-01

    Right ventricular function was assessed using gated blood pool single photon emission computed tomography (GSPECT) in 10 normal subjects and 14 patients with inferior myocardial infarction. Three-dimensional backbround subtraction was achieved by applying an optimal cut off level. The patient group consisted of 6 patients with definite hemodynamic abnormalities indicative of right ventricular infarction (RVI) and 8 other patients with significant obstructive lesion at the proximal portion of right coronary artery without obvious hemodynamic signs of RVI. Right ventricular regional wall motion abnormalities were demonstrated on GSPECT functional images and the indices of right ventricular function (i.e the right ventricular ejection fraction (RVEF), the right ventricular peak ejection rate (RVPER) and the right ventricular peak filling rate (RVPFR)) were significantly reduced in the patient group, not only in the patients with definite RVI but also in those without hemodynamic signs of RVI, even in the absence of definite hemodynamic signs, when the proximal portion of right coronary artery is obstructed. It is concluded that GSPECT is reliable for the assessment of right ventricular function and regional wall motion, and is also useful for the diagnosis of RVI. (author)

  5. Left ventricular volume determination from single-photon emission computed tomography

    International Nuclear Information System (INIS)

    Bunker, S.R.; Hartshorne, M.F.; Schmidt, W.P.; Cawthon, M.A.; Karl, R.D. Jr.; Bauman, J.M.; Howard, W.H. III; Rubal, B.J.

    1985-01-01

    To compare the accuracy of single-photon emission computed tomography (SPECT) with that of contrast cineangiography in measuring left ventricular end-diastolic volume, 25 consecutive patients undergoing catheterizaiton for coronary artery or valvular heart disease were first evaluated scintigraphically. SPECT volume values showed a high degree of correlation with those determined by angiography with a standard error of the estimate of 23 ml. SPECT offers a highly accurate and essentially noninvasive method for measuring chamber volumes that is independent of geometric assumptions about ventricular configuration and chest wall attenuation and does not require blood sample counting

  6. Left ventricular volume determination from single-photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Bunker, S.R.; Hartshorne, M.F.; Schmidt, W.P.; Cawthon, M.A.; Karl, R.D. Jr.; Bauman, J.M.; Howard, W.H. III; Rubal, B.J.

    1985-02-01

    To compare the accuracy of single-photon emission computed tomography (SPECT) with that of contrast cineangiography in measuring left ventricular end-diastolic volume, 25 consecutive patients undergoing catheterizaiton for coronary artery or valvular heart disease were first evaluated scintigraphically. SPECT volume values showed a high degree of correlation with those determined by angiography with a standard error of the estimate of 23 ml. SPECT offers a highly accurate and essentially noninvasive method for measuring chamber volumes that is independent of geometric assumptions about ventricular configuration and chest wall attenuation and does not require blood sample counting.

  7. Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

    Science.gov (United States)

    McCain, Megan L.; Yuan, Hongyan; Pasqualini, Francesco S.; Campbell, Patrick H.

    2014-01-01

    Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease. PMID:24682394

  8. Ventricular assist device use in single ventricle congenital heart disease.

    Science.gov (United States)

    Carlo, Waldemar F; Villa, Chet R; Lal, Ashwin K; Morales, David L

    2017-11-01

    As VAD have become an effective therapy for end-stage heart failure, their application in congenital heart disease has increased. Single ventricle congenital heart disease introduces unique physiologic challenges for VAD use. However, with regard to the mixed clinical results presented within this review, we suggest that patient selection, timing of implant, and center experience are all important contributors to outcome. This review focuses on the published experience of VAD use in single ventricle patients and details physiologic challenges and novel approaches in this growing pediatric and adult population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Increased expression of the auxiliary beta(2-subunit of ventricular L-type Ca(2+ channels leads to single-channel activity characteristic of heart failure.

    Directory of Open Access Journals (Sweden)

    Roger Hullin

    2007-03-01

    Full Text Available Increased activity of single ventricular L-type Ca(2+-channels (L-VDCC is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation.By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1 or beta(3 isoforms, beta(2a and beta(2b induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V1.2 also reveal increased single-channel activity and sarcolemmal beta(2 expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase", reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2 expression. Additional evidence for the cause-effect relationship between beta(2-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V1.2 and inducible beta(2 cardiac overexpression. Here in non-failing hearts induction of beta(2-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure.Our study presents evidence of the pathobiochemical relevance of beta(2-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.

  10. Quantification of ventricular unloading by 3D echocardiography in single ventricle of left ventricular morphology following superior cavo-pulmonary anastomosis and Fontan completion – a feasibility study

    Directory of Open Access Journals (Sweden)

    Deepa Sasikumar

    2017-01-01

    Conclusions: We provide preliminary information on 3DE volume data of single ventricle of LV morphology and the pattern of unloading after SCPA and Fontan operation. Immediate significant volume unloading occurred after SCPA which tended to catch-up after 3 months, whereas continued fall in ventricular volume with time was noted after Fontan.

  11. Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

    Science.gov (United States)

    Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

    2016-12-14

    Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

  12. Adaptive singular value cancelation of ventricular activity in single-lead atrial fibrillation electrocardiograms

    International Nuclear Information System (INIS)

    Alcaraz, Raúl; Rieta, José Joaquín

    2008-01-01

    The proper analysis and characterization of atrial fibrillation (AF) from surface electrocardiographic (ECG) recordings requires to cancel out the ventricular activity (VA), which is composed of the QRS complex and the T wave. Historically, for single-lead ECGs, the averaged beat subtraction (ABS) has been the most widely used technique. However, this method is very sensitive to QRST wave variations and, moreover, high-quality cancelation templates may be difficult to obtain when only short length and single-lead recordings are available. In order to overcome these limitations, a new QRST cancelation method based on adaptive singular value cancelation (ASVC) applied to each single beat is proposed. In addition, an exhaustive study about the optimal set of complexes for better cancelation of every beat is also presented for the first time. The whole study has been carried out with both simulated and real AF signals. For simulated AF, the cancelation performance was evaluated making use of a cross-correlation index and the normalized mean square error (nmse) between the estimated and the original atrial activity (AA). For real AF signals, two additional new parameters were proposed. First, the ventricular residue (VR) index estimated the presence of ventricular activity in the extracted AA. Second, the similarity (S) evaluated how the algorithm preserved the AA segments out of the QRST interval. Results indicated that for simulated AF signals, mean correlation, nmse, VR and S values were 0.945 ± 0.024, 0.332 ± 0.073, 1.552 ± 0.386 and 0.986 ± 0.012, respectively, for the ASVC method and 0.866 ± 0.042, 0.424 ± 0.120, 2.161 ± 0.564 and 0.922 ± 0.051 for ABS. In the case of real signals, the mean VR and S values were 1.725 ± 0.826 and 0.983 ± 0.038, respectively, for ASVC and 3.159 ± 1.097 and 0.951 ± 0.049 for ABS. Thus, ASVC provides a more accurate beat-to-beat ventricular QRST representation than traditional techniques. As a consequence, VA cancelation

  13. Validity of the accuracy of right ventricular volume measurement with single plane Simpson's rule based on a new half-circle model

    International Nuclear Information System (INIS)

    Cui Wei

    2003-01-01

    Objective: Right ventricular volume calculation is the basis of right ventricular function evaluation. The complexity of right ventricular shape makes it more difficult for measuring right ventricular volume, and therefore limits the widespread use of right ventricular function assessment. However, the short-axis view of the right ventricle is usually crescent, and might be assumed as half of a circle. This hypothesis can be applied to calculate right ventricular volume by using the plane Simpson's rule, but the final right ventricular volume should be about half of the original calculated value. The aim of this study was to test the accuracy of right ventricular volume measurement based on this new assumption in human right ventricular casts. Methods: Fifteen human right ventricular casts were obtained within 24 hours after death from 15 subjects who did not have overt cardiac disease. These casts were scanned with Toshiba multislice helical CT (Aquilion) using a scanning protocol similar to clinical practice. Right ventricular sagittal MPR images that correspond to right anterior oblique view were reconstructed later and single-plane Simpson's method was used to calculate right ventricular volumes. The calculated right ventricular volume was defined as the original calculated value divided by 2. The actual right ventricular casts volumes were determined by water displacement method. Results: The actual right ventricular volume was (64.23±24.51) ml, while the calculated volume was (53.18±26.22) ml. The calculated right ventricular volume significantly underestimated the actual volume by (11.05±13.09) ml (t=3.27, P=0.006). However, there was a close correlation between the actual cast volume and the calculated volume (r=0.869, P<0.001), with a regression equation of RV actual volume=21.04+0.812 x RV calculated volume. Conclusion: Right ventricular volume could be calculated accurately with single-plane Simpson's rule based on our new proposed half

  14. Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

    International Nuclear Information System (INIS)

    Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie; Matsuoka, Nobuhiro; Rollins, Douglas; Badger, Troy; Rodesch, Christopher K.; Barry, William H.

    2009-01-01

    Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca 2+ ] i was measured by flow cytometry using fluo-3. Mitochondrial [Ca 2+ ] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca 2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca 2+ ] i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca 2+ ] i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca 2+ ] i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

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

    International Nuclear Information System (INIS)

    Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

    2012-01-01

    Highlights: ► ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. ► Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. ► 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 γ-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.

  16. Monitoring of right ventricular function by single probe system (nuclear stethoscope) and sup(81m)Kr

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Ohmine, Hiromi; Kimura, Motomasa [National Cardiovascular Center, Suita, Osaka (Japan)

    1982-12-01

    A single probe system (nuclear stethoscope) was developed to evaluate the monitoring of right ventricular function by sup(81m)Kr continuous infusion method. Optimal right ventricular and background positions were determined by position/monitor mode on beat-to-beat basis, and right ventricular ejection fraction (RVEF) was calculated by multi-gated method (MUGA). The correlation coefficient of nuclear stethoscope RVEF and camera-computer RVEF (MUGA) was 0.82, while the correlation coefficient of nuclear stethoscope RVEF and camera-computer RVEF (first-pass method) was 0.64. Therefore, the RVEF by nuclear stethoscope is useful for monitoring of right ventricular function. Clinical applications by sup(81m)Kr and nuclear stethoscope were as follows. 1. Exercise/rest RVEF is an extremely sensitive indicator to discriminate coronary artery disease (RCA occlusion) from normal subjects. 2. Beat-to-beat right ventricular volume response is useful for the monitoring of arrythmia such as atrial fibrillation.

  17. Monitoring of right ventricular function by single probe system (nuclear stethoscope) and sup(81m)Kr

    International Nuclear Information System (INIS)

    Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Ohmine, Hiromi; Kimura, Motomasa

    1982-01-01

    A single probe system (nuclear stethoscope) was developed to evaluate the monitoring of right ventricular function by sup(81m)Kr continuous infusion method. Optimal right ventricular and background positions were determined by position/monitor mode on beat-to-beat basis, and right ventricular ejection fraction (RVEF) was calculated by multi-gated method (MUGA). The correlation coefficient of nuclear stethoscope RVEF and camera-computer RVEF (MUGA) was 0.82, while the correlation coefficient of nuclear stethoscope RVEF and camera-computer RVEF (first-pass method) was 0.64. Therefore, the RVEF by nuclear stethoscope is useful for monitoring of right ventricular function. Clinical applications by sup(81m)Kr and nuclear stethoscope were as follows. 1. Exercise/rest RVEF is an extremely sensitive indicator to discriminate coronary artery disease (RCA occlusion) from normal subjects. 2. Beat-to-beat right ventricular volume response is useful for the monitoring of arrythmia such as atrial fibrillation. (author)

  18. Assessment of left ventricular function using 201Tl electrocardiogram-gated myocardial single photon emission computed tomography

    International Nuclear Information System (INIS)

    Nishikubo, Naotsugu; Tamai, Hiroyuki

    2013-01-01

    Advances in computed tomography (CT) technology make it possible to obtain left ventricular wall motion using 3D reconstruction. In this study, we compared the images obtained from CT and 201 Tl electrocardiogram (ECG) gated single photon emission computed tomography (SPECT). In 20 patients with ischemic heart disease, we performed 201 Tl ECG gated SPECT (GE Healthcare Millennium VG) and ECG gated CT (Philips Medical Systems Brilliance iCT) to evaluate of left ventricular wall motion during the resting phase. In SPECT, left ventricular images were reconstructed using quantitative gated SPECT (QGS) software. In CT, the images were reconstructed using Virtual Place (AZE Software). The left ventricle was classified into five regions (anterior, lateral, inferior, septal, and apical). The amplitude of the wall motion was classified into five grades according to AHA classification. The values of the wall motion were separately checked by two radiographers. Assessment of left ventricular function myocardial wall movement using the three-dimensional movie display with ECG gated myocardial SPECT data was in agreement with the evaluation by cardiac CT inspection, and corresponded with wall motion in 88 of all 100 segments. SPECT analysis has the same quantity as that of obtained from CT for evaluation of left ventricular wall motion. (author)

  19. 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...

  20. 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.

  1. 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.

  2. Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

    NARCIS (Netherlands)

    van Borren, Marcel M. G. J.; Vos, Marc A.; Houtman, Marien J. C.; Antoons, Gudrun; Ravesloot, Jan H.

    2013-01-01

    Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes

  3. Single-photon emission computed tomography for the assessment of ventricular perfusion and function

    International Nuclear Information System (INIS)

    Gonzalez, Patricio; Dussaillant, Gaston; Gutierrez, Daniela; Berrocal, Isabel; Alay, Rita; Otarola, Sonia

    2013-01-01

    Background: Single-photon emission computed tomography (SPECT) can be used as a non-invasive tool for the assessment of coronary perfusion. Aim: To assess ventricular perfusion and function by SPECT in patients with single vessel coronary artery disease. Material and Methods: Among patients with indications for a coronary artery angiography, those with significant lesions in one vessel, were selected for the study. Within 24 hours, cardiac SPECT examinations on basal conditions and after high doses of dipyridamole, were performed. SPECT data from 38 patients with a low probability of coronary artery disease was used for comparisons. Results:Ten patients aged 61 ± 8 years (seven men) were studied. Visual analysis of SPECT revealed signs suggestive of ischemia in eight patients. The remaining two patients did not have perfusion disturbances. SPECT detected eight of ten abnormal vessels reported in the coronary artery angiography. There were two false negative results Summed stress, summed rest and summed difference scores were 9.78 ± 6.51, 3.22 ± 5.07 and 6.33 ± 4.97, respectively. The ejection fractions under stress and at rest were 53 ± 11.7% and 61 ± 15.7% respectively (p ≤ 0.01). The figures for the control group were 69.1 ± 13.5% and 75.2 ± 12.04% respectively (significantly different from patients). Two patients had a summed motion score above 14.9. Likewise, two patients had a summed thickening score above 10.9. Conclusions: SPECT detected 80% of coronary lesions found during coronary artery angiography. Visual analysis of perfusion is highly reliable for diagnosis. Quantitative parameters must be considered only as reference parameters

  4. Management of single-ventricle patients with Berlin Heart EXCOR Ventricular Assist Device: single-center experience.

    Science.gov (United States)

    Mackling, Tracey; Shah, Tejas; Dimas, Vivian; Guleserian, Kristine; Sharma, Mahesh; Forbess, Joseph; Ardura, Monica; Gross-Toalson, Jami; Lee, Ying; Journeycake, Janna; Barnes, Aliessa

    2012-06-01

    There are minimal data regarding chronic management of single-ventricle ventricular assist device (VAD) patients. This study aims to describe our center's multidisciplinary team management of single-ventricle patients supported long term with the Berlin Heart EXCOR Pediatric VAD. Patient #1 was a 4-year-old with double-outlet right ventricle with aortic atresia, L-looped ventricles, and heart block who developed heart failure 1 year after Fontan. She initially required extracorporeal membrane oxygenation support and was transitioned to Berlin Heart systemic VAD. She was supported for 363 days (cardiac intensive care unit [CICU] 335 days, floor 28 days). The postoperative course was complicated by intermittent infection including methicillin-resistant Staphylococcus aureus, intermittent hepatic and renal insufficiencies, and transient antithrombin, protein C, and protein S deficiencies resulting in multiple thrombi. She had a total of five pump changes over 10 months. Long-term medical management included anticoagulation with enoxaparin, platelet inhibition with aspirin and dipyridamole, and antibiotic prophylaxis using trimethoprim/sulfamethoxazole. She developed sepsis of unknown etiology and subsequently died from multiorgan failure. Patient #2 was a 4-year-old with hypoplastic left heart syndrome who developed heart failure 2 years after bidirectional Glenn shunt. At systemic VAD implantation, he was intubated with renal insufficiency. Post-VAD implantation, his renal insufficiency resolved, and he was successfully extubated to daytime nasal cannula and biphasic positive airway pressure at night. He was supported for 270 days (CICU 143 days, floor 127 days). The pump was upsized to a 50-mL pump in May 2011 for increased central venous pressures (29 mm Hg). Long-term medical management included anticoagulation with warfarin and single-agent platelet inhibition using dipyridamole due to aspirin resistance. He developed increased work of breathing requiring

  5. Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Sourabh Chand

    Full Text Available Chronic kidney disease (CKD is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS Glu298Asp single nucleotide polymorphism (SNP genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.The median estimated glomerular filtration rate (eGFR was 50 mls/min and left ventricular ejection fraction (LVEF was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006. After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively.eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.

  6. Arrhythmogenic Right Ventricular Cardiomyopathy in an Endurance Athlete Presenting with Ventricular Tachycardia and Normal Right Ventricular Function.

    Science.gov (United States)

    Hedley, Jeffrey S; Al Mheid, Ibhar; Alikhani, Zoubin; Pernetz, Maria A; Kim, Jonathan H

    2017-08-01

    Arrhythmogenic right ventricular cardiomyopathy, a genetically inherited disease that results in fibrofatty replacement of normal cardiac myocytes, has been associated with sudden cardiac death in athletes. Long-term participation in endurance exercise hastens the development of both the arrhythmic and structural arrhythmogenic right ventricular cardiomyopathy phenotypes. We describe the unusual case of a 34-year-old, symptomatic, female endurance athlete who had arrhythmogenic right ventricular cardiomyopathy in the presence of a structurally normal right ventricle. Clinicians should be aware of this infrequent presentation when evaluating athletic patients who have ventricular arrhythmias and normal findings on cardiac imaging studies.

  7. Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

    Science.gov (United States)

    Hanft, Laurin M; McDonald, Kerry S

    2010-08-01

    According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length

  8. Postexertional Supraventricular Tachycardia in Children with Catecholaminergic Polymorphic Ventricular Tachycardia

    Directory of Open Access Journals (Sweden)

    Scott D. N. Else

    2012-01-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a severe arrhythmia associated with sudden death in the young. It is caused by defective calcium handling in ventricular myocytes. The association of supraventricular tachycardia (SVT with CPVT is described in the literature, occurring in the lead-up to ventricular tachycardia during exercise testing. We describe three cases of SVT that were initiated in the recovery period of exercise testing in children with CPVT.

  9. Atrioventricular valve repair in patients with functional single-ventricle physiology: impact of ventricular and valve function and morphology on survival and reintervention.

    Science.gov (United States)

    Honjo, Osami; Atlin, Cori R; Mertens, Luc; Al-Radi, Osman O; Redington, Andrew N; Caldarone, Christopher A; Van Arsdell, Glen S

    2011-08-01

    This study was to determine whether atrioventricular valve repair modifies natural history of single-ventricle patients with atrioventricular valve insufficiency and to identify factors predicting survival and reintervention. Fifty-seven (13.5%) of 422 single-ventricle patients underwent atrioventricular valve repair. Valve morphology, regurgitation mechanism, and ventricular morphology and function were analyzed for effect on survival, transplant, and reintervention with multivariate logistic and Cox regression models. Comparative analysis used case-matched controls. Atrioventricular valve was tricuspid in 67% and common in 28%. Ventricular morphology was right in 83%. Regurgitation mechanisms were prolapse (n = 24, 46%), dysplasia (n = 18, 35%), annular dilatation (n = 8, 15%), and restriction or cleft (n = 2, 4%). Postrepair insufficiency was none or trivial in 14 (26%), mild in 33 (61%), and moderate in 7 (13%). Survival in repair group was lower than in matched controls (78.9% vs 92.7% at 1 year, 68.7% vs 90.6% at 3 years, P = .015). Patients with successful repair and normal ventricular function had equivalent survival to matched controls (P = .36). Independent predictors for death or transplant included increased indexed annular size (P = .05), increased cardiopulmonary bypass time (P = .04), and decreased postrepair ventricular function (P = .01). Ventricular dilation was a time-related factor for all events, including failed repair. Survival was lower in single-ventricle patients operated on for atrioventricular valve insufficiency than in case-matched controls. Patients with little postoperative residual regurgitation and preserved ventricular function had equivalent survival to controls. Lower grade ventricular function and ventricular dilation correlated with death and repair failure, suggesting that timing of intervention may affect outcome. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All

  10. Evaluation of left ventricular function and volume with multidetector-row computed tomography. Comparison with electrocardiogram-gated single photon emission computed tomography

    International Nuclear Information System (INIS)

    Suzuki, Takeya; Yamashina, Shohei; Nanjou, Shuji; Yamazaki, Junichi

    2007-01-01

    This study compared left ventricular systolic function and volume determined by multidetector-row computed tomography (MDCT) and electrocardiogram-gated single photon emission computed tomography (G-SPECT) Thirty-seven patients with coronary artery disease and non-cardiovascular disease underwent MDCT. In this study, left ventricular ejection fraction (EF), left ventricular end-diastolic volume (EDV) and left ventricular end-systolic volume (ESV) were calculated using only two-phase imaging with MDCT. Left ventricular function and volume were compared using measurements from G-SPECT. We conducted MDCT and G-SPECT virtually simultaneously. Both the EF and ESV evaluated by MDCT closely correlated with G-SPECT (r=0.763, P 65 bpm) during MDCT significantly influenced the difference in EF calculated from MDCT and G-SPECT (P<0.05). Left ventricular function can be measured with MDCT as well as G-SPECT. However, a heart rate over 65 bpm during MDCT negatively affects the EF correlation between MDCT and G-SPECT. (author)

  11. Electrophysiological effects of Ro 22-9194, a new antiarrhythmic agent, on guinea-pig ventricular cells.

    OpenAIRE

    Maruyama, K; Kodama, I; Anno, T; Suzuki, R; Toyama, J

    1995-01-01

    1. Cardiac effects of Ro 22-9194 were examined in papillary muscles and single ventricular myocytes isolated from guinea-pigs and compared with those of moricizine. 2. In papillary muscles, both Ro 22-9194 (> or = 10 microM) and moricizine (> or = 1 microM) caused a significant dose-dependent decrease in the maximum upstroke velocity (Vmax) and a shortening of the action potential duration. 3. In the presence of either drug, trains of stimuli at rates > or = 0.2 Hz led to an exponential decli...

  12. Electrocardiograph-gated single photon emission computed tomography radionuclide angiography presents good interstudy reproducibility for the quantification of global systolic right ventricular function.

    Science.gov (United States)

    Daou, Doumit; Coaguila, Carlos; Vilain, Didier

    2007-05-01

    Electrocardiograph-gated single photon emission computed tomography (SPECT) radionuclide angiography provides accurate measurement of right ventricular ejection fraction and end-diastolic and end-systolic volumes. In this study, we report the interstudy precision and reliability of SPECT radionuclide angiography for the measurement of global systolic right ventricular function using two, three-dimensional volume processing methods (SPECT-QBS, SPECT-35%). These were compared with equilibrium planar radionuclide angiography. Ten patients with chronic coronary artery disease having two SPECT and planar radionuclide angiography acquisitions were included. For the right ventricular ejection fraction, end-diastolic volume and end-systolic volume, the interstudy precision and reliability were better with SPECT-35% than with SPECT-QBS. The sample sizes needed to objectify a change in right ventricular volumes or ejection fraction were lower with SPECT-35% than with SPECT-QBS. The interstudy precision and reliability of SPECT-35% and SPECT-QBS for the right ventricle were better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography on the same population. SPECT-35% and SPECT-QBS present good interstudy precision and reliability for right ventricular function, with the results favouring the use of SPECT-35%. The results are better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography. They need to be confirmed in a larger population.

  13. Calcium release-dependent inactivation precedes formation of the tubular system in developing rat cardiac myocytes.

    Science.gov (United States)

    Macková, Katarina; Zahradníková, Alexandra; Hoťka, Matej; Hoffmannová, Barbora; Zahradník, Ivan; Zahradníková, Alexandra

    2017-12-01

    Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes. We characterized the appearance and expansion of the t-tubule system and compared it with the appearance and progress of the calcium current inactivation induced by the release of calcium ions from sarcoplasmic reticulum as structural and functional measures of direct DHPR-RYR interaction. The release-dependent inactivation of calcium current preceded the development of the t-tubular system by several days, indicating formation of the first DHPR-RYR couplons at the surface sarcolemma and their later spreading close to contractile myofibrils with the growing t-tubules. Large variability of both of the measured parameters among individual myocytes indicates uneven maturation of myocytes within the growing myocardium.

  14. Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

    Science.gov (United States)

    Johnson, Robert D; Camelliti, Patrizia

    2018-03-15

    The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

  15. Four-dimensional echocardiography area strain combined with exercise stress echocardiography to evaluate left ventricular regional systolic function in patients with mild single vessel coronary artery stenosis.

    Science.gov (United States)

    Deng, Yan; Peng, Long; Liu, Yuan-Yuan; Yin, Li-Xue; Li, Chun-Mei; Wang, Yi; Rao, Li

    2017-09-01

    The aim of this prospective study was to assess the diagnosis value of four-dimensional echocardiography area strain (AS) combined with exercise stress echocardiography to evaluate left ventricular regional systolic function in patients with mild single vessel coronary artery stenosis. Based on treadmill exercise load status, two-dimensional conventional echocardiography and four-dimensional echocardiography area strain were performed on patients suspected coronary artery disease before coronary angiogram. Thirty patients (case group) with mild left anterior descending coronary artery stenosis (stenosis Four-dimensional echocardiography area strain combined with exercise stress echocardiography could sensitively find left ventricular regional systolic function abnormality in patients with mild single vessel coronary artery stenosis, and locate stenosis coronary artery accordingly. © 2017, Wiley Periodicals, Inc.

  16. Assessment of left ventricular function by electrocardiogram-gated myocardial single photon emission computed tomography using quantitative gated single photon emission computed tomography software

    International Nuclear Information System (INIS)

    Morita, Koichi; Adachi, Itaru; Konno, Masanori

    1999-01-01

    Electrocardiogram (ECG)-gated myocardial single photon emission computed tomography (SPECT) can assess left ventricular (LV) perfusion and function easily using quantitative gated SPECT (QGS) software. ECG-gated SPECT was performed in 44 patients with coronary artery disease under post-stress and resting conditions to assess the values of LV functional parameters, by comparison to LV ejection fraction derived from gated blood pool scan and myocardial characteristics. A good correlation was obtained between ejection fraction using QGS and that using cardiac blood pool scan (r=0.812). Some patients with myocardial ischemia had lower ejection fraction under post-stress compared to resting conditions, indicating post-stress LV dysfunction. LV wall motion and wall thickening were significantly impaired in ischemic and infarcted myocardium, and the degree of abnormality in the infarcted areas was greater than in the ischemia area. LV functional parameters derived using QGS were useful to assess post-stress LV dysfunction and myocardial viability. In conclusion, ECG-gated myocardial SPECT permits simultaneous quantitative assessment of myocardial perfusion and function. (author)

  17. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

    2016-01-01

    in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  18. Single axis controlled hybrid magnetic bearing for left ventricular assist device: hybrid core and closed magnetic circuit.

    Science.gov (United States)

    da Silva, Isaias; Horikawa, Oswaldo; Cardoso, Jose R; Camargo, Fernando A; Andrade, Aron J P; Bock, Eduardo G P

    2011-05-01

    In previous studies, we presented main strategies for suspending the rotor of a mixed-flow type (centrifugal and axial) ventricular assist device (VAD), originally presented by the Institute Dante Pazzanese of Cardiology (IDPC), Brazil. Magnetic suspension is achieved by the use of a magnetic bearing architecture in which the active control is executed in only one degree of freedom, in the axial direction of the rotor. Remaining degrees of freedom, excepting the rotation, are restricted only by the attraction force between pairs of permanent magnets. This study is part of a joint project in development by IDPC and Escola Politecnica of São Paulo University, Brazil. This article shows advances in that project, presenting two promising solutions for magnetic bearings. One solution uses hybrid cores as electromagnetic actuators, that is, cores that combine iron and permanent magnets. The other solution uses actuators, also of hybrid type, but with the magnetic circuit closed by an iron core. After preliminary analysis, a pump prototype has been developed for each solution and has been tested. For each prototype, a brushless DC motor has been developed as the rotor driver. Each solution was evaluated by in vitro experiments and guidelines are extracted for future improvements. Tests have shown good results and demonstrated that one solution is not isolated from the other. One complements the other for the development of a single-axis-controlled, hybrid-type magnetic bearing for a mixed-flow type VAD. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  19. Performance of Thallium-201 Electrocardiography-gated Myocardial Perfusion Single Photon Emission Computed Tomography to Assess Left Ventricular Function

    Directory of Open Access Journals (Sweden)

    Guang-Uei Hung

    2005-05-01

    Full Text Available This study evaluated the performance of gated single photon emission computed tomography (SPECT with thallium-201 (201Tl in assessing left ventricular ejection fraction (LVEF, end-diastolic volume (EDV, and end-systolic volume (ESV in Taiwanese by determining repeatability and correlation with two-dimensional (2D echocardiography. A total of 18 patients underwent two sequential gated SPECT acquisitions within 30 minutes in the resting state to assess repeatability. Another 28 patients who underwent gated SPECT and 2D echocardiography within 7 days were included for comparison. The two sequential measurements were well correlated with respect to LVEF, EDV, and ESV (r = 0.97, 0.95, and 0.97, respectively, all p < 0.0001. Bland-Altman analysis revealed that two standard deviations of the absolute difference between the two sequential measurements for LVEF, EDV, and ESV were 6.4%, 16.8 mL, and 8.6 mL, respectively. For LVEF, EDV, and ESV, correlations between redistribution 201Tl-gated SPECT and echocardiography were also excellent (all r = 0.83, p < 0.0001. LVEF was similar with 201Tl-gated SPECT and echocardiography, but EDV and ESV were significantly higher with echocardiography (p < 0.05. Our study revealed that 201Tl-gated SPECT has high repeatability and excellent correlation with echocardiography for the assessment of LVEF and volumes in Taiwanese. These results support the clinical application of gated SPECT in routine 201Tl myocardial perfusion imaging in Taiwanese.

  20. Assessment of left ventricular function with single breath-hold highly accelerated cine MRI combined with guide-point modeling

    International Nuclear Information System (INIS)

    Heilmaier, Christina; Nassenstein, Kai; Nielles-Vallespin, Sonia; Zuehlsdorff, Sven; Hunold, Peter; Barkhausen, Joerg

    2010-01-01

    Purpose: To prospectively assess the performance of highly accelerated cine MRI in multi-orientations combined with a new guide-point modeling post-processing technique (GPM approach) for assessment of left ventricular (LV) function compared to the standard summation of slices method based on a stack of short axis views (SoS approach). Materials and methods: 33 consecutive patients were examined on a 1.5 T scanner with a standard steady state free precession (SSFP) sequence (TR, 3.0 ms; TE, 1.5 m; flip angle (FA), 60 o ; acceleration factor (AF), 2) analyzed with the SoS method and a highly accelerated, single breath-hold temporal parallel acquisition SSFP sequence (TR, 4.6 ms; TE, 1.1 ms; AF, 3) post-processed with the GPM method. LV function values were measured by two independent readers with different experience in cardiac MRI and compared by using the paired t-test and F-test. Inter- and intraobserver agreements were calculated using Bland-Altman-Plots. Results: Mean acquisition and post-processing time was significantly shorter with the GPM approach (15 s/3 min versus 360 s/6 min). For all LV function parameters interobserver agreement between the experienced and non-experienced reader was significantly improved when the GPM approach was used. However, end-diastolic and end-systolic volumes were larger for the GPM technique when compared to the SoS method (P 0.121). In both readers and for all parameters variances did not differ significantly (P ≥ 0.409) and the two approaches showed an excellent linear correlation (r > 0.951). Conclusion: Due to its accurate, fast and reproducible assessment of LV function parameters highly accelerated MRI combined with the GPM technique may become the technique of first choice for assessment of LV function in clinical routine.

  1. Left ventricular functions in children with newly diagnosed Graves' disease. A single-center study from Upper Egypt.

    Science.gov (United States)

    Metwalley, Kotb Abbass; Farghaly, Hekma Saad; Abdelhamid, Abdelrahman

    2018-01-01

    This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001). Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

  2. What is the clinical significance of ventricular mural antagonism?

    DEFF Research Database (Denmark)

    Lunkenheimer, Paul P; Niederer, Peter; Stephenson, Robert S

    2018-01-01

    alignment, thus deviating from the prevailing tangential orientation. Upon contraction, they produce, in addition to a tangential force, a radial force component that counteracts ventricular constriction and aids widening of the ventricular cavity. In experimental studies, we have provided evidence...... for the existence of such forces, which are auxotonic in nature. This is in contrast to the tangentially aligned myocytes that produce constrictive forces, which are unloading in nature. The ventricular myocardium is, therefore, able to function in an antagonistic fashion, with the prevailing constrictive forces...

  3. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling.

    Science.gov (United States)

    Das, Anindita; Xi, Lei; Kukreja, Rakesh C

    2005-04-01

    We investigated the effect of sildenafil in protection against necrosis or apoptosis in cardiomyocytes. Adult mouse ventricular myocytes were treated with sildenafil (1 or 10 microM) for 1 h before 40 min of simulated ischemia (SI). Necrosis was determined by trypan blue exclusion and lactate dehydrogenase release following SI alone or plus 1 or 18 h of reoxygenation (RO). Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and mitochondrial membrane potential measured using a fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1). Sildenafil reduced necrosis as indicated by decrease in trypan blue-positive myocytes and leakage of lactate dehydrogenase compared with untreated cells after either SI or SI-RO. The number of terminal deoxynucleotidyl transferase-mediated nick end labeling-positive myocytes or loss of JC-1 fluorescence following SI and 18 h of RO was attenuated in the sildenafil-treated group with concomitant inhibition of caspase 3 activity. An early increase in Bcl-2 to Bax ratio with sildenafil treatment was also observed in myocytes after SI-RO. The increase of Bcl-2 expression by sildenafil was inhibited by nitric-oxide synthase (NOS) inhibitor, L-nitro-amino-methyl-ester. The drug also enhanced mRNA and protein content of inducible NOS (iNOS) and endothelial NOS (eNOS) in the myocytes. Sildenafil-induced protection against necrosis and apoptosis was absent in the myocytes derived from iNOS knock-out mice and was attenuated in eNOS knock-out myocytes. The up-regulation of Bcl-2 expression by sildenafil was also absent in iNOS-deficient myocytes. Reverse transcription-PCR, Western blots, and immunohistochemical assay confirmed the expression of phosphodiesterase-5 in mouse cardiomyocytes. These data provide strong evidence for a direct protective effect of sildenafil against necrosis and apoptosis through NO signaling pathway. The results may have possible

  4. Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

    Directory of Open Access Journals (Sweden)

    Daniel Biermann

    Full Text Available The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12. Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3 revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

  5. Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart

    NARCIS (Netherlands)

    F. Piscione; B.E. Jaski; G.J. Wenting (Gert); P.W.J.C. Serruys (Patrick)

    1987-01-01

    textabstractIn 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow

  6. The impact of transcatheter aortic valve implantation on left ventricular performance and wall thickness – single-centre experience

    Science.gov (United States)

    Szymański, Piotr; Dąbrowski, Maciej; Zakrzewski, Dariusz; Michałek, Piotr; Orłowska-Baranowska, Ewa; El-Hassan, Kamal; Chmielak, Zbigniew; Witkowski, Adam; Hryniewiecki, Tomasz

    2015-01-01

    Introduction Transcatheter aortic valve implantation (TAVI) is a treatment alternative for the elderly population with severe symptomatic aortic stenosis (AS) at high risk for surgical aortic valve replacement (SAVR). Aim To assess the impact of TAVI on echocardiographic parameters of left ventricular (LV) performance and wall thickness in patients subjected to the procedure in a single-centre between 2009 and 2013. Material and methods The initial group consisted of 170 consecutive patients with severe AS unsuitable for SAVR. Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 21.73 ±12.42% and mean age was 79.9 ±7.5 years. Results The TAVI was performed in 167 (98.2%) patients. Mean aortic gradient decreased significantly more rapidly after the procedure (from 58.6 ±16.7 mm Hg to 11.9 ±4.9 mm Hg, p < 0.001). The LV ejection fraction (LVEF) significantly increased in both short-term and long-term follow-up (57 ±14% vs. 59 ±13%, p < 0.001 and 56 ±14% vs. 60 ±12%, p < 0.001, respectively). Significant regression of interventricular septum diameter at end-diastole (IVSDD) and end-diastolic posterior wall thickness (EDPWth) was noted in early (15.0 ±2.4 mm vs. 14.5 ±2.3 mm, p < 0.001 and 12.7 ±2.1 mm vs. 12.4 ±1.9 mm, p < 0.028, respectively) and late post-TAVI period (15.1 ±2.5 mm to 14.3 ±2.5 mm, p < 0.001 and 12.8 ±2.0 mm to 12.4 ±1.9 mm, p < 0.007, respectively). Significant paravalvular leak (PL) was noted in 21 (13.1%) patients immediately after TAVI and in 13 (9.6%) patients in follow-up (p < 0.001). Moderate or severe mitral regurgitation (msMR) was seen in 24 (14.9%) patients from the initial group and in 19 (11.8%) patients after TAVI (p < 0.001). Conclusions The TAVI had an immediate beneficial effect on LVEF, LV walls thickness, and the incidence of msMR. The results of the procedure are comparable with those described in other centres. PMID:25848369

  7. Unmasking the mechanism of diffuse left ventricular wall motion abnormality in ischemic cardiomyopathy by resting-redistribution thallium-201 single photon computed tomography

    International Nuclear Information System (INIS)

    Namura, Hiroyuki; Yamabe, Hiroshi; Kakimoto, Tetsuya; Hashimoto, Yasunori; Yasaka, Yoshinori; Yoshida, Hiroaki; Itoh, Kazushi; Yokoyama, Mitsuhiro; Maeda, Kazumi.

    1992-01-01

    The study population comprised patients with ischemic cardiomyopathy (ICM) who had left ventricular wall motion (LVWM) abnormality in 5 or more segments (n=9), those with extensive myocardial infarction (EMI) having LVWM abnormality in 4 or less segments (n=12), and those with dilated left ventricle (DLV) having LVWM abnormality in all 7 segments (n=9). Defect scores (DS), obtained by initial and delayed Tl-201 myocardial single photon emission computed tomography at rest, were visually assessed to compare perfusion patterns in the three patient groups. The group of ICM patients had greater defect segments (DSeg) and % redistribution (Rd) index than the other two groups, although there was no difference in the number of angiographically proven infarct-related coronary vessels between EMI and ICM. In the group of ICM patients, there was inverse correlation not only between left ventricular ejection fraction and the sum of DS but also between left ventricular enddiastolic volume index and both the sum of DSeg and % Rd index. The group of DLV patients had small sum of DSeg and redistribution, compared with the other two groups. Although diffuse LVWM abnormality, as observed in the group of ICM patients, was considered attributable to potential decrease of coronary perfusion shown as defect on SPECT images, it did not always coincide with findings of coronary angiography. Both DSeg and redistribution phenomenon on SPECT images seemed to have the ability to evaluate the severity of ICM, as well as to differentiate ICM, EMI, and DLV. (N.K.)

  8. Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study).

    Science.gov (United States)

    Margossian, Renee; Schwartz, Marcy L; Prakash, Ashwin; Wruck, Lisa; Colan, Steven D; Atz, Andrew M; Bradley, Timothy J; Fogel, Mark A; Hurwitz, Lynne M; Marcus, Edward; Powell, Andrew J; Printz, Beth F; Puchalski, Michael D; Rychik, Jack; Shirali, Girish; Williams, Richard; Yoo, Shi-Joon; Geva, Tal

    2009-08-01

    Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement for qualitative grading of ventricular function by echocardiography was modest for left ventricular (LV) morphology (kappa = 0.42) and weak for right ventricular (RV) morphology (kappa = 0.12). For quantitative assessment, high intraclass correlation coefficients were found for echocardiographic interobserver agreement (LV 0.87 to 0.92, RV 0.82 to 0.85) of systolic and diastolic volumes, respectively. In contrast, intraclass correlation coefficients for LV and RV mass were moderate (LV 0.78, RV 0.72). The corresponding intraclass correlation coefficients by CMR were high (LV 0.96, RV 0.85). Volumes by echocardiography averaged 70% of CMR values. Interobserver reproducibility for the EF was similar for the 2 modalities. Although the absolute mean difference between modalities for the EF was small (<2%), 95% limits of agreement were wide. In conclusion, agreement between observers of qualitative FSV function by echocardiography is modest. Measurements of FSV volume by 2-dimensional echocardiography underestimate CMR measurements, but their reproducibility is high. Echocardiographic and CMR measurements of FSV EF demonstrate similar interobserver reproducibility, whereas measurements of FSV mass and LV diastolic volume are more reproducible by CMR.

  9. Usefulness of lung and right ventricular thallium-201 uptake during single photon emission computed tomography in exercise testing of patients with coronary artery disease

    International Nuclear Information System (INIS)

    Matoh, Fumitaka; Tawarahara, Kei; Mikami, Naoshi

    2005-01-01

    Increased pulmonary or right ventricular 201 Tl uptake during the exercise test has been used as a marker of multivessel coronary artery disease. The most useful method for assessing the severity of coronary artery disease was evaluated among conventional evaluation of single photon emission computed tomography (SPECT), measurement of lung to heart uptake ratio (L/H), and right ventricular to left ventricular uptake ratio (RV/LV) on 201 Tl images during exercise testing. Regions-of-interest (4 x 4 pixels) were placed at the lung and the heart, and L/H was defined as mean lung uptake/mean heart uptake. Correspondingly, regions-of-interest (4 x 4 pixels) were placed at the RV and the LV, and RV/LV was defined as maximum RV uptake/maximum LV uptake. L/H and RV/LV on the initial image were analyzed in 216 patients (angiographically normal coronary arteries: 89, single-vessel disease: 82, multivessel disease: 45). The diagnostic value was evaluated using the receiver operating characteristic curve. All methods showed significantly higher values in patients with multivessel disease than in patients with no coronary artery disease or single-vessel disease. L/H was significantly higher in patients with prior myocardial infarction and RV/LV was significantly higher in patients without infarction. The sensitivity of only conventional SPECT evaluation for multivessel coronary artery disease was low (sensitivity 53%, specificity 94%). However, addition of evaluation of L/H and RV/LV to SPECT improved the sensitivity for multivessel coronary artery disease (sensitivity 93%, specificity 49%). The diagnostic sensitivity for multivessel coronary artery disease was improved by adding L/H and RV/LV to conventional evaluation of exercise 201 Tl SPECT. L/H and RV/LV during exercise 201 Tl imaging may provide additional information regarding the severity of coronary artery disease. (author)

  10. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    Energy Technology Data Exchange (ETDEWEB)

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    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{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} 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{sub K1} 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 {approx}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{sub K1} 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.

