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Sample records for single ventricular myocytes

  1. Effects of mefloquine on cardiac contractility and electrical activity in vivo, in isolated cardiac preparations, and in single ventricular myocytes

    Science.gov (United States)

    Coker, Susan J; Batey, Andrew J; Lightbown, Ian D; Díaz, Mary E; Eisner, David A

    2000-01-01

    To examine the possible cardiotoxicity of the antimalarial drug mefloquine, increasing doses (0.3–30 mg kg−1) were given i.v. to anaesthetized guinea-pigs. Mefloquine did not alter ECG intervals significantly but gradually increased systolic blood pressure (at 3 mg kg−1) then had a depressor effect (at 10 mg kg−1). Death due to profound hypotension, probably resulting from cardiac contractile failure or AV block, occurred after either 10 mg kg−1 (2/6) or 30 mg kg−1 (4/6) mefloquine. In isolated cardiac preparations mefloquine (3–100 μM) did not alter the effective refractory period but at the higher concentrations resting tension increased. Developed tension was reduced by 100 μM mefloquine in left atria (from 5.8±1.7 to 2.2±0.4 mN) whereas in papillary muscles although 30 μM mefloquine reduced developed tension (from 2.6±0.5 to 1.1±0.1 mN) subsequent addition of 100 μM caused a marked, but not sustained, positive inotropic effect (from 1.2±0.1 to 3.8±0.8 mN). In single ventricular myocytes, mefloquine (10 μM) shortened action potential duration (e.g. APD90 from 285±29 to 141±12 ms) and reduced the amplitude of the systolic Ca2+ transient. These effects were accompanied by a decrease in the L-type Ca2+ current. These results indicate that the main adverse effect of mefloquine on the heart is a negative inotropic action. This action can be explained by blockade of L-type Ca2+ channels. PMID:10694239

  2. A method to increase reproducibility in adult ventricular myocyte sizing and flow cytometry: Avoiding cell size bias in single cell preparations.

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    Javier E López

    Full Text Available Flow cytometry (FCM of ventricular myocytes (VMs is an emerging technology in adult cardiac research that is challenged by the wide variety of VM shapes and sizes. Cellular variability and cytometer flow cell size can affect cytometer performance. These two factors of variance limit assay validity and reproducibility across laboratories. Washing and filtering of ventricular cells in suspension are routinely done to prevent cell clumping and minimize data variability without the appropriate standardization. We hypothesize that washing and filtering arbitrarily biases towards sampling smaller VMs than what actually exist in the adult heart.To determine the impact of washing and filtering on adult ventricular cells for cell sizing and FCM.Left ventricular cardiac cells in single-cell suspension were harvested from New Zealand White rabbits and fixed prior to analysis. Each ventricular sample was aliquoted before washing or filtering through a 40, 70, 100 or 200μm mesh. The outcomes of the study are VM volume by Coulter Multisizer and light-scatter signatures by FCM. Data are presented as mean±SD. Myocyte volumes without washing or filtering (NF served as the "gold standard" within the sample and ranged from 11,017 to 46,926μm3. Filtering each animal sample through a 200μm mesh caused no variation in the post-filtration volume (1.01+0.01 fold vs. NF, n = 4 rabbits, p = 0.999 with an intra-assay coefficient of variation (%CV of <5% for all 4 samples. Filtering each sample through a 40, 70 or 100μm mesh invariably reduced the post-filtration volume by 41±10%, 9.0±0.8% and 8.8±0.8% respectively (n = 4 rabbits, p<0.0001, and increased the %CV (18% to 1.3%. The high light-scatter signature by FCM, a simple parameter for the identification of ventricular myocytes, was measured after washing and filtering. Washing discarded VMs and filtering cells through a 40 or 100μm mesh reduced larger VM by 46% or 11% respectively (n = 6 from 2 rabbits, p<0

  3. Calcium-mediated coupling between mitochondrial substrate dehydrogenation and cardiac workload in single guinea-pig ventricular myocytes.

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    Jo, Hikari; Noma, Akinori; Matsuoka, Satoshi

    2006-03-01

    We measured mitochondrial NADH autofluorescence or Ca(2+) using Rhod-2, simultaneously with cell shortening in isolated guinea-pig ventricular myocytes. When both frequency and amplitude of twitch shortening (work intensity) were increased by raising stimulus frequency in incremental steps from 0.1 to 3.3 Hz, the steady level of NADH signal increased in a frequency-dependent manner. Mitochondrial Ca(2+) also increased with increasing work intensity. Applying Ru360, an inhibitor of mitochondrial Ca(2+) uniporter, largely attenuated the response of both NADH fluorescence and mitochondrial Ca(2+). The increase in mitochondrial Ca(2+) was slow with t(1/2)=~12 s and no obvious cyclic changes were observed in the NADH signal. When a step change from 0.1 to 3.3 Hz stimulation was applied, the NADH signal first decreased to 83% and then increased to 155% of the control level. Upon returning to 0.1 Hz, the NADH signal showed an overshoot before declining to the control level. The biphasic onset time course was well explained by the delayed Ca(2+) activation of the substrate dehydrogenation superimposed on the feedback control of the ATP synthesis, while the offset time course with a delayed deactivation of dehydrogenation. A computer simulation using an oxidative phosphorylation linked to the cardiac excitation contraction model well reconstructed the response of NADH. This model simulation predicts that the activation of substrate dehydrogenation provides ~23% of driving force of the ATP synthesis to meet the increased workload induced by the jump of stimulus from 0.1 to 3.3 Hz, and remaining ~77% is supplied by the feedback control.

  4. On the mechanism of isoprenaline- and forskolin-induced depolarization of single guinea-pig ventricular myocytes.

    Science.gov (United States)

    Egan, T M; Noble, D; Noble, S J; Powell, T; Twist, V W; Yamaoka, K

    1988-06-01

    1. Isoprenaline (10 nM to 1 microM) and forskolin (0.6-100 microM) depolarized single guinea-pig myocytes studied in vitro. Under voltage clamp both agents caused an inward current to flow. 2. These effects were abolished by propranolol (100 nM) and the beta1-antagonist metoprolol (100-200 nM), but not by the beta2-agonist [corrected] salbutamol (1 microM). 3. The interaction of isoprenaline with forskolin, caffeine or isobutylmethylxanthine (IBMX) on current amplitude was as expected if all of these drugs were causing inward current by increasing intracellular levels of cyclic adenosine monophosphate (cyclic AMP). Low concentrations of forskolin (less than 600 nM) or IBMX (less than 20 microM) potentiated the effect of isoprenaline, whereas isoprenaline caused no further inward current in cells in which high concentrations of forskolin (600 nM-100 microM) or IBMX (20 microM-1 mM) were already evoking maximum inward current. 4. Isoprenaline-induced inward current was reduced 30-50% by acetylcholine (10-30 microM). This action of acetylcholine was blocked by atropine (100 nM). 5. The effect of isoprenaline on holding current was critically dependent on temperature. The onset of the current was delayed and its amplitude reduced as the myocyte was cooled from 37 degrees C to ambient temperature (22-24 degrees C). 6. Isoprenaline-induced inward current was not affected by the potassium channel blockers barium (2 mM) or tetraethylammonium (TEA; 10-20 mM). The amplitude of the inward current did not vary as a function of [K+]o. 7. The inward current was not affected by the calcium channel blockers cadmium 1 mM, or nifedipine (10 microM), or when internal calcium was reduced by including EGTA in the recording electrode filling solution. 8. The amplitude of the current was also unaffected by caesium (5 mM), which blocks the hyperpolarization-activated, non-specific channel if, or by strophanthidin (10 microM) which blocks the Na+-K+ pump. It was unchanged by substitution

  5. 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.