  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. Gated 99mTc-MIBI single-photon emission computed tomography for the evaluation of left ventricular ejection fraction. Comparison with three-dimensional echocardiography

    International Nuclear Information System (INIS)

    Lipiec, P.; Wejner-Mik, P.; Krzeminska-Pakula, M.; Kapusta, A.; Kasprzak, J.D.; Kusmierek, J.; Plachcinska, A.; Szuminski, R.

    2008-01-01

    Parameters of left ventricular systolic function directly influence the management of patients with suspected coronary artery disease (CAD). Quantitative gated single-photon emission computed tomography (QGS; Cedars-Sinai Medical Center, Los Angeles, CA, USA) allows the computation of left ventricular ejection fraction (LVEF) from myocardial perfusion imaging studies which are frequently performed on patients with suspected CAD. Three-dimensional (3D) echocardiography is considered to be the echocardiographic ''gold standard'' for the quantification of LVEF. We sought to compare QGS with 3D echocardiography in the evaluation of EF in patients with suspected CAD. Ninety-one consecutive patients with suspected CAD, scheduled for coronary angiography, underwent rest electrocardiographic-gated technetium-99m methoxyisobutylisonitrile SPECT (G-SPECT) with measurement of LVEF by QGS and transthoracic 3D echocardiography with off-line measurement of LVEF (Tomtec 4D LV Analysis 1.1). The diagnosis of CAD was based on coronary angiography, performed on every patient. Nine patients were excluded from the analysis owing to unsuitability for 3D echocardiography (8 patients) or G-SPECT (1 patient). In the remaining group of 82 patients, 71 (87%) had significant CAD, 34 (42%) had a history of myocardial infarction, and 50 (61%) had perfusion defects at rest G-SPECT images. The mean LVEF measured by QGS and 3D echocardiography was 53±13% and 53±10%, respectively. The mean difference in LVEF between 3D echocardiography and QGS was 0.1±6.0% (P=0.87), and the correlation between the values obtained by both methods was high (r=0.88, P< 0.001). The largest discrepancies were observed in patients with small ventricular volumes. In patients undergoing diagnostic work-up for CAD, the measurement of LVEF by QGS algorithm provides high correlation and satisfactory agreement with the results of reference ultrasound method- 3D echocardiography. (author)

  13. Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

    Directory of Open Access Journals (Sweden)

    Kotb Abbass Metwalley

    2013-01-01

    Full Text Available Background: Growth hormone deficiency (GHD in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease. In children, relatively few studies have investigated the effect of GHD and replacement therapy on cardiac performance and metabolic abnormalities that may place them at a higher risk of cardiovascular disease (CVD at an early age. Aim: This study was aimed to assess the left ventricular function, lipid profile, and degree of insulin resistance in Egyptian children with GHD before and after 1 year of GH replacement therapy. Settings and Design: Prospective case-control study, single-center study. Materials and Methods: Thirty children with short stature due to GHD were studied in comparison to 20 healthy age- and sex-matched children. All subjects were subjected to history, clinical examination, auxological assessment, and echocardiography to assess the left ventricular function. Blood samples were collected for measuring IGF-1, lipid profile (Total, LDL, HDL cholesterol, triglyceride, and atherogenic index (AI, fasting blood sugar, and fasting insulin levels. In addition, basal and stimulated GH levels were measured in children with suspected GHD. Statistical Analysis Used: Student′s t-test was used for parametric data, and the Mann-Whitney U-test was used for non-parametric data. Results: Total, LDL cholesterol, triglyceride, AI, and insulin were significantly higher in children with GHD than in healthy controls at baseline. After 12 months of GH replacement therapy, total, LDL cholesterol, triglyceride, AI and insulin were significantly decreased, while homeostatic model assessment for insulin resistance index (HOMA-IR was significantly increased compared to both pre-treatment and control values. At baseline, the left ventricular mass (LVM and left ventricular mass index (LVMi were significantly lower in GHD children than in controls. After 12 months of GH

  14. Comparison of pacing algorithms to avoid unnecessary ventricular pacing in patients with sick sinus node syndrome: a single-centre, observational, parallel study.

    Science.gov (United States)

    Poghosyan, Hermine R; Jamalyan, Smbat V

    2012-10-01

    Reduction of unnecessary ventricular pacing (uVP) is an essential component in the treatment strategy in any pacing population in general. The aim of this study was to evaluate the efficacy of different algorithms to reduce uVP in an adult population with sick sinus syndrome (SSS) treated outside of clinical trials. Evaluation of the relationship between different types of pacing algorithms and clinical outcomes is also provided. This was a single-centre, observational, parallel study, based on retrospective analysis of the Arrhythmology Cardiology Center of Armenia electronic clinical database. This study evaluated atrial pacing percentage (AP%), ventricular pacing percentage (VP%), and the incidence of atrial high rate episodes in 56 patients with SSS using three different pacing strategies: managed VP, search atrioventricular (AV), and fixed long AV. We did not find statistically significant differences in the amount of VP between the groups. Although the atrial high rate percentage (AHR%) tended to be higher in the fixed long AV group, this difference was not statistically significant. Mean VP% and AP% were similar in all three groups. In our study, all three programmed strategies produced the same mean AP% and VP%, and were equally efficient in uVP reduction. There was no relationship between chosen algorithms and the incidence of pacemaker syndrome, hospitalizations, or change in New York Heart Association class. The percentage of AHR was not associated with pacing strategy or co-morbidities but showed borderline correlation with left atrial size.

  15. [Acute stent thrombosis and reverse transient left ventricular dilatation after performing a single-photon emission computed tomography myocardial perfusion].

    Science.gov (United States)

    Miranda, B; Pizzi, M N; Aguadé-Bruix, S; Domingo, E; Candell-Riera, J

    2015-01-01

    A 63-year-old male patient with a history of stent implantation in the left anterior descending three months before. Due to the presentation of vegetative symptoms, he was referred for gated-SPECT myocardial perfusion. During acquisition of the resting images he presented chest pain and ST segment elevation, so that urgent cardiac catheterization was performed, showing stent thrombosis. Rest perfusion imaging showed a defect in anterior and apical perfusion, more severe and extensive than in the stress images, with striking left ventricular dilatation and a fall in the ejection fraction related to the acute ischemia phenomenon. Intense exercise is associated with a transient activation of the coagulation system and hemodynamic changes that might induce thrombosis, especially in recently implanted coronary stents that probably still have not become completely endothelialized. Copyright © 2014 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  16. Signaling Pathways in Cardiac Myocyte Apoptosis

    Science.gov (United States)

    Xia, Peng; Liu, Yuening

    2016-01-01

    Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515

  17. 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

    2015-07-05

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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.

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

    International Nuclear Information System (INIS)

    Morton, M.J.; Armstrong, D.; Abi Gerges, N.; Bridgland-Taylor, M.; Pollard, C.E.; Bowes, J.; Valentin, J.-P.

    2014-01-01

    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

  20. PGC-1α accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

    International Nuclear Information System (INIS)

    Chen, Min; Wang, Yanru; Qu, Aijuan

    2010-01-01

    Energy metabolism and Ca 2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) 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-1α in cardiac Ca 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-1α via adenoviral transduction. Our data shows that overexpressing PGC-1α improved myocyte contractility without increasing the amplitude of Ca 2+ transients, suggesting that myofilament sensitivity to Ca 2+ increased. Interestingly, the decay kinetics of global Ca 2+ transients and Ca 2+ waves accelerated in PGC-1α-expressing cells, but the decay rate of caffeine-elicited Ca 2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2a), but not Na + /Ca 2+ exchange (NCX) contribute to PGC-1α-induced cytosolic Ca 2+ clearance. Furthermore, PGC-1α induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1α did not disturb cardiac Ca 2+ homeostasis, because SR Ca 2+ load and the propensity for Ca 2+ waves remained unchanged. These data suggest that PGC-1α can ameliorate cardiac Ca 2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1α-calcium handing pathway sheds new light on the role of PGC-1α in the therapy of cardiac diseases.

  1. Evaluation of left ventricular function and volume in patients with dilated cardiomyopathy: Gated myocardial single-photon emission tomography (SPECT) versus echocardiography

    International Nuclear Information System (INIS)

    Berk, Fatma; Isgoren, S.; Demir, H.; Kozdag, G.; Ural, D.; Komsuoglu, B.

    2005-01-01

    Left ventricular function, volumes and regional wall motion provide valuable diagnostic information and are of long-term prognostic importance in patients with dilated cardiomyopathy (DCM). This study was designed to compare the effectiveness of 2D-echocardiography and gated single-photon emission tomography (SPECT) for evaluation of these parameters in patients with DCM. Gated SPECT and 2D-echocardiography were performed in 33 patients having DCM. Gated SPECT data, including left ventricular ejection fraction (LVEF), were processed using an automated algorithm. Standard technique was used for 2D-echocardiography. Regional wall motion was evaluated using both modalities and was scored by two independent observers using a 16-sement model with a 5-point scoring system. The overall agreement between the two imaging modalities for the assessment of regional wall motion was 56% (298/528 segments). With gated SPECT, LEVF, end-diastolic volume (EDV), and end-diastolic volume (EDV), and end-systolic volume (ESV) were 27+-9%, 217+-73mL, respectively, and 30.8%, 195+-58mL and, 137+-48 mL with echocardiography. The correlation between gated SPECT and 2-D-echocardiography was good (r=0.76, P<0.01) for the assessment of LVEF. The correlation for EDV and ESV were also good, but with wider limits of agreement (r=0.72, P<0.01 and r=0.73, P<0.01, respectively) and significantly higher values were obtained with gated SPECT (P<0.01). Gated SPECT and 2D-echocardiography correlate well for the assessment of LV function and LV volumes. Like 2D-echocardiography, gated SPECT provides reliable information about LV function and dimension with the additional advantage of perfusion data. (author)

  2. Single-center experience of the bridge-to-bridge strategy using the Nipro paracorporeal ventricular assist device.

    Science.gov (United States)

    Yoshitake, Shuichi; Kinoshita, Osamu; Nawata, Kan; Hoshino, Yasuhiro; Itoda, Yoshifumi; Kimura, Mitsutoshi; Yamauchi, Haruo; Ono, Minoru

    2018-06-25

    Currently, we use the Nipro paracorporeal VAD (p-VAD) for initial short-term ventricular support, as a bridge to decision (BTD) or a bridge to candidacy (BTC) treatment, in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 and 2 patients. However, it is possible that compared to patients with primary implantable-VADs (P-iVAD), the bridge-to-bridge (BTB) patients are more likely to develop complications. This retrospective study used data from 24 consecutive BTB patients who were initially implanted with Nipro p-VAD as BTD or BTC treatments between April 2011 and March 2016, and subsequently underwent conversion to an i-VAD. The data from 72 patients who underwent a primary i-VAD (P-iVAD) procedure were used for comparison. Between the two groups, there was no significant difference in the incidence of infectious events (p = 0.72) or stroke (p = 0.44). Orthotropic heart transplantation was performed in 6 of the 24 patients in the BTB group and in 21 of the 72 patients in the P-iVAD group. The 1- and 2-year survival rates were 95.8% and 95.8% in the BTB group and 91% and 85.8% in the P-iVAD group; these values were not significantly different between groups (p = 0.91). Based on these results we conclude that BTB using Nipro p-VAD is a reasonable strategy for treating patients with severe decompensated end-stage heart failure.

  3. Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

    Science.gov (United States)

    Yataco, Maria L; Difato, Thomas; Bargehr, Johannes; Rosser, Barry G; Patel, Tushar; Trejo-Gutierrez, Jorge F; Pungpapong, Surakit; Taner, C Burcin; Aranda-Michel, Jaime

    2014-07-01

    Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition. A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012. Patients who developed NIC were identified. Data collected included demographic and clinical data. A total 1460 transplants were performed in this period and seventeen patients developed NIC. Pretransplant median QTc interval was 459 (range, 405-530), and median E/A ratio was 1 (range, 0.71-1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post-transplant (range, 0-20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50-81) pretransplant to a median of 21% (range, 15-32). Median raw model for end-stage liver disease (MELD) score was 29 in patients with NIC vs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients with NIC vs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a median EF of 44% (range, 25-65%) at the time of discharge. The last echocardiogram available showed a median EF of 59% (range, 49-73%). One-year survival of NIC patients was 94.1%. Non-ischaemic cardiomyopathy is a rare complication after LT. Patients with NIC are critically ill, with high MELD score, and severe malnutrition. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Is anti-platelet therapy needed in continuous flow left ventricular assist device patients? A single-centre experience.

    Science.gov (United States)

    Litzler, Pierre-Yves; Smail, Hassiba; Barbay, Virginie; Nafeh-Bizet, Catherine; Bouchart, François; Baste, Jean-Marc; Abriou, Caroline; Bessou, Jean-Paul

    2014-01-01

    We report our 5-year experience of continuous flow left ventricular assist device (LVAD) implantation without the use of anti-platelet therapy. Between February 2006 and September 2011, 27 patients (26 men; 1 woman) were implanted with a continuous flow LVAD (HeartMate II, Thoratec Corporation, Pleasanton, CA, USA). The mean age was 55.7 ± 9.9 years. The mean duration of support was 479 ± 436 (1-1555) days with 35.4 patient-years on support. Twenty-one patients were implanted as a bridge to transplantation and 6 for destination therapy. The anticoagulation regimen was fluindione for all patients, with aspirin for only 4 patients. At the beginning of our experience, aspirin was administered to 4 patients for 6, 15, 60 and 460 days. Due to gastrointestinal (GI) bleeding and epistaxis, aspirin was discontinued, and since August 2006, no patients have received anti-platelet therapy. At 3 years, the survival rate during support was 76%. The most common postoperative adverse event was GI bleeding (19%) and epistaxis (30%) (median time: 26 days) for patients receiving fluindione and aspirin. The mean International Normalized Ratio (INR) was 2.58 ± 0.74 during support. Fifteen patients have been tested for acquired Von Willebrand disease. A diminished ratio of collagen-binding capacity and ristocetin cofactor activity to Von Willebrand factor antigen was observed in 7 patients. In the postoperative period, 2 patients presented with ischaemic stroke at 1 and 8 months. One of these 2 patients had a previous history of carotid stenosis with ischaemic stroke. There were no patients with haemorrhagic stroke, transient ischaemic attack or pump thrombosis. The event rate of stroke (ischaemic and haemorrhagic) per patient-year was 0.059 among the patients without aspirin with fluindione regimen only. A fluindione regimen without aspirin in long-duration LVAD support appears to not increase thromboembolic events and could lead to a diminished risk of haemorrhagic stroke.

  5. Reciprocal Modulation of IK1-INa Extends Excitability in Cardiac Ventricular Cells.

    Science.gov (United States)

    Varghese, Anthony

    2016-01-01

    The inwardly rectifying potassium current (I K1 ) and the fast inward sodium current (I Na ) are reciprocally modulated in mammalian ventricular myocytes. An increase in the expression of channels responsible for one of these two currents results in a corresponding increase in expression of the other. These currents are critical in the propagation of action potentials (AP) during the normal functioning of the heart. This study identifies a physiological role for I K1 -I Na reciprocal modulation in ventricular fiber activation thresholds and conduction. Simulations of action potentials in single cells and propagating APs in cardiac fibers were carried out using an existing model of electrical activity in cardiac ventricular myocytes. The conductances, G K1 , of the inwardly rectifying potassium current, and G Na , of the fast inward sodium current were modified independently and in tandem to simulate reciprocal modulation. In single cells, independent modulation of G K1 alone resulted in changes in activation thresholds that were qualitatively similar to those for reciprocal G K1 -G Na modulation and unlike those due to independent modulation of G Na alone, indicating that G K1 determines the cellular activation threshold. On the other hand, the variations in conduction velocity in cardiac cell fibers were similar for independent G Na modulation and for tandem changes in G K1 -G Na , suggesting that G Na is primarily responsible for setting tissue AP conduction velocity. Conduction velocity dependence on G K1 -G Na is significantly affected by the intercellular gap junction conductance. While the effects on the passive fiber space constant due to changes in both G K1 and the intercellular gap junction conductance, G gj , were in line with linear cable theory predictions, both conductances had surprisingly large effects on fiber activation thresholds. Independent modulation of G K1 rendered cardiac fibers inexcitable at higher levels of G K1 whereas tandem G K1 -G Na

  6. Formulation and in vitro interaction of rhodamine-B loaded PLGA nanoparticles with cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Antranik Jonderian

    2016-12-01

    Full Text Available This study aims to characterize rhodamine B (Rh B loaded poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized nanoparticles were about 184 nm, 0.19, 40% and -21.7 mV respectively. In vitro release showed that 29% of the Rh B was released within the first 8 hours. Scanning electron microscopy (SEM measurements performed on the optimized nanoparticles showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on fetal cardiac myocytes after 24 and 48 hours of exposure with concentrations up to 200 µg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the first hours. Interestingly, our data show an increase in the nanoparticles’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

  7. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

    Science.gov (United States)

    Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

    2012-01-01

    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 Signaling 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 sinoatrial (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 1–1000 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. PMID:22754533

  8. Modeling the Effects of β1-Adrenergic Receptor Blockers and Polymorphisms on Cardiac Myocyte Ca2+ Handling

    Science.gov (United States)

    Amanfu, Robert K.

    2014-01-01

    β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on cardiac physiology. While some studies indicate that β-blockers are efficacious by inhibiting β-adrenergic signaling, other studies suggest that they work by maintaining β-adrenergic responsiveness. Here, we use a systems pharmacology approach to test the hypothesis that in ventricular myocytes, these two apparently conflicting mechanisms for β-blocker efficacy can occur concurrently. We extended a computational model of the β1-adrenergic pathway and excitation-contraction coupling to include detailed receptor interactions for 19 ligands. Model predictions, validated with Ca2+ and Förster resonance energy transfer imaging of adult rat ventricular myocytes, surprisingly suggest that β-blockers can both inhibit and maintain signaling depending on the magnitude of receptor stimulation. The balance of inhibition and maintenance of β1-adrenergic signaling is predicted to depend on the specific β-blocker (with greater responsiveness for metoprolol than carvedilol) and β1-adrenergic receptor Arg389Gly polymorphisms. PMID:24867460

  9. Persistence of neoangiogenesis and cardiomyocyte divisions in right ventricular myocardium of rats born and raised in hypoxic conditions.

    NARCIS (Netherlands)

    Moravec, M.; Turek, Z.I.; Moravec, J.

    2002-01-01

    Effects of chronic hypoxia on capillary and myocyte growth were examined in rats born and raised in a low pressure chamber (equivalent of 3500 m a.s.l.). The animals were sacrificed at the age of 3 months and their hearts were used to study right ventricular growth and vascularization. The results

  10. Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated 99mTc-MIBI single-photon emission computed tomography study

    International Nuclear Information System (INIS)

    Lipiec, Piotr; Krzeminska-Pakula, Maria; Plewka, Michal; Kasprzak, Jaroslaw D.; Kusmierek, Jacek; Plachcinska, Anna; Szuminski, Remigiusz; Robak, Tadeusz; Korycka, Anna

    2009-01-01

    We investigated the impact of intracoronary injection of autologous mononuclear bone marrow cells (BMC) in patients with acute ST elevation myocardial infarction (STEMI) on left ventricular volumes, global and regional systolic function and myocardial perfusion. The study included 39 patients with first anterior STEMI treated successfully with primary percutaneous coronary intervention. They were randomly assigned to the treatment group or the control group in a 2:1 ratio. The patients underwent baseline gated single-photon emission computed tomography (G-SPECT) 3-10 days after STEMI with quantitative and qualitative analysis of left ventricular perfusion and systolic function. On the following day, patients from the BMC treatment group were subjected to bone marrow aspiration, mononuclear BMC isolation and intracoronary injection. No placebo procedure was performed in the control group. G-SPECT was repeated 6 months after STEMI. Baseline and follow-up G-SPECT studies were available for 36 patients. At 6 months in the BMC group we observed a significantly enhanced improvement in the mean extent of the perfusion defect, the left ventricular perfusion score index, the infarct area perfusion score and the infarct area wall motion score index compared to the control group (p=0.01-0.04). However, the changes in left ventricular volume, ejection fraction and the left ventricular wall motion score index as well as the relative changes in the infarct area wall motion score index did not differ significantly between the groups. Intracoronary injection of autologous mononuclear BMC in patients with STEMI improves myocardial perfusion at 6 months. The benefit in infarct area systolic function is less pronounced and there is no apparent improvement of global left ventricular systolic function. (orig.)

  11. Effect of timing and duration of a single chest compression pause on short-term survival following prolonged ventricular fibrillation.

    Science.gov (United States)

    Walcott, Gregory P; Melnick, Sharon B; Walker, Robert G; Banville, Isabelle; Chapman, Fred W; Killingsworth, Cheryl R; Ideker, Raymond E

    2009-04-01

    Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome. Part A: 48 swine were anesthetized, fibrillated for 7min and randomized. Chest compressions were initiated for 90s followed by defibrillation and then resumption of chest compressions. Four groups were studied-G2000: 40s pause beginning 20s before, and ending 20s after defibrillation, A1: a 20s pause just before defibrillation, A2: a 20s pause ending 30s prior to defibrillation, and group A3: a 10s pause ending 30s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4h. The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p<0.05). Survival did not differ significantly among groups A1, A2, A3, and B. These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit.

  12. Effect of timing and duration of a single chest compression pause on short-term survival following prolonged ventricular fibrillation☆

    Science.gov (United States)

    Walcott, Gregory P.; Melnick, Sharon B.; Walker, Robert G.; Banville, Isabelle; Chapman, Fred W.; Killingsworth, Cheryl R.; Ideker, Raymond E.

    2014-01-01

    Background Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome. Methods Part A: 48 swine were anesthetized, fibrillated for 7 min and randomized. Chest compressions were initiated for 90 s followed by defibrillation and then resumption of chest compressions. Four groups were studied—G2000: 40 s pause beginning 20 s before, and ending 20 s after defibrillation, A1: a 20 s pause just before defibrillation, A2: a 20 s pause ending 30 s prior to defibrillation, and group A3: a 10 s pause ending 30 s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4 h. Results The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p < 0.05). Survival did not differ significantly among groups A1, A2, A3, and B. Conclusions These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit. PMID:19185411

  13. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Christian E. Zaugg

    2004-04-01

    Full Text Available Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

  14. Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-alpha.

    Science.gov (United States)

    Petkova-Kirova, Polina S; Gursoy, Erdal; Mehdi, Haider; McTiernan, Charles F; London, Barry; Salama, Guy

    2006-05-01

    Mice that overexpress the inflammatory cytokine tumor necrosis factor-alpha in the heart (TNF mice) develop heart failure characterized by atrial and ventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias, and increased mortality (males > females). Abnormalities in Ca2+ handling, prolonged action potential duration (APD), calcium alternans, and reentrant atrial and ventricular arrhythmias were previously observed with the use of optical mapping of perfused hearts from TNF mice. We therefore tested whether altered voltage-gated outward K+ and/or inward Ca2+ currents contribute to the altered action potential characteristics and the increased vulnerability to arrhythmias. Whole cell voltage-clamp recordings of K+ currents from left ventricular myocytes of TNF mice revealed an approximately 50% decrease in the rapidly activating, rapidly inactivating transient outward K+ current Ito and in the rapidly activating, slowly inactivating delayed rectifier current IK,slow1, an approximately 25% decrease in the rapidly activating, slowly inactivating delayed rectifier current IK,slow2, and no significant change in the steady-state current Iss compared with controls. Peak amplitudes and inactivation kinetics of the L-type Ca2+ current ICa,L were not altered. Western blot analyses revealed a reduction in the proteins underlying Kv4.2, Kv4.3, and Kv1.5. Thus decreased K+ channel expression is largely responsible for the prolonged APD in the TNF mice and may, along with abnormalities in Ca2+ handling, contribute to arrhythmias.

  15. Left ventricular torsion assessed by two-dimensional echocardiography speckle tracking as a predictor of left ventricular remodeling and short-term outcome following primary percutaneous coronary intervention for acute myocardial infarction: A single-center experience.

    Science.gov (United States)

    Awadalla, Hany; Saleh, Mohamed Ayman; Abdel Kader, Mohamed; Mansour, Amr

    2017-08-01

    Left ventricular (LV) torsion is a novel method to assess systolic LV function. This study aimed at exploring the utility of 2D speckle tracking-based assessment of left ventricular torsion in patients with acute myocardial infarction (AMI) undertaking primary percutaneous intervention (pPCI) in predicting left ventricular remodeling. The study included 115 patients (mean±SD, age 52.2±9.67, males 84.3%) who underwent pPCI for AMI. Echocardiographic assessment of LV torsion by two-dimensional speckle tracking was performed early after the index pPCI. Patients underwent repeat echocardiography at 6 months to detect remodeling. LV torsion in the acute setting was significantly lower in those who demonstrated LV remodeling at follow-up compared to those without remodeling (7.56±1.95 vs 15.16±4.65; P<.005). Multivariate analysis identified peak CK & CK-MB elevation (β=-0.767 and -0.725; P<.001), SWMA index (β=-0.843; P<.001), and Simpson's derived LV ejection fraction (LVEF; β=0.802; P<.001) as independent predictors of baseline LV torsion. It also identified peak LV torsion (β: 0.27; 95% CI: 0.15-0.5, P=.001) and SWMA index (β: 1.07, 95% CI: 1.03-1.12, P=.005) as independent predictors of LV remodeling. Baseline Killip's grades II and higher (β: 48.6; 95% CI 5.5-428, P<.001) and diabetes mellitus (β: 29.7; 95% CI 1.1-763, P<.05) were independent predictors of mortality. Left ventricular torsion in acute MI setting is impaired and predicts subsequent LV remodeling at 6-month follow-up. © 2017, Wiley Periodicals, Inc.

  16. 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.

  17. Jamb and jamc are essential for vertebrate myocyte fusion.

    Directory of Open Access Journals (Sweden)

    Gareth T Powell

    2011-12-01

    Full Text Available Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans for fusion to occur. We also show that jamc is ectopically expressed in prdm1a mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of jamc expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis.

  18. Reverse redistribution phenomenon on rest 99mTc-tetrofosmin myocardial single photon emission computed tomography involves impaired left ventricular contraction in patients with acute myocardial infarction

    International Nuclear Information System (INIS)

    Kurokawa, Kazuyuki; Ohte, Nobuyuki; Miyabe, Hiromichi; Akita, Sachie; Yajima, Kazuhiro; Hayano, Junichiro; Kimura, Genjiro

    2003-01-01

    The purpose of this study was to investigate the clinical significance of the reverse redistribution (RR) phenomenon on technetium-99m ( 99m Tc)-tetrofosmin myocardial single photon emission computed tomography (SPECT) performed at rest. Twenty-five patients underwent myocardial SPECT 3 weeks after the onset of acute myocardial infarction. Myocardial images were acquired at 40 min (early) and 4 h (delayed) after the injection of 740 MBq of 99m Tc-tetrofosmin. The regional myocardial uptake of the tracer in 26 segments of the left ventricular (LV) wall was visually scored from 0 (no activity) to 3 (normal activity), and then the RR was defined as a decrease of more than 1 point in the activity score on the delayed image compared with that on the early image. Regions with an activity score of 3 on both the early and delayed images were defined as normal, and those with a score of 0 or 1 on the early image were considered to have a fixed defect. The regional myocardial 99m Tc-tetrofosmin uptake and washout rate were also quantitatively assessed in each region. In addition, exercise stress electrocardiograph-gated SPECT with 99m Tc-tetrofosmin was performed within 1 week of the rest study, and the percent count increase (%CI) during myocardial contraction in each corresponding region was studied. RR was observed in 18 of the 25 patients. The regional washout rate of 99m Tc-tetrofosmin was significantly higher in the RR regions (45.0±3.8%) than in either the normal regions (36.4±4.1%, p 99m Tc-tetrofosmin SPECT have severely impaired LV wall contraction after exercise. (author)

  19. Factors affecting accuracy of ventricular volume and ejection fraction measured by gated Tl-201 myocardial perfusion single photon emission computed tomography

    International Nuclear Information System (INIS)

    Pai, Moon Sun; Yang, You Jung; Im, Ki Chun; Hong, Il Ki; Yun, Sung Cheol; Kang, Duk Hyun; Song, Jae Kwan; Moon, Dae Hyuk

    2005-01-01

    Systemic errors in the gated single photon emission computed tomography (SPECT) measurement of left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) may occur. We evaluated whether patient-related factors affected the accuracy of EDV, ESV, and EF measured by electrocardiogram-gated Tl-201 SPECT. A total of 518 patients without perfusion defects on Tl-201 SPECT or coronary artery disease were studied. EDV, ESV, and EF were measured from echocardiography and adenosine stress/redistribution gated Tl-201 SPECT using commercially available software packages (QGS and 4D-MSPECT). We identified factors affecting the accuracy of gated SPECT via multiple linear regression analysis of the differences between echocardiography and gated SPECT. Gated SPECT analyzed with QGS underestimated EDV and ESV, and overestimated EF, but 4D-MSPECT overestimated all those values (p<0.001). Independent variables that increased the difference in EDV between echocardiography and gated SPECT were decreasing LV end-diastolic wall thickness, decreasing body surface area, female sex and increasing EDV (p< 0.001). Those for ESV were decreasing LV end-systolic wall thickness, female sex, and decreasing ESV (p<0.001). Increasing end-systolic wall thickness, male sex and decreasing age were independent determinants associated with an increased difference in EF (p< 0.001). Adenosine stress SPECT showed significantly higher EDV and ESV values and a lower EF than did redistribution SPECT (p< 0.001). In determination of EF, QGS demonstrated a smaller bias than did 4D-MSPECT. However, in men with LV hypertrophy, 4D-MSPECT was superior to QGS. Systemic error by gated Tl-201 SPECT is determined by individual patient-characteristics

  20. Evaluation of left ventricular function and volumes in patients with ischaemic cardiomyopathy: gated single-photon emission computed tomography versus two-dimensional echocardiography

    International Nuclear Information System (INIS)

    Vourvouri, E.C.; Poldermans, D.; Sianos, G.; Sozzi, F.B.; Schinkel, A.F.L.; Sutter, J. de; Roelandt, J.R.T.C.; Bax, J.J.; Parcharidis, G.; Valkema, R.

    2001-01-01

    The objective of this study was to perform a head-to-head comparison between two-dimensional (2D) echocardiography and gated single-photon emission computed tomography (SPET) for the evaluation of left ventricular (LV) function and volumes in patients with severe ischaemic LV dysfunction. Thirty-two patients with chronic ischaemic LV dysfunction [mean LV ejection fraction (EF) 25%±6%] were studied with gated SPET and 2D echocardiography. Regional wall motion was evaluated by both modalities and scored by two independent observers using a 16-segment model with a 5-point scoring system (1= normokinesia, 2= mild hypokinesia, 3= severe hypokinesia, 4= akinesia and 5= dyskinesia). LVEF and LV end-diastolic and end-systolic volumes were evaluated by 2D echocardiography using the Simpson's biplane discs method. The same parameters were calculated using quantitative gated SPET software (QGS, Cedars-Sinai Medical Center). The overall agreement between the two imaging modalities for assessment of regional wall motion was 69%. The correlations between gated SPET and 2D echocardiography for the assessment of end-diastolic and end-systolic volumes were excellent (r=0.94, P<0.01, and r=0.96, P<0.01, respectively). The correlation for LVEF was also good (r=0.83, P<0.01). In conclusion: in patients with ischaemic cardiomyopathy, close and significant relations between gated SPET and 2D echocardiography were observed for the assessment of regional and global LV function and LV volumes; gated SPET has the advantage that it provides information on both LV function/dimensions and perfusion. (orig.)

  1. False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Bartram, P.; Hanel, B.; Gustafsson, F.; Mortensen, J.; Hesse, B.; Toft, J.; Ali, S.

    1998-01-01

    Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had ''significant'' (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH. (orig.)

  2. A mathematical model for active contraction in healthy and failing myocytes and left ventricles.

    Directory of Open Access Journals (Sweden)

    Li Cai

    Full Text Available Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV. The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model. We first studied the electro-mechanics coupling in a single myocyte in the healthy and diseased left ventricle, and then the single cell model was embedded in a dynamic LV model to investigate the compensation mechanism of LV pump function due to myocardial dysfunction caused by abnormality in cellular calcium dynamics. The multi-scale LV model was solved using an in-house developed hybrid immersed boundary method with finite element extension. The predictions of the healthy LV model agreed well with the clinical measurements and other studies, and likewise, the results in the failing states were also consistent with clinical observations. In particular, we found that a low level of intracellular Ca2+ transient in myocytes can result in LV pump function failure even with increased myocardial contractility, decreased systolic blood pressure, and increased diastolic filling pressure, even though they will increase LV stroke volume. Our work suggested that treatments targeted at increased contractility and lowering the systolic blood pressure alone are not sufficient in preventing LV pump dysfunction, restoring a balanced physiological Ca2+ handling mechanism is necessary.

  3. Control of cytoplasmic and nuclear protein kinase A by phosphodiesterases and phosphatases in cardiac myocytes

    Science.gov (United States)

    Haj Slimane, Zeineb; Bedioune, Ibrahim; Lechêne, Patrick; Varin, Audrey; Lefebvre, Florence; Mateo, Philippe; Domergue-Dupont, Valérie; Dewenter, Matthias; Richter, Wito; Conti, Marco; El-Armouche, Ali; Zhang, Jin; Fischmeister, Rodolphe; Vandecasteele, Grégoire

    2014-01-01

    Aims The cAMP-dependent protein kinase (PKA) mediates β-adrenoceptor (β-AR) regulation of cardiac contraction and gene expression. Whereas PKA activity is well characterized in various subcellular compartments of adult cardiomyocytes, its regulation in the nucleus remains largely unknown. The aim of the present study was to compare the modalities of PKA regulation in the cytoplasm and nucleus of cardiomyocytes. Methods and results Cytoplasmic and nuclear cAMP and PKA activity were measured with targeted fluorescence resonance energy transfer probes in adult rat ventricular myocytes. β-AR stimulation with isoprenaline (Iso) led to fast cAMP elevation in both compartments, whereas PKA activity was fast in the cytoplasm but markedly slower in the nucleus. Iso was also more potent and efficient in activating cytoplasmic than nuclear PKA. Similar slow kinetics of nuclear PKA activation was observed upon adenylyl cyclase activation with L-858051 or phosphodiesterase (PDE) inhibition with 3-isobutyl-1-methylxantine. Consistently, pulse stimulation with Iso (15 s) maximally induced PKA and myosin-binding protein C phosphorylation in the cytoplasm, but marginally activated PKA and cAMP response element-binding protein phosphorylation in the nucleus. Inhibition of PDE4 or ablation of the Pde4d gene in mice prolonged cytoplasmic PKA activation and enhanced nuclear PKA responses. In the cytoplasm, phosphatase 1 (PP1) and 2A (PP2A) contributed to the termination of PKA responses, whereas only PP1 played a role in the nucleus. Conclusion Our study reveals a differential integration of cytoplasmic and nuclear PKA responses to β-AR stimulation in cardiac myocytes. This may have important implications in the physiological and pathological hypertrophic response to β-AR stimulation. PMID:24550350

  4. Capillary/myocyte mismatch in the heart in renal failure--a role for erythropoietin?

    Science.gov (United States)

    Amann, K; Buzello, M; Simonaviciene, A; Miltenberger-Miltenyi, G; Koch, A; Nabokov, A; Gross, M L; Gless, B; Mall, G; Ritz, E

    2000-07-01

    Chronic renal failure is characterized by remodeling of the heart with left ventricular hypertrophy (increasing oxygen demand) and capillary deficit leading to capillary/myocyte mismatch (decreasing oxygen supply). Erythropoietin (Epo) has known angiogenic properties causing endothelial cell activation, migration and sprouting, mediated at least in part via the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway. In uraemic cardiac hypertrophy the presence of diminished capillary supply implies that capillary growth does not keep pace with development of hypertrophy. To investigate whether this was due to a deficit of the angiogenic hormone Epo we examined whether Epo levels are altered and whether an increase in haematocrit by administration of rhEpo influences capillary supply, i.e. capillary/myocyte mismatch in experimental renal failure. Male Spraque-Dawley rats were either subjected to partial renal ablation or sham operation. Only modest amounts of renal tissue were removed so that the rats were not anemic. Subgroups of rats received either human (rh)Epo alone or in combination with unspecific antihypertensive treatment (dihydralazine plus furosemide) in order to control the Epo induced rise in blood pressure. Capillary supply was measured stereologically as capillary length per volume myocardium using the orientator method. Capillary length density was reduced by approximately 25% after partial renal ablation (3237+/-601 vs 4293+/-501 mm/mm(3) in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620+/-828 mm/mm(3)) compared to partial ablation alone. The study shows that lack of Epo does not cause, or contribute to, the deficit of capillary growth in the hypertrophied left ventricle of rats with renal failure. In addition, a rise in haematocrit is not accompanied by beneficial effects on alterations of cardiovascular structure in experimental renal failure.

  5. Dynamic Changes of QRS Morphology of Premature Ventricular Contractions During Ablation in the Right Ventricular Outflow Tract: A Case Report.

    Science.gov (United States)

    Yue-Chun, Li; Jia-Feng, Lin; Jia-Xuan, Lin

    2015-10-01

    Electrocardiographic characteristics can be useful in differentiating between right ventricular outflow tract (RVOT) and aortic sinus cusp (ASC) ventricular arrhythmias. Ventricular arrhythmias originating from ASC, however, show preferential conduction to RVOT that may render the algorithms of electrocardiographic characteristics less reliable. Even though there are few reports describing ventricular arrhythmias with ASC origins and endocardial breakout sites of RVOT, progressive dynamic changes in QRS morphology of the ventricular arrhythmias during ablation obtained were rare.This case report describes a patient with symptomatic premature ventricular contractions of left ASC origin presenting an electrocardiogram (ECG) characteristic of right ventricular outflow tract before ablation. Pacing at right ventricular outflow tract reproduced an excellent pace map. When radiofrequency catheter ablation was applied to the right ventricular outflow tract, the QRS morphology of premature ventricular contractions progressively changed from ECG characteristics of right ventricular outflow tract origin to ECG characteristics of left ASC origin.Successful radiofrequency catheter ablation was achieved at the site of the earliest ventricular activation in the left ASC. The distance between the successful ablation site of the left ASC and the site with an excellent pace map of the RVOT was 20 mm.The ndings could be strong evidence for a preferential conduction via the myocardial bers from the ASC origin to the breakout site in the right ventricular outflow tract. This case demonstrates that ventricular arrhythmias with a single origin and exit shift may exhibit QRS morphology changes.

  6. Arrhythmogenic right ventricular dysplasia: MRI findings

    International Nuclear Information System (INIS)

    Wall, E.E. van der; Bootsma, M.M.; Schalij, M.J.; Kayser, H.W.M.; Roos, A. de

    2000-01-01

    Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disorder of unknown cause that is characterized pathologically by fibrofatty replacement of the right ventricular myocardium. Clinical manifestations include structural and functional malformations of the right ventricle, electrocardiographic abnormalities, and presentation with ventricular tachycardias with left bundle branch pattern or sudden death. The disease is often familial with an autosomal inheritance. In addition to right ventricular dilatation, right ventricular aneurysms are typical deformities of ARVD and they are distributed in the so-called ''triangle of dysplasia'', i. e., right ventricular outflow tract, apex, and infundibulum. Ventricular aneurysms at these sites can be considered pathognomonic of ARVD. Another typical hallmark of ARVD is fibrofatty infiltration of the right ventricular free wall. These functional and morphologic characteristics are relevant to clinical imaging investigations such as contrast angiography, echocardiography, radionuclide angiography, ultrafast computed tomography, and magnetic resonance imaging (MRI). Among these techniques, MRI allows the clearest visualization of the heart, in particular because the right ventricle is involved, which is usually more difficult to explore with the other imaging modalities. Furthermore, MRI offers the specific advantage of visualizing adipose infiltration as a bright signal of the right ventricular myocardium. MRI provides the most important anatomic, functional, and morphologic criteria for diagnosis of ARVD within one single study. As a result, MRI appears to be the optimal imaging technique for detecting and following patients with clinical suspicion of ARVD. (orig.) [de

  7. 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.

  8. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

    Science.gov (United States)

    Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

    2017-10-24

    Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

  9. Phos-tag-based analysis of myosin regulatory light chain phosphorylation in human uterine myocytes.

    Directory of Open Access Journals (Sweden)

    Hector N Aguilar

    Full Text Available The 'phosphate-binding tag' (phos-tag reagent enables separation of phospho-proteins during SDS-PAGE by impeding migration proportional to their phosphorylation stoichiometry. Western blotting can then be used to detect and quantify the bands corresponding to the phospho-states of a target protein. We present a method for quantification of data regarding phospho-states derived from phos-tag SDS-PAGE. The method incorporates corrections for lane-to-lane loading variability and for the effects of drug vehicles thus enabling the comparison of multiple treatments by using the untreated cellular set-point as a reference. This method is exemplified by quantifying the phosphorylation of myosin regulatory light chain (RLC in cultured human uterine myocytes.We have evaluated and validated the concept that, when using an antibody (Ab against the total-protein, the sum of all phosphorylation states in a single lane represents a 'closed system' since all possible phospho-states and phosphoisotypes are detected. Using this approach, we demonstrate that oxytocin (OT and calpeptin (Calp induce RLC kinase (MLCK- and rho-kinase (ROK-dependent enhancements in phosphorylation of RLC at T18 and S19. Treatment of myocytes with a phorbol ester (PMA induced phosphorylation of S1-RLC, which caused a mobility shift in the phos-tag matrices distinct from phosphorylation at S19.We have presented a method for analysis of phospho-state data that facilitates quantitative comparison to a reference control without the use of a traditional 'loading' or 'reference' standard. This analysis is useful for assessing effects of putative agonists and antagonists where all phospho-states are represented in control and experimental samples. We also demonstrated that phosphorylation of RLC at S1 is inducible in intact uterine myocytes, though the signal in the resting samples was not sufficiently abundant to allow quantification by the approach used here.

  10. Short-term assessment of left ventricular function, coronary hemodynamics, and catecholamine balance in severe congestive heart failure after a single oral dose of milrinone

    NARCIS (Netherlands)

    F. Piscione; B.E. Jaski; P.W.J.C. Serruys (Patrick)

    1988-01-01

    textabstractSystemic and coronary hemodynamics were measured before and every 10 min after oral milrinone (10 mg) administration for 50 min, together with the drug plasma level in 14 patients with congestive heart failure. Left ventricular pressure (tip manometry), volume (angiography), and derived

  11. Excito-oscillatory dynamics as a mechanism of ventricular fibrillation.

    Science.gov (United States)

    Gray, Richard A; Huelsing, Delilah J

    2008-04-01

    The instabilities associated with reentrant spiral waves are of paramount importance to the initiation and maintenance of tachyarrhythmias, especially ventricular fibrillation (VF). In addition to tissue heterogeneities, there are only a few basic purported mechanisms of spiral wave breakup, most notably restitution. We test the hypothesis that oscillatory membrane properties act to destabilize spiral waves. We recorded transmembrane potential (V(m)) from isolated rabbit myocytes using a constant current stimulation protocol. We developed a mathematical model that included both the stable excitable equilibrium point at resting V(m) (-80 mV) and the unstable oscillatory equilibrium point at elevated V(m) (-10 mV). Spiral wave dynamics were studied in 2-dimensional grids using variants of the model. All models showed restitution and reproduced the experimental values of transmembrane resistance at rest and during the action potential plateau. Stable spiral waves were observed when the model showed only 1 equilibrium point. However, spatio-temporal complexity was observed if the model showed both excitable and oscillatory equilibrium points (i.e., excito-oscillatory models). The initial wave breaks resulted from oscillatory waves expanding in all directions; after a few beats, the patterns were characterized by a combination of unstable spiral waves and target patterns consistent with the patterns observed on the heart surface during VF. In our model, this VF-like activity only occurred when the single cell period of V(m) oscillations was within a specific range. The VF-like patterns observed in our excito-oscillatory models could not be explained by the existing proposed instability mechanisms. Our results introduce the important suggestion that membrane dynamics responsible for V(m) oscillations at elevated V(m) levels can destabilize spiral waves and thus may be a novel therapeutic target for preventing VF.

  12. Hypoxic-induced stress protein expression in rat cardiac myocytes

    International Nuclear Information System (INIS)

    Howard, G.; Geoghegan, T.E.

    1986-01-01

    Mammalian stress proteins can be induced in cells and tissues exposed to a variety of conditions including hyperthermia and diminished O 2 supply. The authors have previously shown that the expression of three stress proteins (71, 85, and 95 kDa) was induced in cardiac tissue from mice exposed to hypoxic conditions. The expression of mRNAs coding for the 85 and 95 kDa proteins increase with time of exposure to hypoxia, while the mRNA coding for the 71 kDa protein is transiently induced. The authors extended these studies to investigate the expression of stress proteins in isolated rat cardiac myocytes. Freshly prepared myocytes were exposed to control, hypoxic, anoxic, or heat-shock environments for up to 16 h. The proteins were then labeled for 6 hours with [ 35 S]methionine. Analysis of the solubilized proteins by SDS-PAGE and autoradiography showed that there was a 6-fold increase in synthesis of the 85 kDa protein upon exposure to hypoxia but not heat-shock conditions. The 71 kDa protein was present at high levels in both control and treated myocyte protein preparations, and presumably had been induced during the isolation procedure. Total RNA isolated from intact rat heart and isolated myocytes was compared by cell-free translation analysis and showed induction of RNAs coding for several stress proteins in the myocyte preparation. The induced proteins at 85 and 95 kDa have molecular weights similar to reported cell stress and/or glucose-regulated proteins

  13. 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 LM sections using design-based stereology. MATERIALS AND METHODS: From formalin-fixed left rat ventricles (LV) isotropic uniformly random sections were cut. The total number of myocyte nuclei per LV was estimated using the optical disector. Two-microm-thick serial paraffin sections were stained......BACKGROUND: Counting the total number of cardiac myocytes has not previously been possible in ordinary histological sections using light microscopy (LM) due to difficulties in defining the myocyte borders properly. AIM: To describe a method by which the total number of cardiac myocytes is estimated...... with antibodies against cadherin and type IV collagen to visualise the intercalated discs and the myocyte membranes, respectively. Using the physical disector in "local vertical windows" of the serial sections, the average number of nuclei per myocyte was estimated.RESULTS: The total number of myocyte nuclei...

  14. Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle

    Czech Academy of Sciences Publication Activity Database

    Dealmeida, A.; McQuinn, T. C.; Sedmera, David

    2007-01-01

    Roč. 100, - (2007), s. 1363-1370 ISSN 0009-7330 Institutional research plan: CEZ:AV0Z50450515 Keywords : chick embryo * hemodynamics * fetal surgery * hypoplastic left heart syndrome Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery Impact factor: 9.721, year: 2007

  15. Polygons and adhesion plaques and the disassembly and assembly of myofibrils in cardiac myocytes.

    Science.gov (United States)

    Lin, Z X; Holtzer, S; Schultheiss, T; Murray, J; Masaki, T; Fischman, D A; Holtzer, H

    1989-06-01

    Successive stages in the disassembly of myofibrils and the subsequent assembly of new myofibrils have been studied in cultures of dissociated chick cardiac myocytes. The myofibrils in trypsinized and dispersed myocytes are sequentially disassembled during the first 3 d of culture. They split longitudinally and then assemble into transitory polygons. Multiples of single sarcomeres, the cardiac polygons, are analogous to the transitory polygonal configurations assumed by stress fibers in spreading fibroblasts. They differ from their counterparts in fibroblasts in that they consist of muscle alpha-actinin vertices and muscle myosin heavy chain struts, rather than of the nonmuscle contractile protein isoforms of stress fiber polygons. EM sections reveal the vertices and struts in cardiac polygons to be typical Z and A bands. Most cardiac polygons are eliminated by day 5 of culture. Concurrent with the disassembly and elimination of the original myofibrils new myofibrils are rapidly assembled elsewhere in the same myocyte. Without exception both distal tips of each nascent myofibril terminate in adhesion plaques. The morphology and composition of the adhesion plaques capping each end of each myofibril are similar to those of the termini of stress fibers in fibroblasts. However, whereas the adhesion complexes involving stress fibers in fibroblasts consist of vinculin/nonmuscle alpha-actinin/beta- and gamma-actins, the analogous structures in myocytes involving myofibrils consist of vinculin/muscle alpha-actinin/alpha-actin. The addition of 1.7-2.0 microns sarcomeres to the distal tips of an elongating myofibril, irrespective of whether the myofibril consists of 1, 10, or several hundred tandem sarcomeres, occurs while the myofibril appears to remain linked to its respective adhesion plaques. The adhesion plaques in vitro are the equivalent of the in vivo intercalated discs, both in terms of their molecular composition and with respect to their functioning as initiating

  16. [The reasonable use of right ventricular protection strategy in right ventricular outflow tract reconstruction].

    Science.gov (United States)

    Zhang, Y; Yuan, H Y; Liu, X B; Wen, S S; Xu, G; Cui, H J; Zhuang, J; Chen, J M

    2018-06-01

    As a result of right ventricular outflow tract reconstruction, which is the important and basic step of complex cardiac surgery, the blood flow of right ventricular outflow tract is unobstructed, while pulmonary valve regurgitation and right heart dysfunction could be happened. These problems are often ignored in early days, more and more cases of right heart dysfunction need clinical intervention, which is quite difficult and less effective. How to protect effectively the right ventricular function is the focus. At present main methods to protect the right ventricular function include trying to avoid or reduce length of right ventricular incision, reserving or rebuilding the function of the pulmonary valve, using growth potential material for surgery. The protection of the right ventricular function is a systemic project, it involves many aspects, single measures is difficult to provide complete protection, only the comprehensive use of various protection strategy, can help to improve the long-term prognosis.

  17. Extraction of the 3D local orientation of myocytes in human cardiac tissue using X-ray phase-contrast micro-tomography and multi-scale analysis.

    Science.gov (United States)

    Varray, François; Mirea, Iulia; Langer, Max; Peyrin, Françoise; Fanton, Laurent; Magnin, Isabelle E

    2017-05-01

    This paper presents a methodology to access the 3D local myocyte arrangements in fresh human post-mortem heart samples. We investigated the cardiac micro-structure at a high and isotropic resolution of 3.5 µm in three dimensions using X-ray phase micro-tomography at the European Synchrotron Radiation Facility. We then processed the reconstructed volumes to extract the 3D local orientation of the myocytes using a multi-scale approach with no segmentation. We created a simplified 3D model of tissue sample made of simulated myocytes with known size and orientations, to evaluate our orientation extraction method. Afterwards, we applied it to 2D histological cuts and to eight 3D left ventricular (LV) cardiac tissue samples. Then, the variation of the helix angles, from the endocardium to the epicardium, was computed at several spatial resolutions ranging from 3.6 3  mm 3 to 112 3  µm 3 . We measure an increased range of 20° to 30° from the coarsest resolution level to the finest level in the experimental samples. This result is in line with the higher values measured from histology. The displayed tractography demonstrates a rather smooth evolution of the transmural helix angle in six LV samples and a sudden discontinuity of the helix angle in two septum samples. These measurements bring a new vision of the human heart architecture from macro- to micro-scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Compressed sensing real-time cine cardiovascular magnetic resonance: accurate assessment of left ventricular function in a single-breath-hold.

    Science.gov (United States)

    Kido, Tomoyuki; Kido, Teruhito; Nakamura, Masashi; Watanabe, Kouki; Schmidt, Michaela; Forman, Christoph; Mochizuki, Teruhito

    2016-08-24

    Cardiovascular cine magnetic resonance (CMR) accelerated by compressed sensing (CS) is used to assess left ventricular (LV) function. However, it is difficult for prospective CS cine CMR to capture the complete end-diastolic phase, which can lead to underestimation of the end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF), compared to retrospective standard cine CMR. This prospective study aimed to evaluate the diagnostic quality and accuracy of single-breath-hold full cardiac cycle CS cine CMR, acquired over two heart beats, to quantify LV volume in comparison to multi-breath-hold standard cine CMR. Eighty-one participants underwent standard segmented breath-hold cine and CS real-time cine CMR examinations to obtain a stack of eight contiguous short-axis images with same high spatial (1.7 × 1.7 mm(2)) and temporal resolution (41 ms). Two radiologists independently performed qualitative analysis of image quality (score, 1 [i.e., "nondiagnostic"] to 5 [i.e., "excellent"]) and quantitative analysis of the LV volume measurements. The total examination time was 113 ± 7 s for standard cine CMR and 24 ± 4 s for CS cine CMR (p cine image quality was slightly lower than standard cine (4.8 ± 0.5 for standard vs. 4.4 ± 0.5 for CS; p cine were above 4 (i.e., good). No significant differences existed between standard and CS cine MR for all quantitative LV measurements. The mean differences with 95 % confidence interval (CI), based on Bland-Altman analysis, were 1.3 mL (95 % CI, -14.6 - 17.2) for LV end-diastolic volume, 0.2 mL (95 % CI, -9.8 to10.3) for LV end-systolic volume, 1.1 mL (95 % CI, -10.5 to 12.7) for LV stroke volume, 1.0 g (95 % CI, -11.2 to 13.3) for LV mass, and 0.4 % (95 % CI, -4.8 - 5.6) for LV ejection fraction. The interobserver and intraobserver variability for CS cine MR ranged from -4.8 - 1.6 % and from -7.3 - 9.3 %, respectively, with slopes of the regressions ranging 0.88-1.0 and 0

  19. Mechanisms of IhERG/IKr Modulation by α1-Adrenoceptors in HEK293 Cells and Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Janire Urrutia

    2016-12-01

    Full Text Available Background: The rapid delayed rectifier K+ current (IKr, carried by the hERG protein, is one of the main repolarising currents in the human heart and a reduction of this current increases the risk of ventricular fibrillation. α1-adrenoceptors (α1-AR activation reduces IKr but, despite the clear relationship between an increase in the sympathetic tone and arrhythmias, the mechanisms underlying the α1-AR regulation of the hERG channel are controversial. Thus, we aimed to investigate the mechanisms by which α1-AR stimulation regulates IKr. Methods: α1-adrenoceptors, hERG channels, auxiliary subunits minK and MIRP1, the non PIP2-interacting mutant D-hERG (with a deletion of the 883-894 amino acids in the C-terminal and the non PKC-phosphorylable mutant N-terminal truncated-hERG (NTK-hERG were transfected in HEK293 cells. Cell membranes were extracted by centrifugation and the different proteins were visualized by Western blot. Potassium currents were recorded by the patch-clamp technique. IKr was recorded in isolated feline cardiac myocytes. Results: Activation of the α1-AR reduces the amplitude of IhERG and IKr through a positive shift in the activation half voltage, which reduces the channel availability at physiological membrane potentials. The intracellular pathway connecting the α1-AR to the hERG channel in HEK293 cells includes activation of the Gαq protein, PLC activation and PIP2 hydrolysis, activation of PKC and direct phosphorylation of the hERG channel N-terminal. The PKC-mediated IKr channel phosphorylation and subsequent IKr reduction after α1-AR stimulation was corroborated in feline cardiac myocytes. Conclusions: These findings clarify the link between sympathetic nervous system hyperactivity and IKr reduction, one of the best characterized causes of torsades de pointes and ventricular fibrillation.

  20. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction

    Science.gov (United States)

    Beaumont, Eric; Southerland, Elizabeth M.; Hardwick, Jean C.; Wright, Gary L.; Ryan, Shannon; Li, Ying; KenKnight, Bruce H.; Armour, J. Andrew

    2015-01-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

  1. Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    SANDOR GYÖRKE

    2004-01-01

    Full Text Available Calsequestrin (CASQ2 is a high capacity Ca-binding protein expressed inside the sarcoplasmic reticulum (SR. Mutations in the cardiac calsequestrin gene (CASQ2 have been linked to arrhythmias and sudden death induced by exercise and emotional stress. We have studied the function of CASQ2 and the consequences of arrhythmogenic CASQ2 mutations on intracellular Ca signalling using a combination of approaches of reverse genetics and cellular physiology in adult cardiac myocytes. We have found that CASQ2 is an essential determinant of the ability of the SR to store and release Ca2+ in cardiac muscle. CASQ2 serves as a reservoir for Ca2+ that is readily accessible for Ca2+-induced Ca2+ release (CICR and also as an active Ca2+ buffer that modulates the local luminal Ca-dependent closure of the SR Ca2+ release channels. At the same time, CASQ2 stabilizes the CICR process by slowing the functional recharging of SR Ca2+ stores. Abnormal restitution of the Ca2+ release channels from a luminal Ca-dependent refractory state could account for ventricular arrhythmias associated with mutations in the CASQ2 gene.

  2. Slow conduction in mixed cultured strands of primary ventricular cells and stem cell-derived cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Jan Pavel Kucera

    2015-09-01

    Full Text Available Modern concepts for the treatment of myocardial diseases focus on novel cell therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs. However, functional integration of SCMs requires similar electrophysiological properties as primary cardiomyocytes (PCMs and the ability to establish intercellular connections with host myocytes in order to contribute to the electrical and mechanical activity of the heart. The aim of this project was to investigate the properties of cardiac conduction in a co-culture approach using SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with fetal ventricular cells and seeded in predefined proportions on microelectrode arrays to form patterned strands of mixed cells. Conduction velocity (CV was measured during steady state pacing. SCM excitability was estimated from action potentials measured in single cells using the patch clamp technique. Experiments were complemented with computer simulations of conduction using a detailed model of cellular architecture in mixed cell strands.CV was significantly lower in strands composed purely of SCMs (5.5±1.5 cm/s, n=11 as compared to PCMs (34.9±2.9 cm/s, n=21 at similar refractoriness (100% SCMs: 122±25 ms, n=9; 100% PCMs: 139±67 ms, n=14. In mixed strands combining both cell types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM strands. Computer simulations demonstrated that both intercellular coupling and electrical excitability limit CV.These data provide evidence that in cultures of murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels resulting in slow conduction, which may lead to reentry circuits and arrhythmias.

  3. Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

    Science.gov (United States)

    Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

    2009-07-15

    The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

  4. Skeletal Myocyte Types and Vascularity in the Black Sicilian Pig

    OpenAIRE

    S. Velotto; E. Varricchio; M. R. Di Prisco; T. Stasi; A. Crasto

    2007-01-01

    The objective of this study was to verify the presence of giant fibres in the Black Sicilian pig skeletal muscle and to evaluate the effect of sex on histochemical and morphometric characteristics of the myocytes (myofibres) as well as vascularity of the muscle. Twenty Black Sicilian pigs (10 males, 10 females) from a farm in Sicily (Italy) were slaughtered at two years of age. Muscle tissues were obtained from three muscles: psoas major, longissimus dorsi, and trapezius. Myofibres were stain...

  5. Detection of impaired fatty acid metabolism in right ventricular hypertrophy. Assessment by I-123 {beta}-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong-ih; Goto, Hideki; Kobayashi, Katsuhiro; Sawada, Yoshihiro; Miyake, Yoshitaka; Fujiwara, Go [Nishiyodo Hospital, Osaka (Japan); Chiba, Hiroshi; Okada, Tomoya; Nishimura, Tsunehiko

    1997-08-01

    The subjects consisted of 6 patients with chronic obstructive pulmonary disease, 4 with primary pulmonary hypertension, 2 each with refractory pulmonary tuberculosis, tricuspid insufficiency, pulmonary embolism, 1 each with atrial septal defect, ventricular septal defect (Eisenmenger complex), Ebstein anomaly, and endocardial defect, and 7 healthy controls. SPECT imaging with Tl-201 (Tl) and I-123 BMIPP, and Tc-99m RBC first pass and gated blood pool scintigraphy were performed. Based on Tl planar images, the subjects were classified into 3 groups: 7 patients with no RV visualization (Group A), 11 with moderate RV visualization (Group B) and 9 with marked RV visualization (Group C). As a semi-quantitative evaluation by a myocardial SPECT, 3 regions in 3 representative short axial images were divided into 9 segments, each of which was graded from 0 to +3, and their sum was calculated as the RV score. The right ventricular ejection fraction (RVEF) and the left ventricular ejection fraction were obtained by Tc-99m RBC cardiac scintigraphy. The groups with marked visualization of the right ventricle had lower RVEF, and there was a good correlation between the RVEF and the RV score with both a and BMIPP. Although a good correlation was demonstrated between the RV score with Tl and BMIPP in Groups A and B, in Group C, in which there was marked RV Tl visualization, the RV score with BMIPP was significantly smaller than with Tl. These findings suggest that impaired fatty acid metabolism may exist in severely hypertrophic right ventricle due to RV overload. (K.H.)

  6. Detection of impaired fatty acid metabolism in right ventricular hypertrophy. Assessment by I-123 β-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography

    International Nuclear Information System (INIS)

    Kim, Yong-ih; Goto, Hideki; Kobayashi, Katsuhiro; Sawada, Yoshihiro; Miyake, Yoshitaka; Fujiwara, Go; Chiba, Hiroshi; Okada, Tomoya; Nishimura, Tsunehiko.

    1997-01-01

    The subjects consisted of 6 patients with chronic obstructive pulmonary disease, 4 with primary pulmonary hypertension, 2 each with refractory pulmonary tuberculosis, tricuspid insufficiency, pulmonary embolism, 1 each with atrial septal defect, ventricular septal defect (Eisenmenger complex), Ebstein anomaly, and endocardial defect, and 7 healthy controls. SPECT imaging with Tl-201 (Tl) and I-123 BMIPP, and Tc-99m RBC first pass and gated blood pool scintigraphy were performed. Based on Tl planar images, the subjects were classified into 3 groups: 7 patients with no RV visualization (Group A), 11 with moderate RV visualization (Group B) and 9 with marked RV visualization (Group C). As a semi-quantitative evaluation by a myocardial SPECT, 3 regions in 3 representative short axial images were divided into 9 segments, each of which was graded from 0 to +3, and their sum was calculated as the RV score. The right ventricular ejection fraction (RVEF and the left ventricular ejection fraction were obtained by Tc-99m RBC cardiac scintigraphy. The groups with marked visualization of the right ventricle had lower RVEF, and there was a good correlation between the RVEF and the RV score with both a and BMIPP. Although a good correlation was demonstrated between the RV score with Tl and BMIPP in Groups A and B, in Group C, in which there was marked RV Tl visualization, the RV score with BMIPP was significantly smaller than with Tl. These findings suggest that impaired fatty acid metabolism may exist in severely hypertrophic right ventricle due to RV overload. (K.H.)

  7. Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

    Directory of Open Access Journals (Sweden)

    Shankarjee Krishnamoorthi

    Full Text Available 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 transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

  8. Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

    Science.gov (United States)

    Krishnamoorthi, Shankarjee; Perotti, Luigi E; Borgstrom, Nils P; Ajijola, Olujimi A; Frid, Anna; Ponnaluri, Aditya V; Weiss, James N; Qu, Zhilin; Klug, William S; Ennis, Daniel B; Garfinkel, Alan

    2014-01-01

    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 transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

  9. Pre- and post-operative risk factors associated with cerebrovascular accidents in patients supported by left ventricular assist device. -Single center's experience in japan-.

    Science.gov (United States)

    Nakajima, Ikutaro; Kato, Tomoko S; Komamura, Kazuo; Takahashi, Ayako; Oda, Noboru; Sasaoka, Taro; Asakura, Masanori; Hashimura, Kazuhiko; Kitakaze, Masafumi

    2011-01-01

    Cerebrovascular accident (CVA) is a major adverse event following left ventricular assist device (LVAD) surgery. This study investigates pre- and post-operative factors associated with CVA in this population. A total of 118 consecutive patients who underwent LVAD surgery at our institution between April 1994 and April 2009 were retrospectively reviewed. Clinical characteristics, hemodynamic data, and laboratory indexes associated with CVA after LVAD surgery were analyzed. In total, 57 (48.3%) patients developed CVA 133.5 ± 184.7 days after surgery. The combination of baseline heart disease, type of LVAD surgery, mean right atrial pressure (mRA), serum total bilirubin and total protein concentration, and right ventricular end-diastolic dimension (RVEDd) was associated with CVA at any time after LVAD surgery, with a discriminant probability of 718%. With regard to CVA development later than 3 months after surgery, the combination of mRA and RVEDd before surgery [odds ratio (OR), 1.24, 1.20; 95% confidential interval (CI), 1.07-1.42, 1.06-1.34; P = 0.004, P = 0.006, respectively], positive blood culture, and C-reactive protein after surgery (OR, 7.66, 2.19; 95%CI, 1.50-39.0, 1.47-3.25; P = 0.015, P < 0.0001, respectively) was associated with CVA with a discriminant probability of 85.9%. Patients' general condition including malnutrition, in addition to device selection, contributed to overall CVA development after surgery. In the chronic phase after surgery, pre-LVAD right heart failure and post-LVAD systemic infection were highly associated with CVA development.

  10. Effect of dual-chamber minimal ventricular pacing on paroxysmal atrial fibrillation incidence in myotonic dystrophy type 1 patients: A prospective, randomized, single-blind, crossover study.

    Science.gov (United States)

    Russo, Vincenzo; Papa, Andrea Antonio; Rago, Anna; Ciardiello, Carmine; Nigro, Gerardo

    2018-03-08

    Atrial fibrillation (AF) is a common finding in the myotonic dystrophy type 1 (DM1) population. Pacemakers (PMs) may facilitate the diagnosis and management of frequent subclinical asymptomatic AF episodes. The purpose of this study was to evaluate the effect of minimal ventricular pacing on paroxysmal AF incidence in DM1 patients during a 24-month follow-up period. We enrolled 70 DM1 patients (age 43.4 ± 13.8 years; 39 women) who underwent dual-chamber PM implantation. Patients were randomized to minimizing ventricular pacing features (ON) or not (OFF). Patients crossed over to the opposite pacing programming 12 months later. We counted the number of DM1 patients with at least 1 episode of AF, the AF total duration, and the burden recorded by PM diagnostics during the MVP ON and OFF phases. Twenty-five DM1 patients (41.7%) showed at least 1 AF episode. Seven patients (11.7%) demonstrated AF episodes during MVP ON phase and 25 patients (41.7%) during MVP OFF phase (P MVP ON or OFF phase, 3 patients had AF episodes only during MVP ON phase, 21 patients had AF episodes only during MVP OFF phase, and 4 patients had AF episodes during MVP ON and OFF phases. Activation of the MVP algorithm was associated with a 44% reduction in relative risk of developing AF. Furthermore, during the MVP ON phases, the study population showed a shorter total AF duration and a lower AF burden. MVP is an efficacy strategy for reducing the risk of AF in DM1 patients who have undergone PM implantation. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. SMOOTH MYOCYTES AND COLLAGENOUS FIBERS OF THE URINARY BLADDER OF RATS IN DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Nadiya Tokaruk

    2015-12-01

    Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine   Key words: diabetes mellitus; smooth myocytes; collagenous fibers.   Introduction. Diabetes mellitus (DM causes diabetic cystopathy, which is associated with detrusor dysfunction and the content of collagenous fibers. The results of the performed studies are ambiguous and often contradictory, requiring objective data which could be obtained on the basis of the simultaneous determination of relative areas of smooth myocytes and collagenous fibers and their ultrastructural study. Objective: To determine the peculiarities of the structural and metric organization of smooth myocytes and collagenous fibers of the urinary bladder (UB of rats during different stages of DM. Materials and methods. DM was modeled by streptozotocin in Wistar rats. Relative areas of the studied structures were defined on digital images of histological sections of UB stained by Mason using the original automatic way. Smooth myocytes were studied ultrastructurally. Results. During the 14th-28th day of DM development the percent of collagenous fibers area decreases and the percentage of smooth myocytes area of UB wall increases. The expanding of intercellular spaces and the development of vacuolar degeneration of myocytes are observed. During the 42nd-56th days the percentage of collagenous fibers area increases and the percentage of the area of smooth myocytes decreases. Ultrastructurally subsiding of vacuolar dystrophy, short-term baloon dystrophy, the appearance of dark myocytes, moderate karyorrhexis were observed. During the 70th day of the experiment the percentage of collagenous fibers and smooth myocytes areas does not change significantly, most dark myocytes are involutive, there are local fibrosis and myocyte sequestration areas. Conclusions. Ultrastructural changes are characterized by a pronounced polymorphism and have a chronological relationship. Author’s worked out original method of determination of the

  12. Lone ventricular cardiomyopathy,

    African Journals Online (AJOL)

    ... (I) cardiac catheterisation, including coronary arteriography and pulmonary ... described existence of lone ventricular idiopathic ... spectrum of classic idiopathic dilated cardiomyopathy. ... endomyocardial fibrosis, and from discussions at an.

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

    Science.gov (United States)

    Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

    2014-01-01

    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 that CaMKII is

  14. Prophylactic catheter ablation of ventricular tachycardia before cardioverter-defibrillator implantation in patients with non-ischemic cardiomyopathy: Clinical outcomes after a single endocardial ablation

    Directory of Open Access Journals (Sweden)

    Atsushi Suzuki, MD

    2015-06-01

    Conclusion: Single endocardial PCA can decrease ES occurrence in NICM patients. However, high rates of VT recurrence and low success rates are issues to be resolved; therefore, the efficacy of single endocardial PCA is currently limited.

  15. New and emerging biomarkers in left ventricular systolic dysfunction--insight into dilated cardiomyopathy.

    Science.gov (United States)

    Gopal, Deepa M; Sam, Flora

    2013-08-01

    Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance, impaired contraction and dilation of the left ventricle (or both ventricles). Blood markers--known as "biomarkers"--allow insight into underlying pathophysiologic mechanisms and biologic pathways while predicting outcomes and guiding heart failure management and/or therapies. In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment, integrating these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones, and (h) renal biomarkers. Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure.

  16. New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction - Insight into Dilated Cardiomyopathy

    Science.gov (United States)

    Gopal, Deepa M.; Sam, Flora

    2013-01-01

    Background Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance and impaired contraction and dilation of the left (or both) ventricles. Blood markers – known as “biomarkers” allow insight into underlying pathophysiologic mechanisms and biologic pathways, while predicting outcomes and guiding heart failure management and/or therapies. Content In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment with clear interaction between these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones and (h) renal biomarkers. Summary Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure. PMID:23609585

  17. Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes

    International Nuclear Information System (INIS)

    Hallaq, H.; Leaf, A.; Sellmayer, A.; Smith, T.W.

    1990-01-01

    Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3 endash 5 days in culture medium enriched with 5 μM arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3 endash 5 days with 5 μM eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable 86 Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 ± 29 and 757 ± 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3 endash 5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes

  18. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  19. Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

    Directory of Open Access Journals (Sweden)

    Kraemer Rachel

    2009-05-01

    Full Text Available Abstract Background We conducted a genome-wide association study (GWAS and validation study for left ventricular (LV mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101 and controls (N = 101 were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (Q Results Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (P ≤ 0.05 associated with LV mass after correction for multiple testing. One SNP (rs756529 is intragenic within KCNB1, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population. Conclusion These findings suggest KCNB1 may be involved in the development of LV hypertrophy in humans.

  20. Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

    Science.gov (United States)

    Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

    2016-01-01

    Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

  1. Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content

    Science.gov (United States)

    Vaughan, Roger A.; Gannon, Nicholas P.; Carriker, Colin R.

    2015-01-01

    Beetroot (甜菜 tián cài) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription–polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits. PMID:26870674

  2. Amphiphile-induced heart muscle-cell (myocyte) injury: effects of intracellular fatty acid overload.

    Science.gov (United States)

    Janero, D R; Burghardt, C; Feldman, D

    1988-10-01

    Lipid amphiphile toxicity may be an important contributor to myocardial injury, especially during ischemia/reperfusion. In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)-induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5-(tetradecyloxy)-2-furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high-energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile-induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA "wash-out." Although the development and severity of amphiphile-induced myocyte injury could be correlated with both the intracellular TOFA/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid beta oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile-induced bioenergetic abnormalities appeared to constitute a state of "metabolic anoxia" underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.

  3. Reversible left ventricular dysfunction - important clinical problem of contemporary cardiology

    International Nuclear Information System (INIS)

    Witkowski, A.

    1994-01-01

    An important clinical issue there is determination whether left ventricular damages are reversible or not single photon emission computed tomography and positron computed tomography techniques are shown to provide valuable data in this problem. Article describes basic syndromes connected with left ventricular dysfunction, namely: hibernating myocardium, stunned myocardium and ischemic myocardium preconditioning. (author). 18 refs

  4. Evaluation of left ventricular volumes measured by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Møgelvang, J; Thomsen, C; Mehlsen, J

    1986-01-01

    Left ventricular end-diastolic and end-systolic volumes were determined in 17 patients with different levels of left ventricular function by magnetic resonance imaging (MRI). A 1.5 Tesla Magnet was used obtaining ECG triggered single and multiple slices. Calculated cardiac outputs were compared...

  5. Thallium-201 right lung/heart ratio during exercise in patients with coronary artery disease: relation to thallium-201 myocardial single-photon emission tomography, rest and exercise left ventricular function and coronary angiography

    International Nuclear Information System (INIS)

    Morel, O.; Pezard, P.; Le Jeune, J.J.; Denizot, B.; Jallet, P.; Furber, A.; Vielle, B.

    1999-01-01

    The aim of this study was to correlate lung thallium-201 uptake on exercise with 201 Tl single-photon emission tomography (SPET) myocardial perfusion imaging, rest and exercise equilibrium radionuclide angiographic and coronary angiographic findings in patients with coronary artery disease (CAD) using a simple, reproducible lung/heart (L/H) ratio that would be easy to use in clinical practice. L/H ratio was defined on the anterior planar image obtained during exercise 201 Tl SPET acquisition as the mean counts per pixel in an entire right lung field region of interest divided by the mean counts per pixel in the hottest myocardial wall region of interest. We studied 103 patients. Fifty-nine patients (group I) with 201 Tl SPET, radionuclide angiographic and coronary angiographic variables. The group I L/H ratio of 0.35±0.05 (mean ±1 SD) was significantly lower (P 0.45 (mean+2 SD in group I) was considered abnormal. In group II, L/H ratio showed a significant correlation with stress and rest 201 Tl perfusion defect size (r=0.39 and r=0.42, P<0.01, respectively), but not with extent of ischaemic myocardium. The mean L/H ratio was 0.41±0.10 in patients with one-vessel disease (n=15), 0.46±0.08 in those with two-vessel disease (n=17) and 0.47±0.12 in those with three-vessel disease (n=12), but no significant difference was found between the three subgroups. L/H ratio showed a significant inverse relation with rest and exercise left ventricular ejection fraction (r=-0.37 and r=-0.50, P<0.05 and P<0.001, respectively). Using stepwise multiple regression analysis, exercise left ventricular ejection fraction and previous history of hypertension were the sole two variables independently predictive of the L/H ratio. In conclusion, although lung thallium uptake is usually found to correlate with extent and severity of CAD, increased L/H ratio should primarily be considered as a marker of exercise-induced left ventricular systolic and perhaps diastolic dysfunction, probably

  6. Prediction of left ventricular functional recovery in patients with acute myocardial infarction using single photon emission computed tomography with thallium-201 and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid

    International Nuclear Information System (INIS)

    Hashimoto, Akiyoshi; Nakata, Tomoaki; Nagao, Kazuhiko

    1995-01-01

    The relationships between myocardial perfusion, fatty acid metabolism, and cardiac function were investigated using dual single photon emission computed tomography (SPECT) with thallium and iodine-123-β-methyl-p-iodophenyl-pentadecanoic acid ( 123 I-BMIPP) during the acute ( 10±1 days) and recovery (60±14 days) phases in 29 patients with acute myocardial infarction. There were 18 patients who underwent successful primary coronary angioplasty (PTCA group) and 11 patients who received conservative therapy (non PTCA group). Thallium and BMIPP uptakes were scored visually by a 4-point system and left ventricular ejection fraction (LVEF) was calculated by radionuclide ventriculography. Although significant positive correlations between thallium and 123 I-BMIPP scores were observed during both phases, BMIPP scores were significantly lower than thallium scores in both acute and recovery phases in the PTCA group. No significant difference in thallium and 123 I-BMIPP scores was observed at the recovery phase in the non PTCA group. LVEF significantly correlated with thallium and 123 I-BMIPP scores in both phases in the PTCA group. Furthermore, the difference between thallium and 123 I-BMIPP scores during the acute phase significantly correlated with the improvement of LVEF during the follow-up period in the PTCA group (y=0.92x-0.77, r=0.65, p 123 I-BMIPP SPECT is increased by reperfusion therapy and persists at least until the recovery phase of myocardial infarction. The recovery of left ventricular function depends on the extent of the mismatched uptake, indicating a predictor for functional recovery following acute myocardial infarction. (author)

  7. Left ventricular dilatation and pulmonary thallium uptake after single-photon emission computer tomography using thallium-201 during adenosine-induced coronary hyperemia

    International Nuclear Information System (INIS)

    Iskandrian, A.S.; Heo, J.; Nguyen, T.; Lyons, E.; Paugh, E.

    1990-01-01

    This study examined the implications of left ventricular (LV) dilatation and increased pulmonary thallium uptake during adenosine-induced coronary hyperemia. The lung-to-heart thallium ratio in the initial images was significantly higher in patients with coronary artery disease (CAD) than normal subjects; 0.48 +/- 0.16 in 3-vessel disease (n = 16), 0.43 +/- 0.10 in 2-vessel disease (n = 20), 0.43 +/- 0.08 in 1-vessel disease (n = 16) and 0.36 +/- 0.05 in normal subjects (n = 7) (p less than 0.001, 0.09 and 0.06, respectively). There was a significant correlation between the severity and the extent of the perfusion abnormality (determined from the polar maps) and the lung-to-heart thallium ratio (r = 0.51 and 0.52, respectively, p less than 0.0002). There was also a significant correlation between lung thallium washout and lung-to-heart thallium ratio (r = 0.42, p = 0.0009) and peak heart rate (r = -0.49, p less than 0.0001). The LV dilatation was mostly due to an increase in cavity dimension (30% increase) and to a lesser extent (6% increase) due to increase in LV size. (The cavity dimensions were measured from the short-axis slices at the midventricular level in the initial and delayed images). The dilation was seen in patients with CAD but not in the normal subjects. These changes correlated with the extent and severity of the thallium perfusion abnormality. Thus, adenosine-induced coronary hyperemia may cause LV dilation and increased lung thallium uptake on the basis of subendocardial ischemia

  8. Renal Function and Outcomes With Use of Left Ventricular Assist Device Implantation and Inotropes in End-Stage Heart Failure: A Retrospective Single Center Study.

    Science.gov (United States)

    Verma, Sean; Bassily, Emmanuel; Leighton, Shane; Mhaskar, Rahul; Sunjic, Igor; Martin, Angel; Rihana, Nancy; Jarmi, Tambi; Bassil, Claude

    2017-07-01

    Left ventricular assist device (LVAD) and inotrope therapy serve as a bridge to transplant (BTT) or as destination therapy in patients who are not heart transplant candidates. End-stage heart failure patients often have impaired renal function, and renal outcomes after LVAD therapy versus inotrope therapy have not been evaluated. In this study, 169 patients with continuous flow LVAD therapy and 20 patients with continuous intravenous inotrope therapy were analyzed. The two groups were evaluated at baseline and at 3 and 6 months after LVAD or inotrope therapy was started. The incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), BTT rate, and mortality for 6 months following LVAD or inotrope therapy were studied. Results between the groups were compared using Mann-Whitney U test and Chi-square with continuity correction or Fischer's exact at the significance level of 0.05. Mean glomerular filtration rate (GFR) was not statistically different between the two groups, with P = 0.471, 0.429, and 0.847 at baseline, 3 and 6 months, respectively. The incidence of AKI, RRT, and BTT was not statistically different. Mortality was less in the inotrope group (P < 0.001). Intravenous inotrope therapy in end-stage heart failure patients is non-inferior for mortality, incidence of AKI, need for RRT, and renal function for 6-month follow-up when compared to LVAD therapy. Further studies are needed to compare the effectiveness of inotropes versus LVAD implantation on renal function and outcomes over a longer time period.

  9. Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

    Science.gov (United States)

    Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

    2018-06-08

    The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device

  10. Leading ventricular cardiomyocytes

    OpenAIRE

    Rosero Salazar, Doris Haydee; Ortiz Salaza, Mario Alejandro; Monsalve, Liliana Salazar

    2015-01-01

    Objetivo: Exponer las características histológicas y funcionales que se presentan en el tejido muscular estriado cardiaco especializado en la conducción del estímulo eléctrico y sus implicaciones actuales en las arritmias cardiacas. Materiales y métodos: Se seleccionaron publicaciones en revistas indexadas en las bases PubMed, Wiley, Ovid-Medline y Science Direct. Los descriptores MESH utilizados para la búsqueda fueron cardiac myocytes, myocardium, heart conduction system. Se acoplaron los c...

  11. 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.

  12. Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

    Science.gov (United States)

    Reichert, Karla; Pereira do Carmo, Helison Rafael; Galluce Torina, Anali; Diógenes de Carvalho, Daniela; Carvalho Sposito, Andrei; de Souza Vilarinho, Karlos Alexandre; da Mota Silveira-Filho, Lindemberg; Martins de Oliveira, Pedro Paulo

    2016-01-01

    Purpose Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Methods Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. Results End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Conclusion Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events. PMID:27880844

  13. Comparison of circadian, weekly, and seasonal variations of electrical storms and single events of ventricular fibrillation in patients with Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Yoshiyasu Aizawa

    2016-06-01

    Full Text Available In patients with Brugada syndrome (BS, VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.

  14. Ventricular Septal Defect (VSD)

    Science.gov (United States)

    ... Call your doctor if your baby or child: Tires easily when eating or playing Is not gaining ... heart procedures. Risk factors Ventricular septal defects may run in families and sometimes may occur with other ...

  15. Study on the effect of hypoxia on apoptosis of cultured newly born rat cardiac myocytes

    International Nuclear Information System (INIS)

    Su Weidong; Li Huiqiang; Yao Zhi

    2005-01-01

    Objective: To investigate the possible hypoxia-mediated cellular apoptosis after ischemic cardiac injury via a model of cultured newly born rat cardiac myocytes. Methods: Cardiac myocytes cultures from newly born rats (1-3d) were examined for apoptosis with HE stain and flow cytometry after cultured 96h and again examined after exposure to hypoxic environment for 16h. Results: Apoptotic changes were evident in the hypoxic culture cells. The HE stain revealed cellular shrinkage, nuclear chromosomal condensation with cytoplasmic eosinophilia. Also, distinct apoptosis peak was observed in the flow cytometry. Conclusion: This experiment proved that hypoxic model of cardiac myocyte culture showed definite apoptosis of the cells. (authors)

  16. Evaluation of Right Ventricular Function with Radionuclide Cardiac Angiography - Right Ventricular Ejection Fraction in Chronic Obstructive Lung Disease

    International Nuclear Information System (INIS)

    Sohn, In; Shin, Sung Hae; Chung, June Key; Lee, Myung Chul; Cho, Bo Youn; Lee, Young Woo; Han, Yong Cheol; Koh, Chang Soon

    1982-01-01

    To evaluate the usefulness of radionuclide cardiac angiography in the assessment of the right ventricular function, we measured right ventricular ejection fraction (RVEF) using single pass method. In 12 normal persons, RVEF averaged 52.7±5.9% (mean±S.D.). In 25 patients with chronic obstructive lung disease, RVEF was 37.2±10.6% and significantly lower than that of normal person (p<0.01). All 10 patients with right ventricular failure had abnormal RVEF, which was significantly lower than that of 14 persons without right ventricular failure (27.6±5.7%, 43.9±8.5%, respectively, p<0.01). It concluded that RVEF measured by single pass radionuclide cardiac angiography was a useful, noninvasive method to assess right ventricular function.