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

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    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

  7. 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

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

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    Li, Chen; Meng, Qingli; Yu, Xinfeng; Jing, Xian; Xu, Pingxiang; Luo, Dali

    2012-01-01

    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. 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. These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2+) signaling in normal ventricular myocytes, in

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload.

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    Li, Wei; Wang, Yue-peng; Gao, Ling; Zhang, Peng-pai; Zhou, Qing; Xu, Quan-fu; Zhou, Zhi-wen; Guo, Kai; Chen, Ren-hua; Yang, Huang-tian; Li, Yi-gang

    2013-09-01

    To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms. Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes. H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

  14. Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

    OpenAIRE

    Siedlecka, U.; Arora, M.; Kolettis, T.; Soppa, G. K. R.; Lee, J.; Stagg, M. A.; Harding, S. E.; Yacoub, M. H.; Terracciano, C. M. N.

    2008-01-01

    Clenbuterol, a compound classified as a β2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomer...

  15. 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...

  16. Effect of haloperidol on transient outward potassium current in rat ventricular myocytes

    Czech Academy of Sciences Publication Activity Database

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Nováková, M.

    2006-01-01

    Roč. 550, - (2006), s. 15-23 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA305/04/1385 Institutional research plan: CEZ:AV0Z20760514 Keywords : rat ventricular myocytes * transient outward current * haloperidol * whole-cell patch clamp Subject RIV: BO - Biophysics Impact factor: 2.522, year: 2006

  17. Changes of Ventricular Myocytes Membrane Capacitance in Rabbit with Myocardial Infarction and Effects of Carvedilol

    DEFF Research Database (Denmark)

    Niu, Hui-Yan; Liang, Bo; Liu, Nian

    2005-01-01

    Objective: To investigate effects of long-term treatment of oral Carvedilol on ventricular myocytes membrane capacitance in HMI. Methods: 30 rabbits were randomly assigned in three groups: HMI group, ligation of circumflex coronary artery; Carvedilol group, with operation the same as HMI group......, and administration of oral Carvedilol 0.33 mg/kg×3 months beginning on the day of operation; Sham group, left thoracotomy with no coronary artery ligation. 3 months after surgery, rabbits were harvested. Myocytes were isolated by enzymatic method. The cell membrane capacitance was recorded by using the whole cell...

  18. Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes

    Czech Academy of Sciences Publication Activity Database

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

    2010-01-01

    Roč. 200, č. 4 (2010), s. 301-314 ISSN 1748-1708 Institutional research plan: CEZ:AV0Z20760514 Keywords : action potential * ethanol * rat ventricular myocyte Subject RIV: BO - Biophysics Impact factor: 3.138, year: 2010 http://apps.isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=15&SID=Y1pmpi@7k2HPEc8ehEE&page=1&doc=1&colname=WOS

  19. An Experimental Model Using Cultured Cardiac Myocytes for a Study of the Generation of Premature Ventricular Contractions Under Ultrasound Exposure

    Science.gov (United States)

    Kudo, Nobuki; Yamamoto, Masaya

    2011-09-01

    It is known that use of a contrast agents in echocardiography increases the probability of generation of premature ventricular contractions (PVCs). As a basic study to elucidate the mechanisms and to reduce adverse effects, the generation of PVCs was investigated using cultured cardiac myocytes instead of the intact heart in vivo. Cardiac myocytes were isolated from neonatal rats and cultured on a cover slip. The myocyte sample was exposed to pulsed ultrasound with microbubbles adjacent to the myocytes, and generation of PVCs was examined with ultrasound exposure at various delay times after onset of myocyte contraction. The experimental results showed that generation of PVCs had a stable threshold delay time and that PVCs were generated only when myocytes were exposed to ultrasound with delay times longer than the threshold. The results indicate that the model used in this study is useful for revealing the mechanisms by which PVCs are induced by ultrasound exposure.

  20. Perforated patch recording of L-type calcium current with beta-escin in guinea pig ventricular myocytes.

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    Fu, Li-Ying; Wang, Fang; Chen, Xue-Song; Zhou, Hong-Yi; Yao, Wei-Xing; Xia, Guo-Jin; Jiang, Ming-Xing

    2003-11-01

    To establish a perforated patch recording (PPR) mode with beta-escin and compare L-type calcium current (I(Ca,L)) recorded under PPR and normal whole-cell recording (WCR) condition in isolated guinea-pig ventricular myocytes. Single myocytes were dissociated by enzymatic dissociation method. beta-escin was added to the pipette solution to perforate the cell membrane and obtain PPR mode. I(Ca,L) was recorded using PPR and WCR techniques. beta-Escin 20, 25, and 30 micromol/L could permeabilize the cell membrane and obtain PPR mode. With beta-escin 25 micromol/L, the success rate was highest (16/17, 94 %) and the time required for permibilization was 2-15 (8+/-4) min. Run-down of I(Ca,L) was considerably slower in PPR than in WCR condition. The amplitude of I(Ca,L) was decreased by 36 % at 20 min after the formation of WCR, while it was slowly decreased by 8 % at 30 min after the formation of PPR. The current-voltage relation (I-V) curves, activation and inactivation curves of I(Ca,L) were not significantly different between WCR and PPR. The inactivation rate of ICa,L was slower in PPR than in WCR, the faster inactivation time constant (tau(f)) was longer in PPR than in WCR at membrane potentials of -20 mV -- +10 mV (n=6, Pescin 25 micromol/L can easily obtain stable PPR in isolated guinea-pig ventricular myocytes, and this method is useful in dealing with channels, which show run-down under normal WCR such as L-type Ca channel.

  1. Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

    Science.gov (United States)

    Siedlecka, U.; Arora, M.; Kolettis, T.; Soppa, G. K. R.; Lee, J.; Stagg, M. A.; Harding, S. E.; Yacoub, M. H.; Terracciano, C. M. N.