  17. Oxidized CaMKII (Ca2+/Calmodulin-Dependent Protein Kinase II) Is Essential for Ventricular Arrhythmia in a Mouse Model of Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Wang, Qiongling; Quick, Ann P; Cao, Shuyi; Reynolds, Julia; Chiang, David Y; Beavers, David; Li, Na; Wang, Guoliang; Rodney, George G; Anderson, Mark E; Wehrens, Xander H T

    2018-04-01

    Duchenne muscular dystrophy patients are prone to ventricular arrhythmias, which may be caused by abnormal calcium (Ca 2+ ) homeostasis and elevated reactive oxygen species. CaMKII (Ca 2+ /calmodulin-dependent protein kinase II) is vital for normal Ca 2+ homeostasis, but excessive CaMKII activity contributes to abnormal Ca 2+ homeostasis and arrhythmias in cardiomyocytes. Reactive oxygen species induce CaMKII to become autonomously active. We hypothesized that genetic inhibition of CaMKII oxidation (ox-CaMKII) in a mouse model of Duchenne muscular dystrophy can alleviate abnormal Ca 2+ homeostasis, thus, preventing ventricular arrhythmia. The objective of this study was to test if selective loss of ox-CaMKII affects ventricular arrhythmias in the mdx mouse model of Duchenne muscular dystrophy. 5-(6)-Chloromethyl-2,7-dichlorodihydrofluorescein diacetate staining revealed increased reactive oxygen species production in ventricular myocytes isolated from mdx mice, which coincides with elevated ventricular ox-CaMKII demonstrated by Western blotting. Genetic inhibition of ox-CaMKII by knockin replacement of the regulatory domain methionines with valines (MM-VV [CaMKII M281/282V]) prevented ventricular tachycardia in mdx mice. Confocal calcium imaging of ventricular myocytes isolated from mdx :MM-VV mice revealed normalization of intracellular Ca 2+ release events compared with cardiomyocytes from mdx mice. Abnormal action potentials assessed by optical mapping in mdx mice were also alleviated by genetic inhibition of ox-CaMKII. Knockout of the NADPH oxidase regulatory subunit p47 phox normalized elevated ox-CaMKII, repaired intracellular Ca 2+ homeostasis, and rescued inducible ventricular arrhythmias in mdx mice. Inhibition of reactive oxygen species or ox-CaMKII protects against proarrhythmic intracellular Ca 2+ handling and prevents ventricular arrhythmia in a mouse model of Duchenne muscular dystrophy. © 2018 American Heart Association, Inc.

  18. Systolic ventricular filling.

    Science.gov (United States)

    Torrent-Guasp, Francisco; Kocica, Mladen J; Corno, Antonio; Komeda, Masashi; Cox, James; Flotats, A; Ballester-Rodes, Manel; Carreras-Costa, Francesc

    2004-03-01

    The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles

  19. Left ventricular function in right ventricular overload

    International Nuclear Information System (INIS)

    Iwanaga, Shiro; Handa, Shunnosuke; Abe, Sumihisa; Onishi, Shohei; Nakamura, Yoshiro; Kunieda, Etsuo; Ogawa, Koichi; Kubo, Atsushi

    1989-01-01

    This study clarified regional and global functions of the distorted left ventricle due to right ventricular overload by gated radionuclide ventriculography (RNV). Cardiac catheterization and RNV were performed in 13 cases of atrial septal defect (ASD), 13 of pure mitral stenosis (MS), 10 of primary pulmonary hypertension (PPH), and 10 of normal subjects (NL). Right ventricular systolic pressure (RVSP) was 32.9±13.9, 45.0±12.2, 88.3±17.1, and 21.2±4.5 mmHg, respectively. The end-systolic LAO view of the left ventricle was halved into septal and free-wall sides. The end-diastolic halves were determined in the same plane. Ejection fractions of the global left ventricle (LVEF), global right ventricle (RVEF), the septal half of the left ventricle (SEPEF), and the free-wall half of the left ventricle (FWEF) were obtained. LVEF was 56.8±9.8% in NL, 52.8±10.5% in ASD, and 49.5±12.9% in PPH. In MS, LVEF (47.0±13.0%) was smaller than those in the other groups. RVEF was 37.0±5.2% in NL, 43.7±15.5% in ASD, and 32.8±11.5% in MS. In PPH, RVEF (25.0±10.6%) was smaller than those in the other groups. SEPEF was smaller in ASD (42.5±13.2%), MS (40.4±13.1%), PPH (40.5±12.5%) than in NL (53.5±8.5%). Systolic function of the septal half of the left ventricle was disturbed by right ventricular overload. RVEF (r=-0.35, p<0.05) and SEPEF (r=-0.51, p<0.01) had negative correlations with RVSP. As RVSP rose, systolic function of the septal half of the left ventricle was more severely disturbed. FWEF was the same among the four groups; NL (57.0±12.6%), ASD (48.6±15.2%), MS (50.5±12.0%), and PPH (51.1±12.3%). There was a good correlation between SEPEF and LVEF in NL (r=0.81), although in PPH this correlation was poor (r=0.64). These data showed that the distorted left ventricular due to right ventricular overload maintains its global function with preserved function of the free-wall side. (J.P.N.)

  20. Modulation of the transient outward current (Ito) in rat cardiac myocytes and human Kv4.3 channels by mefloquine

    International Nuclear Information System (INIS)

    Perez-Cortes, E.J.; Islas, A.A.; Arevalo, J.P.; Mancilla, C.; Monjaraz, E.; Salinas-Stefanon, E.M.

    2015-01-01

    The antimalarial drug mefloquine, is known to be a potassium channel blocker, although its mechanism of action has not being elucidated and its effects on the transient outward current (I to ) and the molecular correlate, the K v 4.3 channel has not being studied. Here, we describe the mefloquine-induced inhibition of the rat ventricular I to and of CHO cells co-transfected with human K v 4.3 and its accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat I to and hK v 4.3 + KChIP2C currents in a concentration-dependent manner with a limited voltage dependence and similar potencies (IC 50 = 8.9 μM and 10.5 μM for cardiac myocytes and K v 4.3 channels, respectively). In addition, mefloquine did not affect the activation of either current but significantly modified the hK v 4.3 steady-state inactivation and recovery from inactivation. The effects of this drug was compared with that of 4-aminopyridine (4-AP), a well-known potassium channel blocker and its binding site does not seem to overlap with that of 4-AP. - Highlights: • Mefloquine inhibited ventricular I to and hK v 4.3 channels. IC 50 = 8.9 and 10.5 μM. • Inactivation and recovery from inactivation in the hK v 4.3 channels were modified by mefloquine. • Mefloquine displayed a higher affinity for the inactivated state. • The binding site for mefloquine may be located in the extracellular side of the channel.

  1. De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    Veronique Hamel

    2017-01-01

    Full Text Available The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts, from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells, and from human embryonic stem cells (hESCs. Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

  2. Characterization of human septic sera induced gene expression modulation in human myocytes

    Science.gov (United States)

    Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

    2009-01-01

    To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera. Septic sera treatment of myocytes resulted in the down-regulation of 178 genes and the up-regulation of 4 genes. Our data indicate that septic sera induced cell cycle, metabolic, transcription factor and apoptotic gene expression changes in human myocytes. Identification and characterization of gene expression changes that occur during sepsis may lead to the development of novel therapeutics and diagnostics. PMID:19684886

  3. β1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.

    Science.gov (United States)

    Wang, Sen; Xu, Di; Wu, Ting-Ting; Guo, Yan; Chen, Yan-Hong; Zou, Jian-Gang

    2014-05-01

    Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective β1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.

  4. 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.

  5. Characterization of human septic sera induced gene expression modulation in human myocytes

    OpenAIRE

    Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

    2009-01-01

    To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera....

  6. Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study.

    Science.gov (United States)

    Kochiadakis, G E; Kanoupakis, E M; Kalebubas, M D; Igoumenidis, N E; Vardakis, K E; Mavrakis, H E; Vardas, P E

    2001-01-01

    To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation. The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

  7. Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Koenig, Xaver; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz

    2017-03-04

    Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current I K1 , which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential I K1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that I K1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels.

  8. Arrhythmogenic right ventricular dysplasia

    International Nuclear Information System (INIS)

    Vignolo Puglia, W.; Freire Colla, D.; Rivara Urrutia, D.; Lujambio Grene, M.; Arbiza Bruno, T.; Oliveira, G.; Cobas Rodriguez, J.

    1997-01-01

    The arrhythmogenic right ventricular dysplasia is a condition predominantly well defined with arrhythmic events. We analyze three cases diagnosed by the group. These cases were presented as ventricular tachycardia with a morphology of left bundle branch block, presenting one of them aborted sudden death in evolution. The baseline electrocardiogram and signal averaging were abnormal in two of the three cases, like the echocardiogram. The electrophysiological study was able to induce in the three patients with sustained monomorphic ventricular tachycardia morphology of left bundle branch block. The definitive diagnosis was made by right ventriculography in two cases and magnetic resonance imaging in the other. Treatment included antiarrhythmic drugs in the three cases and the placement of an automatic defibrillator which survived a sudden death (Author)

  9. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.

    Directory of Open Access Journals (Sweden)

    Daniel M Lombardo

    2016-08-01

    Full Text Available 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.

  10. Vasodilator stress impairs the left ventricular function obtained with gated single-photon emission computed tomography in patients with known or suspected coronary artery disease

    International Nuclear Information System (INIS)

    Odagiri, Keiichi; Uehara, Akihiko; Kurata, Chinori

    2010-01-01

    Transient ischemic dilatation (TID) and post-stress dysfunction of the left ventricle (LV) are important markers of severe coronary artery disease (CAD). To clarify the effects of stressor type on TID and post-stress LV dysfunction, changes in LV measurements were compared between patients with exercise- or vasodilator-induced stress. The 689 patients referred for technetium-99m tetrofosmin myocardial perfusion imaging were included. Patients were stressed with either a vasodilator (n=236) or exercise (n=453). LV measurements were obtained with electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT). LV end-diastolic and end-systolic volume indexes (LVEDVI, LVESVI) increased and LV ejection fraction (LVEF) decreased after stress in the vasodilator-stress group. Vasodilator-stress and the summed difference score (SDS) were independent variables that decreased LVEF after stress. Even in patients without reversible defects, vasodilator-stress impaired LV function. There were no differences in the stress-to-rest ratios of LVEDVI (rEDV) and LVESVI (rESV) among patients with normal myocardial perfusion, fixed defects and reversible defects in the vasodilator-stress group, whereas in the exercise-stress group, rESV was significantly higher in the patients with reversible defects than in those without reversible defects. Within the vasodilator-stress group, neither rEDV nor rESV correlated with the SDS. Vasodilator-stress by itself decreases LVEF after stress. TID should be carefully interpreted when vasodilator-stress is used to detect severe CAD. (author)

  11. Skeletal Myocyte Types and Vascularity in the Black Sicilian Pig

    Directory of Open Access Journals (Sweden)

    S. Velotto

    2007-01-01

    Full Text Available The objective of this study was to verify the presence of giant fibres in the Black Sicilian pig skeletal muscle and to evaluate the effect of sex on histochemical and morphometric characteristics of the myocytes (myofibres as well as vascularity of the muscle. Twenty Black Sicilian pigs (10 males, 10 females from a farm in Sicily (Italy were slaughtered at two years of age. Muscle tissues were obtained from three muscles: psoas major, longissimus dorsi, and trapezius. Myofibres were stained for myosin ATPase, succinic dehydrogenase, and α-amylase-PAS. For all fibre types, area and perimeter were measured. Slow-twitch oxidative fibres, fast-twitch glycolytic fibres and fast-twitch oxidative-glycolytic fibres were histochemically differentiated; an image-analyzing system was used. The results showed no differences between males and females in percentage of the fibre types, but there were significant differences between sexes in size of all the three fibre types. Psoas major muscle had a high percentage of slow-twitch oxidative fibres and contained more capillaries per fibre and per mm2 than trapezius and longissimus dorsi, in which fast-twitch glycolytic fibres dominated. The cross-sectional area of all fibres types was larger in longissimus dorsi than in trapezius and psoas major muscles; the giant fibres were absent in all the muscles studied. Fibre type composition may contribute to the variation of meat quality.

  12. The timing statistics of spontaneous calcium release in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Mesfin Asfaw

    Full Text Available A variety of cardiac arrhythmias are initiated by a focal excitation that disrupts the regular beating of the heart. In some cases it is known that these excitations are due to calcium (Ca release from the sarcoplasmic reticulum (SR via propagating subcellular Ca waves. However, it is not understood what are the physiological factors that determine the timing of these excitations at both the subcellular and tissue level. In this paper we apply analytic and numerical approaches to determine the timing statistics of spontaneous Ca release (SCR in a simplified model of a cardiac myocyte. In particular, we compute the mean first passage time (MFPT to SCR, in the case where SCR is initiated by spontaneous Ca sparks, and demonstrate that this quantity exhibits either an algebraic or exponential dependence on system parameters. Based on this analysis we identify the necessary requirements so that SCR occurs on a time scale comparable to the cardiac cycle. Finally, we study how SCR is synchronized across many cells in cardiac tissue, and identify a quantitative measure that determines the relative timing of SCR in an ensemble of cells. Using this approach we identify the physiological conditions so that cell-to-cell variations in the timing of SCR is small compared to the typical duration of an SCR event. We argue further that under these conditions inward currents due to SCR can summate and generate arrhythmogenic triggered excitations in cardiac tissue.

  13. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    Science.gov (United States)

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  14. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo

    2013-01-01

    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  15. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial.

    Science.gov (United States)

    Hohlfeld, Jens M; Vogel-Claussen, Jens; Biller, Heike; Berliner, Dominik; Berschneider, Korbinian; Tillmann, Hanns-Christian; Hiltl, Simone; Bauersachs, Johann; Welte, Tobias

    2018-02-21

    Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic. Eligible participants were patients aged at least 40 years with COPD, pulmonary hyperinflation (defined by a baseline residual volume >135% of predicted), a smoking history of at least ten pack-years, and airflow limitation (FEV 1 <80% predicted and post-bronchodilator FEV 1 : forced vital capacity <0·7). Patients with stable cardiovascular disease were eligible, but those with arrhythmias, heart failure, unstable ischaemic heart disease, or uncontrolled hypertension were not. We randomly assigned participants (1:1) to either receive a combined inhaled dual bronchodilator containing the LABA indacaterol (110 μg as maleate salt) plus the LAMA glycopyrronium (50 μg as bromide salt) once per day for 14 days, followed by a 14-day washout, then a matched placebo for 14 days, or to receive the same treatments in reverse order. The randomisation was done using lists and was concealed from patients and investigators. The primary endpoint was the effect of indacaterol-glycopyrronium versus placebo on left-ventricular end-diastolic volume measured by MRI done on day 1 (visit 4) and day 15 (visit 5) in treatment period 1 and on day 29 (visit 6) and day 43 (visit 7) in treatment period 2 in the per-protocol population. Left-ventricular end-diastolic volume was indexed to body surface area. Safety was assessed in all participants who received

  16. Repressive histone methylation regulates cardiac myocyte cell cycle exit.

    Science.gov (United States)

    El-Nachef, Danny; Oyama, Kyohei; Wu, Yun-Yu; Freeman, Miles; Zhang, Yiqiang; Robb MacLellan, W

    2018-05-22

    Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D. Although H3K9me3 is found across the genome, its loss in CMs preferentially disrupts cell cycle gene silencing. KDM4D binds directly to cell cycle genes and reduces H3K9me3 levels at these promotors. Loss of H3K9me3 preferentially leads to increased cell cycle gene expression resulting in enhanced CM cycling. Heart mass was increased in KDM4D overexpressing mice by postnatal day 14 (P14) and continued to increase until 9-weeks of age. ACM number, but not size, was significantly increased in KDM4D expressing hearts, suggesting CM hyperplasia accounts for the increased heart mass. Inducing KDM4D after normal development specifically in ACMs resulted in increased cell cycle gene expression and cycling. We demonstrated that H3K9me3 is required for CM cell cycle exit and terminal differentiation in ACMs. Depletion of H3K9me3 in adult hearts prevents and reverses permanent cell cycle exit and allows hyperplastic growth in adult hearts in vivo. Copyright © 2017. Published by Elsevier Ltd.

  17. 26S Proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells

    International Nuclear Information System (INIS)

    Samaras, Susan E.; Chen, Billy; Koch, Stephen R.; Sawyer, Douglas B.; Lim, Chee Chew; Davidson, Jeffrey M.

    2012-01-01

    Highlights: ► The 26S proteasome regulates Ankrd1 levels in cardiomyocytes and endothelial cells. ► Ankrd1 protein degrades 60-fold faster in endothelial cells than cardiomyocytes. ► Differential degradation appears related to nuclear vs. sarcolemmal localization. ► 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.

  18. Comparative study of cellular kinetics of reporter probe [{sup 131}I]FIAU in neonatal cardiac myocytes after transfer of HSV1-tk reporter gene with two vectors

    Energy Technology Data Exchange (ETDEWEB)

    Lan Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022 (China)], E-mail: lxl730724@hotmail.com; Yin Xiaohua; Wang Ruihua; Liu Ying [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022 (China); Zhang Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China) and Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022 (China)], E-mail: zhyx1229@163.com

    2009-02-15

    Aim: Reporter gene imaging is a promising approach for noninvasive monitoring of cardiac gene therapy. In this study, HSV1-tk (herpes simplex virus type 1 thymidine kinase) and FIAU (2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuranosyl-5-iodouracil) were used as the reporter gene and probe, respectively. Cellular uptakes of radiolabeled FIAU of neonatal rat cardiac myocytes transferred with HSV1-tk were compared between two vectors, adenovirus and liposome. The aims of this study were to choose the better vector and to provide a theoretical basis for good nuclide images. Methods: Neonatal cardiac myocytes were obtained from rat heart by single collagenase digestion. HSV1-tk inserted into adenovirus vector (recombinant adenovirus type 5, Ad5-tk) and plasmid (pDC316-tk) coated with Lipofectamine 2000 (pDC316-tk/lipoplex) were developed; thus, HSV1-tk could be transferred into neonatal cardiac myocytes. FAU (2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuranosyluracil) was labeled with {sup 131}I, and the product was assessed after purification with reversed-phase Sep-Pak C-18 column. The uptake rates of [{sup 131}I]FIAU in the transferred cardiac myocytes at different times (0.5, 1, 2, 3, 4 and 5 h) were detected. Furthermore, mRNA expression and protein expression of HSV1-tk were detected by semiquantitative reverse-transcriptase polymerase chain reaction and immunocytochemistry. Results: FAU could be labeled with {sup 131}I, and the labeling efficiency and radiochemical purity rates were 53.82{+-}2.05% and 94.85{+-}1.76%, respectively. Time-dependent increase of the accumulation of [{sup 131}I]FIAU was observed in both the Ad5-tk group and the pDC316/lipoplex group, and the highest uptake rate occurred at 5 h, with peak values of 12.55{+-}0.37% and 2.09{+-}0.34%, respectively. Greater uptakes of [{sup 131}I]FIAU in Ad5-tk-infected cells compared with pDC316/lipoplex-transfected ones occurred at all the time points (t=12.978-38.253, P<.01). The exogenous gene

  19. 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....

  20. Image Processing Techniques for Assessing Contractility in Isolated Adult Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Carlos Bazan

    2009-01-01

    The physiologic application of the methodology is evaluated by assessing overall contraction in enzymatically dissociated adult rat cardiocytes. Our results demonstrate the effectiveness of the proposed approach in characterizing the true, two-dimensional, “shortening” in the contraction process of adult cardiocytes. We compare the performance of the proposed method to that of a popular edge detection system in the literature. The proposed method not only provides a more comprehensive assessment of the myocyte contraction process but also can potentially eliminate historical concerns and sources of errors caused by myocyte rotation or translation during contraction. Furthermore, the versatility of the image processing techniques makes the method suitable for determining myocyte shortening in cells that usually bend or move during contraction. The proposed method can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease modeling, transgeneity, or other common applications to mammalian cardiocytes.

  1. Left Ventricular Assist Devices

    Directory of Open Access Journals (Sweden)

    Khuansiri Narajeenron

    2017-04-01

    Full Text Available Audience: The audience for this classic team-based learning (cTBL session is emergency medicine residents, faculty, and students; although this topic is applicable to internal medicine and family medicine residents. Introduction: A left ventricular assist device (LVAD is a mechanical circulatory support device that can be placed in critically-ill patients who have poor left ventricular function. After LVAD implantation, patients have improved quality of life.1 The number of LVAD patients worldwide continues to rise. Left-ventricular assist device patients may present to the emergency department (ED with severe, life-threatening conditions. It is essential that emergency physicians have a good understanding of LVADs and their complications. Objectives: Upon completion of this cTBL module, the learner will be able to: 1 Properly assess LVAD patients’ circulatory status; 2 appropriately resuscitate LVAD patients; 3 identify common LVAD complications; 4 evaluate and appropriately manage patients with LVAD malfunctions. Method: The method for this didactic session is cTBL.

  2. Raman probing of lipids, proteins, and mitochondria in skeletal myocytes: a case study on obesity

    DEFF Research Database (Denmark)

    Brazhe, Nadezda A.; Nikelshparg, Evelina I.; Prats, Clara

    2017-01-01

    We propose a novel approach to assess simultaneously lipid composition in lipid droplets, the redox state of cytochromes, and the relative amount of [Fe–S] clusters in the electron transport chain in the mitochondria of skeletal myocytes by means of near-infrared Raman spectroscopy. Mitochondria...... technique allows to estimate qualitatively the relative amount of cholesterol and unsaturated lipids, ordering of lipid phase in lipid droplets, changes in the redox state of c-type and b-type cytochromes, and the relative amount of [Fe–S] clusters in the mitochondria of intact myocytes. The proposed...

  3. PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signaling in cardiac myocytes.

    Science.gov (United States)

    Bedioune, Ibrahim; Lefebvre, Florence; Lechêne, Patrick; Varin, Audrey; Domergue, Valérie; Kapiloff, Michael S; Fischmeister, Rodolphe; Vandecasteele, Grégoire

    2018-05-03

    β1- and β2-adrenergic receptors (β-ARs) produce different acute contractile effects on the heart partly because they impact on different cytosolic pools of cAMP-dependent protein kinase (PKA). They also exert different effects on gene expression but the underlying mechanisms remain unknown. The aim of this study was to understand the mechanisms by which β1- and β2-ARs regulate nuclear PKA activity in cardiomyocytes. We used cytoplasmic and nuclear targeted biosensors to examine cAMP signals and PKA activity in adult rat ventricular myocytes upon selective β1- or β2-ARs stimulation. Both β1- and β2-AR stimulation increased cAMP and activated PKA in the cytoplasm. While the two receptors also increased cAMP in the nucleus, only β1-ARs increased nuclear PKA activity and up-regulated the PKA target gene and pro-apoptotic factor, inducible cAMP element repressor (ICER). Inhibition of PDE4, but not Gi, PDE3, GRK2 nor caveolae disruption disclosed nuclear PKA activation and ICER induction by β2-ARs. Both nuclear and cytoplasmic PKI prevented nuclear PKA activation and ICER induction by β1-ARs, indicating that PKA activation outside the nucleus is required for subsequent nuclear PKA activation and ICER mRNA expression. Cytoplasmic PKI also blocked ICER induction by β2-AR stimulation (with concomitant PDE4 inhibition). However, in this case nuclear PKI decreased ICER up-regulation by only 30%, indicating that other mechanisms are involved. Down-regulation of mAKAPβ partially inhibited nuclear PKA activation upon β1-AR stimulation, and drastically decreased nuclear PKA activation upon β2-AR stimulation in the presence of PDE4 inhibition. β1- and β2-ARs differentially regulate nuclear PKA activity and ICER expression in cardiomyocytes. PDE4 insulates a mAKAPβ-targeted PKA pool at the nuclear envelope that prevents nuclear PKA activation upon β2-AR stimulation.

  4. Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients

    DEFF Research Database (Denmark)

    Bang, Casper; Gerdts, Eva; Aurigemma, Gerard P

    2013-01-01

    Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation...... [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV)] in hypertensive patients....

  5. Angiotensin-converting enzyme gene polymorphism in arrhythmogenic right ventricular dysplasia: is DD genotype helpful in predicting syncope risk?

    Science.gov (United States)

    Ozben, Beste; Altun, Ibrahim; Sabri Hancer, Veysel; Bilge, Ahmet Kaya; Tanrikulu, Azra Meryem; Diz-Kucukkaya, Reyhan; Fak, Ali Serdar; Yilmaz, Ercument; Adalet, Kamil

    2008-12-01

    Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterised by fibrofatty replacement of right ventricular myocytes and increased risk of ventricular arrhythmias and sudden cardiac death. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects myocardial ACE levels. DD genotype favours myocardial fibrosis and is associated with malignant ventricular tachycardia. The aim of this study was to explore ACE gene polymorphism in ARVD patients. Twenty-nine patients with ARVD and 24 controls were included. All ARVD patients had documented sustained ventricular tachycardia. Thirteen patients had syncopal episodes. Six patients were resuscitated from sudden cardiac death. ACE gene polymorphism was identified by polymerase chain reaction technique. There was no significant difference in DD genotype frequency between ARVD patients and controls (44.8% vs. 45.8%, p=0.94). However, DD genotype frequency was significantly higher in ARVD patients with syncopal episodes compared to those without syncope (69.2% vs. 25.0%, p=0.017, odds ratio:6.750, 95% confidence interval: 1.318-34.565). DD genotype was detected in higher frequency also in patients with a family history of sudden cardiac death (66.7% vs. 39.1%,p=0.36). High prevalence of DD genotype in ARVD patients with syncope suggests that ACE I/D polymorphism might be useful in identifying high-risk patients for syncope.

  6. Depletion of Tip60 from In Vivo Cardiomyocytes Increases Myocyte Density, Followed by Cardiac Dysfunction, Myocyte Fallout and Lethality.

    Directory of Open Access Journals (Sweden)

    Joseph B Fisher

    Full Text Available Tat-interactive protein 60 (Tip60, encoded by the Kat5 gene, is a member of the MYST family of acetyltransferases. Cancer biology studies have shown that Tip60 induces the DNA damage response, apoptosis, and cell-cycle inhibition. Although Tip60 is expressed in the myocardium, its role in cardiomyocytes (CMs is unclear. Earlier studies here showed that application of cardiac stress to globally targeted Kat5+/-haploinsufficient mice resulted in inhibition of apoptosis and activation of the CM cell-cycle, despite only modest reduction of Tip60 protein levels. It was therefore of interest to ascertain the effects of specifically and substantially depleting Tip60 from CMs using Kat5LoxP/-;Myh6-Cre mice in the absence of stress. We report initial findings using this model, in which the effects of specifically depleting Tip60 protein from ventricular CMs, beginning at early neonatal stages, were assessed in 2-12 week-old mice. Although 5'-bromodeoxyuridine immunostaining indicated that CM proliferation was not altered at any of these stages, CM density was increased in 2 week-old ventricles, which persisted in 4 week-old hearts when TUNEL staining revealed inhibition of apoptosis. By week 4, levels of connexin-43 were depleted, and its patterning was dysmorphic, concomitant with an increase in cardiac hypertrophy marker expression and interstitial fibrosis. This was followed by systolic dysfunction at 8 weeks, after which extensive apoptosis and CM fallout occurred, followed by lethality as mice approached 12 weeks of age. In summary, chronic depletion of Tip60 from the ventricular myocardium beginning at early stages of neonatal heart development causes CM death after 8 weeks; hence, Tip60 protein has a crucial function in the heart.

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

    International Nuclear Information System (INIS)

    Maldonado, Carola; Cea, Paola; Adasme, Tatiana; Collao, Andres; Diaz-Araya, Guillermo; Chiong, Mario; Lavandero, Sergio

    2005-01-01

    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 Ca 2+ increase, we assessed whether the cyclic AMP response element-binding protein (CREB) is activated by IGF-1 through Ca 2+ -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 Ca 2+ /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

  8. Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone?

    Science.gov (United States)

    Havekes, Bas; Sauerwein, Hans P

    2010-11-01

    To review original research studies and reviews that present data on adipocyte-myocyte crosstalk in the development of skeletal muscle insulin resistance with a specific focus on thyroid hormone. Adipose tissue communicates with skeletal muscle not only through free fatty acids but also through secretion of various products called adipokines. Adipokines came out as governors of insulin sensitivity and are deregulated in obesity. In addition to well known leptin, adiponectin, interleukin-6 and tumor necrosis factor-alpha, newer adipokines like retinol-binding protein 4 have been associated with insulin resistance. There is mounting evidence that not only adipose tissue but also skeletal muscle produces and secretes biologically active proteins or 'myokines' that facilitate metabolic crosstalk between organ systems. In recent years, increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Both hypothyroidism and hyperthyroidism affect insulin sensitivity in multiple ways that might overlap adipocyte-myocyte crosstalk. Recent studies have provided new insights in effects of processing of the parent hormone T4 to the active T3 at the level of the skeletal muscle. Adipocyte-myocyte crosstalk is an important modulator in the development of skeletal muscle insulin resistance. Thyroid disorders are very common and may have detrimental effects on skeletal muscle insulin resistance, potentially by interacting with adipocyte-myocyte crosstalk.

  9. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs

    DEFF Research Database (Denmark)

    Xing, Dezhi; Kjølbye, Anne Louise; Nielsen, Morten S

    2003-01-01

    INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments...... demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation...... AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT....

  10. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    Science.gov (United States)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  11. Genetics Home Reference: arrhythmogenic right ventricular cardiomyopathy

    Science.gov (United States)

    ... cardiomyopathy Merck Manual Consumer Version: Cardiomyopathy Merck Manual Consumer Version: Overview of Abnormal Heart Rhythms Orphanet: Arrhythmogenic right ventricular cardiomyopathy Orphanet: Familial isolated arrhythmogenic right ventricular ...

  12. TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma

    Directory of Open Access Journals (Sweden)

    Huaxing Wu

    2015-03-01

    Full Text Available Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580. Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.

  13. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

    Science.gov (United States)

    Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

    2011-07-01

    Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  14. 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

    2014-05-01

    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. 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-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. 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. © 2014 American Heart Association, Inc.

  15. Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits.

    Science.gov (United States)

    Li, Bao; Tian, Jing; Sun, Yi; Xu, Tao-Rui; Chi, Rui-Fang; Zhang, Xiao-Li; Hu, Xin-Ling; Zhang, Yue-An; Qin, Fu-Zhong; Zhang, Wei-Fang

    2015-05-01

    Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase activity and endoplasmic reticulum (ER) stress are increased after myocardial infarction (MI). In this study, we proposed to test whether activation of the NADPH oxidase in the remote non-infarcted myocardium mediates ER stress and left ventricular (LV) remodeling after MI. Rabbits with MI or sham operation were randomly assigned to orally receive an NADPH oxidase inhibitor apocynin or placebo for 30 days. The agents were administered beginning at 1 week after surgery. MI rabbits exhibited decreases in LV fractional shortening, LV ejection fraction and the first derivative of the LV pressure rise, which were abolished by apocynin treatment. NADPH oxidase Nox2 protein and mRNA expressions were increased in the remote non-infarcted myocardium after MI. Immunolabeling further revealed that Nox2 was increased in cardiac myocytes in the remote myocardium. The apocynin treatment prevented increases in the Nox2 expression, NADPH oxidase activity, oxidative stress, myocyte apoptosis and GRP78, CHOP and cleaved caspase 12 protein expression in the remote myocardium. The apocynin treatment also attenuated increases in myocyte diameter and cardiac fibrosis. In cultured H9C2 cardiomyocytes exposed to angiotensin II, an important stimulus for post-MI remodeling, Nox2 knockdown with siRNA significantly inhibited angiotensin II-induced NADPH oxidase activation, reactive oxygen species and GRP78 and CHOP protein expression. We conclude that NADPH oxidase inhibition attenuates increased ER stress in the remote non-infarcted myocardium and LV remodeling late after MI in rabbits. These findings suggest that the activation of NADPH oxidase in the remote non-infarcted myocardium mediates increased ER stress, contributing to myocyte apoptosis and LV remodeling after MI. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.

    Science.gov (United States)

    Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam

    2010-10-01

    Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.

  17. 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)

    Yin Xiaohua; Lan Xiaoli; Wang Ruihua; Liu Ying; Zhang Yongxue

    2009-01-01

    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 131 I 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 131 I 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 131 I-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

  18. A case of appropriate inappropriate device therapy: Hyperkalemia-induced ventricular oversensing

    Science.gov (United States)

    Oudit, Gavin Y; Cameron, Doug; Harris, Louise

    2008-01-01

    The present case describes a patient who received inappropriate, but potentially life-saving, therapy from her implantable cardioverter defibrillator (ICD) in the setting of acute hyperkalemia (plasma potassium concentration = 8 mM). Hyperkalemia was associated with the development of a slow sinusoidal ventricular tachycardia, at a rate of 100 beats/min to 125 beats/min (610 ms to 480 ms) in a patient who is pacemaker-dependent. There was associated fractionation of the ICD electrogram and T wave oversensing, leading to ventricular oversensing with resultant detection in the ventricular fibrillation rate zone. This was followed by shock therapy, even though the ventricular tachycardia rate was below the programmed detection rate of the ICD. The subsequent emergency treatment of the hyperkalemia normalized the electrogram, corrected the ventricular oversensing and arrhythmia, and restored rate-adaptive single-chamber ventricular pacing. PMID:18340383

  19. Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the rabbit heart.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

    2011-01-01

    Ventricular arrhythmias represent one of leading causes for sudden cardiac death, a significant problem in public health. Noninvasive imaging of cardiac electric activities associated with ventricular arrhythmias plays an important role in better our understanding of the mechanisms and optimizing the treatment options. The present study aims to rigorously validate a novel three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping during paced rhythm and ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous norepinephrine (NE). The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72 and a relative error of 0.30 averaged over all paced beats and NE-induced PVCs and VT beats. The averaged distance from imaged site of initial activation to measured site determined from intra-cardiac mapping was ∼5mm. These promising results suggest that 3-DCEI is feasible to non-invasively localize the origins and image activation sequence of focal ventricular arrhythmias.

  20. The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.

    Science.gov (United States)

    Cui, Shanyu; Park, Hyewon; Park, Hyelim; Mun, Dasom; Lee, Seung Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui Nam; Lee, Moon Hyoung; Joung, Boyoung

    2018-03-01

    The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP). During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(-/-)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. © Copyright: Yonsei University College of Medicine 2018

  1. Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

    Science.gov (United States)

    Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

    2013-09-01

    Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

  2. 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

  3. Life-threatening hobbies in the youth? Two autoptic cases suggesting arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Wingenfeld, Lisa; Freislederer, Andreas; Schulze-Bahr, Eric; Paul, Matthias; Bajanowski, Thomas

    2007-08-24

    Determining the cause for the sudden death in young adults tends to be complex and difficult. Two cases of death of young people were autoptically investigated who died suddenly while carrying out their hobbies (a 22-year-old male musician and a 20-year-old female dancer). In both cases neither the police investigation, the autopsy, nor the toxicological investigations gave any relevant results. However, when investigating the histology fatty and fibrotic tissue in the right ventricle of the myocardium were found, whereas the myocytes proved to be degenerated--typical for arrhythmogenic right ventricular cardiomyopathy (ARVC). It is important to consider the possibility of heart rhythm failure if a clear reason for sudden death in young adults cannot be detected. Heart rhythm failure often involves the genetic background of the case, which suggests that genetic analysis should be carried out as a supportive means of diagnostics.

  4. Measurement of ventricular function using Doppler ultrasound

    International Nuclear Information System (INIS)

    Teague, S.M.

    1986-01-01

    Doppler has wide application in the evaluation of valvular heart disease. The need to know ventricular function is a much more common reason for an echocardiographic evaluation. Interestingly, Doppler examinations can assess ventricular function from many perspectives. Description of ventricular function entails measurement of the timing, rate and volume of ventricular filling and ejection. Doppler ultrasound examination reveals all of these aspects of ventricular function noninvasively, simply, and without great expense or radiation exposure, as described in this chapter

  5. Idiopathic ventricular tachycardia and fibrillation.

    Science.gov (United States)

    Belhassen, B; Viskin, S

    1993-06-01

    Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healty patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellent.

  6. Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

    Science.gov (United States)

    Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

    1996-01-01

    To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

  7. [Virus-like inclusions in the myocytes of the skeletal muscle in lateral amyotrophic sclerosis].

    Science.gov (United States)

    Musaeva, L S; Sakharova, A V; Zavalishin, I A

    2004-01-01

    Microscopic examination of musculus gastrocnemius biopsies was made in four cases of sporadic lateral amyotrophic sclerosis (LAS). The validity of the clinical diagnosis was confirmed by detected neurotrophic atrophy of the muscular fibers typical for LAS. Electron microscopic study revealed virus-like inclusions 200-450 nm in size in sarcoplasm of myocytes of all the patients. The inclusions consist of lined cells of hexagonal shape at the distance of 37-41 nm from each other. The inclusions resemble enteroviruses but are not identical to them both by size and structure of their elements. There were also specific ultrastructural changes of myocytes corresponding to viral infection. The above virus-like inclusions should be considered as specific structures formed as a result of metabolic shifts caused by productive action on the cell of infective or unknown factor.

  8. Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes

    DEFF Research Database (Denmark)

    Väremo, Leif; Henriksen, Tora Ida; Scheele, Camilla

    2017-01-01

    BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize...... in sphingolipid metabolism was transcriptionally regulated. CONCLUSIONS: Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D....... intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor...

  9. Left ventricular apical ballooning syndrome

    International Nuclear Information System (INIS)

    Rahman, N.; Tai, J.; Soofi, A.

    2007-01-01

    The transient left ventricular apical ballooning syndrome, also known as Takotsubo cardiomyopathy, is characterized by transient left ventricular dysfunction in the absence of obstructive epicardial coronary disease. Although the syndrome has been reported in Japan since 1990, it is rare in other regions. Rapid recognition of the syndrome can modify the diagnostic and therapeutic attitude i.e. avoiding thrombolysis and performing catheterization in the acute phase. (author)

  10. EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.

    OpenAIRE

    Siwik Deborah A; Kuster Gabriela M; Brahmbhatt Jamin V; Zaidi Zaheer; Malik Julia; Ooi Henry; Ghorayeb Ghassan

    2008-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricu...

  11. The absence of 2,3-diphosphoglycerate from myocytes, hepatocytes and adipocytes.

    Science.gov (United States)

    Reddy, W J; Burns, A H

    1976-04-23

    Myocytes, hepatocytes and adipocytes were prepared from heart, liver and epididymal fat pad of the rat. No detectable level of 2,3-diphosphoglycerate was found. Evidence is also presented which indicates the absence from these cells of 2,3-diphosphoglycerate mutase and 2,3-diphosphoglycerate phosphatase. Previous findings by others of the presence of 2,3-diphosphoglycerate and 2,3-diphosphoglycerate mutase probably resulted from erythrocytes sequestered in the tissue.

  12. Comparison of dobutamine stress echocardiography and technetium-99m sestamibi single-photon emission tomography for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy

    International Nuclear Information System (INIS)

    Elhendy, A.; Geleijnse, M.L.; Van Domburg, R.T.; Bax, J.J.; Nierop, P.R.; Beerens, S.A.M.; Mohsen Ibrahim, M.; Roelandt, J.R.T.C.; Valkema, R.; Krenning, E.P.

    1998-01-01

    The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine stress echocardiography in conjunction with sestamibi (MIBI) SPET was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Significant coronary artery disease (≥50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%-82%), 83% (CI 75%-91%) and 75% (CI 66%-84%), those for MIBI were 67% (CI 57%-77%), 83% (CI 75%-91%) and 70% (CI 60%-80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%-69%), 90% (CI 86%-94%) and 77% (CI 72%-82%). Those for MIBI were 58% (CI 51%-64%), 91% (CI 87%-94%) and 75% (CI 69%-80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET.(orig./MG) (orig.)

  13. Ventricular arrhythmias in Chagas disease

    Directory of Open Access Journals (Sweden)

    Marco Paulo Tomaz Barbosa

    2015-02-01

    Full Text Available Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

  14. Comparison of the accuracy of three angiographic methods for calculating left ventricular volume measurement

    International Nuclear Information System (INIS)

    Hu Lin; Cui Wei; Shi Hanwen; Tian Yingping; Wang Weigang; Feng Yanguang; Huang Xueyan; Liu Zhisheng

    2003-01-01

    Objective: To compare the relative accuracy of three methods measuring left ventricular volume by X-ray ventriculography: single plane area-length method, biplane area-length method, and single-plane Simpson's method. Methods: Left ventricular casts were obtained within 24 hours after death from 12 persons who died from non-cardiac causes. The true left ventricular cast volume was measured by water displacement. The calculated volume of the casts was obtained with 3 angiographic methods, i.e., single-plane area-length method, biplane area-length method, and single-plane Simpson's method. Results: The actual average volume of left ventricular casts was (61.17±26.49) ml. The left ventricular volume was averagely (97.50±35.56) ml with single plane area-length method, (90.51±36.33) ml with biplane area-length method, and (65.00± 23.63) ml with single-plane Simpson's method. The left ventricular volumes calculated with single-plane and biplane area-length method were significantly larger than that the actual volumes (P 0.05). The left ventricular volumes calculated with single-plane and biplane area-length method were significantly larger than those calculated with single-plane Simpson's method (P 0.05). The over-estimation of left ventricular volume by single plane area-length method (36.34±17.98) ml and biplane area-length method (29.34±15.59) ml was more obvious than that calculated by single-plane Simpson's method (3.83±8.48) ml. Linear regression analysis showed that there was close correlations between left ventricular volumes calculated with single plane area-length method, biplane area-length method, Simpson's method and the true volume (all r>0.98). Conclusion: Single-plane Simpson's method is more accurate than single plane area-length method and biplane area-length method for left ventricular volume measurement; however, both the single-plane and biplane area-length methods could be used in clinical practice, especially in those imaging modality

  15. The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Beiru Zhang

    2014-08-01

    Full Text Available β-Amyloid (Aβ is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer’s disease (AD. Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Aβ had an effect on cardiovascular cells. We represent as a major discovery that Aβ25–35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Aβ25–35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Aβ25–35 played a critical role in cardiac myocytes, suggesting that Alzheimer’s disease (AD had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.

  16. 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.

  17. The overloaded right heart and ventricular interdependence.

    Science.gov (United States)

    Naeije, Robert; Badagliacca, Roberto

    2017-10-01

    The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored. Published on behalf of the European Society of Cardiology. All rights

  18. Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

    Science.gov (United States)

    Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

    2017-03-01

    Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  19. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Directory of Open Access Journals (Sweden)

    Philip Gemmell

    Full Text Available Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+, inward rectifying K(+, L-type Ca(2+, and Na(+/K(+ pump currents in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al. at multiple cycle lengths (400, 600, 1,000 ms was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in

  20. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Science.gov (United States)

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

  1. Effect of trimetazidine on recurrent angina pectoris and left ventricular structure in elderly multivessel coronary heart disease patients with diabetes mellitus after drug-eluting stent implantation: a single-centre, prospective, randomized, double-blind study at 2-year follow-up.

    Science.gov (United States)

    Xu, Xiaohan; Zhang, Weijun; Zhou, Yujie; Zhao, Yingxin; Liu, Yuyang; Shi, Dongmei; Zhou, Zhiming; Ma, Hanying; Wang, Zhijian; Yu, Miao; Ma, Qian; Gao, Fei; Shen, Hua; Zhang, Jianwei

    2014-04-01

    Trimetazidine has been shown to improve angina pectoris and left ventricular (LV) function in diabetic patients with ischaemic cardiomyopathy. The objective of this study was to evaluate the effects of trimetazidine on recurrent angina pectoris and LV structure after drug-eluting stent (DES) implantation in elderly multivessel coronary heart disease (CHD) patients with diabetes mellitus (DM) and a left ventricular ejection fraction (LVEF) of ≥ 50 %. This was a single-centre, prospective, randomized, double-blind evaluation study. Between January 2010 and September 2010, 700 CHD patients with DM who were aged ≥ 65 years and undergoing coronary angiography at An Zhen Hospital (Beijing, China) were recruited and prospectively randomized to receive trimetazidine (20 mg three times daily) or placebo after DES implantation as an addition to conventional CHD treatment. The primary end points were the incidence of recurrent angina pectoris and measures of various echocardiographic parameters, which included LVEF. At 2-year follow-up, patients in the trimetazidine group (n = 255) showed significant improvements in the incidence (P = 0.024) and severity of angina pectoris, compared with the control group, as well as silent myocardial ischaemia (P = 0.009) and angina pectoris-free survival (P = 0.011). LV function and structure in trimetazidine-treated patients were relatively stable at 2-year follow-up, while they deteriorated in the control group (n = 255) with a significant difference between groups (all P angina pectoris as well as LV function and structure in elderly multivessel CHD patients with DM.

  2. A large ventricular septal defect complicating resuscitation after blunt trauma

    Directory of Open Access Journals (Sweden)

    Henry D I De′Ath

    2012-01-01

    Full Text Available A young adult pedestrian was admitted to hospital after being hit by a car. On arrival to the Accident and Emergency Department, the patient was tachycardic, hypotensive, hypoxic, and acidotic with a Glasgow Coma Scale of 3. Despite initial interventions, the patient remained persistently hypotensive. An echocardiogram demonstrated a traumatic ventricular septal defect (VSD with right ventricular strain and increased pulmonary artery pressure. Following a period of stabilization, open cardiothoracic surgery was performed and revealed an aneurysmal septum with a single large defect. This was repaired with a bovine patch, resulting in normalization of right ventricular function. This case provides a vivid depiction of a large VSD in a patient following blunt chest trauma with hemodynamic compromise. In all thoracic trauma patients, and particularly those poorly responsive to resuscitation, VSDs should be considered. Relevant investigations and management strategies are discussed.

  3. Transcatheter device closure of perimembranous ventricular septal defect in children treated with prophylactic oral steroids: acute and mid-term results of a single-centre, prospective, observational study.

    Science.gov (United States)

    Thakkar, Bhavesh; Patel, Nehal; Bohora, Shomu; Bhalodiya, Dharmin; Singh, Tarandeep; Madan, Tarun; Shah, Saurin; Poptani, Vishal; Shukla, Anand

    2016-04-01

    Background and Objective Although transcatheter closure of perimembranous ventricular septal defect is emerging as an accepted, viable alternative, conduction disturbances still remain a major concern. Although steroid treatment has shown encouraging results with complete recovery, efficacy of prophylactic use of steroids is still speculative. We aim to study the mid-term outcome of perimembranous ventricular septal defect closure in children who received prophylactic oral steroids. Materials and methods A prospective study was designed and antegrade device closure was attempted in eligible children who met the following inclusion criteria: age 3-18 years and weight >10 kg, defect diameter ⩽12 mm, and symptomatic, haemodynamic changes or history of infective endocarditis. Prophylactic steroid protocol consisted of 2 weeks oral prednisolone (1 mg/kg/day) initiated immediately after the procedure, and in the event of bradyarrhythmia it was escalated to 2 mg/kg. Patients were regularly followed-up at 1, 6, and 12 months and then annually. Patients with post-procedure heart block underwent Holter monitoring after a minimum of 1 year interval. Between May, 2007 and August, 2012, successful device closure was accomplished in 290/297 patients. Mean age and weight were 9±3.12 years and 21±8.27 kg, respectively. The defect measured 5±1.38 mm on echocardiography. Mean fluoroscopy time was 12.98±8.64 minutes. Eight patients with major complications included one each with device embolisation, haemolysis, severe aortic regurgitation, and five with bradyarrhythmias, including complete atrioventricular block in three, Mobitz II in one, and bifascicular block in one. Patients with complete atrioventricular block responded to high-dose steroid and temporary pacemaker. Minor complications included post-procedure heart block (n=22) and blood loss (n=2). At 18.23±13.15 months follow-up, 8/27 (five major, 22 minor) with arrhythmia had persistent post-procedure heart block of no

  4. A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.

    Science.gov (United States)

    Naveed, Muhammad; Wenhua, Li; Gang, Wang; Mohammad, Imran Shair; Abbas, Muhammad; Liao, Xiaoqian; Yang, Mengqi; Zhang, Li; Liu, Xiaolin; Qi, Xiaoming; Chen, Yineng; Jiadi, Lv; Ye, Linlan; Zhijie, Wang; Ding, Chen Ding; Feng, Yu; Xiaohui, Zhou

    2017-11-01

    A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P valueASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    Wang, Guo-zhong; Liu, Jing-hua; Lü, Shu-zheng; Lü, Yun; Guo, Cheng-jun; Zhao, Dong-hui; Fang, Dong-ping; He, Dong-fang; Zhou, Yuan; Ge, Chang-jiang

    2011-05-01

    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. 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. 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 ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced β-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). Ultrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into

  6. Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

    Directory of Open Access Journals (Sweden)

    Attila Kristóf

    Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

  7. Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

    Science.gov (United States)

    Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

    2012-01-01

    Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

  8. Role of ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Alberto Cipriani

    2017-11-01

    Full Text Available Arrhythmogenic right ventricular cardiomyopathy (ARVC is characterized by progressive fibro-fatty replacement of the myocardium that represents the substrate for recurrent sustained ventricular tachycardia (VT. These arrhythmias characterize the clinical course of a sizeable proportion of patients and have significant implications for their quality of life and long-term prognosis. Antiarrhythmic drugs are often poorly tolerated and usually provide incomplete control of arrhythmia relapses. Catheter ablation is a potentially effective strategy to treat frequent VT episodes and ICD shocks in ARVC patients. The aims of this review are to discuss the electrophysiological and electroanatomic substrates of ventricular tachycardia in patients with ARVC and to analyze the role of catheter ablation in their management with particular reference to selection of patients, technical issues, potential complications and outcomes.

  9. Usefulness of ventricular endocardial electric reconstruction from body surface potential maps to noninvasively localize ventricular ectopic activity in patients

    Science.gov (United States)

    Lai, Dakun; Sun, Jian; Li, Yigang; He, Bin

    2013-06-01

    As radio frequency (RF) catheter ablation becomes increasingly prevalent in the management of ventricular arrhythmia in patients, an accurate and rapid determination of the arrhythmogenic site is of important clinical interest. The aim of this study was to test the hypothesis that the inversely reconstructed ventricular endocardial current density distribution from body surface potential maps (BSPMs) can localize the regions critical for maintenance of a ventricular ectopic activity. Patients with isolated and monomorphic premature ventricular contractions (PVCs) were investigated by noninvasive BSPMs and subsequent invasive catheter mapping and ablation. Equivalent current density (CD) reconstruction (CDR) during symptomatic PVCs was obtained on the endocardial ventricular surface in six patients (four men, two women, years 23-77), and the origin of the spontaneous ectopic activity was localized at the location of the maximum CD value. Compared with the last (successful) ablation site (LAS), the mean and standard deviation of localization error of the CDR approach were 13.8 and 1.3 mm, respectively. In comparison, the distance between the LASs and the estimated locations of an equivalent single moving dipole in the heart was 25.5 ± 5.5 mm. The obtained CD distribution of activated sources extending from the catheter ablation site also showed a high consistency with the invasively recorded electroanatomical maps. The noninvasively reconstructed endocardial CD distribution is suitable to predict a region of interest containing or close to arrhythmia source, which may have the potential to guide RF catheter ablation.

  10. Effect of chronic right ventricular apical pacing on left ventricular function.

    Science.gov (United States)

    O'Keefe, James H; Abuissa, Hussam; Jones, Philip G; Thompson, Randall C; Bateman, Timothy M; McGhie, A Iain; Ramza, Brian M; Steinhaus, David M

    2005-03-15

    The determinants of change in left ventricular (LV) ejection fraction (EF) over time in patients with impaired LV function at baseline have not been clearly established. Using a nuclear database to assess changes in LV function over time, we included patients with a baseline LVEF of 25% to 40% on a gated single-photon emission computed tomographic study at rest and only if second-gated photon emission computed tomography performed approximately 18 months after the initial study showed an improvement in LVEF at rest of > or =10 points or a decrease in LVEF at rest of > or =7 points. In all, 148 patients qualified for the EF increase group and 59 patients for the EF decrease group. LVEF on average increased from 33 +/- 4% to 51 +/- 8% in the EF increase group and decreased from 35 +/- 4% to 25 +/- 5% in the EF decrease group. The strongest multivariable predictor of improvement of LVEF was beta-blocker therapy (odds ratio 3.9, p = 0.002). The strongest independent predictor of LVEF decrease was the presence of a permanent right ventricular apical pacemaker (odds ratio 6.6, p = 0.002). Thus, this study identified beta-blocker therapy as the major independent predictor for improvement in LVEF of > or =10 points, whereas a permanent pacemaker (right ventricular apical pacing) was the strongest predictor of a LVEF decrease of > or =7 points.

  11. Intraoperative Transesophageal Echocardiography and Right Ventricular Failure After Left Ventricular Assist Device Implantation.

    Science.gov (United States)

    Silverton, Natalie A; Patel, Ravi; Zimmerman, Josh; Ma, Jianing; Stoddard, Greg; Selzman, Craig; Morrissey, Candice K

    2018-02-15

    To determine whether intraoperative measures of right ventricular (RV) function using transesophageal echocardiography are associated with subsequent RV failure after left ventricular assist device (LVAD) implantation. Retrospective, nonrandomized, observational study. Single tertiary-level, university-affiliated hospital. The study comprised 100 patients with systolic heart failure undergoing elective LVAD implantation. Transesophageal echocardiographic images before and after cardiopulmonary bypass were analyzed to quantify RV function using tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S'), fractional area change (FAC), RV global longitudinal strain, and RV free wall strain. A chart review was performed to determine which patients subsequently developed RV failure (right ventricular assist device placement or prolonged inotrope requirement ≥14 days). Nineteen patients (19%) subsequently developed RV failure. Postbypass FAC was the only measure of RV function that distinguished between the RV failure and non-RV failure groups (21.2% v 26.5%; p = 0.04). The sensitivity, specificity, and area under the curve of an abnormal RV FAC (failure after LVAD implantation were 84%, 20%, and 0.52, respectively. No other intraoperative measure of RV function was associated with subsequent RV failure. RV failure increased ventilator time, intensive care unit and hospital length of stay, and mortality. Intraoperative measures of RV function such as tricuspid annular plane systolic excursion, tricuspid annular systolic velocity, and RV strain were not associated with RV failure after LVAD implantation. Decreased postbypass FAC was significantly associated with RV failure but showed poor discrimination. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Importance of the atrial channel for ventricular arrhythmia therapy in the dual chamber implantable cardioverter defibrillator.

    Science.gov (United States)

    Dijkman, B; Wellens, H J

    2000-12-01

    Performance of dual chamber implantable cardioverter defibrillator (ICD) systems has been judged based on functioning of the ventricular tachycardia:supraventricular tachycardia (VT:SVT) discrimination criteria and DDD pacing. The purpose of this study was to evaluate the use of dual chamber diagnostics to improve the electrical and antiarrhythmic therapy of ventricular arrhythmias. Information about atrial and ventricular rhythm in relation to ventricular arrhythmia occurrence and therapy was evaluated in 724 spontaneous arrhythmia episodes detected and treated by three types of dual chamber ICDs in 41 patients with structural heart disease. Device programming was based on clinically documented and induced ventricular arrhythmias. In ambulatory patients, sinus tachycardia preceded ventricular arrhythmias more often than in the hospital during exercise testing. The incidence of these VTs could be reduced by increasing the dose of a beta-blocking agent in only two patients. In five patients in whom sinus tachycardia developed after onset of hemodynamic stable VT, propranolol was more effective than Class III antiarrhythmics combined with another beta-blocking agent with regard to the incidence of VT and pace termination. In all but three cases, atrial arrhythmias were present for a longer time before the onset of ventricular arrhythmias. During atrial arrhythmias, fast ventricular rates before the onset of ventricular rate were observed more often than RR irregularities and short-long RR sequences. Dual chamber diagnostics allowed proper interpretation of detection and therapy outcome in patients with different types of ventricular arrhythmia. The advantages of the dual chamber ICD system go further than avoiding the shortcomings of the single chamber system. Information from the atrial chamber allows better device programming and individualization of drug therapy for ventricular arrhythmia.

  13. Right ventricular function after acute myocardial infarction: dependence upon infarct related coronary artery

    International Nuclear Information System (INIS)

    Cho, Ihn Ho; Chun, Kyung A; Won, Kyu Chang; Lee, Hyung Woo; Hong, Geu Ru; Park, Jong Seon; Shin, Dong Gu; Kim, Young Jo; Shim, Bong Sub

    2004-01-01

    We studied to know the relation between right ventricular function and infarct-related artery after acute myocardial infarction. The right and left ventricular function after a first myocardial infarction was assessed ECG-gated blood pool single photon emission computed tomography (GBPS) algorithms (Cedars-Sinai Medical Center, Los Angels, Calif) (12 after LAD related infarction (group 1) and 15 after RCA related infarction (group 2)). The left ventricular ejection fraction, end-diastolic volume and end-systolic volume did not differ significantly between two groups( group 1 vs 2 :LVEF 50.8% vs 55.1%. LVEDV=73.2 vs 79.7 ml, LVESV=38 vs 44 ml : P>0.05), but right ventricular ejection fraction, end-diastolic volume and end-systolic volume were significantly different after anterior myocardial infarction between two groups( group 1 vs 2 : RVEF=57.3% vs 46.3%. RVEDV=56.4 vs 95.1 ml, RVESV=25.6 vs 54.6ml : P<0.05). There was evidence of right ventricular dilatation in the group with RCA related infarction. Six with inferior infarction had abnormal right ventricular ejection fractions (< 40%). The relation between right and left ventricular ejection fractions was markedly different in the two groups. In the group with RCA related infarction there was a significant linear relation between right and left ventricular ejection fraction(R=0.5). Whereas in the group with LAD related infarction there was not (R=-0.3). Thus right ventricular dysfunction commonly occurs after RCA related infarction. Right ventricular impairment is related after RCA related infarction, but are independent after LAD related infarction. Finally, the different effects of LAD and RCA related infarction on right ventricular function may be explained by site of the myocardial wall involvement after infarction

  14. Right Ventricular Pseudoaneurysm Following Endomyocardial Biopsy.

    Science.gov (United States)

    Pita; Santos; Manteiga; Rodriguez; Beiras

    1996-03-01

    Ventricular perforation is an unusual complication after endomyocardial biopsy in heart transplanted patients. We report a case of asymptomatic right ventricular perforation and pseudoaneurysm formation, secondary to endomyocardial biopsy, diagnosed by angiography. The spontaneous obliteration of the pseudoaneurysm was observed.

  15. Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.

    Science.gov (United States)

    Knezevic, Tijana; Myers, Valerie D; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K; Gordon, Jennifer; Weiner, Kristen N; Rabinowitz, Joseph; Ramsey, Frederick V; Tilley, Douglas G; Khalili, Kamel; Cheung, Joseph Y; Feldman, Arthur M

    2016-12-01

    The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. MI-BAG3 mice demonstrated a significantly (p BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (pBAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

  16. Adeno-associated Virus Serotype 9 – Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction

    Science.gov (United States)

    Knezevic, Tijana; Myers, Valerie D.; Su, Feifei; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Gao, Erhe; Gao, Guofeng; Muniswamy, Madesh; Gupta, Manish K.; Gordon, Jennifer; Weiner, Kristen N.; Rabinowitz, Joseph; Ramsey, Frederick V.; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.; Feldman, Arthur M.

    2016-01-01

    Objectives The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. Background BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure. Methods Eight-week-old C57/BL6 mice underwent ligation of the left coronary artery (MI) or sham surgery (Sham). Eight weeks later, mice in both groups were randomly assigned to receive either a retro-orbital injection of rAAV9-BAG3 (MI-BAG3 or Sham-BAG3) or rAAV9-GFP (MI-GFP or Sham GFP). Mice were sacrificed at 3 weeks post-injection and myocytes were isolated from the left ventricle. Results MI-BAG3 mice demonstrated a significantly (p BAG3 injection with further improvement in LVEF, fractional shortening and stroke volume at 3 weeks post-injection without changes in LV mass or LV volume. Injection of rAAV9-BAG3 had no effect on LVEF in Sham mice. The salutary benefits of rAAV9-BAG3 were also observed in myocytes isolated from MI hearts including improved cell shortening (pBAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure. PMID:28164169

  17. Fibrosis-Related Gene Expression in Single Ventricle Heart Disease.

    Science.gov (United States)

    Nakano, Stephanie J; Siomos, Austine K; Garcia, Anastacia M; Nguyen, Hieu; SooHoo, Megan; Galambos, Csaba; Nunley, Karin; Stauffer, Brian L; Sucharov, Carmen C; Miyamoto, Shelley D

    2017-12-01

    To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure. Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression. Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right

  18. Left ventricular aneurysm in short axis: a comparison of magnetic resonance, ultrasound and thallium-201 SPECT images

    International Nuclear Information System (INIS)

    Ahmad, M.; Johnson, R.F. Jr.; Fawcett, H.D.; Schreiber, M.H.

    1987-01-01

    Short axis magnetic resonance images of a left ventricular aneurysm were compared to similar views obtained by echocardiography and by thallium-201 single photon emission computed tomography. Images of the dyskinetic left ventricular apex and the contractile left ventricular base were analyzed and compared. Unlike the previously reported orthogonal plane magnetic resonance images, short axis imaging provided representative and quantitative information in views comparable to those obtained by standard noninvasive imaging techniques. These data indicate that short axis magnetic resonance imaging is capable of identifying and sizing the aneurysmal and the residual segments of the left ventricle. The findings may be of prognostic value in patients with left ventricular aneurysm

  19. Beat-to-beat left ventricular performance in atrial fibrillation: radionuclide assessment with the computerized nuclear probe

    International Nuclear Information System (INIS)

    Schneider, J.; Berger, H.J.; Sands, M.J.; Lachman, A.B.; Zaret, B.L.

    1983-01-01

    There is wide beat-to-beat variability in cycle length and left ventricular performance in patients with atrial fibrillation. In this study, left ventricular ejection fraction and relative left ventricular volumes were evaluated on a beat-to-beat basis with the computerized nuclear probe, an instrument with sufficiently high sensitivity to allow continuous evaluation of the radionuclide time-activity curve. Of 18 patients with atrial fibrillation, 5 had mitral stenosis, 6 had mitral regurgitation, and 7 had coronary artery disease. Fifty consecutive beats were analyzed in each patient. The mean left ventricular ejection fraction ranged from 17 to 51%. There was substantial beat-to-beat variation in cycle length and left ventricular ejection fraction in all patients, including those with marked left ventricular dysfunction. In 14 patients who also underwent multiple gated cardiac blood pool imaging, there was an excellent correlation between mean ejection fraction derived from the nuclear probe and gated ejection fraction obtained by gamma camera imaging (r . 0.90). Based on beat-to-beat analysis, left ventricular function was dependent on relative end-diastolic volume and multiple preceding cycle lengths, but not preceding end-systolic volumes. This study demonstrates that a single value for left ventricular ejection fraction does not adequately characterize left ventricular function in patients with atrial fibrillation. Furthermore, both the mean beat-to-beat and the gated ejection fraction may underestimate left ventricular performance at rest in such patients

  20. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    Science.gov (United States)

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  1. Impact of diabetes mellitus on worsening of the left ventricular ejection fraction in exercise-gated 201Tl myocardial single photon emission computed tomography in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Yamagishi, Hiroyuki; Yoshiyama, Minoru; Shirai, Naoya; Akioka, Kaname; Takeuchi, Kazuhide; Yoshikawa, Junichi

    2003-01-01

    It remains uncertain whether factors other than the severity of coronary artery disease (CAD) are associated with the worsening of the left ventricular ejection fraction (LVEF) by exercise. In the present study the impact of coronary risk factors on the worsening of LVEF by exercise was investigated in 391 patients with known or suspected CAD using exercise-gated 201 Tl scanning to calculate the LVEF. Significant worsening of the LVEF by exercise was defined as >4.7% (mean plus 1 SD of the value in 116 patients without CAD). Multivariate analysis revealed that diabetes mellitus (DM) was an independent risk factor for the worsening of LVEF by exercise in patients with multivessel (2- or 3-vessel) CAD with an odds ratio (95% confidence interval) of 2.2 (1.1-4.5, p=0.037). In 157 patients with 2- or 3-vessel CAD, 20 (23.5%) of 85 nondiabetic patients and 31 (43.1%, p=0.009 vs nondiabetic patients) of 72 diabetic patients showed significant worsening of LVEF by exercise. In patients with 2- or 3-vessel CAD, there was no significant difference in Gensini score or reversibility of perfusion defects between nondiabetic and diabetic patients. Thus, DM is a risk factor for worsening LVEF by exercise in addition to the severity of CAD. (author)

  2. GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Javier Duran

    Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

  3. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  4. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  5. Signal analysis of ventricular fibrillation

    NARCIS (Netherlands)

    Herbschleb, J.N.; Heethaar, R.M.; Tweel, L.H. van der; Zimmerman, A.N.E.; Meijler, F.L.

    Signal analysis of electro(cardio)grams during ventricular fibrillation (VF) in dogs and human patients indicates more organization and regularity than the official WHO definition suggests. The majority of the signal is characterized by a power spectrum with narrow, equidistant peaks. In a further

  6. Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors.

    Science.gov (United States)

    Patel, Hemal H; Head, Brian P; Petersen, Heidi N; Niesman, Ingrid R; Huang, Diane; Gross, Garrett J; Insel, Paul A; Roth, David M

    2006-07-01

    The role of caveolae, membrane microenvironments enriched in signaling molecules, in myocardial ischemia is poorly defined. In the current study, we used cardiac myocytes prepared from adult rats to test the hypothesis that opioid receptors (OR), which are capable of producing cardiac protection in vivo, promote cardiac protection in cardiac myocytes in a caveolae-dependent manner. We determined protein expression and localization of delta-OR (DOR) using coimmunohistochemistry, caveolar fractionation, and immunoprecipitations. DOR colocalized in fractions with caveolin-3 (Cav-3), a structural component of caveolae in muscle cells, and could be immunoprecipitated by a Cav-3 antibody. Immunohistochemistry confirmed plasma membrane colocalization of DOR with Cav-3. Cardiac myocytes were subjected to simulated ischemia (2 h) or an ischemic preconditioning (IPC) protocol (10 min ischemia, 30 min recovery, 2 h ischemia) in the presence and absence of methyl-beta-cyclodextrin (MbetaCD, 2 mM), which binds cholesterol and disrupts caveolae. We also assessed the cardiac protective effects of SNC-121 (SNC), a selective DOR agonist, on cardiac myocytes with or without MbetaCD and MbetaCD preloaded with cholesterol. Ischemia, simulated by mineral oil layering to inhibit gas exchange, promoted cardiac myocyte cell death (trypan blue staining), a response blunted by SNC (37 +/- 3 vs. 59 +/- 3% dead cells in the presence and absence of 1 muM SNC, respectively, P protective effects of IPC or SNC, resulting in cell death comparable to that of the ischemic group. By contrast, SNC-induced protection was not abrogated in cells incubated with cholesterol-saturated MbetaCD, which maintained caveolae structure and function. These findings suggest a key role for caveolae, perhaps through enrichment of signaling molecules, in contributing to protection of cardiac myocytes from ischemic damage.

  7. Alternative right ventricular pacing sites.

    Science.gov (United States)

    Łuciuk, Dariusz; Łuciuk, Marek; Gajek, Jacek

    2015-01-01

    The main adverse effect of chronic stimulation is stimulation-induced heart failure in case of ventricular contraction dyssynchrony. Because of this fact, new techniques of stimulation should be considered to optimize electrotherapy. One of these methods is pacing from alternative right ventricular sites. The purpose of this article is to review currently accumulated data about alternative sites of cardiac pacing. Medline and PubMed bases were used to search English and Polish reports published recently. Recent studies report a deleterious effect of long term apical pacing. It is suggested that permanent apical stimulation, by omitting physiological conduction pattern with His-Purkinie network, may lead to electrical and mechanical dyssynchrony of heart muscle contraction. In the long term this pathological situation can lead to severe heart failure and death. Because of this, scientists began to search for some alternative sites of cardiac pacing to reduce the deleterious effect of stimulation. Based on current accumulated data, it is suggested that the right ventricular outflow tract, right ventricular septum, direct His-bundle or biventricular pacing are better alternatives due to more physiological electrical impulse propagation within the heart and the reduction of the dyssynchrony effect. These methods should preserve a better left ventricular function and prevent the development of heart failure in permanent paced patients. As there is still not enough, long-term, randomized, prospective, cross-over and multicenter studies, further research is required to validate the benefits of using this kind of therapy. The article should pay attention to new sites of cardiac stimulation as a better and safer method of treatment.

  8. Laser microdissection and capture of pure cardiomyocytes and fibroblasts from infarcted heart regions: perceived hyperoxia induces p21 in peri-infarct myocytes.

    Science.gov (United States)

    Kuhn, Donald E; Roy, Sashwati; Radtke, Jared; Khanna, Savita; Sen, Chandan K

    2007-03-01

    Myocardial infarction caused by ischemia-reperfusion in the coronary vasculature is a focal event characterized by an infarct-core, bordering peri-infarct zone and remote noninfarct zone. Recently, we have reported the first technique, based on laser microdissection pressure catapulting (LMPC), enabling the dissection of infarction-induced biological responses in multicellular regions of the heart. Molecular mechanisms in play at the peri-infarct zone are central to myocardial healing. At the infarct site, myocytes are more sensitive to insult than robust fibroblasts. Understanding of cell-specific responses in the said zones is therefore critical. In this work, we describe the first technique to collect the myocardial tissue with a single-cell resolution. The infarcted myocardium was identified by using a truncated hematoxylin-eosin stain. Cell elements from the infarct, peri-infarct, and noninfarct zones were collected in a chaotropic RNA lysis solution with micron-level surgical precision. Isolated RNA was analyzed for quality by employing microfluidics technology and reverse transcribed to generate cDNA. Purity of the collected specimen was established by real-time PCR analyses of cell-specific genes. Previously, we have reported that the oxygen-sensitive induction of p21/Cip1/Waf1/Sdi1 in cardiac fibroblasts in the peri-infarct zone plays a vital role in myocardial remodeling. Using the novel LMPC technique developed herein, we confirmed that finding and report for the first time that the induction of p21 in the peri-infarct zone is not limited to fibroblasts but is also evident in myocytes. This work presents the first account of an analytical technique that applies the LMPC technology to study myocardial remodeling with a cell-type specific resolution.

  9. Optimal Population of Embryonic Stem Cells in "Hanging Drop" Culture for in-vitro Differentiation to Cardiac Myocytes

    OpenAIRE

    MIWA, Keiko; LEE, Jong-Kook; HIDAKA, Kyoko; SHI, Rong-qian; MORISAKI, Takayuki; KODAMA, Itsuo

    2002-01-01

    Pluripotent embryonic stem (ES) cells differentiate to cardiac myocytes in vitro by many other previous reports demonstrated "hanging-drop" method. In this study, the number of ES cells in each hanging-drop plays an important role in the cultivation of cardiac myocytes. We examined the optimal hanging-drop size to obtain embryonic stem cell-derived cardiac cells (ESCMs) in vitro using specific labeled mouse ES cells (hCGP7) which were stably transfected with the enhanced green fluorescent pro...

  10. Four cases of right ventricular dysplasia

    International Nuclear Information System (INIS)

    Takamura, Ichiro; Ando, Joji; Miyamoto, Atsushi; Kobayashi, Takeshi; Sakamoto, Sanya; Yasuda, Hisakazu

    1985-01-01

    Finding of 81 Kr right ventriculography and 201 Tl myocardial perfusion imaging in 4 patients with right ventricular dysplasia (RVD) were compared with those in 28 patients with dilated cardiomyopathy. Remarkably dilated right ventricle was detected on 201 Tl myocardial perfusion imaging in the RVD group. In a patient with RVD who died suddenly, perfusion defect of the left ventricular myocardium, a decreased right ventricular ejection fraction, and an increased right ventricular end diastolic volume were seen. Perfusion defect of the left ventricular myocardium was seen in 10 of the 28 patients with dilated cardiomyopathy, 4 of whom died suddenly. In these 4 patients, a decreased left ventricular ejection fraction and an increased right ventricular end diastolic volume were seen. These findings obtained by the radionuclide techniques suggested that there are differences in cardiac dysfunction of the both ventricles between the groups with RVD and dilated cardiomyopathy. (Namekawa, K.)

  11. Adeno-Associated Virus Serotype 9–Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts With Left Ventricular Dysfunction Secondary to a Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Tijana Knezevic, PhD

    2016-12-01

    Full Text Available Mutations in Bcl-2–associated athanogene 3 (BAG3 were associated with skeletal muscle dysfunction and dilated cardiomyopathy. Retro-orbital injection of an adeno-associated virus serotype 9 expressing BAG3 (rAAV9-BAG3 significantly (p < 0.0001 improved left ventricular ejection fraction, fractional shortening, and stroke volume 9 days post-injection in mice with cardiac dysfunction secondary to a myocardial infarction. Furthermore, myocytes isolated from mice 3 weeks after injection showed improved cell shortening, enhanced systolic [Ca2+]i and increased [Ca2+]i transient amplitudes, and increased maximal L-type Ca2+ current amplitude. These results suggest that BAG3 gene therapy may provide a novel therapeutic option for the treatment of heart failure.

  12. Robust generation and expansion of skeletal muscle progenitors and myocytes from human pluripotent stem cells.

    Science.gov (United States)

    Shelton, Michael; Kocharyan, Avetik; Liu, Jun; Skerjanc, Ilona S; Stanford, William L

    2016-05-15

    Human pluripotent stem cells provide a developmental model to study early embryonic and tissue development, tease apart human disease processes, perform drug screens to identify potential molecular effectors of in situ regeneration, and provide a source for cell and tissue based transplantation. Highly efficient differentiation protocols have been established for many cell types and tissues; however, until very recently robust differentiation into skeletal muscle cells had not been possible unless driven by transgenic expression of master regulators of myogenesis. Nevertheless, several breakthrough protocols have been published in the past two years that efficiently generate cells of the skeletal muscle lineage from pluripotent stem cells. Here, we present an updated version of our recently described 50-day protocol in detail, whereby chemically defined media are used to drive and support muscle lineage development from initial CHIR99021-induced mesoderm through to PAX7-expressing skeletal muscle progenitors and mature skeletal myocytes. Furthermore, we report an optional method to passage and expand differentiating skeletal muscle progenitors approximately 3-fold every 2weeks using Collagenase IV and continued FGF2 supplementation. Both protocols have been optimized using a variety of human pluripotent stem cell lines including patient-derived induced pluripotent stem cells. Taken together, our differentiation and expansion protocols provide sufficient quantities of skeletal muscle progenitors and myocytes that could be used for a variety of studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. YY1 Protects Cardiac Myocytes from Pathologic Hypertrophy by Interacting with HDAC5

    Science.gov (United States)

    Dockstader, Karen; McKinsey, Timothy A.

    2008-01-01

    YY1 is a transcription factor that can repress or activate the transcription of a variety of genes. Here, we show that the function of YY1 as a repressor in cardiac myocytes is tightly dependent on its ability to interact with histone deacetylase 5 (HDAC5). YY1 interacts with HDAC5, and overexpression of YY1 prevents HDAC5 nuclear export in response to hypertrophic stimuli and the increase in cell size and re-expression of fetal genes that accompany pathological cardiac hypertrophy. Knockdown of YY1 results in up-regulation of all genes present during fetal development and increases the cell size of neonatal cardiac myocytes. Moreover, overexpression of a YY1 deletion construct that does not interact with HDAC5 results in transcription activation, suggesting that HDAC5 is necessary for YY1 function as a transcription repressor. In support of this relationship, we show that knockdown of HDAC5 results in transcription activation by YY1. Finally, we show that YY1 interaction with HDAC5 is dependent on the HDAC5 phosphorylation domain and that overexpression of YY1 reduces HDAC5 phosphorylation in response to hypertrophic stimuli. Our results strongly suggest that YY1 functions as an antihypertrophic factor by preventing HDAC5 nuclear export and that up-regulation of YY1 in human heart failure may be a protective mechanism against pathological hypertrophy. PMID:18632988

  14. Effect of PPAR γ activators on hypertrophic cardiac myocytes in vitro

    International Nuclear Information System (INIS)

    Wu Shimin; Zhou Xin; Ye Ping; Wang Qiong; Gao Yue; Liu Yongxue

    2004-01-01

    Objective: To investigate the effects of peroxisome proliferator-activated receptor γ (PPAR γ) activators pioglitazone and 15-deoxy-Δ 12,14 prostaglandin J 2 (15d-PGJ 2 ) on hypertrophic cardiac myocytes (MC) of neonatal rats in vitro. Methods; With the stimulation of angiotensin II(Ang II), a model of hypertrophy of MC was established. With the method of reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was amplified; with the aid of NIH Image J software the surface area of MC was analyzed and with 3 H-leucine incorporation, the synthesizing rate of protein in MC was measured. Results: Increases in surface area of MC, mRNA expression of ANP and BNP and 3 H-leucine incorporation in MC were observed in the model of cardiac hypertrophy. Pioglitazone and 15d-PGJ 2 , two kinds of PPAR γ activators, inhibited the above changes in a dose-dependent manner. Conclusion: It is suggested that PPAR γ activators inhibit hypertrophy of cardiac myocytes and PPAR γ-dependent pathway be involved in the inhibitory course

  15. Expression of androgen-binding protein (ABP) in human cardiac myocytes.

    Science.gov (United States)

    Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

    2006-04-01

    Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

  16. Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes

    International Nuclear Information System (INIS)

    Luttrell, L.M.; Hewlett, E.L.; Romero, G.; Rogol, A.D.

    1988-01-01

    The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 mycocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with [ 32 P]NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on [ 3 H]thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated [ 3 H]thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin

  17. Acute desensitization of acetylcholine and endothelin-1 activated inward rectifier K+ current in myocytes from the cardiac atrioventricular node.

    Science.gov (United States)

    Choisy, Stéphanie C M; James, Andrew F; Hancox, Jules C

    2012-07-06

    The atrioventricular node (AVN) is a vital component of the pacemaker-conduction system of the heart, co-ordinating conduction of electrical excitation from cardiac atria to ventricles and acting as a secondary pacemaker. The electrical behaviour of the AVN is modulated by vagal activity via activation of muscarinic potassium current, IKACh. However, it is not yet known if this response exhibits 'fade' or desensitization in the AVN, as established for the heart's primary pacemaker--the sinoatrial node. In this study, acute activation of IKACh in rabbit single AVN cells was investigated using whole-cell patch clamp at 37 °C. 0.1-1 μM acetylcholine (ACh) rapidly activated a robust IKACh in AVN myocytes during a descending voltage-ramp protocol. This response was inhibited by tertiapin-Q (TQ; 300 nM) and by the M2 muscarinic ACh receptor antagonist AFDX-116 (1 μM). During sustained ACh exposure the elicited IKACh exhibited bi-exponential fade (τf of 2.0 s and τs 76.9 s at -120 mV; 1 μM ACh). 10 nM ET-1 elicited a current similar to IKACh, which faded with a mono-exponential time-course (τ of 52.6 s at -120 mV). When ET-1 was applied following ACh, the ET-1 activated response was greatly attenuated, demonstrating that ACh could desensitize the response to ET-1. For neither ACh nor ET-1 was the rate of current fade dependent upon the initial response magnitude, which is inconsistent with K+ flux mediated changes in electrochemical driving force as the underlying mechanism. Collectively, these findings demonstrate that TQ sensitive inwardly rectifying K+ current in cardiac AVN cells, elicited by M2 muscarinic receptor or ET-1 receptor activation, exhibits fade due to rapid desensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. The right ventricular response to ventricular hypofunction in anteroseptal infarction

    International Nuclear Information System (INIS)

    Kanayama, Sugako

    1992-01-01

    Thirty-seven patients with acute anteroseptal infarction but not significant right coronary artery stenosis were examined by using thallium-201 (Tl-201) myocardial perfusion SPECT to determine how the right ventricular (RV) free wall responded to a severely impaired ventricular septum. The patients were divided into the group in which RV free wall was visualized on Tl-201 myocardial SPECT (n=19, RV(+) Group) and the group in which it was not visualized (n=18, RV(-) Group). The relationship between visualization of RV free wall and both RV and left ventricular (LV) function was evaluated. RV(+) Group had larger extent of anteroseptal necrosis and severer impairment of RV free wall, as compared with RV(-) Group. LV ejection fraction (LVEF) was significantly lower in RV(+) Group than RV(-) Group in both acute and chronic phases. Although RV ejection fraction (RVEF) in acute phase was significantly lower in RV(+) Group than RV(-) Group, it did not differ in chronic phase between the two groups. In RV(+) Group, RV stroke work index (RVSWI), pulmonary artery end diastolic pressure (PAEDP), and mean pulmonary artery pressure (MPA) in chronic phase showed a statistically significant increase compared with those in acute phase; these hemodynamic variables in chronic phase were also significantly higher than those in RV(-) Group. RV/LV ratio inversely correlated with LVEF, and both necrotic extent and impairment severity positively correlated with both PAEDP and MPA. RV free wall could be visualized more clearly, corresponding to extremely decreased LV function. These findings suggest that RV free wall may play an important role in maintaining LV and RV function when ventricular septum is severely impaired by anteroseptal infarction. (N.K.)

  19. Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia.

    LENUS (Irish Health Repository)

    Corrado, Domenico

    2010-09-21

    The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy\\/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue.

  20. Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.

    Science.gov (United States)

    Nisbet, Ashley M; Camelliti, Patrizia; Walker, Nicola L; Burton, Francis L; Cobbe, Stuart M; Kohl, Peter; Smith, Godfrey L

    2016-05-01

    Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Calculation of cardiac pressures using left ventricular ejection fraction (LVEF) derived from radionuclide angiography

    International Nuclear Information System (INIS)

    Hommer, E.

    1981-01-01

    An attempt has been made to develop formulas to determine cardiac pressures in an undisturbed flow in patients without valvular or shunt diseases. These are based entirely on the results of left ventricular ejection fraction rates, permitting pressure analysis of several compartments at the same tine. According to BORER et al. they also enable determination of left ventricular 'Functional Reserve' after bycycle exercise as well as left ventricular 'Relaxation Reserve'. They support the views of NYHA in determining the grades of cardiac insufficiency proving the system- and low-pressure participation. A single formula for pulmonary flow can determine the pulmonary arterial pressure. The left ventricular enddiastolic pressure can also be exclusively calculated by values of left ventricular functions, thus both formulas may be used in disorders of the mitral valves. The possibility to calculate pressures of all the compartments of the heart from left ventricular ejection rate shows, that in undisturbed flow global heart function depends on left ventricular function. Therefore the mutual dependence of these formulas presents an intercompartimental pressure regulation of the heart through pulmonary flow and pulmonary vascular pressure, which leaves an aspect of autonomous cardiac regulation open to discussion. (orig.) [de

  2. Late deterioration of left ventricular function after right ventricular pacemaker implantation.

    Science.gov (United States)

    Bellmann, Barbara; Muntean, Bogdan G; Lin, Tina; Gemein, Christopher; Schmitz, Kathrin; Schauerte, Patrick

    2016-09-01

    Right ventricular (RV) pacing induces a left bundle branch block pattern on ECG and may promote heart failure. Patients with dual chamber pacemakers (DCPs) who present with progressive reduction in left ventricular ejection fraction (LVEF) secondary to RV pacing are candidates for cardiac resynchronization therapy (CRT). This study analyzes whether upgrading DCP to CRT with the additional implantation of a left ventricular (LV) lead improves LV function in patients with reduced LVEF following DCP implantation. Twenty-two patients (13 males) implanted with DCPs and a high RV pacing percentage (>90%) were evaluated in term of new-onset heart failure symptoms. The patients were enrolled in this retrospective single-center study after obvious causes for a reduced LVEF were excluded with echocardiography and coronary angiography. In all patients, DCPs were then upgraded to biventricular devices. LVEF was analyzed with a two-sided t-test. QRS duration and brain natriuretic peptide (BNP) levels were analyzed with the unpaired t-test. LVEF declined after DCP implantation from 54±10% to 31±7%, and the mean QRS duration was 161±20 ms during RV pacing. NT-pro BNP levels were elevated (3365±11436 pmol/L). After upgrading to a biventricular device, a biventricular pacing percentage of 98.1±2% was achieved. QRS duration decreased to 108±16 ms and 106±20 ms after 1 and 6 months, respectively. There was a significant increase in LVEF to 38±8% and 41±11% and a decrease in NT-pro BNP levels to 3088±2326 pmol/L and 1860±1838 pmol/L at 1 and 6 months, respectively. Upgrading to CRT may be beneficial in patients with DCPs and heart failure induced by a high RV pacing percentage.

  3. Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle

    NARCIS (Netherlands)

    Le, C. T.; Hollaar, L.; van der Valk, E. J.; Franken, N. A.; van Ravels, F. J.; Wondergem, J.; van der Laarse, A.