    2008-01-01

    Clenbuterol, a compound classified as a β2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomere shortening, Ca2+ transients, and L-type Ca2+ current and compared these effects to two other clinically used β2-AR agonists: fenoterol and salbutamol. Clenbuterol (30 μM) produced a negative inotropic response, whereas fenoterol showed a positive inotropic response. Salbutamol had no significant effects. Clenbuterol reduced Ca2+ transient amplitude and L-type Ca2+ current. Selective β1-AR blockade did not affect the action of clenbuterol on sarcomere shortening but significantly reduced contractility in the presence of fenoterol and salbutamol (P clenbuterol. In addition, overexpression of inhibitory G protein (Gi) by adenoviral transfection induced a stronger clenbuterol-mediated negative inotropic effect, suggesting the involvement of the Gi protein. We conclude that clenbuterol does not increase and, at high concentrations, significantly depresses contractility of isolated ventricular myocytes, an effect not seen with fenoterol or salbutamol. In its negative inotropism, clenbuterol predominantly acts through Gi, and the consequent downstream signaling pathways activation may explain the beneficial effects observed during chronic administration of clenbuterol in patients treated with LVADs. PMID:18775853

  2. LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

    Science.gov (United States)

    Puglisi, J. L.; Bers, D. M.

    2001-01-01

    An interactive computer program, LabHEART, was developed to simulate the action potential (AP), ionic currents, and Ca handling mechanisms in a rabbit ventricular myocyte. User-oriented, its design allows switching between voltage and current clamp and easy on-line manipulation of key parameters to change the original formulation. The model reproduces normal rabbit ventricular myocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I(to)) and inward rectifying K currents (I(K1)), enhanced Na/Ca exchange expression, and reduced sarcoplasmic reticulum Ca-ATPase function, but unaltered Ca current density. These changes caused reduced Ca transient amplitude and increased AP duration (especially at lower frequency) as observed experimentally. The model shows that the increased Na/Ca exchange current (I(NaCa)) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I(K1) reduces the threshold to 600 nM. Changes in I(to) have no effect. Combining enhanced Na/Ca exchange with reduced I(K1) (as in HF) lowers the threshold to trigger an AP to 380 nM. These changes reproduce experimental results in HF, where the contributions of different factors are not readily distinguishable. We conclude that the triggered APs that contribute to nonreentrant ventricular tachycardia in HF are due approximately equally (and nearly additively) to alterations in I(NaCa) and I(K1). A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Comparative proteomics analysis of differentially expressed phosphoproteins in adult rat ventricular myocytes subjected to diazoxide preconditioning.

    Science.gov (United States)

    Li, Hong; Xiao, Ying-Bin; Gao, Yu-Qi; Yang, Tian-De

    2006-01-01

    Mitochondrial ATP sensitive potassium channels (mitoK(ATP) channels) are involved in the cardioprotection afforded by ischemic preconditioning (IPC) and diazoxide, a selective mitoK(ATP) channel opener. The activation of some kinases, including phoshoprotein kinase (PKC)-epsilon and mitogen-activating protein kinases (MAPK), is involved in signal conduction of preconditioning downstream from mitoK(ATP) channel opening. Diazoxide can open mitoK(ATP) channels and activate PKC-epsilon, which will phosphorylate some substrate proteins. These proteins that exhibit altered post-translational modification via phosphorylation due to diazoxide pretreatment may be the target molecules and play an important role in cellular protection after mitoK(ATP) channel opening. To analyze and identify the phosphoproteins associated with diazoxide preconditioning, phosphoprotein enrichment and comparative two-dimensional gel electrophoresis (2D-GE) were used. Cultured adult rat ventricular myocytes were pretreated in the presence and absence of 100 micronol/1l diazoxide for 10 min and enriched phosphoproteins from control myocytes and those pretreated with 100 micromol/l diazoxide were separated by 2D-GE and stained with a silver staining kit. Phosphoproteins of interest were further identified by matrix-assisted laser desorption ionization tandem mass spectrometry (MALDI-TOF MS). Eight protein spots with different abundance were found, of which six differentially expressed proteins were identified by MALDI-TOF MS. They included 94 kDa glucose-regulated protein, calpactin I heavy chain, chaperonin containing TCP-1 zeta subunit, hypothetical protein XP_346548, ferritin light chain and ferritin light chain 2. These findings provide new clues to understanding the mechanism of ischemic preconditioning in cardiomyocytes downstream from mitoK(ATP) channel opening.

  8. 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 , the fibroblast resting-membrane potential, the fibroblast conductance , and the MF gap-junctional coupling . 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 , and , 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 decreases as a function of , for zero-sided and one-sided couplings; however, for two-sided coupling, decreases initially and then increases as a function of , and, eventually, we observe that conduction failure occurs for low values of . In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling or . 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 tissue, in our MF model both with and without heterogeneities. PMID:24023798

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

    Directory of Open Access Journals (Sweden)

    Alok Ranjan Nayak

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

  10. Global intracoronary infusion of allogeneic cardiosphere-derived cells improves ventricular function and stimulates endogenous myocyte regeneration throughout the heart in swine with hibernating myocardium.

    Directory of Open Access Journals (Sweden)

    Gen Suzuki

    Full Text Available Cardiosphere-derived cells (CDCs improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the "stop-flow" technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation.Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25. CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼ 33 × 10(6 icCDCs. Global icCDC infusion was safe and while ∼ 3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23 ± 6 to 51 ± 5% (p<0.01. In diseased hearts, myocyte proliferation (phospho-histone-H3 increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs.Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair.

  11. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    Science.gov (United States)

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (pmyocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  12. 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.

  13. Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers.

    Science.gov (United States)

    de Diego, Carlos; Chen, Fuhua; Xie, Yuanfang; Pai, Rakesh K; Slavin, Leonid; Parker, John; Lamp, Scott T; Qu, Zhilin; Weiss, James N; Valderrábano, Miguel

    2011-01-01

    Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Ca(i)) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CV(L)/CV(T), where CV(L) and CV(T) are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CV(L) and CV(T) proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CV(T) more than CV(L), increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Ca(i) chelator 1,2-bis oaminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions.

  14. Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes.

    Science.gov (United States)

    Luo, Antao; Ma, Jihua; Song, Yejia; Qian, Chunping; Wu, Ying; Zhang, Peihua; Wang, Leilei; Fu, Chen; Cao, Zhenzhen; Shryock, John C

    2014-02-01

    An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial and ventricular tissues, but the densities of INa.L and thus the potential relative contributions of this current to sodium ion (Na(+)) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch-clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in left atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 (n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, and 9 μM) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.