    1995-01-01

    The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG),

  4. 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.

  5. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

    NARCIS (Netherlands)

    M. Rosa-Garrido (Manuel); Chapski, D.J. (Douglas J.); Schmitt, A.D. (Anthony D.); Kimball, T.H. (Todd H.); Karbassi, E. (Elaheh); Monte, E. (Emma); Balderas, E. (Enrique); Pellegrini, M. (Matteo); Shih, T.-T. (Tsai-Ting); Soehalim, E. (Elizabeth); D.A. Liem (David); Ping, P. (Peipei); N.J. Galjart (Niels); Ren, S. (Shuxun); Wang, Y. (Yibin); Ren, B. (Bing); Vondriska, T.M. (Thomas M.)

    2017-01-01

    textabstractBACKGROUND: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined.METHODS: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation

  6. Right ventricular function in patients with ischemic heart disease

    International Nuclear Information System (INIS)

    Araki, Haruo; Hisano, Ryuichi; Nagata, Yoshiyuki; Caglar, N.; Nakamura, Motoomi

    1985-01-01

    Thirty-five patients with ischemic heart disease (IHD) and 10 normal subjects were studied. Right and left ventricular ejecction fractions (EF) were determined using equilibrium radionuclide ventriculography with technetium-99m. Furthermore, abnormal motion of the right ventricular septal wall was obtained by cardiac cathetelization, and its relation to the right ventricular EF was examined. In IHD patients with anterior myocardial infarction, left ventricular EF decreased, but right ventricular EF was normal. This suggested that left ventricular dysfunction does not always have an effect on right ventricular function. Right ventricular EF was normal even when akinesis or dyskinesis was present in the ventricular septul, suggesting that abnormal motion of the ventricular septal wall has no significantly stimulant effect on right ventricular function. A decreased right ventricular EF was likely to occur only when the right ventricular free wall became ischemic or necrotic simultaneously with occurrence of posterior myocardial infarction. (Namekawa, K.)

  7. Surgical ablation of ventricular tachycardia secondary to congenital ventricular septal aneurysm.

    Science.gov (United States)

    Graffigna, A; Minzioni, G; Ressia, L; Vigano, M

    1994-04-01

    Three patients underwent surgical ablation for ventricular tachycardia resulting from an aneurysm of the membranous portion of the ventricular septum. Two patients had a definite history of cardiac murmur during infancy, and one of them was found at the time of operation to have a left-to-right shunt through the apex of the aneurysm. The earliest ventricular activation sites were located around the neck of the aneurysm and were ablated in 1 patient by encircling the endocardial ventriculotomy and by cryoablation in the remaining 2. After focus resection had been completed, aneurysm resection and ventricular septal reconstruction were performed. All patients were alive and free of ventricular tachycardia and did not need medication as of 61, 66, and 88 months postoperatively. Spontaneous closure of a ventricular septal defect may lead to the formation of an aneurysm in the ventricular septum that may sustain ventricular tachycardias. Such arrhythmias can be effectively treated using electrically guided surgical techniques.

  8. Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy.

    Science.gov (United States)

    Liu, Dan; Hu, Kai; Nordbeck, Peter; Ertl, Georg; Störk, Stefan; Weidemann, Frank

    2016-05-10

    Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.

  9. Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

    Science.gov (United States)

    Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V.; Tai, TC; Saleh, Mazen; Parrillo, Joseph E.; Kumar, Anand

    2012-01-01

    Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-stranded RNA (dsRNA). Here, we identify bacterial RNA as a distinct pathogenic pattern recognized by PKR. Our results indicate that natural RNA derived from bacteria directly binds to and activates PKR. We further show that bacterial RNA induces human cardiac myocyte apoptosis and identify the requirement for PKR in mediating this response. In addition to bacterial immunity, the results presented here may also have implications in cardiac pathophysiology. PMID:22833816

  10. Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

    Science.gov (United States)

    Werneck-de-Castro, Joao P.; Fonseca, Tatiana L.; Ignacio, Daniele L.; Fernandes, Gustavo W.; Andrade-Feraud, Cristina M.; Lartey, Lattoya J.; Ribeiro, Marcelo B.; Ribeiro, Miriam O.; Gereben, Balazs

    2015-01-01

    The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

  11. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

    International Nuclear Information System (INIS)

    Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

    2005-01-01

    The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

  12. Myocyte specific overexpression of myoglobin impairs angiogenesis after hind-limb ischemia.

    Science.gov (United States)

    Hazarika, Surovi; Angelo, Michael; Li, Yongjun; Aldrich, Amy J; Odronic, Shelley I; Yan, Zhen; Stamler, Jonathan S; Annex, Brian H

    2008-12-01

    In preclinical models of peripheral arterial disease the angiogenic response is typically robust, though it can be impaired in conditions such as hypercholesterolemia and diabetes where the endothelium is dysfunctional. Myoglobin (Mb) is expressed exclusively in striated muscle cells. We hypothesized that myocyte specific overexpression of myoglobin attenuates ischemia-induced angiogenesis even in the presence of normal endothelium. Mb overexpressing transgenic (MbTg, n=59) and wild-type (WT, n=56) C57Bl/6 mice underwent unilateral femoral artery ligation/excision. Perfusion recovery was monitored using Laser Doppler. Ischemia-induced changes in muscle were assessed by protein and immunohistochemistry assays. Nitrite/nitrate and protein-bound NO, and vasoreactivity was measured. Vasoreactivity was similar between MbTg and WT. In ischemic muscle, at d14 postligation, MbTg increased VEGF-A, and activated eNOS the same as WT mice but nitrate/nitrite were reduced whereas protein-bound NO was higher. MbTg had attenuated perfusion recovery at d21 (0.37+/-0.03 versus 0.47+/-0.02, P<0.05), d28 (0.40+/-0.03 versus 0.50+/-0.04, P<0.05), greater limb necrosis (65.2% versus 15%, P<0.001), a lower capillary density, and greater apoptosis versus WT. Increased Mb expression in myocytes attenuates angiogenesis after hind-limb ischemia by binding NO and reducing its bioavailability. Myoglobin can modulate the angiogenic response to ischemia even in the setting of normal endothelium.

  13. The Managed Ventricular pacing versus VVI 40 Pacing (MVP) Trial: clinical background, rationale, design, and implementation.

    Science.gov (United States)

    Sweeney, Michael O; Ellenbogen, Kenneth A; Miller, Elaine Hogan; Sherfesee, Lou; Sheldon, Todd; Whellan, David

    2006-12-01

    Implantable cardioverter defibrillators (ICDs) reduce mortality among appropriately selected patients who have had or are at risk for life-threatening ventricular arrhythmia. Right ventricular apical (RVA) pacing has been implicated in worsening heart failure and death. The optimal pacemaker mode for bradycardia support while minimizing unnecessary and potentially harmful RVA pacing has not been determined. The Managed Ventricular pacing vs. VVI 40 Pacing Trial (MVP) is a prospective, multicenter, randomized, single-blind, parallel, controlled clinical trial designed to establish whether atrial-based dual-chamber managed ventricular pacing mode (MVP) is equivalent or superior to back-up only ventricular pacing (VVI 40) among patients with standard indications for ICD therapy and no indication for bradycardia pacing. The MVP Trial is designed with 80% power to detect a 10% reduction in the primary endpoint of new or worsening heart failure or all-cause mortality in the MVP-treated group. Approximately 1,000 patients at 80 centers in the United States, Canada, Western Europe, and Israel will be randomized to MVP or VVI 40 pacing after successful implantation of a dual-chamber ICD. Heart failure therapies will be optimized in accordance with evidence-based guidelines. Prespecified secondary endpoints will include ventricular arrhythmias, atrial fibrillation, new indication for bradycardia pacing, health-related quality of life, and cost effectiveness. Enrollment began in October 2004 and concluded in April 2006. The study will be terminated upon recommendation of the Data Monitoring Committee or when the last patient enrolled and surviving has reached a minimum 2 years of follow-up. The MVP Trial will meet the clinical need for carefully designed prospective studies to define the benefits of atrial-based dual-chamber minimal ventricular pacing versus single-chamber ventricular pacing in conventional ICD patients.

  14. Right Ventricular Outflow Tract Tachycardia with Structural Abnormalities of the Right Ventricle and Left Ventricular Diverticulum

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    Bortolo Martini

    2015-01-01

    Full Text Available A 43-year-old woman presented to the emergency room with a sustained ventricular tachycardia (VT. ECG showed a QRS in left bundle branch block morphology with inferior axis. Echocardiography, ventricular angiography, and cardiac magnetic resonance imaging (CMRI revealed a normal right ventricle and a left ventricular diverticulum. Electrophysiology studies with epicardial voltage mapping identified a large fibrotic area in the inferolateral layer of the right ventricular wall and a small area of fibrotic tissue at the anterior right ventricular outflow tract. VT ablation was successfully performed with combined epicardial and endocardial approaches.

  15. Mechanical stress is associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot.

    Science.gov (United States)

    Tang, Dalin; Yang, Chun; Del Nido, Pedro J; Zuo, Heng; Rathod, Rahul H; Huang, Xueying; Gooty, Vasu; Tang, Alexander; Billiar, Kristen L; Wu, Zheyang; Geva, Tal

    2016-03-01

    Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement. Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis. Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1. Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  16. Electrical Signs predictors of malignant ventricular arrhythmias

    International Nuclear Information System (INIS)

    Aleman Fernandez, Ailema Amelia; Dorantes Sanchez, Margarita

    2012-01-01

    Recurrence of malignant ventricular arrhythmia is frequent in cardioverter-defibrillators related patients. The risk stratification is difficult, there are numerous electrocardiographic predictors but his sensibility and specificity are not absolute. The limit between normal and pathological is not defined, besides the complexity of ventricular arrhythmias. We expose different electrocardiographic predictors that can help to better individual risk stratification

  17. Bidirectional ventricular tachycardia of unusual etiology

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    Praloy Chakraborty

    2015-11-01

    Full Text Available Bidirectional ventricular tachycardia (BDVT is a rare form of ventricular arrhythmia, characterized by changing QRS axis of 180 degrees. Digitalis toxicity is considered as commonest cause of BDVT; other causes include aconite toxicity, myocarditis, myocardial infarction, metastatic cardiac tumour and cardiac channelopathies. We describe a case of BDVT in a patient with Anderson-Tawil syndrome.

  18. Detection of premature ventricular contractions on a ventricular electrocardiogram for patients with left ventricular assist devices.

    Science.gov (United States)

    Park, Sung Min; Lee, Jin Hong; Choi, Seong Wook

    2014-12-01

    The ventricular electrocardiogram (v-ECG) was developed for long-term monitoring of heartbeats in patients with a left ventricular assist device (LVAD) and does not normally have the functionality necessary to detect additional heart irregularities that can progress to critical arrhythmias. Although the v-ECG has the benefits of physiological optimization and counterpulsation control, when abnormal heartbeats occur, the v-ECG does not show the distinct abnormal waveform that enables easy detection of an abnormal heartbeat among normal heartbeats on the conventional ECG. In this study, the v-ECGs of normal and abnormal heartbeats are compared with each other with respect to peak-to-peak voltage, area, and maximal slopes, and a new method to detect abnormal heartbeats is suggested. In a series of animal experiments with three porcine models (Yorkshire pigs weighing 30-40 kg), a v-ECG and conventional ECG were taken simultaneously during LVAD perfusion. Clinical experts found 104 abnormal heartbeats from the saved conventional ECG data and confirmed that the other 3159 heartbeats were normal. Almost all of the abnormal heartbeats were premature ventricular contractions (PVCs), and there was short-term tachycardia for 3 s. A personal computer was used to automatically detect abnormal heartbeats with the v-ECG according to the new method, and its results were compared with the clinicians' results. The new method found abnormal heartbeats with 90% accuracy, and less than 15% of the total PVCs were missed. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  19. 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

  20. Predictors of the left ventricular dysfunction induced by ventricular arrhythmia

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    А. І. Vytryhovskiy

    2016-08-01

    Full Text Available The most powerful predictor of life-threatening arrhythmia risk is a combination of low heart rate variability with low ejection fraction (EF of the left ventricle. Aim. To identify predictors of left ventricle dysfunction which is induced by ventricular arrhythmia. Materials and methods. To diagnose structural changes of left ventricular functional capacity and reserves in patients with previous myocardial infarction and patients with high and very high cardiovascular risk by SCORE scale and for establishment the relationship between morphological heart changes and pathological phenomenon of heart turbulence echocardiography and study of heart rate turbulence variability were performed. 603 patients were selected for the research. All patients were divided into groups: group 1 – patients with coronary heart disease, but without associated risk factors, such as smoking, obesity, metabolic syndrome; group 2 – patients who smoke tobacco more than 2 years (very high cardiovascular risk by scale SCORE; group 3 – patients with metabolic syndrome without coronary heart disease or arterial hypertension (very high cardiovascular risk by scale SCORE. The control group consisted of 149 persons. Results. The feature of structural changes in patients with myocardial infarction and in patients with a high cardiovascular risk by SCORE with heart rate turbulence compared with cases without НRT is considerably thickening of the left interventricular septum in systole. Based on this, it can be argued that the emergence of ventricular arrhythmia and accordingly phenomenon of heart rate turbulence in patients with existing cardiovascular diseases and risk factors has both morphological and functional character. Significant difference of echocardioscopy parameters in patients with postinfarction cardiosclerosis and risk factors by the SCORE system was established by index of intraventricular septum thickness in systole, and in persons with high risk – in

  1. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  2. Troponin and anti-troponin autoantibody levels in patients with ventricular noncompaction.

    Directory of Open Access Journals (Sweden)

    Hatice Betül Erer

    Full Text Available Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24 and noncompaction with reduced EF (LVEF <35%, n = 26 groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group, troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG. Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.

  3. Troponin and Anti-Troponin Autoantibody Levels in Patients with Ventricular Noncompaction

    Science.gov (United States)

    Erer, Hatice Betül; Güvenç, Tolga Sinan; Kemik, Ahu Sarbay; Yılmaz, Hale Yaka; Kul, Şeref; Altay, Servet; Sayar, Nurten; Kaya, Yüksel; Eren, Mehmet

    2013-01-01

    Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients. PMID:23469039

  4. Left and right ventricular dyssynchrony and strains from cardiovascular magnetic resonance feature tracking do not predict deterioration of ventricular function in patients with repaired tetralogy of Fallot.

    Science.gov (United States)

    Jing, Linyuan; Wehner, Gregory J; Suever, Jonathan D; Charnigo, Richard J; Alhadad, Sudad; Stearns, Evan; Mojsejenko, Dimitri; Haggerty, Christopher M; Hickey, Kelsey; Valente, Anne Marie; Geva, Tal; Powell, Andrew J; Fornwalt, Brandon K

    2016-08-22

    Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF. A database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, >6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and RV peak global longitudinal strains. Three outcomes were defined, whose changes were assessed over time: RV end-diastolic volume, and RV and LV ejection fraction. Multivariate linear mixed models were fit to investigate relationships of outcomes to predictors and ten potential baseline confounders. One hundred fifty-three patients with rTOF (23 ± 14 years, 50 % male) were included. The mean follow-up duration between the first and last CMR was 2.9 ± 1.3 years. After adjustment for confounders, none of the 7 primary predictors were significantly associated with change over time in the 3 outcome variables. Only 1-17 % of the variability in the change over time in the outcome variables was explained by the baseline predictors and potential confounders. In patients with repaired tetralogy of Fallot, ventricular dyssynchrony and global strain derived from cine CMR were not significantly related to changes in ventricular size and function over time. The ability to predict deterioration in ventricular function in patients with rTOF using current methods is limited.

  5. Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition.

    Science.gov (United States)

    Chia, Karin K M; Liu, Chia-Chi; Hamilton, Elisha J; Garcia, Alvaro; Fry, Natasha A; Hannam, William; Figtree, Gemma A; Rasmussen, Helge H

    2015-08-15

    Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na(+)-K(+) pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na(+)-K(+) pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na(+)-K(+) pump current (Ip). Coexposure to 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na(+)-K(+) pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47(phox) NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22(phox) subunit, and it decreased O2 (·-)-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47(phox) indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22(phox) and p47(phox) NADPH oxidase subunits and decrease β1-Na(+)-K(+) pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. Copyright © 2015 the American Physiological Society.

  6. Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

    International Nuclear Information System (INIS)

    Nan, Changlong; Li, Yuejin; Jean-Charles, Pierre-Yves; Chen, Guozhen; Kreymerman, Alexander; Prentice, Howard; Weissbach, Herbert; Huang, Xupei

    2010-01-01

    Research highlights: → Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. → Mitochondrial damage happens in the heart lacking MsrA. → More protein oxidation in myocardial cells lacking MsrA. → MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA -/- ) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA -/- mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2 Hz), is significantly reduced in MsrA -/- cardiac myocytes. MsrA -/- cardiac myocytes also show a significant decrease in contractility after oxidative stress using H 2 O 2 . Corresponding changes in Ca 2+ transients are observed in MsrA -/- cardiomyocytes treated with 2 Hz stimulation or with H 2 O 2 . Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA -/- mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA -/- mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.

  7. α-Catenin localization and sarcomere self-organization on N-cadherin adhesive patterns are myocyte contractility driven.

    Directory of Open Access Journals (Sweden)

    Anant Chopra

    Full Text Available The N-cadherin (N-cad complex plays a crucial role in cardiac cell structure and function. Cadherins are adhesion proteins linking adjacent cardiac cells and, like integrin adhesions, are sensitive to force transmission. Forces through these adhesions are capable of eliciting structural and functional changes in myocytes. Compared to integrins, the mechanisms of force transduction through cadherins are less explored. α-catenin is a major component of the cadherin-catenin complex, thought to provide a link to the cell actin cytoskeleton. Using N-cad micropatterned substrates in an adhesion constrainment model, the results from this study show that α-catenin localizes to regions of highest internal stress in myocytes. This localization suggests that α-catenin acts as an adaptor protein associated with the cadherin mechanosensory apparatus, which is distinct from mechanosensing through integrins. Myosin inhibition in cells bound by integrins to fibronectin-coated patterns disrupts myofibiril organization, whereas on N-cad coated patterns, myosin inhibition leads to better organized myofibrils. This result indicates that the two adhesion systems provide independent mechanisms for regulating myocyte structural organization.

  8. β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

    Science.gov (United States)

    Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

    2013-11-01

    To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab. In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

  9. Remodelado ventricular y cirugía

    Directory of Open Access Journals (Sweden)

    Ignacio Moriones

    2008-01-01

    Se han diseñado anillos mitrales como el de Carpentier- McCarthy-Adams (IMR ETlogix™ para pacientes isquémicos, o el Edwards-Geoform™ en miocardiopatías. La asistencia ventricular puede conseguir en determinados casos recuperación permanente del volumen de la cavidad y función ventricular, particularmente en miocarditis y determinadas miocardiopatías. Paralelamente, se han iniciado experiencias con el sistema de contención CorCap o el sistema Myosplint. Finalmente, la actuación sobre las valvulopatías y la revascularización favorecen la restauración ventricular.

  10. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes.

    Science.gov (United States)

    Zimmermann, W H; Fink, C; Kralisch, D; Remmers, U; Weil, J; Eschenhagen, T

    2000-04-05

    A technique is presented that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3-dimensional engineered heart tissue (EHT) in vitro, either as a plane biconcaval matrix anchored at both sides on Velcro-coated silicone tubes or as a ring. Contractile activity was monitored in standard organ baths or continuously in a CO(2) incubator for up to 18 days (=26 days after casting). Long-term measurements showed an increase in force between days 8 and 18 after casting and stable forces thereafter. At day 10, the twitch amplitude (TA) of electrically paced EHTs (average length x width x thickness, 11 x 6 x 0.4 mm) was 0.51 mN at length of maximal force development (L(max)) and a maximally effective calcium concentration. EHTs showed typical features of neonatal rat heart: a positive force-length and a negative force-frequency relation, high sensitivity to calcium (EC(50) 0.24 mM), modest positive inotropic (increase in TA by 46%) and pronounced positive lusitropic effect of isoprenaline (decrease in twitch duration by 21%). Both effects of isoprenaline were sensitive to the muscarinic receptor agonist carbachol in a pertussis toxin-sensitive manner. Adenovirus-mediated gene transfer of beta-galactosidase into EHTs reached 100% efficiency. In summary, EHTs retain many of the physiological characteristics of rat cardiac tissue and allow efficient gene transfer with subsequent force measurement. Copyright 2000 John Wiley & Sons, Inc.

  11. Slow [Na+]i dynamics impacts arrhythmogenesis and spiral wave reentry in cardiac myocyte ionic model.

    Science.gov (United States)

    Krogh-Madsen, Trine; Christini, David J

    2017-09-01

    Accumulation of intracellular Na + is gaining recognition as an important regulator of cardiac myocyte electrophysiology. The intracellular Na + concentration can be an important determinant of the cardiac action potential duration, can modulate the tissue-level conduction of excitation waves, and can alter vulnerability to arrhythmias. Mathematical models of cardiac electrophysiology often incorporate a dynamic intracellular Na + concentration, which changes much more slowly than the remaining variables. We investigated the dependence of several arrhythmogenesis-related factors on [Na + ] i in a mathematical model of the human atrial action potential. In cell simulations, we found that [Na + ] i accumulation stabilizes the action potential duration to variations in several conductances and that the slow dynamics of [Na + ] i impacts bifurcations to pro-arrhythmic afterdepolarizations, causing intermittency between different rhythms. In long-lasting tissue simulations of spiral wave reentry, [Na + ] i becomes spatially heterogeneous with a decreased area around the spiral wave rotation center. This heterogeneous region forms a functional anchor, resulting in diminished meandering of the spiral wave. Our findings suggest that slow, physiological, rate-dependent variations in [Na + ] i may play complex roles in cellular and tissue-level cardiac dynamics.

  12. Surgery for ventricular tachycardia in patients undergoing surgical ventricular restoration: the Karolinska approach.

    Science.gov (United States)

    Sartipy, Ulrik; Albåge, Anders; Insulander, Per; Lindblom, Dan

    2007-09-01

    This article presents a review on the efficacy of surgical ventricular restoration and direct surgery for ventricular tachycardia in patients with left ventricular aneurysm or dilated ischemic cardiomyopathy. The procedure includes a non-electrophysiologically guided subtotal endocardiectomy and cryoablation in addition to endoventricular patch plasty of the left ventricle. Coronary artery bypass surgery and mitral valve repair are performed concomitantly as needed. In our experience, this procedure yielded a 90% success rate in terms of freedom from spontaneous ventricular tachycardia, with an early mortality rate of 3.8%. A practical guide to the pre- and postoperative management of these patients is provided.

  13. Right Ventricular Endomyocardial Fibrosis Presenting With Ventricular Tachycardia And Apical Thrombus - An Interesting Presentation

    Directory of Open Access Journals (Sweden)

    Amitesh Aggarwal

    2009-11-01

    Full Text Available Endomyocardial fibrosis is a progressive disease of unknown origin affecting children and young adults. It involves inflow portion of right and/or left ventricle and apex. It may be associated with thrombus. Literature regarding right ventricular endomyocardial fibrosis with thrombus is scarce. Here we report a rare case of right ventricular endomyocardial fibrosis presenting as ventricular tachycardia and echocardiographic evidence of apical thrombus. Interestingly there was no pulmonary involvement or evidence of deep venous thrombosis. This case also underscores the importance of urgent echocardiography in diagnosis of obscure cases of ventricular tachycardia.

  14. Left ventricular function in patients with ventricular arrhythmias and aortic valve disease

    International Nuclear Information System (INIS)

    Santinga, J.T.; Kirsh, M.M.; Brady, T.J.; Thrall, J.; Pitt, B.

    1983-01-01

    Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease

  15. Rest and exercise ventricular function in adults with congenital ventricular septal defects

    International Nuclear Information System (INIS)

    Jablonsky, G.; Hilton, J.D.; Liu, P.P.; Morch, J.E.; Druck, M.N.; Bar-Shlomo, B.Z.; McLaughlin, P.R.

    1983-01-01

    Rest and exercise right and left ventricular function were compared using equilibrium gated radionuclide angiography in 19 normal sedentary control subjects and 34 patients with hemodynamically documented congenital ventricular septal defect (VSD). Gated radionuclide angiography was performed at rest and during each level of graded supine bicycle exercise to fatigue. Heart rate, blood pressure, maximal work load achieved, and right and left ventricular ejection fractions were assessed. The control subjects demonstrated an increase in both the left and right ventricular ejection fractions with exercise. All study groups failed to demonstrate an increase in ejection fraction in either ventricle with exercise. Furthermore, resting left ventricular ejection fraction in Groups 2 and 3 was lower than that in the control subjects and resting right ventricular ejection fraction was lower in Group 3 versus control subjects. Thus left and right ventricular function on exercise were abnormal in patients with residual VSD as compared with control subjects; rest and exercise left ventricular ejection fractions remained abnormal despite surgical closure of VSD in the remote past; resting left and right ventricular function was abnormal in patients with Eisenmenger's complex; lifelong volume overload may be detrimental to myocardial function

  16. Arrhythmogenic right ventricular dysplasia: A case report

    Directory of Open Access Journals (Sweden)

    Tessa Negrín Valdés

    2015-10-01

    Full Text Available Arrhythmogenic right ventricular dysplasia is a heart muscle disease that predominantly affects the right ventricle, bringing about the replacement of normal myocardium with fatty or fibrofatty tissue and causing sudden death in young individuals. Ventricular tachycardia is an important clinical manifestation, although there are reports of right or global heart failure. The diagnosis is confirmed by echocardiography and magnetic resonance imaging. The case of a 65-year-old former smoker, with hypertension and ischemic heart disease, a history of effort syncope symptoms and proven non-sustained ventricular tachycardia, with morphology of left bundle branch block, is reported. Relevant diagnostic studies were performed, and echocardiographic elements which were compatible with arrhythmogenic right ventricular dysplasia were found. Therefore, an implantable cardioverter defibrillator was implanted, after which the patient has had a favorable outcome.

  17. Ventricular repolarization measures for arrhythmic risk stratification

    Institute of Scientific and Technical Information of China (English)

    Francesco Monitillo; Marta Leone; Caterina Rizzo; Andrea Passantino; Massimo Iacoviello

    2016-01-01

    Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave(QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice.

  18. Salbutamol Abuse is Associated with Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Emin UYSAL

    2015-06-01

    Full Text Available SUMMARY: Salbutamol-induced cardiac complications are well-established. Herein, we describe a case of a 24-year female who was admitted to the emergency department because of a suicide attempt with salbutamol (76 mg. Salbutamol abuse induced the development of supraventricular tachycardia and ventricular fibrillation. Regular sinus rhythm was restored with defibrillation. The hypokalemic patient who stayed in the intensive care unit was discharged after 48 hours of hospitalization. Key words: Salbutamol, suicide, ventricular fibrillation

  19. Clustering Of Left Ventricular Wall Motion Patterns

    Science.gov (United States)

    Bjelogrlic, Z.; Jakopin, J.; Gyergyek, L.

    1982-11-01

    A method for detection of wall regions with similar motion was presented. A model based on local direction information was used to measure the left ventricular wall motion from cineangiographic sequence. Three time functions were used to define segmental motion patterns: distance of a ventricular contour segment from the mean contour, the velocity of a segment and its acceleration. Motion patterns were clustered by the UPGMA algorithm and by an algorithm based on K-nearest neighboor classification rule.

  20. Ventricular tachycardia induced by weight loss pills

    DEFF Research Database (Denmark)

    Pareek, Manan; Hansson, Nils Henrik; Grove, Erik Lerkevang

    2013-01-01

    A previously healthy 29-year-old man was admitted with palpitations, dizziness, and near-syncope after he had recently started taking weight loss pills purchased on the internet. The pills contained caffeine and ephedrine. An electrocardiogram and telemetry revealed multiple episodes of non......-sustained monomorphic ventricular tachycardia, which was successfully treated with amiodarone. In conclusion, unauthorized weight loss pills can be harmful. In particular, ephedrine-containing drugs carry a risk of ventricular tachycardia and should be discouraged....

  1. Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding.

    Directory of Open Access Journals (Sweden)

    Yoichiro Kusakari

    Full Text Available Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling has not yet been clarified. We developed an animal model of right ventricular (RV hypertrophy with fibrosis by pulmonary artery (PA banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca2+ concentration of RV papillary muscles were simultaneously measured (n = 33. The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca2+ responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca2+ had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca2+ responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1 the decrease in Ca2+ responsiveness and 2 the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication.

  2. Resolving the True Ventricular Mural Architecture

    Directory of Open Access Journals (Sweden)

    Robert S. Stephenson

    2018-06-01

    Full Text Available The precise nature of packing together of the cardiomyocytes within the ventricular walls has still to be determined. The spiraling nature of the chains of interconnected cardiomyocytes has long been recognized. As long ago as the end of the nineteenth century, Pettigrew had emphasized that the ventricular cone was not arranged on the basis of skeletal muscle. Despite this guidance, subsequent anatomists described entities such as “bulbo-spiral muscles”, with this notion of subunits culminating in the suggestion that the ventricular cone could be unwrapped so as to produce a “ventricular myocardial band”. Others, in contrast, had suggested that the ventricular walls were arranged on the basis of “sheets”, or more recently “sheetlets”, with investigators seeking to establishing the angulation of these entities using techniques such as magnetic resonance imaging. Our own investigations, in contrast, have shown that the cardiomyocytes are aggregated together within the supporting fibrous matrix so as to produce a three-dimensional myocardial mesh. In this review, we summarize the previous accounts, and provide the anatomical evidence we have thus far accumulated to support the model of the myocardial mesh. We show how these anatomic findings underscore the concept of the myocardial mesh functioning in antagonistic fashion. They lend evidence to support the notion that the ventricular myocardium works as a muscular hydrostat.

  3. Large right ventricular sinusoids in an infant with aorta-left ventricular tunnel and proximal right coronary artery atresia.

    Science.gov (United States)

    Chen, Peter C; Spinner, Joseph A; Heinle, Jeffrey S

    2018-07-01

    We report a 1-month-old infant diagnosed with an aorta-left ventricular tunnel, ventricular septal defect, and right coronary atresia with right ventricular sinusoids. The patient's anatomy and physiology did not indicate right-ventricular-dependent coronary circulation, and therefore right ventricular decompression could be performed without compromising coronary perfusion during surgical correction. A detailed understanding of the coronary anatomy is critical in managing this defect when coronary anomalies are present.

  4. Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart

    DEFF Research Database (Denmark)

    Osadchii, Oleg E.

    2016-01-01

    examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. DESIGN: ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon...... a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. RESULTS: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged...

  5. Mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes.

    Science.gov (United States)

    Farese, R V; Cooper, D R; Konda, T S; Nair, G; Standaert, M L; Davis, J S; Pollet, R J

    1988-01-01

    We previously suggested that insulin increases diacylglycerol (DAG) in BC3H-1 myocytes, both by increases in synthesis de novo of phosphatidic acid (PA) and by hydrolysis of non-inositol-containing phospholipids, such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE). We have now evaluated these insulin effects more thoroughly, and several potential mechanisms for their induction. In studies of the effect on PA synthesis de novo, insulin stimulated [2-3H]glycerol incorporation into PA, DAG, PC/PE and total glycerolipids of BC3H-1 myocytes, regardless of whether insulin was added simultaneously with, or after 2 h or 3 or 10 days of prelabelling with, [2-3H]glycerol. In prelabelled cells, time-related changes in [2-3H]glycerol labelling of DAG correlated well with increases in DAG content: both were maximal in 30-60 s and persisted for 20-30 min. [2-3H]Glycerol labelling of glycerol 3-phosphate, on the other hand, was decreased by insulin, presumably reflecting increased utilization for PA synthesis. Glycerol 3-phosphate concentrations were 0.36 and 0.38 mM before and 1 min after insulin treatment, and insulin effects could not be explained by increases in glycerol 3-phosphate specific radioactivity. In addition to that of [2-3H]glycerol, insulin increased [U-14C]glucose and [1,2,3-3H]glycerol incorporation into DAG and other glycerolipids. Effects of insulin on [2-3H]glycerol incorporation into DAG and other glycerolipids were half-maximal and maximal at 2 nM- and 20 nM-insulin respectively, and were not dependent on glucose concentration in the medium, extracellular Ca2+ or protein synthesis. Despite good correlation between [3H]DAG and DAG content, calculated increases in DAG content from glycerol 3-phosphate specific radioactivity (i.e. via the pathway of PA synthesis de novo) could account for only 15-30% of the observed increases in DAG content. In addition to increases in [3H]glycerol labelling of PC/PE, insulin rapidly (within 30 s) increased PC

  6. Intermittent Hypoxia Causes Inflammation and Injury to Human Adult Cardiac Myocytes.

    Science.gov (United States)

    Wu, Jing; Stefaniak, Joanna; Hafner, Christina; Schramel, Johannes Peter; Kaun, Christoph; Wojta, Johann; Ullrich, Roman; Tretter, Verena Eva; Markstaller, Klaus; Klein, Klaus Ulrich

    2016-02-01

    Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia. HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression. In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways. Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia

  7. Lysine and Leucine Deficiencies Affect Myocytes Development and IGF Signaling in Gilthead Sea Bream (Sparus aurata.

    Directory of Open Access Journals (Sweden)

    Sheida Azizi

    Full Text Available Optimizing aquaculture production requires better knowledge of growth regulation and improvement in diet formulation. A great effort has been made to replace fish meal for plant protein sources in aquafeeds, making necessary the supplementation of such diets with crystalline amino acids (AA to cover the nutritional requirements of each species. Lysine and Leucine are limiting essential AA in fish, and it has been demonstrated that supplementation with them improves growth in different species. However, the specific effects of AA deficiencies in myogenesis are completely unknown and have only been studied at the level of hepatic metabolism. It is well-known that the TOR pathway integrates the nutritional and hormonal signals to regulate protein synthesis and cell proliferation, to finally control muscle growth, a process also coordinated by the expression of myogenic regulatory factors (MRFs. This study aimed to provide new information on the impact of Lysine and Leucine deficiencies in gilthead sea bream cultured myocytes examining their development and the response of insulin-like growth factors (IGFs, MRFs, as well as key molecules involved in muscle growth regulation like TOR. Leucine deficiency did not cause significant differences in most of the molecules analyzed, whereas Lysine deficiency appeared crucial in IGFs regulation, decreasing significantly IGF-I, IGF-II and IGF-IRb mRNA levels. This treatment also down-regulated the gene expression of different MRFs, including Myf5, Myogenin and MyoD2. These changes were also corroborated by a significant decrease in proliferation and differentiation markers in the Lysine-deficient treatment. Moreover, both Lysine and Leucine limitation induced a significant down-regulation in FOXO3 gene expression, which deserves further investigation. We believe that these results will be relevant for the production of a species as appreciated for human consumption as it is gilthead sea bream and demonstrates

  8. Stress induced right ventricular dysfunction: An indication of reversible right ventricular ischaemia

    International Nuclear Information System (INIS)

    Underwood, S.R.; Walton, S.; Emanuel, R.W.; Swanton, R.H.; Campos Costa, D.; Laming, P.J.; Ell, P.J.

    1987-01-01

    Stress induced changes in left ventricular ejection fraction are widely used in the detection and assessment of coronary artery disease. This study demonstrates that right ventricular dysfunction may also occur, and assesses its significance in terms of coronary artery anatomy. This study involved 14 normal subjects and 26 with coronary artery disease investigated by equilibrium radionuclide ventriculography, at rest and during maximal dynamic exercise. Mean normal resting right ventricular ejection fraction (RVEF) was 0.40 (SD 0.118), and all normal subjects increased RVEF with stress (mean ΔRVEF+0.13 SD 0.099). Mean ΔRVEF in the subjects with coronary artery disease was significantly lower at 0.00 (SD 0.080), but there was overlap between the two groups. The largest falls in RVEF were seen if the right coronary artery was occluded without retrograde filling. In this subgroup with the most severely compromised right ventricular perfusion (nine subjects), RVEF always fell with stress, and mean ΔRVEF was -0.08 (SD 0.050). There was no significant correlation between ΔLVEF and ΔRVEF, implying that the right ventricular dysfunction was due to right ventricular ischaemia, rather than secondary to left ventricular dysfunction. Stress induced right ventricular ischaemia can therefore be detected readily by radionuclide ventriculography. (orig.)

  9. Action potential conduction between a ventricular cell model and an isolated ventricular cell

    NARCIS (Netherlands)

    Wilders, R.; Kumar, R.; Joyner, R. W.; Jongsma, H. J.; Verheijck, E. E.; Golod, D.; van Ginneken, A. C.; Goolsby, W. N.

    1996-01-01

    We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded

  10. Right ventricular failure after implantation of a continuous-flow left ventricular assist device

    DEFF Research Database (Denmark)

    Cordtz, Johan Joakim; Nilsson, Jens C; Hansen, Peter B

    2014-01-01

    Right ventricular failure (RVF) is a significant complication after implantation of a left ventricular assist device. We aimed to identify haemodynamic changes in the early postoperative phase that predicted subsequent development of RVF in a cohort of HeartMate II (HMII) implanted patients....

  11. Regional ejection fraction: a quantitative radionuclide index of regional left ventricular performance

    International Nuclear Information System (INIS)

    Maddox, D.E.; Wynne, J.; Uren, R.; Parker, J.A.; Idoine, J.; Siegel, L.C.; Neill, J.M.; Cohn, P.F.; Holman, B.L.

    1979-01-01

    Left ventricular regional ejection fractions were derived from background-corrected, time-activity curves in 43 patients assessed by both gated equilibrium radionuclide angiocardiography and left ventricular contrast angiography. From a single, modified left anterior oblique projection, the regional change in background corrected counts was determined in each of three anatomic regions. The normal range for regional radionuclide ejection fraction was determined in 10 patients with normal contrast ventriculograms and without obstructive coronary artery disease at coronary arteriography. Regional ejection fraction was compared with percent segmental axis shortening and extent of akinetic segments in corresponding regions of the contrast ventriculogram. Radionuclide and roentgenographic methods were in agreement as to the presence or absence of abnormal wall motion in 83 of 99 left ventricular regions (84%) in 33 patients evaluated prospectively. Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis hypokinesis, and akinesis. We conclude that the left ventricular regional ejection fraction provides a reliable quantitative assessment of regional left ventricular performance

  12. Echocardiographic assessment of the different left ventricular geometric patterns in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Delma Maria Cunha

    2001-01-01

    Full Text Available OBJECTIVE: To identiy left ventricular geometric patterns in hypertensive patients on echocardiography, and to correlate those patterns with casual blood pressure measurements and with the parameters obtained on a 24-hour ambulatory blood pressure monitoring. METHODS: We studied sixty hypertensive patients, grouped according to the Joint National Committee stages of hypertension.. Using the single- and two-dimensional Doppler Echocardiography, we analyzed the left ventricular mass and the geometric patterns through the correlation of left ventricular mass index and relative wall thickness. On ambulatory blood pressure monitoring we assessed the means and pressure loads in the different geometric patterns detected on echocardiography RESULTS: We identified three left ventricular geometric patterns: 1 concentric hypertrophy, in 25% of the patients; 2 concentric remodeling, in 25%; and 3 normal geometry, in 50%. Casual systolic blood pressure was higher in the group with concentric hypertrophy than in the other groups (p=0.001. Mean systolic pressure in the 24h, daytime and nighttime periods was also higher in patients with concentric hypertrophy, as compared to the other groups (p=0.003, p=0.004 and p=0.007. Daytime systolic load and nighttime diastolic load were higher in patients with concentric hypertrophy ( p=0.004 and p=0.01, respectively. CONCLUSIONS: Left ventricular geometric patterns show significant correlation with casual systolic blood pressure, and with means and pressure loads on ambulatory blood pressure monitoring.

  13. Exercise thallium testing in ventricular preexcitation

    Energy Technology Data Exchange (ETDEWEB)

    Archer, S.; Gornick, C.; Grund, F.; Shafer, R.; Weir, E.K.

    1987-05-01

    Ventricular preexcitation, as seen in Wolff-Parkinson-White syndrome, results in a high frequency of positive exercise electrocardiographic responses. Why this occurs is unknown but is not believed to reflect myocardial ischemia. Exercise thallium testing is often used for noninvasive assessment of coronary artery disease in patients with conditions known to result in false-positive electrocardiographic responses. To assess the effects of ventricular preexcitation on exercise thallium testing, 8 men (aged 42 +/- 4 years) with this finding were studied. No subject had signs or symptoms of coronary artery disease. Subjects exercised on a bicycle ergometer to a double product of 26,000 +/- 2,000 (+/- standard error of mean). All but one of the subjects had at least 1 mm of ST-segment depression. Tests were terminated because of fatigue or dyspnea and no patient had chest pain. Thallium test results were abnormal in 5 patients, 2 of whom had stress defects as well as abnormally delayed thallium washout. One of these subjects had normal coronary arteries on angiography with a negative ergonovine challenge, and both had normal exercise radionuclide ventriculographic studies. Delayed thallium washout was noted in 3 of the subjects with ventricular preexcitation and normal stress images. This study suggests that exercise thallium testing is frequently abnormal in subjects with ventricular preexcitation. Ventricular preexcitation may cause dyssynergy of ventricular activation, which could alter myocardial thallium handling, much as occurs with left bundle branch block. Exercise radionuclide ventriculography may be a better test for noninvasive assessment of coronary artery disease in patients with ventricular preexcitation.

  14. Exercise thallium testing in ventricular preexcitation

    International Nuclear Information System (INIS)

    Archer, S.; Gornick, C.; Grund, F.; Shafer, R.; Weir, E.K.

    1987-01-01

    Ventricular preexcitation, as seen in Wolff-Parkinson-White syndrome, results in a high frequency of positive exercise electrocardiographic responses. Why this occurs is unknown but is not believed to reflect myocardial ischemia. Exercise thallium testing is often used for noninvasive assessment of coronary artery disease in patients with conditions known to result in false-positive electrocardiographic responses. To assess the effects of ventricular preexcitation on exercise thallium testing, 8 men (aged 42 +/- 4 years) with this finding were studied. No subject had signs or symptoms of coronary artery disease. Subjects exercised on a bicycle ergometer to a double product of 26,000 +/- 2,000 (+/- standard error of mean). All but one of the subjects had at least 1 mm of ST-segment depression. Tests were terminated because of fatigue or dyspnea and no patient had chest pain. Thallium test results were abnormal in 5 patients, 2 of whom had stress defects as well as abnormally delayed thallium washout. One of these subjects had normal coronary arteries on angiography with a negative ergonovine challenge, and both had normal exercise radionuclide ventriculographic studies. Delayed thallium washout was noted in 3 of the subjects with ventricular preexcitation and normal stress images. This study suggests that exercise thallium testing is frequently abnormal in subjects with ventricular preexcitation. Ventricular preexcitation may cause dyssynergy of ventricular activation, which could alter myocardial thallium handling, much as occurs with left bundle branch block. Exercise radionuclide ventriculography may be a better test for noninvasive assessment of coronary artery disease in patients with ventricular preexcitation

  15. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

    Science.gov (United States)

    Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2003-12-01

    The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

  16. Prevention of adenosine A2A receptor activation diminishes beat-to-beat alternation in human atrial myocytes.

    Science.gov (United States)

    Molina, Cristina E; Llach, Anna; Herraiz-Martínez, Adela; Tarifa, Carmen; Barriga, Montserrat; Wiegerinck, Rob F; Fernandes, Jacqueline; Cabello, Nuria; Vallmitjana, Alex; Benitéz, Raúl; Montiel, José; Cinca, Juan; Hove-Madsen, Leif

    2016-01-01

    Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 ± 0.1 to 0.5 ± 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 ± 3 to 51 ± 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 ± 0.12 to 1.86 ± 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 ± 0.1 to 1.2 ± 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation.

  17. Diastolic And Systolic Right Ventricular Dysfunction Precedes Left Ventricular Dysfunction In Patients Paced From Right Ventricular Apex

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    Dwivedi SK

    2006-07-01

    Full Text Available Background: Cardiac dysfunction after right ventricular (RV apical pacing is well known but its extent, time frame of appearance and individual effect on left ventricular (LV, RV systolic and diastolic parameters has not evaluated in a systematic fashion. Methods: Patients with symptomatic bradycardia and ACC-AHA Class I indication for permanent pacemaker implantation (PPI were implanted a single chamber (VVI pacemaker. They were followed prospectively by echocardiographic examination which was done at baseline, 1 week, 1 month and 6 months after implantation. Parameters observed were chamber dimensions (M-line, chamber volumes, cardiac output (modified Simpson's method, systolic functions (ejection fraction, pre-ejection period, ejection time and ratio and diastolic functions( isovolumic relaxation time & deceleration time of left and right heart. Results: Forty eight consecutive patients (mean age 65.6±11.8 yrs, 66.7% males, mean EF 61.82±10.36% implanted a VVI pacemaker were enrolled in this study. The first significant change to appear in cardiac function after VVI pacing was in diastolic properties of RV as shown by increase in RV isovolumic relaxation time (IVRT from 65.89±15.93 to 76.58±17.00 ms,(p<0.001 at 1week and RV deceleration time (DT from 133.84±38.13 to 153.09±31.41 ms, (p=0.02 at 1 month. Increase in RV internal dimension (RVID from 1.26±0.41 to 1.44±0.44, (p<0.05 was also noticed at 1 week. The LV diastolic parameters were significantly altered after 1 month with increase in LV-IVRT from 92.36±21.47 to 117.24±27.21ms, (p<0.001 and increase in LV DT from 147.56±31.84 to 189.27±28.49ms,(p<0.01. This was followed by LV systolic abnormality which appeared at 6 months with an increase in LVPEP from 100.33±14.43 to 118.41±21.34ms, (p<0.001 and increase in LVPEP/LVET ratio from 0.34±0.46 to 0.44±0.10, (p<0.001]. The reduction in LV EF was manifested at 6 months falling from 61.82±10.36% to52.52±12.11%, (p<0

  18. Muscular anatomy of the human ventricular folds.

    Science.gov (United States)

    Moon, Jerald; Alipour, Fariborz

    2013-09-01

    Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. Although variability of expression was evident, a well-defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens.

  19. Changes of left ventricular function at exercise after lung resection

    International Nuclear Information System (INIS)

    Fujisaki, Takashi; Gomibuchi, Makoto; Shoji, Tasuku

    1992-01-01

    To determine the effect of lung resection on left ventricular function, 29 surgical patients were examined by using a nuclear stethoscope as a non-invasive means for measuring ventricular function at exercise. Pre- and post-operative parameters were obtained at rest and exercise. At rest, postoperative stroke volume (SV), end-diastolic volume (EDV), ejection fraction (EF), and ejection rate (ER) were significantly decreased; heart rate (HR) was significantly increased; and both filling rate (FR) and cardiac output (CO) remained unchanged. At maximum exercise, postoperative EDV, SV, ER and FR were significantly decreased; and there was no significant difference in either HR or EF, resulting in a significantly decreased CO. A ratio of CO and FR at maximum exercise to at rest was significantly decreased after surgery, as compared with that before surgery. According to the number of lobe resection, similar findings for all parameters, except for EF, were observed in the group of two lobe or more resection (n=13); and only two parameters, ER and FR, had the same tendency as those mentioned above in the group of a single lobe resection (n=16). The age group of 60 years or less (n=14) had similar findings for all parameters. In the group of 65 years or more (n=10), resting HR after surgery was not different from that before surgery; and postoperative CO was significantly decreased at rest, but not different from preoperative value at maximum exercise. In conclusion, left ventricular function associated with lung resection is reflected by decreased EDV and SV resulting from reduced pre-load. These changes may be corrected at rest, but not corrected at maximum exercise, resulting in decreased CO. More noticeable decrease in EDV and SV seems to be associated with larger lung resection. In older patients, HR is not corrected well, resulting in a decrease in CO at rest. (N.K.)

  20. Passive and active ventricular elastances of the left ventricle

    Directory of Open Access Journals (Sweden)

    Ng Eddie YK

    2005-02-01

    Full Text Available Abstract Background Description of the heart as a pump has been dominated by models based on elastance and compliance. Here, we are presenting a somewhat new concept of time-varying passive and active elastance. The mathematical basis of time-varying elastance of the ventricle is presented. We have defined elastance in terms of the relationship between ventricular pressure and volume, as: dP = EdV + VdE, where E includes passive (Ep and active (Ea elastance. By incorporating this concept in left ventricular (LV models to simulate filling and systolic phases, we have obtained the time-varying expression for Ea and the LV-volume dependent expression for Ep. Methods and Results Using the patient's catheterization-ventriculogram data, the values of passive and active elastance are computed. Ea is expressed as: ; Epis represented as: . Ea is deemed to represent a measure of LV contractility. Hence, Peak dP/dt and ejection fraction (EF are computed from the monitored data and used as the traditional measures of LV contractility. When our computed peak active elastance (Ea,max is compared against these traditional indices by linear regression, a high degree of correlation is obtained. As regards Ep, it constitutes a volume-dependent stiffness property of the LV, and is deemed to represent resistance-to-filling. Conclusions Passive and active ventricular elastance formulae can be evaluated from a single-beat P-V data by means of a simple-to-apply LV model. The active elastance (Ea can be used to characterize the ventricle's contractile state, while passive elastance (Ep can represent a measure of resistance-to-filling.

  1. Hyperdynamic left ventricular ejection fraction in the intensive care unit.

    Science.gov (United States)

    Paonessa, Joseph R; Brennan, Thomas; Pimentel, Marco; Steinhaus, Daniel; Feng, Mengling; Celi, Leo Anthony

    2015-08-07

    Limited information exists on the etiology, prevalence, and significance of hyperdynamic left ventricular ejection fraction (HDLVEF) in the intensive care unit (ICU). Our aim in the present study was to compare characteristics and outcomes of patients with HDLVEF with those of patients with normal left ventricular ejection fraction in the ICU using a large, public, deidentified critical care database. We conducted a longitudinal, single-center, retrospective cohort study of adult patients who underwent echocardiography during a medical or surgical ICU admission at the Beth Israel Deaconess Medical Center using the Multiparameter Intelligent Monitoring in Intensive Care II database. The final cohort had 2867 patients, of whom 324 had HDLVEF, defined as an ejection fraction >70%. Patients with an ejection fraction <55% were excluded. Compared with critically ill patients with normal left ventricular ejection fraction, the finding of HDLVEF in critically ill patients was associated with female sex, increased age, and the diagnoses of hypertension and cancer. Patients with HDLVEF had increased 28-day mortality compared with those with normal ejection fraction in multivariate logistic regression analysis adjusted for age, sex, Sequential Organ Failure Assessment score, Elixhauser score for comorbidities, vasopressor use, and mechanical ventilation use (odds ratio 1.38, 95% confidence interval 1.039-1.842, p =0.02). The presence of HDLVEF portended increased 28-day mortality, and may be helpful as a gravity marker for prognosis in patients admitted to the ICU. Further research is warranted to gain a better understanding of how these patients respond to common interventions in the ICU and to determine if pharmacologic modulation of HDLVEF improves outcomes.

  2. Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

    Science.gov (United States)

    Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

    2017-06-06

    We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. Ventricular and myocardial scintiscanning: Methodical fundamentals

    International Nuclear Information System (INIS)

    Standke, R.; Hoer, G.; Maul, F.D.

    1984-01-01

    Nuclear cardiology is concerned with non invasive procedures to quantitate global and regional left ventricular function (Radionuclide ventriculography), also the imaging of vitally perfused myocardium (Myocardial scintigraphy) is achieved. A gammacamera and a minicomputer are necessary. Radionuclide ventriculography enables the analysis of global and regional time dependent left ventricular volume curves and hence the evaluation of contraction and contractility of the heart muscle. The basis is a sequence of scans covering an average heartcycle. This sequence may be produced either by first pass or equilibrium technique. Myocardial scintigraphy at rest images vital myocardium, scans immediately after exercise represent the interference of myocardial perfusion and muscle mass. The regional difference (Redistribution) between normalized exercise- and rest scans provide quantitative parameters to detect impairment of exercise-induced myocardial perfusion anomalies. The procedures of sectorial analysis of left ventricular function and myocardial perfusion are presented. (orig.) [de

  4. Left ventricular hypertrophy: virtuous intentions, malign consequences.

    Science.gov (United States)

    Pokharel, Saraswati; Sharma, Umesh C; Pinto, Yigal M

    2003-06-01

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there are structural changes in myofilaments, disorganization of the cytoskeletal framework and increased collagen synthesis. LVH is associated with progressive left ventricular remodeling that culminates to heart failure. The modern treatment of left ventricular hypertrophy is now largely based on the hypothesis that neuroendocrine activation is important in the progression of the disease and inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Drugs specifically designed to unload the left ventricle, such as diuretics and vasodilators, appears to be less effective in reducing LV mass and improving prognosis. Thus, the evolution of treatment for LVH itself has provided much enlightenment for our understanding of the fundamental biology of the disorder.

  5. Proteome- and transcriptome-driven reconstruction of the human myocyte metabolic network and its use for identification of markers for diabetes

    DEFF Research Database (Denmark)

    Väremo, Leif; Scheele, Camilla; Broholm, Christa

    2015-01-01

    -analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism......Skeletal myocytes are metabolically active and susceptible to insulin resistance and are thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes, and their elucidation at the systems level requires genome-wide data and biological networks. Genome...

  6. Differing Effects of Younger and Older Human Plasma on C2C12 Myocytes in Vitro

    Directory of Open Access Journals (Sweden)

    Ifigeneia Kalampouka

    2018-02-01

    Full Text Available Ageing is associated with a general reduction of physiological function and a reduction of muscle mass and strength. Endocrine factors such as myostatin, activin A, growth and differentiation factor 11 (GDF-11 and their inhibitory peptides influence muscle mass in health and disease. We hypothesised that myocytes cultured in plasma from older and younger individuals would show an ageing effect, with reduced proliferation and differentiation in older environments. C2C12 myoblasts were grown as standard and stimulated with media conditioned with 5% plasma from healthy male participants that were either younger (n = 6, 18–35 years of age or older (n = 6, >57 years of age. Concentration of plasma myostatin (total and free, follistatin-like binding protein (FLRG, GDF-11 and activin A were quantified by ELISA. Both FLRG and activin A were elevated in older individuals (109.6 and 35.1% increase, respectively, whilst myostatin (free and total and GDF-11 were not. Results indicated that plasma activin A and FLRG were increased in older vs. younger participants, GDF11 and myostatin did not differ. Myoblasts in vitro showed no difference in proliferation rate between ages, however scratch closure was greater in younger vs. older plasma stimulated myoblasts (78.2 vs. 87.2% of baseline scratch diameter, respectively. Myotube diameters were larger in cells stimulated with younger plasma than with older at 24 and 48 h, but not at 2 h. A significant negative correlation was noted between in vivo plasma FLRG concentration and in vitro myotube diameter 48 h following plasma stimulation (r2 = 0.392, p = 0.030. Here we show that myoblasts and myotubes cultured in media conditioned with plasma from younger or older individuals show an ageing effect, and further this effect moderately correlates with circulating FLRG concentration in vivo. The effect of ageing on muscle function may not be innate to the tissue, but involve a general cellular environment change

  7. Contribution of NADPH Oxidase to Membrane CD38 Internalization and Activation in Coronary Arterial Myocytes

    Science.gov (United States)

    Xu, Ming; Li, Xiao-Xue; Ritter, Joseph K.; Abais, Justine M.; Zhang, Yang; Li, Pin-Lan

    2013-01-01

    The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2 ·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase signaling pathway to exert its action in these CAMs. These findings led us hypothesize that NOX1-derived O2 ·− serves in an autocrine fashion to enhance CD38 internalization, leading to redox activation of CD38-ADP-ribosylcyclase activity in mouse CAMs. To test this hypothesis, confocal microscopy, flow cytometry and a membrane protein biotinylation assay were used in the present study. We first demonstrated that CD38 internalization induced by endothelin-1 (ET-1) was inhibited by silencing of NOX1 gene, but not NOX4 gene. Correspondingly, NOX1 gene silencing abolished ET-1-induced O2 ·− production and increased CD38-ADP-ribosylcyclase activity in CAMs, while activation of NOX1 by overexpression of Rac1 or Vav2 or administration of exogenous O2 ·− significantly increased CD38 internalization in CAMs. Lastly, ET-1 was found to markedly increase membrane raft clustering as shown by increased colocalization of cholera toxin-B with CD38 and NOX1. Taken together, these results provide direct evidence that Rac1-NOX1-dependent O2 ·− production mediates CD38 internalization in CAMs, which may represent an important mechanism linking receptor activation with CD38 activity in these cells. PMID:23940720

  8. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Tassi, Eduardo Marinho, E-mail: etassi@ibest.com.br [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Continentino, Marcelo Abramoff [Hospital Frei Galvão, Guaratinguetá, SP (Brazil); Nascimento, Emília Matos do; Pereira, Basílio de Bragança [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Coppe - Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia - UFRJ, Rio de Janeiro, RJ (Brazil); Pedrosa, Roberto Coury [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2014-05-15

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups.

  9. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    International Nuclear Information System (INIS)

    Tassi, Eduardo Marinho; Continentino, Marcelo Abramoff; Nascimento, Emília Matos do; Pereira, Basílio de Bragança; Pedrosa, Roberto Coury

    2014-01-01

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups

  10. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Bhuiyan, Zahurul A.; Crotti, Lia; Facchini, Mario; de Ferrari, Gaetano M.; Paul, Thomas; Ferrandi, Chiara; Koolbergen, Dave R.; Odero, Attilio; Schwartz, Peter J.

    2008-01-01

    Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to

  11. Evaluation of right ventricular volumes measured by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Møgelvang, J; Stubgaard, M; Thomsen, C

    1988-01-01

    stroke volume was calculated as the difference between end-diastolic and end-systolic volume and compared to left ventricular stroke volume and to stroke volume determined simultaneously by a classical indicator dilution technique. There was good agreement between right ventricular stroke volume......Right ventricular volumes were determined in 12 patients with different levels of right and left ventricular function by magnetic resonance imaging (MRI) using an ECG gated multisection technique in planes perpendicular to the diastolic position of the interventricular septum. Right ventricular...... determined by MRI and by the indicator dilution method and between right and left ventricular stroke volume determined by MRI. Thus, MRI gives reliable values not only for left ventricular volumes, but also for right ventricular volumes. By MRI it is possible to obtain volumes from both ventricles...

  12. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes.

    Science.gov (United States)

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-09-14

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.

  13. An Incidentally Detected Right Ventricular Pseudoaneurysm

    Directory of Open Access Journals (Sweden)

    Vamsi C. Gaddipati

    2017-01-01

    Full Text Available Ventricular pseudoaneurysm is an uncommon, potentially fatal complication that has been associated with myocardial infarction, cardiac surgery, chest trauma, and infectious processes. Diagnosis can be challenging, as cases are rare and slowly progressing and typically lack identifiable features on clinical presentation. As a result, advanced imaging techniques have become the hallmark of identification. Ahead, we describe a patient who presents with acute decompensated heart failure and was incidentally discovered to have a large right ventricular pseudoaneurysm that developed following previous traumatic anterior rib fracture.

  14. Left ventricular performance during psychological stress

    International Nuclear Information System (INIS)

    Young, D.Z.; Massachusetts General Hospital, Boston; Dimsdale, J.E.; Moore, R.H.; Barlai-Kovach, M.; Newell, J.B.; McKusick, K.A.; Boucher, C.A.; Fifer, M.A.; Strauss, H.W.

    1989-01-01

    Left ventricular ejection fraction, systolic blood pressure and plasma norepinephrine were measured in six normotensive and six mildly hypertensive subjects during rest and psychological stress. Compared with rest, 8 of the 12 subjects developed significant changes in ejection fraction (increase in 6, decrease in 2); 10 of 12 subjects developed significant elevations of plasma norepinephrine; and all developed significant increases in systolic blood pressure. When the stress effects were examined for the total group, as opposed to within subjects, there were significant increases in plasma norepinephrine and systolic blood pressure but, interestingly, mean ejection fraction and stroke volume remained unchanged, implying stress led to increased left ventricular contractility. (orig.)

  15. Nuclear medical diagnostic with ventricular aneurysm

    International Nuclear Information System (INIS)

    Litter, H.

    1987-01-01

    In the diagnostic of ventricular aneurysms myocardial scintigraphy and above all radionuclide ventriculography (RNV) have special importance. Because of the non-invasive method and the as a result safe and easy use even with stress studies, RNV can provide a very valuable aid with aneurysm patients in early diagnosis, evaluation of the operability and as well as in the prognosis. It must be noted, however, that the differentiation of multivascular diseases and sometimes ventricular aneurysms can be difficult and the inclusion of an angiocardiograph as a radiological invasive examination procedure seems fitting. (orig./MG) [de

  16. Bidirectional ventricular tachycardia of unknown etiology

    International Nuclear Information System (INIS)

    Ali, M.; Khan, J.A.; Masood, T.; Shamsi, F.; Dero, M.H.; Khan, S.

    2013-01-01

    A 45 years old male presented to the emergency department with palpitations, headache and apprehension. His electrocardiogram revealed bidirectional ventricular tachycardia. He remained vitally stable and responded to intravenous beta-blocker. Initially digitalis toxicity was suspected but history was negative for digitalis intake. The cause remained unidentified in patient despite detailed investigations. During a short follow-up (of 6 months) he remained asymptomatic and no cause was further identified during this period. Some other unseen causes of bidirectional ventricular tachycardia need to be explored. (author)

  17. Catecholaminergic polymorphic ventricular tachycardia in 2012

    Directory of Open Access Journals (Sweden)

    Christian van der Werf

    2011-12-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a rare, potentially lethal inherited arrhythmia syndrome characterized by stress or emotion-induced ventricular arrhythmias. CPVT was first described in 1960, while the genetic basis underlying this syndrome was discovered in 2001. The past decade has seen substantial advances in understanding the pathophysiology of CPVT. In addition, significant advances have been made in elucidating clinical characteristics of CPVT patients and new treatment options have become available. Here, we review current literature on CPVT to present state-of-the-art knowledge on the subject of the genetic basis, pathophysiology, clinical presentation, diagnosis, treatment and prognosis.

  18. Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

    Science.gov (United States)

    Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

    2011-07-01

    Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

  19. Isolated left ventricular non-compaction cardiomyopathy associated with polymorphous ventricular tachycardia mimicking torsades de pointes

    Directory of Open Access Journals (Sweden)

    Oana Dickinson

    2013-02-01

    Full Text Available Left ventricular non-compaction (LVNC cardiomyopathy is a rare congenital disorder, classified by the American Heart Association as a primary genetic cardiomyopathy and characterized by multiple trabeculations within the left ventricle. LVNC cardiomyopathy has been associated with 3 major clinical manifestations: heart failure, atrial and ventricular arrhythmias and thromboembolic events, including stroke. In this case report, we describe a female patient with apparently isolated LVNC in whom pause-dependent polymorphic ventricular tachycardia suggesting torsades de pointes occurred in the presence of a normal QT interval.

  20. Hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm

    Directory of Open Access Journals (Sweden)

    N.D. Oryshchyn

    2016-11-01

    Full Text Available A case report of apical left ventricular aneurysm in patient with hypertrophic cardiomyopathy with mid-ventricular obstruction (diagnosis and surgical treatment is presented. We revealed apical aneurysm and mid-ventricular obstruction during echocardiography and specified anatomical characteristics of aneurysm during computer tomography. There was no evidence of obstructive coronary artery disease during coronary angiography. Taking into consideration multiple cerebral infarcts, aneurysm resection and left ventricular plastics was performed. Electronic microscopy of myocardium confirmed the diagnosis of hypertrophic cardiomyopathy.

  1. Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy: Progress and Pitfalls.

    Science.gov (United States)

    Oomen, Ad W G J; Semsarian, Christopher; Puranik, Rajesh; Sy, Raymond W

    2018-04-04

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that predominantly affects the right ventricle. With a prevalence in the range of 1:5000 to 1:2000 persons, ARVC is one of the leading causes of sudden cardiac death in young people and in athletes. Although early detection and treatment is important, the diagnosis of ARVC remains challenging. There is no single pathognomonic diagnostic finding in ARVC; rather, current international task force criteria specify diagnostic major and minor criteria in six categories: right ventricular imaging (including echocardiography and cardiac magnetic resonance imaging (MRI)), histology, repolarisation abnormalities, depolarisation and conduction abnormalities, arrhythmias and family history (including genetic testing). Combining findings from differing diagnostic modalities can establish a "definite", "borderline" or "possible" diagnosis of ARVC. However, there are limitations inherent in the current task force criteria, including the lack of specificity for ARVC; future iterations may be improved, for example, by enhanced imaging protocols able to detect subtle changes in the structure and function of the right ventricle, incorporation of electro-anatomical data, response to adrenergic challenge, and validated criteria for interpreting genetic variants. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  2. follow-up of patients with arrhythmogenic right ventricular

    African Journals Online (AJOL)

    was sudden, 1 patient died due to left ventricular failure, and ... Arrhythmogenic right ventricular cardiomyopathy/ dysplasia .... hypertension and from atrial fibrillation that developed 2.4 .... of left ventricular function was global without regional ..... 99mTc he brain si before a acid (G minute his sem next 3 - his sem showed.

  3. Left Ventricular Geometry In Nigerians With Type II Diabetes Mellitus ...

    African Journals Online (AJOL)

    Background: Left ventricular hypertrophy is independently associated with increased incidence of cardiovascular disease, cardiovascular and all cause mortality. In a relatively healthy hypertensive adult population, type II diabetes is associated with higher left ventricular mass, concentric left ventricular geometry and lower ...

  4. Noninvasive imaging of three-dimensional cardiac activation sequence during pacing and ventricular tachycardia.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

    2011-08-01

    Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. This study sought to rigorously assess the imaging performance of a 3-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of 3D intracardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE)-induced ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in 13 healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computed tomography images were obtained to construct geometry models. The noninvasively imaged activation sequence correlated well with invasively measured counterpart, with a correlation coefficient of 0.72 ± 0.04, and a relative error of 0.30 ± 0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from the imaged site of initial activation to the pacing site or site of arrhythmias determined from intracardiac mapping was ∼5 mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. 3DCEI can noninvasively delineate important features of focal or multifocal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequences of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

    NARCIS (Netherlands)

    van der Werf, Christian; Kannankeril, Prince J.; Sacher, Frederic; Krahn, Andrew D.; Viskin, Sami; Leenhardt, Antoine; Shimizu, Wataru; Sumitomo, Naokata; Fish, Frank A.; Bhuiyan, Zahurul A.; Willems, Albert R.; van der Veen, Maurits J.; Watanabe, Hiroshi; Laborderie, Julien; Haïssaguerre, Michel; Knollmann, Björn C.; Wilde, Arthur A. M.

    2011-01-01

    Objectives This study evaluated the efficacy and safety of flecainide in addition to conventional drug therapy in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac

  6. Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the canine heart.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

    2012-01-01

    Single-beat imaging of myocardial activation promises to aid in both cardiovascular research and clinical medicine. In the present study we validate a three-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of simultaneous 3D intracardiac mapping to assess its capability to localize endocardial and epicardial initiation sites and image global activation sequences during pacing and ventricular tachycardia (VT) in the canine heart. Body surface potentials were measured simultaneously with bipolar electrical recordings in a closed-chest condition in healthy canines. Computed tomography images were obtained after the mapping study to construct realistic geometry models. Data analysis was performed on paced rhythms and VTs induced by norepinephrine (NE). The noninvasively reconstructed activation sequence was in good agreement with the simultaneous measurements from 3D cardiac mapping with a correlation coefficient of 0.74 ± 0.06, a relative error of 0.29 ± 0.05, and a root mean square error of 9 ± 3 ms averaged over 460 paced beats and 96 ectopic beats including premature ventricular complexes, couplets, and nonsustained monomorphic VTs and polymorphic VTs. Endocardial and epicardial origins of paced beats were successfully predicted in 72% and 86% of cases, respectively, during left ventricular pacing. The NE-induced ectopic beats initiated in the subendocardium by a focal mechanism. Sites of initial activation were estimated to be ∼7 mm from the measured initiation sites for both the paced beats and ectopic beats. For the polymorphic VTs, beat-to-beat dynamic shifts of initiation site and activation pattern were characterized by the reconstruction. The present results suggest that 3DCEI can noninvasively image the 3D activation sequence and localize the origin of activation of paced beats and NE-induced VTs in the canine heart with good accuracy. This 3DCEI technique offers the potential to aid interventional therapeutic procedures for

  7. The influence of right ventricular apical pacing on left atrial volume in patients with normal left ventricular function

    Directory of Open Access Journals (Sweden)

    AR Moaref1

    2008-03-01

    Full Text Available Background: Right ventricular apical (RVA pacing has been reported to induce several deleterious effects particularly in the presence of structural heart disease but can also involve patients with normal left ventricular (LV function. Left atrial (LA enlargement is one of these effects, but the majority of studies have measured LA dimension rather than volume.Objective: The present prospective study was designed to assess the effect of RVA pacing on LA volume in patients with normal LV function.Patients and Methods: The study comprised 41 consecutive patients with LV ejection fraction ≥ 45% and LV end diastolic dimension ≤ 56 mm who underwent single-or dual- chamber pacemaker implantation in RVA and followed for LA volume measurement and pacemaker analysis at least during the ensuing 4.2 months. Results: In all, 21 patients were excluded from the study due to five spontaneous wide QRS complex (≥120msec, one recent acute coronary syndrome,one significant valvular heart disease, three pacing frequency <90%, eight death or losing follow up in three cases. In remaining 20 patients, LA volume ragned from 21 to 54 mm3 with mean of 37.3±9.7 mm3 prior to pacemaker implantation that increased to 31 to 103 mm3 (54.3±17.0 during follow-up (P<0.001.Conclusion: RVA pacing might lead to an increase in LA volume even in patients with normal LV function.

  8. Factors in ventricular and atrioventricular valve growth: An embryologist's perspective

    Czech Academy of Sciences Publication Activity Database

    Sedmera, David

    2010-01-01

    Roč. 29, č. 1 (2010), s. 11-14 ISSN 1058-9813 Institutional research plan: CEZ:AV0Z50110509 Keywords : chick embryo * myocyte proliferation * hypoplastic left heart syndrome Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  9. Acute Right Ventricular Dysfunction Complicating Prolonged ...

    African Journals Online (AJOL)

    We report a case of transient right ventricular dysfunction associated with prolonged cardiac tamponade, an unusual complication of uncertain etiology. We believe that in this case dynamic coronary flow restriction resulted in ischemic injury and stunning of the right ventricle. Other possible causes are briefly reviewed. Right ...

  10. Left ventricular hypertrophy : virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, S; Sharma, UC; Pinto, YM

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca2+ homeostasis, there

  11. Left ventricular hypertrophy: virtuous intentions, malign consequences

    NARCIS (Netherlands)

    Pokharel, Saraswati; Sharma, Umesh C.; Pinto, Yigal M.

    2003-01-01

    Left ventricular hypertrophy (LVH) is currently the focus of intense cardiovascular research, with the resultant rapid evolution of novel concepts relating to its exceedingly complex pathophysiology. In addition to the alterations in signal transduction and disturbances in Ca(2+) homeostasis, there

  12. Right ventricular myxoma with heart failure

    International Nuclear Information System (INIS)

    Nuri, M.M.H.; Naseem, A.; Raza, A.; Ahmad, W.; Raja, M.K.; Ahmad, A.; Rasheed, A.; Gohar, A.

    2005-01-01

    Cardiac myxomas are histologically benign tumors but they may be lethal because of their strategic position. These are mostly located in the left atrium and uncommonly in the right atrium. We report a case of a large right ventricular myxoma presenting with heart failure. (author)

  13. Radionuclide analysis of right and left ventricular response to exercise in patients with atrial and ventricular septal defects

    International Nuclear Information System (INIS)

    Peter, C.A.; Bowyer, K.; Jones, R.H.

    1983-01-01

    In patients with ventricular or atrial septal defect, the ventricle which is chronically volume overloaded might not appropriately respond to increased demand for an augmentation in output and thereby might limit total cardiac function. In this study we simultaneously measured right and left ventricular response to exercise in 10 normal individuals, 10 patients with ventricular septal defect (VSD), and 10 patients with atrial septal defect (ASD). The normal subjects increased both right and left ventricular ejection fraction, end-diastolic volume, and stroke volume to achieve a higher cardiac output during exercise. Patients with VSD failed to increase right ventricular ejection fraction, but increased right ventricular end-diastolic volume and stroke volume. Left ventricular end-diastolic volume did not increase in these patients but ejection fraction, stroke volume, and forward left ventricular output achieved during exercise were comparable to the response observed in healthy subjects. In the patients with ASD, no rest-to-exercise change occurred in either right ventricular ejection fraction, end-diastolic volume, or stroke volume. In addition, left ventricular end-diastolic volume failed to increase, and despite an increase in ejection fraction, left ventricular stroke volume remained unchanged from rest to exercise. Therefore, cardiac output was augmented only by the heart rate increase in these patients. Right ventricular function appeared to be the major determinant of total cardiac output during exercise in patients with cardiac septal defects and left-to-right shunt

  14. Up-regulation of mRNA ventricular PRNP prion protein gene expression in air pollution highly exposed young urbanites: endoplasmic reticulum stress, glucose regulated protein 78, and nanosized particles.

    Science.gov (United States)

    Villarreal-Calderon, Rodolfo; Franco-Lira, Maricela; González-Maciel, Angélica; Reynoso-Robles, Rafael; Harritt, Lou; Pérez-Guillé, Beatriz; Ferreira-Azevedo, Lara; Drecktrah, Dan; Zhu, Hongtu; Sun, Qiang; Torres-Jardón, Ricardo; Aragón-Flores, Mariana; Calderón-Garcidueñas, Ana; Diaz, Philippe; Calderón-Garcidueñas, Lilian

    2013-11-28

    Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role.

  15. Up-Regulation of mRNA Ventricular PRNP Prion Protein Gene Expression in Air Pollution Highly Exposed Young Urbanites: Endoplasmic Reticulum Stress, Glucose Regulated Protein 78, and Nanosized Particles

    Directory of Open Access Journals (Sweden)

    Rodolfo Villarreal-Calderon

    2013-11-01

    Full Text Available Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4 vs. high (n:26 air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005. Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role.

  16. Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

    International Nuclear Information System (INIS)

    Hoffman, J.M.; Standaert, M.L.; Nair, G.P.; Farese, R.V.

    1991-01-01

    Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in [ 3 H]glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked the later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 μM sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis

  17. 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.

  18. Na/K pump inactivation, subsarcolemmal Na measurements, and cytoplasmic ion turnover kinetics contradict restricted Na spaces in murine cardiac myocytes

    OpenAIRE

    Lu, Fang-Min; Hilgemann, Donald W.

    2017-01-01

    The Na/K pump exports cytoplasmic Na ions while importing K ions, and its activity is thought to be affected by restricted intracellular Na diffusion in cardiac myocytes. Lu and Hilgemann find instead that the pump can enter an inactivated state and that inactivation can be relieved by cytoplasmic Na.

  19. Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells.

    Science.gov (United States)

    Yao, Takako; Fujimura, Tsutomu; Murayama, Kimie; Okumura, Ko; Seko, Yoshinori

    2017-10-18

    We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself.

  20. Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, J.M.; Standaert, M.L.; Nair, G.P.; Farese, R.V. (Univ. of South Florida, Tampa (USA))

    1991-04-02

    Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in ({sup 3}H)glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked the later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 {mu}M sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis.

  1. 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.

    Science.gov (United States)

    Lafontant, Pascal J; Behzad, Ali R; Brown, Evelyn; Landry, Paul; Hu, Norman; Burns, Alan R

    2013-01-01

    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.

  2. 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

    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...

  3. Hollow mandrin facilitates external ventricular drainage placement.

    Science.gov (United States)

    Heese, O; Regelsberger, J; Kehler, U; Westphal, M

    2005-07-01

    Placement of ventricular catheters is a routine procedure in neurosurgery. Ventricle puncture is done using a flexible ventricular catheter stabilised by a solid steel mandrin in order to improve stability during brain penetration. A correct catheter placement is confirmed after removing the solid steel mandrin by observation of cerebrospinal fluid (CSF) flow out of the flexible catheter. Incorrect placement makes further punctures necessary. The newly developed device allows CSF flow observation during the puncture procedure and in addition precise intracranial pressure (ICP) measurement. The developed mandrin is hollow with a blunt tip. On one side 4-5 small holes with a diameter of 0.8 mm are drilled corresponding exactly with the holes in the ventricular catheter, allowing CSF to pass into the hollow mandrin as soon as the ventricle is reached. By connecting a small translucent tube at the distal portion of the hollow mandrin ICP can be measured without loss of CSF. The system has been used in 15 patients with subarachnoid haemorrhage (SAH) or intraventricular haemeorrhage (IVH) and subsequent hydrocephalus. The new system improved the external ventricular drainage implantation procedure. In all 15 patients catheter placement was correct. ICP measurement was easy to perform immediately at ventricle puncture. In 4 patients at puncture no spontaneous CSF flow was observed, therefore by connecting a syringe and gentle aspiration of CSF correct placement was confirmed in this unexpected low pressure hydrocephalus. Otherwise by using the conventional technique further punctures would have been necessary. Advantages of the new technique are less puncture procedures with a lower risk of damage to neural structures and reduced risk of intracranial haemorrhages. Implantation of the ventricular catheter to far into the brain can be monitored and this complication can be overcome. Using the connected pressure monitoring tube an exact measurement of the opening

  4. Left ventricular function in chronic aortic regurgitation

    International Nuclear Information System (INIS)

    Iskandrian, A.S.; Hakki, A.H.; Manno, B.; Amenta, A.; Kane, S.A.

    1983-01-01

    Left ventricular performance was determined in 42 patients with moderate or severe aortic regurgitation during upright exercise by measuring left ventricular ejection fraction and volume with radionuclide ventriculography. Classification of the patients according to exercise tolerance showed that patients with normal exercise tolerance (greater than or equal to 7.0 minutes) had a significantly higher ejection fraction at rest (probability [p] . 0.02) and during exercise (p . 0.0002), higher cardiac index at exercise (p . 0.0008) and lower exercise end-systolic volume (p . 0.01) than did patients with limited exercise tolerance. Similar significant differences were noted in younger patients compared with older patients in ejection fraction at rest and exercise (both p . 0.001) and cardiac index at rest (p . 0.03) and exercise (p . 0.0005). The end-diastolic volume decreased during exercise in 60% of the patients. The patients with a decrease in volume were significantly younger and had better exercise tolerance and a larger end-diastolic volume at rest than did patients who showed an increase in volume. The mean corrected left ventricular end-diastolic radius/wall thickness ratio was significantly greater in patients with abnormal than in those with normal exercise reserve (mean +/- standard deviation 476 +/- 146 versus 377 +/- 92 mm Hg, p less than 0.05). Thus, in patients with chronic aortic regurgitation: 1) left ventricular systolic function during exercise was related to age, exercise tolerance and corrected left ventricular end-diastolic radius/wall thickness ratio, and 2) the end-diastolic volume decreased during exercise, especially in younger patients and patients with normal exercise tolerance or a large volume at rest

  5. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

    Science.gov (United States)

    Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

    2017-04-01

    Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

  6. Measurement of ventricular function by ECG gating during atrial fibrillation

    International Nuclear Information System (INIS)

    Bacharach, S.L.; Green, M.V.; Bonow, R.O.; Findley, S.L.; Ostrow, H.G.; Johnston, G.S.

    1981-01-01

    The assumptions necessary to perform ECG-gated cardiac studies are seemingly not valid for patients in atrial fibrillation (AF). To evaluate the effect of AF on equilibrium gated scintigraphy, beat-by-beat measurements of left-ventricular function were made on seven subjects in AF (mean heart rate 64 bpm), using a high-efficiency nonimaging detector. The parameters evaluated were ejection fraction (EF), time to end-systole (TES), peak rates of ejection and filling (PER,PFR), and their times of occurrence (TPER, TPFR). By averaging together single-beat values of EF, PER, etc., it was possible to determine the true mean values of these parameters. The single-beam mean values were compared with the corresponding parameters calculated from one ECG-gated time-activity curve (TAC) obtained by superimposing all the single-beat TACs irrespective of their length. For this population with slow heart rates, we find that the values for EF, etc., produced from ECG-gated time-activity curves, are very similar to those obtained from the single-beat data. Thus use of ECG gating at low heart rates may allow reliable estimation of average cardiac function even in subjects with AF

  7. Arrhythmogenic right ventricular cardiomyopathy in a dog : case report

    Directory of Open Access Journals (Sweden)

    A.J. Möhr

    2000-07-01

    Full Text Available An 8-month-old Labrador retriever bitch was evaluated for sudden-onset, progressive abdominal distension. Physical examination revealed an exaggerated inspiratory effort, severe ascites, bilateral jugular vein distension, and hypokinetic femoral arterial pulses. Thoracic auscultation detected tachycardia with muffled heart sounds, without audible cardiac murmurs. Thoracic radiographs identified severe right ventricular enlargement and pleural effusion. The electrocardiogram was consistent with incomplete right bundle branch block or right ventricular enlargement. Echocardiography demonstrated severe right ventricular and atrial dilation, secondary tricuspid regurgitation, and thinning and hypocontractility of the right ventricular myocardium. Left heart chamber sizes were slightly decreased, with normal left ventricular contractility. Adiagnosis of arrhythmogenic right ventricular cardiomyopathy was reached, based on the characteristic clinical, electrocardiographic, radiographic and echocardiographic findings, and the exclusion of other causes of isolated right ventricular failure. Treatment effected good control of clinical signs, until acutely decompensated congestive right heart failure led to euthanasia after 4 months. Arrhythmogenic right ventricular cardiomyopathy is a well-described clinical entity in humans, and has previously been documented in 3 male dogs. The condition is characterised by progressive fibro-adipose replacement of right ventricular myocardium, while the left ventricle usually remains unaffected. It should be considered a differential diagnosis in any young dog presented with isolated right heart failure, syncope, or unexplained ventricular tachyarrhythmias. This article reports the 1st case of arrhythmogenic right ventricular cardiomyopathy in a female dog, and highlights its echocardiographic features.

  8. Echocardiographic left ventricular masses in distance runners and weight lifters

    Science.gov (United States)

    Longhurst, J. C.; Gonyea, W. J.; Mitchell, J. H.; Kelly, A. R.

    1980-01-01

    The relationships of different forms of exercise training to left ventricular mass and body mass are investigated by echocardiographic studies of weight lifters, long-distance runners, and comparatively sized untrained control subjects. Left ventricular mass determinations by the Penn convention reveal increased absolute left ventricular masses in long-distance runners and competitive weight lifters with respect to controls matched for age, body weight, and body surface area, and a significant correlation between ventricular mass and lean body mass. When normalized to lean body mass, the ventricular masses of distance runners are found to be significantly higher than those of the other groups, suggesting that dynamic training elevates left ventricular mass compared to static training and no training, while static training increases ventricular mass only to the extent that lean body mass is increased.

  9. Two-dimensional echocardiographic features of right ventricular infarction

    International Nuclear Information System (INIS)

    D'Arcy, B.; Nanda, N.C.

    1982-01-01

    Real-time, two-dimensional echocardiographic studies were performed in 10 patients with acute myocardial infarction who had clinical features suggestive of right ventricular involvement. All patients showed right ventricular wall motion abnormalities. In the four-chamber view, seven patients showed akinesis of the entire right ventricular diaphragmatic wall and three showed akinesis of segments of the diaphragmatic wall. Segmental dyskinetic areas involving the right ventricular free wall were identified in four patients. One patient showed a large right ventricular apical aneurysm. Other echocardiographic features included enlargement of the right ventricle in eight cases, paradoxical ventricular septal motion in seven cases, tricuspid incompetence in eight cases, dilation of the stomach in four cases and localized pericardial effusion in two cases. Right ventricular infarction was confirmed by radionuclide methods in seven patients, at surgery in one patient and at autopsy in two patients

  10. Errors during MRT measurements of the left ventricular volume using a multi-slice technique

    International Nuclear Information System (INIS)

    Pitton, M.B.; Just, M.; Grebe, P.; Kreitner, K.F.; Erbel, R.; Thelen, M.

    1992-01-01

    A multi-slice technique for MRT measurements of the left ventricular volume is much faster than the use of single-slice methods and is therefore better tolerated, leaving time for additional measurements. The end-diastolic left ventricular volume can be reliably measured by this method (123.3±13.5 ml vs. 124.1±ml). The end-systolic volume is consistently overestimated by 23.7±18,3% compared with the reference value obtained by single slice measurements (47.9±8.9 ml vs 39.1±7.9 ml). Correspondingly, stroke volume and ejection fraction is underestimated on average by 10.6±9.7% and 10.6±7.6% respectively). (orig.) [de

  11. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    Science.gov (United States)

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  12. Crosstalk between monocytes and myometrial smooth muscle in culture generates synergistic pro-inflammatory cytokine production and enhances myocyte contraction, with effects opposed by progesterone.