  15. Effect of antipsychotic drug perphenazine on fast sodium current and transient outward potassium current in rat ventricular myocytes

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

    Roč. 380, č. 2 (2009), s. 125-133 ISSN 0028-1298 Institutional research plan: CEZ:AV0Z20760514 Keywords : perphenazine * antipsychotic drug * sodium current * transient outward current * rat ventricular myocytes Subject RIV: ED - Physiology Impact factor: 2.631, year: 2009 http://apps.isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=1&SID=T1JpdjJ8PNNeAL7D3il&page=1&doc=3&colname=WOS

  16. The peptide "FRCRCFa", dialysed intracellularly, inhibits the Na/Ca exchange in rabbit ventricular myocytes with high affinity.

    Science.gov (United States)

    Hobai, I A; Khananshvili, D; Levi, A J

    1997-02-01

    We investigated the effect in rabbit ventricular myocytes of "FRCRCFa", a newly developed peptide inhibitor of the Na/Ca exchange. Myocytes were whole-cell patch clamped and experiments were carried out at 36 degrees C. The Na/Ca exchange was measured selectively, by blocking interfering ion channel currents and the Na/K pump, as the membrane current which could be inhibited by 5 mM nickel (Ni; a known blocker of the Na/Ca exchange). Increasing concentrations of FRCRCFa dialysed into the cell from the patch-pipette inhibited the Na/Ca exchange current. The dose/response curve could be fitted by a function for co-operative ligand binding, which predicted a KD for FRCRCFa-mediated inhibition of 22.7 +/- 3.7 nM, with a Hill coefficient of 0.61 +/- 0.06. Pipette FRCRCFa concentrations of 1 micro;M and above were sufficient to cause complete inhibition of Na/Ca exchange current. The inhibitory effect of FRCRCFa was independent of membrane potential and relatively selective: 10 micro;M FRCRCFa dialysed into the cell had no effect on the L-type Ca current and delayed rectifier and inward rectifier K currents. Thus FRCRCFa appears to be a potent and relatively selective inhibitor of the Na/Ca exchange in intact cardiac myocytes, and may be of value for studies of the Na/Ca exchange.

  17. Numerical Simulations of Calcium Ions Spiral Wave in Single Cardiac Myocyte

    Science.gov (United States)

    Bai, Yong-Qiang; Zhu, Xing

    2010-04-01

    The calcium ions (Ca2+) spark is an elementary Ca2+ release event in cardiac myocytes. It is believed to buildup cell-wide Ca2+ signals, such as Ca2+ transient and Ca2+ wave, through a Ca2+-induced Ca2+ release (CICR) mechanism. Here the excitability of the Ca2+ wave in a single cardiac myocyte is simulated by employing the fire-diffuse-fire model. By modulating the dynamic parameters of Ca2+ release and re-uptake channels, we find three Ca2+ signaling states in a single cardiac myocyte: no wave, plane wave, and spiral wave. The period of a spiral wave is variable in the different regimes. This study indicates that the spiral wave or the excitability of the system can be controlled through micro-modulation in a living excitable medium.

  18. Electrical coupling of single cardiac rat myocytes to field-effect and bipolar transistors.

    Science.gov (United States)

    Kind, Thomas; Issing, Matthias; Arnold, Rüdiger; Müller, Bernt

    2002-12-01

    A novel bipolar transistor for extracellular recording the electrical activity of biological cells is presented, and the electrical behavior compared with the field-effect transistor (FET). Electrical coupling is examined between single cells separated from the heart of adults rats (cardiac myocytes) and both types of transistors. To initiate a local extracellular voltage, the cells are periodically stimulated by a patch pipette in voltage clamp and current clamp mode. The local extracellular voltage is measured by the planar integrated electronic sensors: the bipolar and the FET. The small signal transistor currents correspond to the local extracellular voltage. The two types of sensor transistors used here were developed and manufactured in the laboratory of our institute. The manufacturing process and the interfaces between myocytes and transistors are described. The recordings are interpreted by way of simulation based on the point-contact model and the single cardiac myocyte model.

  19. 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

  20. 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.

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

    Science.gov (United States)

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

    1995-01-01

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

  2. Adult Ventricular Myocytes Segregate KCNQ1 and KCNE1 to Keep theIKsAmplitude in Check Until When LargerIKsIs Needed.

    Science.gov (United States)

    Jiang, Min; Wang, Yuhong; Tseng, Gea-Ny

    2017-06-01

    KCNQ1 and KCNE1 assemble to form the slow delayed rectifier ( I Ks ) channel critical for shortening ventricular action potentials during high β-adrenergic tone. However, too much I Ks under basal conditions poses an arrhythmogenic risk. Our objective is to understand how adult ventricular myocytes regulate the I Ks amplitudes under basal conditions and in response to stress. We express fluorescently tagged KCNQ1 and KCNE1 in adult ventricular myocytes and follow their biogenesis and trafficking paths. We also study the distribution patterns of native KCNQ1 and KCNE1, and their relationship to I Ks amplitudes, in chronically stressed ventricular myocytes, and use COS-7 cell expression to probe the underlying mechanism. We show that KCNQ1 and KCNE1 are both translated in the perinuclear region but traffic by different routes, independent of each other, to their separate subcellular locations. KCNQ1 mainly resides in the jSR (junctional sarcoplasmic reticulum), whereas KCNE1 resides on the cell surface. Under basal conditions, only a small portion of KCNQ1 reaches the cell surface to support the I Ks function. However, in response to chronic stress, KCNQ1 traffics from jSR to the cell surface to boost the I Ks amplitude in a process depending on Ca binding to CaM (calmodulin). In adult ventricular myocytes, KCNE1 maintains a stable presence on the cell surface, whereas KCNQ1 is dynamic in its localization. KCNQ1 is largely in an intracellular reservoir under basal conditions but can traffic to the cell surface and boost the I Ks amplitude in response to stress. © 2017 American Heart Association, Inc.

  3. Contribution of mineralocorticoid and glucocorticoid receptors to the chronotropic and hypertrophic actions of aldosterone in neonatal rat ventricular myocytes.

    Science.gov (United States)

    Rossier, Michel F; Python, Magaly; Maturana, Andrés D

    2010-06-01

    Mineralocorticoids and glucocorticoids have been involved in the genesis of ventricular arrhythmias associated with pathological heart hypertrophy. We previously observed, using isolated neonate rat ventricular cardiomyocytes, that both aldosterone (Aldo) and corticosterone induced in vitro a marked acceleration of the spontaneous contractions of these cells, a phenomenon dependent on the expression of the low threshold T-type calcium channels. Because both mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mediated the chronotropic response to corticosteroids, we characterized the role of each receptor using spironolactone and mifepristone (RU-486) as specific antagonists. We first observed that GR antagonism, but not MR antagonism, completely disrupted the significant correlation existing between the level of T channel mRNA and the beating frequency; this difference could not be explained by a specific regulation of channel expression or activity by one of the receptors. Moreover, the chronotropic action of Aldo was additive to that of forskolin, a direct activator of the cAMP pathway. This additive response was selectively abolished upon GR inhibition. Finally, myocyte hypertrophy induced in vitro by Aldo was completely prevented by GR antagonism, whereas spironolactone had only a marginal effect. These results suggest that, in isolated rat ventricular cardiomyocytes, the activation of both MR and GR is necessary for a complete electrical remodeling and a maximal chronotropic response to corticosteroids. However, GR alone appears involved in the sensitization of the cells to the chronotropic regulation through the cAMP pathway and in the hypertrophic response to steroids. These observations have therapeutic implications given the fact that MR becomes a major target of pharmacological drugs in the clinical practice for preventing cardiac function decompensation and evolution toward heart failure and lethal arrhythmias.