    Science.gov (United States)

    Rajagopal, S P; Hutchinson, J L; Dorward, D A; Rossi, A G; Norman, J E

    2015-08-01

    Both term and preterm parturition are characterized by an influx of macrophages and neutrophils into the myometrium and cervix, with co-incident increased peripheral blood monocyte activation. Infection and inflammation are strongly implicated in the pathology of preterm labour (PTL), with progesterone considered a promising candidate for its prevention or treatment. In this study, we investigated the effect of monocytes on myometrial smooth muscle cell inflammatory cytokine production both alone and in response to LPS, a TLR4 agonist used to trigger PTL in vivo. We also investigated the effect of monocytes on myocyte contraction. Monocytes, isolated from peripheral blood samples from term pregnant women, were cultured alone, or co-cultured with PHM1-41 myometrial smooth muscle cells, for 24 h. In a third set of experiments, PHM1-41 myocytes were cultured for 24 h in isolation. Cytokine secretion was determined by ELISA or multiplex assays. Co-culture of monocytes and myocytes led to synergistic secretion of pro-inflammatory cytokines and chemokines including IL-6, IL-8 and MCP-1, with the secretion being further enhanced by LPS (100 ng/ml). The synergistic secretion of IL-6 and IL-8 from co-cultures was mediated in part by direct cell-cell contact, and by TNF. Conditioned media from co-cultures stimulated contraction of PHM1-41 myocytes, and the effect was inhibited by progesterone. Both progesterone and IL-10 inhibited LPS-stimulated IL-6 and IL-8 secretion from co-cultures, while progesterone also inhibited chemokine secretion. These data suggest that monocytes infiltrating the myometrium at labour participate in crosstalk that potentiates pro-inflammatory cytokine secretion, an effect that is enhanced by LPS, and can augment myocyte contraction. These effects are all partially inhibited by progesterone. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

  13. Assessment of subclinical right ventricular systolic dysfunction in coal miners using myocardial isovolumic acceleration.

    Science.gov (United States)

    Ozcan Abacıoglu, Ozge; Kaplan, Mehmet; Abacıoglu, Serkan; Quisi, Ala

    2017-09-01

    Several studies have been conducted regarding the effects of coal mining on the respiratory system. However, there is a lack of data concerning potential effects of coal mining on the cardiovascular system. In this study, we aimed to evaluate the potential subclinical right and left ventricular dysfunction in coal miners. This single-center, prospective study included a total of 102 patients. Patient and control groups consisted of 54 coal miners and 48 healthy men, respectively. All patients underwent 12-lead electrocardiography, transthoracic echocardiography, and pulmonary function test. As compared to control group, coal miners had significantly higher right ventricular myocardial performance index (RVMPI) (0.41 ± 0.03 vs 0.37 ± 0.02, P right ventricular fractional area change (RVFAC) (33.55% ± 6.70% vs 37.04 ± 9.26 P right and left ventricular dysfunction, including RVMPI, RVFAC, TAPSE, IVA, and AD, are impaired in coal miners. © 2017 The Authors Echocardiography Published by Wiley Periodicals, Inc.

  14. The management of patients with aortic regurgitation and severe left ventricular dysfunction: a systematic review.

    Science.gov (United States)

    Badar, Athar A; Brunton, Alan P T; Mahmood, Ammad H; Dobbin, Stephen; Pozzi, Andrea; McMinn, Jenna F; Sinclair, Andrew J E; Gardner, Roy S; Petrie, Mark C; Curry, Phil A; Al-Attar, Nawwar H K; Pettit, Stephen J

    2015-01-01

    A systematic search of Medline, EMBASE and CINAHL electronic databases was performed. Original research articles reporting all-cause mortality following surgery in patients with aortic regurgitation and severe left ventricular systolic dysfunction (LVSD) were identified. Nine of the 10 eligible studies were observational, single-center, retrospective analyses. Survival ranged from 86 to 100% at 30 days; 81 to 100% at 1 year and 68 to 84% at 5 years. Three studies described an improvement in mean left ventricular ejection fraction (LVEF) following aortic valve replacement (AVR) of 5-14%; a fourth study reported an increase in mean left ventricular ejection fraction (LVEF) of 9% in patients undergoing isolated AVR but not when AVR was combined with coronary artery bypass graft and/or mitral valve surgery. Three studies demonstrated improvements in functional New York Heart Association (NYHA) class following AVR. Additional studies are needed to clarify the benefits of AVR in patients with more extreme degrees of left ventricular systolic dysfunction (LVSD) and the potential roles of cardiac transplantation and transaortic valve implantation.

  15. Blood pressure and left ventricular hypertrophy during American-style football participation.

    Science.gov (United States)

    Weiner, Rory B; Wang, Francis; Isaacs, Stephanie K; Malhotra, Rajeev; Berkstresser, Brant; Kim, Jonathan H; Hutter, Adolph M; Picard, Michael H; Wang, Thomas J; Baggish, Aaron L

    2013-07-30

    Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known. We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116±8 versus 125±13 mm Hg; Phistory of hypertension were the strongest independent predictors of postseason BP. Among linemen, there was a significant increase in the prevalence of concentric left ventricular hypertrophy (2 of 64 [3%] versus 20 of 64 [31%]; P<0.001) and change in left ventricular mass correlated with intraseason change in systolic BP (R=0.46, P<0.001). Collegiate ASF athletes may be at risk for clinically relevant increases in BP and the development of hypertension. Enhanced surveillance and carefully selected interventions may represent important opportunities to improve later-life cardiovascular health outcomes in this population.

  16. Non-invasive, kinetic measurements of [3H]nitrendipine binding to isolated rat myocytes by condensed phase radioluminescence

    International Nuclear Information System (INIS)

    Tscharner, V. von; Bailey, I.A.

    1983-01-01

    The binding of 3 H-labelled drug molecules to membranes of living cells give rise to photon emission from tryptophan residues at proteinaceous binding sites. This phenomenon, called condensed phase radioluminescence, has been used to measure non-invasively the kinetics of [ 3 H]nitrendipine binding and dissociation on the same samples of cultured beating cardiac myocytes. Signal arose only from bound drug molecules. Binding was monoexponential (tau = 5.5 min) as was dissociation (14.3 min). Preincubating cells with non-radioactive nifedipine reduced the amplitude and rate of [ 3 H]nitrendipine but not of [ 3 H]dihydroalprenolol binding. The potential uses of this phenomenon are discussed. (Auth.)

  17. Case report: Greater meningeal inflammation in lumbar than in ventricular region in human bacterial meningitis

    OpenAIRE

    Naija, Walid; Matéo, Joaquim; Raskine, Laurent; Timsit, Jean-François; Lukascewicz, Anne-Claire; George, Bernard; Payen, Didier; Mebazaa, Alexandre

    2004-01-01

    Differences in the composition of ventricular and lumbar cerebrospinal fluid (CSF) based on single pairs of samples have previously been described. We describe a patient that developed post-surgical recurrent meningitis monitored by daily biochemical and bacteriological CSF analysis, simultaneously withdrawn from lumbar space and ventricles. A 20-year-old Caucasian man was admitted to the ICU after a resection of a chordoma that extended from the sphenoidal sinus to the anterior face of C2. C...

  18. KChIP2 regulates the cardiac Ca2+ transient and myocyte contractility by targeting ryanodine receptor activity.

    Directory of Open Access Journals (Sweden)

    Drew M Nassal

    Full Text Available Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss. Therefore, KChIP2 was acutely silenced in isolated guinea pig myocytes, which led to significant reductions in the Ca2+ transient amplitude and prolongation of the transient duration. This change was reinforced by a decline in sarcomeric shortening. Notably, these results were unexpected when considering previous observations showing enhanced ICa,L and prolonged action potential duration following KChIP2 loss, suggesting a disruption of fundamental Ca2+ handling proteins. Evaluation of SERCA2a, phospholamban, RyR, and sodium calcium exchanger identified no change in protein expression. However, assessment of Ca2+ spark activity showed reduced spark frequency and prolonged Ca2+ decay following KChIP2 loss, suggesting an altered state of RyR activity. These changes were associated with a delocalization of the ryanodine receptor activator, presenilin, away from sarcomeric banding to more diffuse distribution, suggesting that RyR open probability are a target of KChIP2 loss mediated by a dissociation of presenilin. Typically, prolonged action potential duration and enhanced Ca2+ entry would augment cardiac contractility, but here we see KChIP2 fundamentally disrupts Ca2+ release events and compromises myocyte contraction. This novel role targeting presenilin localization and RyR activity reveals a significance for KChIP2 loss that reflects adverse remodeling observed in cardiac disease settings.

  19. Protein kinase A and C regulate leak potassium currents in freshly isolated vascular myocytes from the aorta.

    Directory of Open Access Journals (Sweden)

    Sébastien Hayoz

    Full Text Available We tested the hypothesis that protein kinase A (PKA inhibits K2P currents activated by protein kinase C (PKC in freshly isolated aortic myocytes. PDBu, the PKC agonist, applied extracellularly, increased the amplitude of the K2P currents in the presence of the "cocktail" of K(+ channel blockers. Gö 6976 significantly reduced the increase of the K2P currents by PDBu suggesting the involvement of either α or β isoenzymes of PKC. We found that forskolin, or membrane permeable cAMP, did not inhibit K2P currents activated by the PKC. However, when PKA agonists were added prior to PDBu, they produced a strong decrease in the K2P current amplitudes activated by PKC. Inhibition of PDBu-elicited K2P currents by cAMP agonists was not prevented by the treatment of vascular smooth muscle cells with PKA antagonists (H-89 and Rp-cAMPs. Zn(2+ and Hg(2+ inhibited K2P currents in one population of cells, produced biphasic responses in another population, and increased the amplitude of the PDBu-elicited K(+ currents in a third population of myocytes, suggesting expression of several K2P channel types. We found that cAMP agonists inhibited biphasic responses and increase of amplitude of the PDBu-elicited K2P currents produced by Zn(2+ and Hg(2. 6-Bnz-cAMp produced a significantly altered pH sensitivity of PDBu-elicited K2P-currents, suggesting the inhibition of alkaline-activated K2P-currents. These results indicate that 6-Bnz-cAMP and other cAMP analogs may inhibit K2P currents through a PKA-independent mechanism. cAMP analogs may interact with unidentified proteins involved in K2P channel regulation. This novel cellular mechanism could provide insights into the interplay between PKC and PKA pathways that regulate vascular tone.

  20. Enhancement of Autophagy by Simvastatin through Inhibition of Rac1-mTOR Signaling Pathway in Coronary Arterial Myocytes

    Directory of Open Access Journals (Sweden)

    Yu-Miao Wei

    2013-06-01

    Full Text Available Background/Aims: In addition to their action of lowering blood cholesterol levels, statins modulate biological characteristics and functions of arterial myocytes such as viability, proliferation, apoptosis, survival and contraction. The present study tested whether simvastatin, as a prototype statin, enhances autophagy in coronary arterial myocytes (CAMs to thereby exert their beneficial effects in atherosclerosis. Methods and Results: Using flow cytometry, we demonstrated that simvastatin significantly increased the autophagsome formation in CAMs. Western blot analysis confirmed that simvastatin significantly increased protein expression of typical autophagy markers LC3B and Beclin1 in these CAMs. Confocal microscopy further demonstrated that simvastatin increased fusion of autophagosomes with lysosomes, which was blocked by autophagy inhibitor 3-methyladenine or silencing of Atg7 genes. Simvastatin reduced mammalian target of rapamycin (mTOR activity, which was reversed by Rac1-GTPase overexpression and the mTOR agonist phosphatidic acid. Moreover, both Rac1-GTPase overexpression and activation of mTOR by phosphatidic acid drastically blocked simvastatin-induced autophagosome formation in CAMs. Interestingly, simvastatin increased protein expression of a contractile phenotype marker calponin in CAMs, which was blocked by autophagy inhibitor 3-methyladenine. Simvastatin markedly reduced proliferation of CAMs under both control and proatherogenic stimulation. However, this inhibitory effect of simvastatin on CAM proliferation was blocked by by autophagy inhibitor 3-methyladenine or silencing of Atg7 genes. Lastly, animal experiments demonstrated that simvastatin increased protein expression of LC3B and calponin in mouse coronary arteries. Conclusion: Our results indicate that simvastatin inhibits the Rac1-mTOR pathway and thereby increases autophagy in CAMs which may stabilize CAMs in the contractile phenotype to prevent proliferation and growth

  1. RSK3 is required for concentric myocyte hypertrophy in an activated Raf1 model for Noonan syndrome.

    Science.gov (United States)

    Passariello, Catherine L; Martinez, Eliana C; Thakur, Hrishikesh; Cesareo, Maria; Li, Jinliang; Kapiloff, Michael S

    2016-04-01

    Noonan syndrome (NS) is a congenital disorder resulting from mutations of the Ras-Raf signaling pathway. Hypertrophic cardiomyopathy associated with RAF1 "RASopathy" mutations is a major risk factor for heart failure and death in NS and has been attributed to activation of MEK1/2-ERK1/2 mitogen-activated protein kinases. We recently discovered that type 3 p90 ribosomal S6 kinase (RSK3) is an ERK effector that is required, like ERK1/2, for concentric myocyte hypertrophy in response to pathological stress such as pressure overload. In order to test whether RSK3 also contributes to NS-associated hypertrophic cardiomyopathy, RSK3 knock-out mice were crossed with mice bearing the Raf1(L613V) human NS mutation. We confirmed that Raf1(L613V) knock-in confers a NS-like phenotype, including cardiac hypertrophy. Active RSK3 was increased in Raf1(L613V) mice. Constitutive RSK3 gene deletion prevented the Raf1(L613V)-dependent concentric growth in width of the cardiac myocyte and attenuated cardiac hypertrophy in female mice. These results are consistent with RSK3 being an important mediator of ERK1/2-dependent growth in RASopathy. In conjunction with previously published data showing that RSK3 is important for pathological remodeling of the heart, these data suggest that targeting of this downstream MAP-kinase pathway effector should be considered in the treatment of RASopathy-associated hypertrophic cardiomyopathy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes.

    Science.gov (United States)

    Pabbidi, M R; Ji, X; Maxwell, J T; Mignery, G A; Samarel, A M; Lipsius, S L

    2016-01-01

    We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinterol (0.1 μM; zint-β2-AR) to stimulate ICa,L in atrial myocytes in the absence (+PKA) and presence (-PKA) of the PKA inhibitor (1 μM) KT5720 and compared these results with atrial myocytes attached to laminin (+LMN). Inhibition of Raf-1 (10 μM GW5074), phospholipase C (PLC; 0.5 μM edelfosine), PKC (4 μM chelerythrine) or IP3 receptor (IP3R) signaling (2 μM 2-APB) significantly inhibited zint-β2-AR stimulation of ICa,L in-PKA but not +PKA myocytes. Western blots showed that zint-β2-AR stimulation increased ERK1/2 phosphorylation in-PKA compared to +PKA myocytes. Adenoviral (Adv) expression of dominant negative (dn) -PKCα, dn-Raf-1 or an IP3 affinity trap, each inhibited zint-β2-AR stimulation of ICa,L in + LMN myocytes compared to control +LMN myocytes infected with Adv-βgal. In +LMN myocytes, zint-β2-AR stimulation of ICa,L was enhanced by adenoviral overexpression of wild-type cPLA2 and inhibited by double dn-cPLA2S505A/S515A mutant compared to control +LMN myocytes infected with Adv-βgal. In-PKA myocytes depletion of intracellular Ca2+ stores by 5 μM thapsigargin failed to inhibit zint-β2-AR stimulation of ICa,L via cPLA2. However, disruption of caveolae formation by 10 mM methyl-β-cyclodextrin inhibited zint-β2-AR stimulation of ICa,L in-PKA myocytes significantly more than in +PKA myocytes. We conclude that inhibition of PKA removes inhibition of Raf-1 and thereby allows β2-AR stimulation to act via PKCα/Raf-1/MEK/ERK1/2 and IP3-mediated Ca2+ signaling to stimulate cPLA2 signaling within caveolae. These findings may be relevant to the remodeling of

  3. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome

    DEFF Research Database (Denmark)

    Nielsen, Jens Cosedis; Thomsen, Poul Erik B; Højberg, Søren

    2011-01-01

    In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any ...

  4. Right ventricular hydatid cyst ruptured to pericardium

    Directory of Open Access Journals (Sweden)

    Feridoun Sabzi

    2015-01-01

    Full Text Available Cardiac hydatidosis is rare presentation of body hydatidosis. Incidence of cardiac involvements range from 5% to 5% of patients with hydatid disease. Most common site of hydatid cyst in heart is interventricular septum and left ventricular free wall. Right ventricular free wall involvement by cyst that ruptured to pericardial cavity is very rare presentation of hydatid cyst. Cardiac involvement may have serious consequences such as rupture to blood steam or pericardial cavity. Both the disease and its surgical treatment carry a high complication rate, including rupture leading to cardiac tamponade, anaphylaxis and also death. In the present report, a 43-year-old man with constrictive pericarditis secondary to a pericardial hydatid cyst is described.

  5. [Ventricular tachyarrhythmias in patients with cardiomyopathy

    DEFF Research Database (Denmark)

    Henningsen, K.; Christensen, A.H.; Svendsen, Jesper Hastrup

    2008-01-01

    by disease, gender, age, previous cardiac arrest and treatment with implantable cardioverter-defibrillator (ICD). RESULTS: 993 patients were screened and 128 patients with cardiomyopathy were identified, corresponding to 13% of the screened patients. 58 (45%) of the patients had dilated cardiomyopathy (DCM......), 57 (45%) patients had arrhythmogenic right ventricular cardiomyopathy (ARVC) and 13 (10%) had hypertrophic cardiomyopathy (HCM). The average age was 44 years for HCM, 41 years for ARVC and 58 years for DCM. The majority of the patients were male. ICD treatment was used in 95% of the patients...... with ARVC, 70% of the patients with HCM and 59% of the patients with DCM. Only 5 patients had previous cardiac arrest without reversible cause. CONCLUSION: The study shows that cardiomyopathies are relatively frequent causes of ventricular tachyarrhythmias in patients discharged from a specialised...

  6. Detection of left ventricular thrombi by computerised tomography

    International Nuclear Information System (INIS)

    Nair, C.K.; Sketch, M.H.; Mahoney, P.D.; Lynch, J.D.; Mooss, A.N.; Kenney, N.P.

    1981-01-01

    Sixteen patients suspected of having left ventricular mural thrombi were studied. All had suffered transmural myocardial infarction. Fifteen patients had a ventricular aneurysm. One had had systemic emboli. The mean length of time between the myocardial infarction and the study was 14.8 months, with a range of one month to 79 months. All patients underwent computerised tomography of the heart, M-mode echocardiography (M-mode), and two-dimensional echocardiography (2-D). Eight patients underwent left ventricular cineangiography. Five patients had surgical confirmation. Computerised tomography, two-dimensional, and M-mode echocardiography predicted left ventricular mural thrombi in 10, eight, and one of the 16 patients, respectively. Left ventricular cineangiography predicted left ventricular mural thrombi in four out of eight patients. Computerised tomography and left ventricular cineangiography correctly predicted the presence or absence of left ventricular thrombi in all five patients who underwent operation. In the same group, however, two-dimensional and M-mode echocardiography failed to predict the presence of thrombi in one and three patients, respectively. Among the 11 patients without surgical confirmation, one, in whom no left ventricular thrombi were shown by M-mode and two-dimensional echocardiography, was found to have thrombi on computerised tomography. In another, two-dimensional echocardiography was positive but this finding was not confirmed either by computerised tomography or by left ventricular angiography. (author)

  7. Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Hugo Van Herendael

    2010-06-01

    Full Text Available Hugo Van Herendael, Paul DorianDivision of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, CanadaAbstract: Amiodarone has emerged as the leading antiarrhythmic therapy for termination and prevention of ventricular arrhythmia in different clinical settings because of its proven efficacy and safety. In patients with shock refractory out-of-hospital cardiac arrest and hemodynamically destabilizing ventricular arrhythmia, amiodarone is the most effective drug available to assist in resuscitation. Although the superiority of the transvenous implantable cardioverter defibrillator (ICD over amiodarone has been well established in the preventive treatment of patients at high risk of life-threatening ventricular arrhythmias, amiodarone (if used with a beta-blocker is the most effective antiarrhythmic drug to prevent ICD shocks and treat electrical storm. Both the pharmacokinetics and the electrophysiologic profile of amiodarone are complex, and its optimal and safe use requires careful patient surveillance with respect to potential adverse effects.Keywords: amiodarone, ventricular fibrillation, unstable ventricular tachycardia

  8. Left Ventricular Myocardial Function in Children With Pulmonary Hypertension: Relation to Right Ventricular Performance and Hemodynamics.

    Science.gov (United States)

    Burkett, Dale A; Slorach, Cameron; Patel, Sonali S; Redington, Andrew N; Ivy, D Dunbar; Mertens, Luc; Younoszai, Adel K; Friedberg, Mark K

    2015-08-01

    Through ventricular interdependence, pulmonary hypertension (PH) induces left ventricular (LV) dysfunction. We hypothesized that LV strain/strain rate, surrogate measures of myocardial contractility, are reduced in pediatric PH and relate to invasive hemodynamics, right ventricular strain, and functional measures of PH. At 2 institutions, echocardiography was prospectively performed in 54 pediatric PH patients during cardiac catheterization, and in 54 matched controls. Patients with PH had reduced LV global longitudinal strain (LS; -18.8 [-17.3 to -20.4]% versus -20.2 [-19.0 to -20.9]%; P=0.0046) predominantly because of reduced basal (-12.9 [-10.8 to -16.3]% versus -17.9 [-14.5 to -20.7]%; Pright ventricular free-wall LS (r=0.64; PBrain natriuretic peptide levels correlated moderately with septal LS (r=0.48; P=0.0038). PH functional class correlated moderately with LV free-wall LS (r=-0.48; P=0.0051). The septum, shared between ventricles and affected by septal shift, was the most affected LV region in PH. Pediatric PH patients demonstrate reduced LV strain/strain rate, predominantly within the septum, with relationships to invasive hemodynamics, right ventricular strain, and functional PH measures. © 2015 American Heart Association, Inc.

  9. The helical ventricular myocardial band: global, three-dimensional, functional architecture of the ventricular myocardium.

    Science.gov (United States)

    Kocica, Mladen J; Corno, Antonio F; Carreras-Costa, Francesc; Ballester-Rodes, Manel; Moghbel, Mark C; Cueva, Clotario N C; Lackovic, Vesna; Kanjuh, Vladimir I; Torrent-Guasp, Francisco

    2006-04-01

    We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.

  10. Assessment of left ventricular global function

    International Nuclear Information System (INIS)

    Breuel, H.-P.; Baehre, M.

    1985-01-01

    Radionuclide ventriculography (RNV), i.e. noninvasive evaluation of left venticular performance following the application of radionuclides has had a major impact on many aspects of cardiology and has proven its clinical value and reliability in the last few years. This article deals mainly with the changes in global left ventricular function. The clinical applications of RNV for coronary artery diseases and valvular heart diseases are described. (Auth.)

  11. Left ventricular heart failure and pulmonary hypertension†

    Science.gov (United States)

    Rosenkranz, Stephan; Gibbs, J. Simon R.; Wachter, Rolf; De Marco, Teresa; Vonk-Noordegraaf, Anton; Vachiéry, Jean-Luc

    2016-01-01

    Abstract In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65–80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a ‘left ventricular phenotype’ to a ‘right ventricular phenotype’ across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context. PMID:26508169

  12. Ventricular enlargement in patients with affective disorders

    International Nuclear Information System (INIS)

    Murashita, Jun; Kato, Tadafumi; Shioiri, Toshiki; Hamakawa, Inubushi, Toshiro; Hiroshi; Takahashi, Saburo

    1994-01-01

    Ventricular enlargement was determined using linear measurement on MR images in a total of 71 patients with affective disorders, including bipolar affective disorder (41) and depression (30). Fourty-one healthy persons served as controls. Evans ratio, Huckman number and minimum distance of caudate nuclei (MDCN) were used as indices for ventricular enlargment. No significant difference in Evans ratio was observed between both the group of bipolar affective disorder and the group of depression and the control group. Nor did it correlate with age in any of the groups. Huckman number was significantly higher in the group of bipolar affective disorder than the other two groups. It positively correlated with age in the group of depression. MDCN was significantly increased in the group of bipolar affective disorder, as compared with the control group; and there was a positive correlation between MDCN and age in both the group of dipolar affective disorder and the group of depression. In conclusion, ventricular enlargement was dependent upon aging in affetive disorder patients. This tendency was more noticeable in the group of depression. In addition, atrophy of the caudate nuclei was likely to be severer in the group of dipolar affective disorder than the group of depression. (N.K.)

  13. Simulation of Ventricular, Cavo-Pulmonary, and Biventricular Ventricular Assist Devices in Failing Fontan.

    Science.gov (United States)

    Di Molfetta, Arianna; Amodeo, Antonio; Fresiello, Libera; Trivella, Maria Giovanna; Iacobelli, Roberta; Pilati, Mara; Ferrari, Gianfranco

    2015-07-01

    Considering the lack of donors, ventricular assist devices (VADs) could be an alternative to heart transplantation for failing Fontan patients, in spite of the lack of experience and the complex anatomy and physiopathology of these patients. Considering the high number of variables that play an important role such as type of Fontan failure, type of VAD connection, and setting (right VAD [RVAD], left VAD [LVAD], or biventricular VAD [BIVAD]), a numerical model could be useful to support clinical decisions. The aim of this article is to develop and test a lumped parameter model of the cardiovascular system simulating and comparing the VAD effects on failing Fontan. Hemodynamic and echocardiographic data of 10 Fontan patients were used to simulate the baseline patients' condition using a dedicated lumped parameter model. Starting from the simulated baseline and for each patient, a systolic dysfunction, a diastolic dysfunction, and an increment of the pulmonary vascular resistance were simulated. Then, for each patient and for each pathology, the RVAD, LVAD, and BIVAD implantations were simulated. The model can reproduce patients' baseline well. In the case of systolic dysfunction, the LVAD unloads the single ventricle and increases the cardiac output (CO) (35%) and the arterial systemic pressure (Pas) (25%). With RVAD, a decrement of inferior vena cava pressure (Pvci) (39%) was observed with 34% increment of CO, but an increment of the single ventricle external work (SVEW). With the BIVAD, an increment of Pas (29%) and CO (37%) was observed. In the case of diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci, while both increase the SVEW. In the case of pulmonary vascular resistance increment, the highest CO (50%) and Pas (28%) increment is obtained with an RVAD with the highest decrement of Pvci (53%) and an increment of the SVEW but with the lowest VAD power consumption. The use of numerical models could be helpful in this innovative

  14. The angulation of the septal structures impacts ventricular imbalance in atrioventricular septal defects with a common atrioventricular junction.

    Science.gov (United States)

    Ahmad, Zaheer; Lim, Zek; Roman, Kevin; Haw, Marcus; Anderson, Robert H; Vettukattil, Joseph

    2016-02-01

    Multiplanar re-formatting of full-volume three-dimensional echocardiography data sets offers new insights into the morphology of atrioventricular septal defects. We hypothesised that distortion of the alignment between the atrial and ventricular septums results in imbalanced venous return to the ventricles, with consequent proportional ventricular hypoplasia. A single observer evaluated 31 patients, with a mean age of 52.09 months, standard deviation of 55, and with a range from 2 to 264 months, with atrioventricular septal defects, of whom 17 were boys. Ventricular imbalance, observed in nine patients, was determined by two-dimensional assessment, and confirmed at surgical inspection in selected cases when a univentricular strategy was undertaken. Offline analysis using multiplanar re-formatting was performed. A line was drawn though the length of the ventricular septum and a second line along the plane of the atrial septum, taking the angle between these two lines as the atrioventricular septal angle. We compared the angle between 22 patients with adequately sized ventricles, and those with ventricular imbalance undergoing univentricular repair. In the 22 patients undergoing biventricular repair, the septal angle was 0 in 14 patients; the other eight patients having angles ranging from 1 to 36, with a mean angle of 7.4°, and standard deviation of 11.1°.The mean angle in the nine patients with ventricle imbalance was 28.6°, with a standard deviation of 3.04°, and with a range from 26 to 35°. Of those undergoing univentricular repair, two patients died, with angles of 26 and 30°, respectively. The atrioventricular septal angle derived via multiplanar formatting gives important information regarding the degree of ventricular hypoplasia and imbalance. When this angle is above 25°, patients are likely to have ventricular imbalance requiring univentricular repair.

  15. Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left Ventricular Mass: A Prospective Multicenter Study.

    Science.gov (United States)

    Weber, Thomas; Wassertheurer, Siegfried; Schmidt-Trucksäss, Arno; Rodilla, Enrique; Ablasser, Cornelia; Jankowski, Piotr; Lorenza Muiesan, Maria; Giannattasio, Cristina; Mang, Claudia; Wilkinson, Ian; Kellermair, Jörg; Hametner, Bernhard; Pascual, Jose Maria; Zweiker, Robert; Czarnecka, Danuta; Paini, Anna; Salvetti, Massimo; Maloberti, Alessandro; McEniery, Carmel

    2017-12-01

    We investigated the relationship between left ventricular mass and brachial office as well as brachial and central ambulatory systolic blood pressure in 7 European centers. Central systolic pressure was measured with a validated oscillometric device, using a transfer function, and mean/diastolic pressure calibration. M-mode images were obtained by echocardiography, and left ventricular mass was determined by one single reader blinded to blood pressure. We studied 289 participants (137 women) free from antihypertensive drugs (mean age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively. Mean left ventricular mass was 93.3 kg/m 2 , and 25.6% had left ventricular hypertrophy. The correlation coefficient between left ventricular mass and brachial office, brachial ambulatory, and central ambulatory systolic pressure was 0.29, 0.41, and 0.47, respectively ( P =0.003 for comparison between brachial office and central ambulatory systolic pressure and 0.32 for comparison between brachial and central ambulatory systolic pressure). The results were consistent for men and women, and young and old participants. The areas under the curve for prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for brachial office, brachial, and central ambulatory systolic pressure, respectively ( P =0.03 for comparison between brachial and central ambulatory systolic pressure). In younger participants, central ambulatory systolic pressure was superior to both other measurements. Central ambulatory systolic pressure, measured with an oscillometric cuff, shows a strong trend toward a closer association with left ventricular mass and hypertrophy than brachial office/ambulatory systolic pressure. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01278732. © 2017 American Heart Association, Inc.

  16. Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Taimur Dad

    2018-05-01

    Full Text Available Introduction: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. Methods: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin−angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. Results: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both. Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively. Conclusion: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI. Keywords: autosomal dominant polycystic kidney disease, hypertension, left ventricular hypertrophy, left ventricular mass index

  17. Ventricular Effective Refraction Period and Ventricular Repolarization Analysis in Experimental Tachycardiomyopathy in Swine.

    Science.gov (United States)

    Noszczyk-Nowak, Agnieszka; Pasławska, Urszula; Gajek, Jacek; Janiszewski, Adrian; Pasławski, Robert; Zyśko, Dorota; Nicpoń, Józef

    2016-01-01

    Swine are recognized animal models of human cardiovascular diseases. However, little is known on the CHF-associated changes in the electrophysiological ventricular parameters of humans and animals. The aim of this study was to analyze changes in the durations of ventricular effective refraction period (VERP), QT and QTc intervals of pigs with chronic tachycardia-induced tachycardiomyopathy (TIC). The study was comprised of 28 adult pigs (8 females and 20 males) of the Polish Large White breed. A one-chamber pacemaker was implanted in each of the 28 pigs. Electrocardiographic, echocardiographic and electrophysiological studies were carried out prior to the pacemaker implantation and at subsequent 4-week intervals. All electrocardiographic, echocardiographic and short electrophysiological study measurements in all swine were done under general anesthesia (propofol) after premedication with midazolam, medetomidine, and ketamine. No significant changes in the duration of QT interval and corrected QT interval (QTc) were observed during consecutive weeks of the experiment. The duration of the QTc interval of female pigs was shown to be significantly longer than that of the males throughout the whole study period. Beginning from the 12th week of rapid ventricular pacing, a significant increase in duration of VERP was observed in both male and female pigs. Males and females did not differ significantly in terms of VERP duration determined throughout the whole study period. Ventricular pacing, stimulation with 2 and 3 premature impulses at progressively shorter coupling intervals and an imposed rhythm of 130 bpm or 150 bpm induced transient ventricular tachycardia in one female pig and four male pigs. One episode of permanent ventricular tachycardia was observed. The number of induced arrhythmias increased proportionally to the severity of heart failure and duration of the experiment. However, relatively aggressive protocols of stimulation were required in order to induce

  18. Computational Cardiac Modeling Reveals Mechanisms of Ventricular Arrhythmogenesis in Long QT Syndrome Type 8: CACNA1C R858H Mutation Linked to Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Jieyun Bai

    2017-10-01

    Full Text Available Functional analysis of the L-type calcium channel has shown that the CACNA1C R858H mutation associated with severe QT interval prolongation may lead to ventricular fibrillation (VF. This study investigated multiple potential mechanisms by which the CACNA1C R858H mutation facilitates and perpetuates VF. The Ten Tusscher-Panfilov (TP06 human ventricular cell models incorporating the experimental data on the kinetic properties of L-type calcium channels were integrated into one-dimensional (1D fiber, 2D sheet, and 3D ventricular models to investigate the pro-arrhythmic effects of CACNA1C mutations by quantifying changes in intracellular calcium handling, action potential profiles, action potential duration restitution (APDR curves, dispersion of repolarization (DOR, QT interval and spiral wave dynamics. R858H “mutant” L-type calcium current (ICaL augmented sarcoplasmic reticulum calcium content, leading to the development of afterdepolarizations at the single cell level and focal activities at the tissue level. It also produced inhomogeneous APD prolongation, causing QT prolongation and repolarization dispersion amplification, rendering R858H “mutant” tissue more vulnerable to the induction of reentry compared with other conditions. In conclusion, altered ICaL due to the CACNA1C R858H mutation increases arrhythmia risk due to afterdepolarizations and increased tissue vulnerability to unidirectional conduction block. However, the observed reentry is not due to afterdepolarizations (not present in our model, but rather to a novel blocking mechanism.

  19. Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance

    Science.gov (United States)

    2013-01-01

    Background Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. Methods 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. Results Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). Conclusions Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria. PMID:23398958

  20. Effects of suture position on left ventricular fluid mechanics under mitral valve edge-to-edge repair.

    Science.gov (United States)

    Du, Dongxing; Jiang, Song; Wang, Ze; Hu, Yingying; He, Zhaoming

    2014-01-01

    Mitral valve (MV) edge-to-edge repair (ETER) is a surgical procedure for the correction of mitral valve regurgitation by suturing the free edge of the leaflets. The leaflets are often sutured at three different positions: central, lateral and commissural portions. To study the effects of position of suture on left ventricular (LV) fluid mechanics under mitral valve ETER, a parametric model of MV-LV system during diastole was developed. The distribution and development of vortex and atrio-ventricular pressure under different suture position were investigated. Results show that the MV sutured at central and lateral in ETER creates two vortex rings around two jets, compared with single vortex ring around one jet of the MV sutured at commissure. Smaller total orifices lead to a higher pressure difference across the atrio-ventricular leaflets in diastole. The central suture generates smaller wall shear stresses than the lateral suture, while the commissural suture generated the minimum wall shear stresses in ETER.

  1. Ventricular Septal Dissection Complicating Inferior Wall Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Lindsey Kalvin

    2017-01-01

    Full Text Available Postmyocardial infarction ventricular septal defect is an increasingly rare mechanical complication of acute myocardial infarction. We present a case of acute myocardial infarction from right coronary artery occlusion that developed hypotension and systolic murmur 12 hours after successful percutaneous coronary intervention. Although preoperative imaging suggested a large ventricular septal defect and a pseudoaneurysm, intraoperative findings concluded a serpiginous dissection of the ventricular septum. The imaging technicalities are discussed.

  2. Effect of programmed ventricular stimulation on myocardial lactate extraction in patients with and without coronary artery disease

    International Nuclear Information System (INIS)

    Morady, F.; DiCarlo, L.A. Jr.; Krol, R.B.; de Buitleir, M.; Nicklas, J.M.; Annesley, T.M.

    1986-01-01

    The arterial-coronary sinus lactate difference was measured in 17 patients after each step of a programmed ventricular stimulation protocol consisting of single, double, and triple extrastimuli, first at a basic drive cycle length of 600 msec, then at 400 msec, with an inter-train interval of 4 seconds. Four patients had no structural heart disease, four had an idiopathic dilated cardiomyopathy, and nine had coronary artery disease with a significant stenosis in at least one branch of the left coronary artery. Net myocardial lactate production during programmed ventricular stimulation was observed in three patients with coronary artery disease, but not in any patient without coronary artery disease. Among the patients who had coronary artery disease, net myocardial lactate production generally occurred in the patients who had more severe coronary artery disease. Exercise-induced ischemia, as demonstrated by a stress thallium-201 test, did not correlate with myocardial lactate production during programmed ventricular stimulation. Programmed ventricular stimulation, with a stimulation protocol typically used in many electrophysiology laboratories, is capable of inducing myocardial ischemia in at least some patients who have coronary artery disease. This finding suggests that myocardial ischemia may potentially influence the results of programmed ventricular stimulation in some patients with coronary artery disease

  3. Right ventricular strain in heart failure: Clinical perspective.

    Science.gov (United States)

    Tadic, Marijana; Pieske-Kraigher, Elisabeth; Cuspidi, Cesare; Morris, Daniel A; Burkhardt, Franziska; Baudisch, Ana; Haßfeld, Sabine; Tschöpe, Carsten; Pieske, Burket

    2017-10-01

    The number of studies demonstrating the importance of right ventricular remodelling in a wide range of cardiovascular diseases has increased in the past two decades. Speckle-tracking imaging provides new variables that give comprehensive information about right ventricular function and mechanics. In this review, we summarize current knowledge of right ventricular mechanics in heart failure with reduced ejection fraction and preserved ejection fraction. We searched PubMed, MEDLINE, Ovid and Embase databases for studies published from January 2000 to December 2016 in the English language using the following keywords: "right ventricle"; "strain"; "speckle tracking"; "heart failure with reduced ejection fraction"; and "heart failure with preserved ejection fraction". Investigations showed that right ventricular dysfunction is associated with higher cardiovascular and overall mortality in patients with heart failure, irrespective of ejection fraction. The number of studies investigating right ventricular strain in patients with heart failure with reduced ejection fraction is constantly increasing, whereas data on right ventricular mechanics in patients with heart failure with preserved ejection fraction are limited. Given the high feasibility, accuracy and clinical implications of right ventricular strain in the population with heart failure, it is of great importance to try to include the evaluation of right ventricular strain as a regular part of each echocardiographic examination in patients with heart failure. However, further investigations are necessary to establish right ventricular strain as a standard variable for decision-making. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    International Nuclear Information System (INIS)

    Erol, Cengiz; Koplay, Mustafa; Olcay, Ayhan; Kivrak, Ali Sami; Ozbek, Seda; Seker, Mehmet; Paksoy, Yahya

    2012-01-01

    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.

  5. Beat-to-beat evaluation of left ventricular ejection in cardiac arrhythmias

    International Nuclear Information System (INIS)

    Itti, R.; Philippe, L.; Lorgeron, J.M.

    1982-01-01

    Conventional multi-gated cardiac blood pool studies suffer from two kinds of superimpositions: the spatial overlapping of various heart chambers and the temporal superimposition of a large number of cardiac cycles. The first problem can be partially solved by first pass techniques or by emission tomography. For the second one, which is specially critical arrhythmias, the single probe device (''nuclear stethoscope'') represents an original solution. Patients with normal cardiac rythm and patients presenting various kinds of cardiac rythm alterations were examined using a commercial ''nuclear stethoscope''. Some characteristic results achieved in these cases, were presented. For blood pool labeling, 20 mCi of 99mTc albumin was injected. The single probe detector was then positioned over the left ventricular area. The beat-to-beat left ventricular activity curve was then recorded for several minutes on paper in the same time as the E.C.G. signal. In cases with irregular cardiac rythm, the multigated techniques yield an average value of left ventricular ejection. Due to the relatively constant duration of systole, the superimposition of cycles may be valid during contration: differences mainly appear during diastole. But, as it could be demonstrated using the ''nuclear stethoscope'', individual cycles can show a large variability of ejection and average ejection fraction is only a very partial aspect of the real cardiac function

  6. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6

    DEFF Research Database (Denmark)

    Scheele, Camilla; Nielsen, Søren; Broholm, Christa

    2012-01-01

    isolated satellite cells from skeletal muscle of people that were healthy (He), obese (Ob) or were obese and had type 2 diabetes (DM), and differentiated them in vitro into myocytes. Down-regulation of IL-6Rα was conserved in Ob myocytes. In addition, acute IL-6 administration for 30, 60 and 120 minutes......Obesity and type 2 diabetes are associated with chronically elevated systemic levels of IL-6, a pro-inflammatory cytokine with a role in skeletal muscle metabolism that signals through the IL-6 receptor (IL-6Rα). We hypothesized that skeletal muscle in obesity-associated type 2 diabetes develops...... a resistance to IL-6. By utilizing western blot analysis, we demonstrate that IL-6Rα protein was down regulated in skeletal muscle biopsies from obese persons with and without type 2 diabetes. To further investigate the status of IL-6 signaling in skeletal muscle in obesity-associated type 2 diabetes, we...

  7. Use of 5-Bromodeoxyuridine and irradiation for the estimation of the myoblast and myocyte content of primary rat heart cell cultures

    International Nuclear Information System (INIS)

    Masse, M.J.O.; Harary, I.

    1980-01-01

    A method for killing dividing cells was adapted for the elimination of dividing heart muscle cells (myoblasts) in cultures. We have used this method to demonstrate their presence and to estimate their number as well as the number of nondividing heart muscle cells (myocytes) in the neo-natal rat heart. Cells were cultivated in BUdR (5-bromodeoxyuridine) 10 -4 M for 3 days and then irradiated with long uv light. The selective elimination of dividing cells led to a loss of myosin Ca 2+ -activated ATPase in the cultures. The percent of ATPase left after irradiation was 32% of the control in cultures derived from 1-day postnatal rats and 48% in cultures from 4-day postnatal rats. This reflects an in vivo shift of myoblasts to myocytes in the muscle cell population as the rat ages<