  4. 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

  5. Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy

    NARCIS (Netherlands)

    Pilichou, K.; Remme, C.A.; Basso, C.; Campian, M.E.; Rizzo, S.; Barnett, P.; Scicluna, B.P.; Bauce, B.; van den Hoff, M.J.B.; de Bakker, J.M.T.; Tan, H.L.; Valente, M.; Nava, A.; Wilde, A.A.M.; Moorman, A.F.M.; Thiene, G.; Bezzina, C.R.

    2009-01-01

    Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse

  6. Role of the T-type calcium channel CaV3.2 in the chronotropic action of corticosteroids in isolated rat ventricular myocytes.

    Science.gov (United States)

    Maturana, Andrés; Lenglet, Sébastien; Python, Magaly; Kuroda, Shun'ichi; Rossier, Michel F

    2009-08-01

    The mineralocorticoid receptor is involved in the development of several cardiac dysfunctions, including lethal ventricular arrhythmias associated with heart failure or hyperaldosteronism, but the molecular mechanisms responsible for these effects remain to be clarified. Reexpression of low voltage-activated T-type calcium channels in ventricular myocytes together with other fetal genes during cardiac pathologies could confer automaticity to these cells and would represent a pro-arrhythmogenic condition if occurring in vivo. In the present study, we demonstrated that in isolated neonatal rat ventricular myocytes, corticosteroids selectively induced the expression of a particular isoform of T channel, Ca(V)3.2/alpha1H. This response was accompanied by an increase of the Ca(V)3.2 T-type current, identified with the patch clamp technique by its sensitivity to nickel, and a concomitant acceleration of the myocyte spontaneous contractions. Silencing Ca(V)3.2 expression markedly reduced the chronotropic response to steroids. Moreover, modulation of the frequency of cell contractions by different redox agents was independent of channel expression but involved a direct regulation of channel activity. Although oxidants increased both Ca(V)3.2 current amplitude and beating frequency, they decreased L-type channel activity. Reducing agents had the opposite effect on these parameters. In conclusion, the acceleration of ventricular myocyte spontaneous contractions induced by corticosteroids in vitro appears dependent on the expression of the Ca(V)3.2 T channel isoform and modulated by the redox potential of the cells. These results provide a molecular model that could explain the high incidence of arrhythmias observed in patients upon combination of inappropriate activation of the mineralocorticoid receptor and oxidative stress.

  7. Inhibition by external Cd2+ of Na/Ca exchange and L-type Ca channel in rabbit ventricular myocytes.

    Science.gov (United States)

    Hobai, I A; Bates, J A; Howarth, F C; Levi, A J

    1997-05-01

    We investigated the effect of external Cd2+ on the Na/Ca exchange and the L-type Ca channel current (ICa,L) in whole cell patch-clamped rabbit ventricular myocytes at 36 degrees C. After the interfering ion channels and the Na/K pump were blocked, the exchange current was measured as the membrane current that was inhibited by 5 mM nickel. External Cd2+ inhibited Na/Ca exchange with a dissociation constant (KD) of 320.6 +/- 12.4 microM and a Hill coefficient of 1.5 +/- 0.09 (n = 13 cells) and ICa,L with a KD of 2.14 +/- 0.15 microM and a Hill coefficient of 0.74 +/- 0.03 (n = 11 cells). We observed some overlap in the Cd2+ concentration that blocked each mechanism. Cd2+ (100-500 microM) is used commonly to block ICa,L completely. However, 100 microM Cd2+ also inhibits 20% of the Na/Ca exchange activity, whereas 500 microM Cd2+ inhibits 60%.

  8. Influence of a constitutive increase in myofilament Ca(2+)-sensitivity on Ca(2+)-fluxes and contraction of mouse heart ventricular myocytes.

    Science.gov (United States)

    Puglisi, Jose L; Goldspink, Paul H; Gomes, Aldrin V; Utter, Megan S; Bers, Donald M; Solaro, R John

    2014-06-15

    Chronic increases in myofilament Ca(2+)-sensitivity in the heart are known to alter gene expression potentially modifying Ca(2+)-homeostasis and inducing arrhythmias. We tested age-dependent effects of a chronic increase in myofilament Ca(2+)-sensitivity on induction of altered alter gene expression and activity of Ca(2+) transport systems in cardiac myocytes. Our approach was to determine the relative contributions of the major mechanisms responsible for restoring Ca(2+) to basal levels in field stimulated ventricular myocytes. Comparisons were made from ventricular myocytes isolated from non-transgenic (NTG) controls and transgenic mice expressing the fetal, slow skeletal troponin I (TG-ssTnI) in place of cardiac TnI (cTnI). Replacement of cTnI by ssTnI induces an increase in myofilament Ca(2+)-sensitivity. Comparisons included myocytes from relatively young (5-7months) and older mice (11-13months). Employing application of caffeine in normal Tyrode and in 0Na(+) 0Ca(2+) solution, we were able to dissect the contribution of the sarcoplasmic reticulum Ca(2+) pump (SR Ca(2+)-ATPase), the Na(+)/Ca(2+) exchanger (NCX), and "slow mechanisms" representing the activity of the sarcolemmal Ca(2+) pump and the mitochondrial Ca(2+) uniporter. The relative contribution of the SR Ca(2+)-ATPase to restoration of basal Ca(2+) levels in younger TG-ssTnI myocytes was lower than in NTG (81.12±2.8% vs 92.70±1.02%), but the same in the older myocytes. Younger and older NTG myocytes demonstrated similar contributions from the SR Ca(2+)-ATPase and NCX to restoration of basal Ca(2+). However, the slow mechanisms for Ca(2+) removal were increased in the older NTG (3.4±0.3%) vs the younger NTG myocytes (1.4±0.1%). Compared to NTG, younger TG-ssTnI myocytes demonstrated a significantly bigger contribution of the NCX (16±2.7% in TG vs 6.9±0.9% in NTG) and slow mechanisms (3.3±0.4% in TG vs 1.4±0.1% in NTG). In older TG-ssTnI myocytes the contributions were not significantly

  9. 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.

  10. 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

  11. 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.

  12. Ventricular beat detection in single channel electrocardiograms.

    Science.gov (United States)

    Dotsinsky, Ivan A; Stoyanov, Todor V

    2004-01-29

    Detection of QRS complexes and other types of ventricular beats is a basic component of ECG analysis. Many algorithms have been proposed and used because of the waves' shape diversity. Detection in a single channel ECG is important for several applications, such as in defibrillators and specialized monitors. The developed heuristic algorithm for ventricular beat detection includes two main criteria. The first of them is based on steep edges and sharp peaks evaluation and classifies normal QRS complexes in real time. The second criterion identifies ectopic beats by occurrence of biphasic wave. It is modified to work with a delay of one RR interval in case of long RR intervals. Other algorithm branches classify already detected QRS complexes as ectopic beats if a set of wave parameters is encountered or the ratio of latest two RR intervals RRi-1/RRi is less than 1:2.5. The algorithm was tested with the AHA and MIT-BIH databases. A sensitivity of 99.04% and a specificity of 99.62% were obtained in detection of 542014 beats. The algorithm copes successfully with different complicated cases of single channel ventricular beat detection. It is aimed to simulate to some extent the experience of the cardiologist, rather than to rely on mathematical approaches adopted from the theory of signal analysis. The algorithm is open to improvement, especially in the part concerning the discrimination between normal QRS complexes and ectopic beats.

  13. Soluble epoxide hydrolase inhibitors might prevent ischemic arrhythmias via microRNA-1 repression in primary neonatal mouse ventricular myocytes.

    Science.gov (United States)

    Liu, Qiong; Zhao, Xuan; Peng, Ran; Wang, Mi; Zhao, Wang; Gui, Ya-Jun; Liao, Cai-Xiu; Xu, Dan-Yan

    2017-02-28

    Ischemic arrhythmias are the main causes of sudden cardiac death. It has been reported that soluble epoxide hydrolase inhibitors (sEHis) could prevent arrhythmias; however, the underlying molecular mechanisms remain unclear. In recent years, the proarrhythmic role of microRNA-1 (miR-1) has been investigated. This study aimed to elucidate whether sEHis prevented ischemic arrhythmias by suppressing miR-1. The primary neonatal mouse ventricular myocyte model of miR-1 overexpression was established by incubating with agonist microONTM mmu-miR-1a-3p agomir (DAEDstain TM Dye) (agomiR-1). The sEHi, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was administered following miR-1 overexpression. Quantitative real-time PCR (qPCR) and western blotting were used to test alterations in the expression of miR-1 and its target mRNAs GJA1 and KCNJ2 and their respective encoded proteins connexin 43 (Cx43) and the K + channel subunit (Kir2.1). The whole-cell patch-clamp technique was used to record the alterations of the inward rectifying K + current (I K1 ). Compared with the control group, miR-1 levels were significantly increased in the agomiR-1 group (p < 0.05), which suggested the successful construction of the miR-1 overexpression model. Compared with the control group, the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins in the agomiR-1 group were significantly decreased, and I K1 was significantly impaired (all p < 0.05). The miR-1 levels were dose-dependently decreased by t-AUCB, whereas t-AUCB dose-dependently increased the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins. Furthermore, t-AUCB restored the impaired I K1 (all p < 0.05). In conclusion, the sEHi t-AUCB has the ability to down-regulate proarrhythmic miR-1 and up-regulate its target genes and proteins, eventually restoring I K1 .

  14. Conditional FKBP12.6 overexpression in mouse cardiac myocytes prevents triggered ventricular tachycardia through specific alterations in excitation-contraction coupling.

    Science.gov (United States)

    Gellen, Barnabas; Fernández-Velasco, María; Briec, François; Vinet, Laurent; LeQuang, Khai; Rouet-Benzineb, Patricia; Bénitah, Jean-Pierre; Pezet, Mylène; Palais, Gael; Pellegrin, Noémie; Zhang, Andy; Perrier, Romain; Escoubet, Brigitte; Marniquet, Xavier; Richard, Sylvain; Jaisser, Fréderic; Gómez, Ana María; Charpentier, Flavien; Mercadier, Jean-Jacques

    2008-04-08

    Ca(2+) release from the sarcoplasmic reticulum via the ryanodine receptor (RyR2) activates cardiac myocyte contraction. An important regulator of RyR2 function is FKBP12.6, which stabilizes RyR2 in the closed state during diastole. Beta-adrenergic stimulation has been suggested to dissociate FKBP12.6 from RyR2, leading to diastolic sarcoplasmic reticulum Ca(2+) leakage and ventricular tachycardia (VT). We tested the hypothesis that FKBP12.6 overexpression in cardiac myocytes can reduce susceptibility to VT in stress conditions. We developed a mouse model with conditional cardiac-specific overexpression of FKBP12.6. Transgenic mouse hearts showed a marked increase in FKBP12.6 binding to RyR2 compared with controls both at baseline and on isoproterenol stimulation (0.2 mg/kg i.p.). After pretreatment with isoproterenol, burst pacing induced VT in 10 of 23 control mice but in only 1 of 14 transgenic mice (P<0.05). In isolated transgenic myocytes, Ca(2+) spark frequency was reduced by 50% (P<0.01), a reduction that persisted under isoproterenol stimulation, whereas the sarcoplasmic reticulum Ca(2+) load remained unchanged. In parallel, peak I(Ca,L) density decreased by 15% (P<0.01), and the Ca(2+) transient peak amplitude decreased by 30% (P<0.001). A 33.5% prolongation of the caffeine-evoked Ca(2+) transient decay was associated with an 18% reduction in the Na(+)-Ca(2+) exchanger protein level (P<0.05). Increased FKBP12.6 binding to RyR2 prevents triggered VT in normal hearts in stress conditions, probably by reducing diastolic sarcoplasmic reticulum Ca(2+) leak. This indicates that the FKBP12.6-RyR2 complex is an important candidate target for pharmacological prevention of VT.

  15. Kir6.2 limits Ca(2+) overload and mitochondrial oscillations of ventricular myocytes in response to metabolic stress.

    Science.gov (United States)

    Storey, Nina M; Stratton, Rebecca C; Rainbow, Richard D; Standen, Nicholas B; Lodwick, David

    2013-11-15

    ATP-sensitive K(+) (KATP) channels are abundant membrane proteins in cardiac myocytes that are directly gated by intracellular ATP and form a signaling complex with metabolic enzymes, such as creatine kinase. KATP channels are known to be essential for adaption to cardiac stress, such as ischemia; however, how all the molecular components of the stress response interact is not fully understood. We examined the effects of decreasing the KATP current density on Ca(2+) and mitochondrial homeostasis and ischemic preconditioning. Acute knockdown of the pore-forming subunit, Kir6.2, was achieved using adenoviral delivery of short hairpin RNA targeted to Kir6.2. The acute nature of the knockdown of Kir6.2 accurately shows the effects of Kir6.2 depletion without any compensatory effects that may arise in transgenic studies. We also investigated the effect of reducing the KATP current while maintaining KATP channel protein in the sarcolemmal membrane using a nonconducting Kir6.2 construct. Only 50% KATP current remained after Kir6.2 knockdown, yet there were profound effects on myocyte responses to metabolic stress. Kir6.2 was essential for cardiac myocyte Ca(2+) homeostasis under both baseline conditions before any metabolic stress and after metabolic stress. Expression of nonconducting Kir6.2 also resulted in increased Ca(2+) overload, showing the importance of K(+) conductance in the protective response. Both ischemic preconditioning and protection during ischemia were lost when Kir6.2 was knocked down. KATP current density was also important for the mitochondrial membrane potential at rest and prevented mitochondrial membrane potential oscillations during oxidative stress. KATP channel density is important for adaption to metabolic stress.

  16. Role of Sodium-Calcium Exchanger in Modulating the Action Potential of Ventricular Myocytes From Normal and Failing Hearts

    OpenAIRE

    Armoundas, Antonis A.; Hobai, Ion A.; Tomaselli, Gordon F.; Winslow, Raimond L.; O’Rourke, Brian

    2003-01-01

    Increased Na+-Ca2+ exchange (NCX) activity in heart failure and hypertrophy may compensate for depressed sarcoplasmic reticular Ca2+ uptake, provide inotropic support through reverse-mode Ca2+ entry, and/or deplete intracellular Ca2+ stores. NCX is electrogenic and depends on Na+ and Ca2+ transmembrane gradients, making it difficult to predict its effect on the action potential (AP). Here, we examine the effect of [Na+]i on the AP in myocytes from normal and pacing-induced failing canine hear...

  17. 2.1 GHz electromagnetic field does not change contractility and intracellular Ca2+ transients but decreases β-adrenergic responsiveness through nitric oxide signaling in rat ventricular myocytes.

    Science.gov (United States)

    Olgar, Yusuf; Hidisoglu, Enis; Celen, Murat Cenk; Yamasan, Bilge Eren; Yargicoglu, Piraye; Ozdemir, Semir

    2015-01-01

    Due to the increasing use of wireless technology in developing countries, particularly mobile phones, the influence of electromagnetic fields (EMF) on biologic systems has become the subject of an intense debate. Therefore, in this study we investigated the effect of 2.1 GHz EMF on contractility and beta-adrenergic (β-AR) responsiveness of ventricular myocytes. Rats were randomized to the following groups: Sham rats (SHAM) and rats exposed to 2.1 GHz EMF for 2 h/day for 10 weeks (EM-10). Sarcomere shortening and Ca(2+) transients were recorded in isolated myocytes loaded with Fura2-AM and electrically stimulated at 1 Hz, while L-type Ca(2+) currents (I(CaL)) were measured using whole-cell patch clamping at 36 ± 1°C. Cardiac nitric oxide (NO) levels were measured in tissue samples using a colorimetric assay kit. Fractional shortening and amplitude of the matched Ca(2+) transients were not changed in EM-10 rats. Although the isoproterenol-induced (10(-6) M) I(CaL) response was reduced in rats exposed to EMF, basal I(CaL) density in myocytes was similar between the two groups (p < 0.01). Moreover, EMF exposure led to a significant increase in nitric oxide levels in rat heart (p < 0.02). Long-term exposure to 2.1 GHz EMF decreases β-AR responsiveness of ventricular myocytes through NO signaling.

  18. Role of sodium-calcium exchanger in modulating the action potential of ventricular myocytes from normal and failing hearts.

    Science.gov (United States)

    Armoundas, Antonis A; Hobai, Ion A; Tomaselli, Gordon F; Winslow, Raimond L; O'Rourke, Brian

    2003-07-11

    Increased Na+-Ca2+ exchange (NCX) activity in heart failure and hypertrophy may compensate for depressed sarcoplasmic reticular Ca2+ uptake, provide inotropic support through reverse-mode Ca2+ entry, and/or deplete intracellular Ca2+ stores. NCX is electrogenic and depends on Na+ and Ca2+ transmembrane gradients, making it difficult to predict its effect on the action potential (AP). Here, we examine the effect of [Na+]i on the AP in myocytes from normal and pacing-induced failing canine hearts and estimate the direction of the NCX driving force using simultaneously recorded APs and Ca2+ transients. AP duration shortened with increasing [Na+]i and was correlated with a shift in the reversal point of the NCX driving force. At [Na+]i > or =10 mmol/L, outward NCX current during the plateau facilitated repolarization, whereas at 5 mmol/L [Na+]i, NCX had a depolarizing effect, confirmed by partially inhibiting NCX with exchange inhibitory peptide. Exchange inhibitory peptide shortened the AP duration at 5 mmol/L [Na+]i and prolonged it at [Na+]i > or =10 mmol/L. With K+ currents blocked, total membrane current was outward during the late plateau of an AP clamp at 10 mmol/L [Na+]i and became inward close to the predicted reversal point for the NCX driving force. The results were reproduced using a computer model. These results indicate that NCX plays an important role in shaping the AP of the canine myocyte, helping it to repolarize at high [Na+]i, especially in the failing heart, but contributing a depolarizing, potentially arrhythmogenic, influence at low [Na+]i.

  19. 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.

  20. 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

  1. Inhibition of the sarcoplasmic reticulum Ca2+ pump with thapsigargin to estimate the contribution of Na+-Ca2+ exchange to ventricular myocyte relaxation

    Directory of Open Access Journals (Sweden)

    Bassani R.A.

    2003-01-01

    Full Text Available Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the cytosol, which is performed by three main transport systems: sarcoplasmic reticulum Ca2+-ATPase (SR-A, Na+-Ca2+ exchanger (NCX and the so-called slow mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake. To estimate the relative contribution of each system to twitch relaxation, SR Ca2+ accumulation must be selectively inhibited, usually by the application of high caffeine concentrations. However, caffeine has been reported to often cause changes in membrane potential due to NCX-generated inward current, which compromises the reliability of its use. In the present study, we estimated integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch relaxation, and compared the results when using caffeine application (Cf-NT and an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW. Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with indo-1. For transients in which one or more transporters were inhibited, Ca2+ fluxes were estimated from the measured free Ca2+ concentration and myocardial Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was significantly higher with TG-TW than with Cf-NT (12 vs 7 µM, whereas SR-dependent flux was lower with TG-TW (77 vs 81 µM. The relative participations of NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively and SR-A (85 vs 89.5% with TG-TW and Cf-NT, respectively in total relaxation-associated Ca2+ flux were also significantly different. We thus propose TG-TW as a reliable alternative to estimate NCX contribution to twitch relaxation in this kind of analysis.

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

    African Journals Online (AJOL)

    Rania Gaber

    2015-10-09

    Oct 9, 2015 ... Abstract Background: Strain and strain rate imaging is currently the most popular echocardio- graphic technique that reveals subclinical myocardial damage, and data are not available on this imaging method with regard to assessing right ventricular involvement in single LAD lesion. Aim: To evaluate right ...

  3. 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

  4. Effect of myocyte-fibroblast coupling on the onset of pathological dynamics in a model of ventricular tissue

    Science.gov (United States)

    Sridhar, S.; Vandersickel, Nele; Panfilov, Alexander V.

    2017-01-01

    Managing lethal cardiac arrhythmias is one of the biggest challenges in modern cardiology, and hence it is very important to understand the factors underlying such arrhythmias. While early afterdepolarizations (EAD) of cardiac cells is known to be one such arrhythmogenic factor, the mechanisms underlying the emergence of tissue level arrhythmias from cellular level EADs is not fully understood. Another known arrhythmogenic condition is fibrosis of cardiac tissue that occurs both due to aging and in many types of heart diseases. In this paper we describe the results of a systematic in-silico study, using the TNNP model of human cardiac cells and MacCannell model for (myo)fibroblasts, on the possible effects of diffuse fibrosis on arrhythmias occurring via EADs. We find that depending on the resting potential of fibroblasts (VFR), M-F coupling can either increase or decrease the region of parameters showing EADs. Fibrosis increases the probability of occurrence of arrhythmias after a single focal stimulation and this effect increases with the strength of the M-F coupling. While in our simulations, arrhythmias occur due to fibrosis induced ectopic activity, we do not observe any specific fibrotic pattern that promotes the occurrence of these ectopic sources.

  5. Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion

    OpenAIRE

    Brunetti, Tonya M.; Fremin, Brayon J.; Cripps, Richard M.

    2015-01-01

    In Drosophila, myoblast fusion is a conserved process in which founder cells (FCs) and fusion competent myoblasts (FCMs) fuse to form a syncytial muscle fiber. Mutants for the myogenic regulator Myocyte enhancer factor-2 (MEF2) show a failure of myoblast fusion, indicating that MEF2 regulates the fusion process. Indeed, chromatin immunoprecipitation studies show that several genes involved in myoblast fusion are bound by MEF2 during embryogenesis. Of these, the MARVEL domain gene singles bar ...

  6. 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

  7. Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular Ca2+ in a model of the rat cardiac ventricular myocyte

    Czech Academy of Sciences Publication Activity Database

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

    2012-01-01

    Roč. 41, č. 6 (2012), s. 491-503 ISSN 0175-7571 Institutional research plan: CEZ:AV0Z20760514 Keywords : t-tubules * rat * cardiac myocyte * computer model * calcium Subject RIV: BO - Biophysics Impact factor: 2.274, year: 2012

  8. Engineering design of a cardiac myocyte

    Science.gov (United States)

    Adams, W. J.; Pong, T.; Geisse, N. A.; Sheehy, S. P.; Diop-Frimpong, B.; Parker, K. K.

    2007-04-01

    We describe a design algorithm to build a cardiac myocyte with specific spatial dimensions and physiological function. Using a computational model of a cardiac muscle cell, we modeled calcium (Ca2+) wave dynamics in a cardiac myocyte with controlled spatial dimensions. The modeled myocyte was replicated in vitro when primary neonate rat ventricular myocytes were cultured on micropatterned substrates. The myocytes remodel to conform to the two dimensional boundary conditions and assume the shape of the printed extracellular matrix island. Mechanical perturbation of the myocyte with an atomic force microscope results in calcium-induced calcium release from intracellular stores and the propagation of a Ca2+ wave, as indicated by high speed video microscopy using fluorescent indicators of intracellular Ca2+. Analysis and comparison of the measured wavefront dynamics with those simulated in the computer model reveal that the engineered myocyte behaves as predicted by the model. These results are important because they represent the use of computer modeling, computer-aided design, and physiological experiments to design and validate the performance of engineered cells. The ability to successfully engineer biological cells and tissues for assays or therapeutic implants will require design algorithms and tools for quality and regulatory assurance.

  9. 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.

  10. 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.

  11. Functional Cross-Talk between the α1- and β1-Adrenergic Receptors Modulates the Rapidly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Di Xu

    2014-08-01

    Full Text Available The rapidly activating delayed rectifier potassium current (IKr plays a critical role in cardiac repolarization. Although IKr is known to be regulated by both α1- and β1-adrenergic receptors (ARs, the cross-talk and feedback mechanisms that dictate its response to α1- and β1-AR activation are not known. In the present study, IKr was recorded using the whole-cell patch-clamp technique. IKr amplitude was measured before and after the sequential application of selective adrenergic agonists targeting α1- and β1-ARs. Stimulation of either receptor alone (α1-ARs using 1 μM phenylephrine (PE or β1-ARs using 10 μM xamoterol (Xamo reduced IKr by 0.22 ± 0.03 and 0.28 ± 0.01, respectively. The voltage-dependent activation curve of IKr shifted in the negative direction. The half-maximal activation voltage (V0.5 was altered by −6.35 ± 1.53 and −1.95 ± 2.22 mV, respectively, with no major change in the slope factor (k. When myocytes were pretreated with Xamo, PE-induced reduction in IKr was markedly blunted and the corresponding change in V0.5 was significantly altered. Similarly, when cells were pretreated with PE, Xamo-induced reduction of IKr was significantly attenuated. The present results demonstrate that functional cross-talk between α1- and β1-AR signaling regulates IKr. Such non-linear regulation may form a protective mechanism under excessive adrenergic stimulation.

  12. Inhibition by nickel of the L-type Ca channel in guinea pig ventricular myocytes and effect of internal cAMP.

    Science.gov (United States)

    Hobai, I A; Hancox, J C; Levi, A J

    2000-08-01

    The characteristics of nickel (Ni) block of L-type Ca current (I(Ca, L)) were studied in whole cell patch-clamped guinea pig cardiac myocytes at 37 degrees C in the absence and presence of 100 microM cAMP in the pipette solution. Ni block of peak I(Ca,L) had a dissociation constant (K(d)) of 0.33 +/- 0.03 mM in the absence of cAMP, whereas in the presence of cAMP, the K(d) was 0.53 +/- 0.05 mM (P = 0.006). Ni blocked Ca entry via Ca channels (measured as I(Ca, L) integral over 50 ms) with similar kinetics (K(d) of 0.35 +/- 0.03 mM in cAMP-free solution and 0.30 +/- 0.02 mM in solution with cAMP, P = not significant). Under both conditions, 5 mM Ni produced a maximal block that was complete for the first pulse after application. Ni block of I(Ca,L) was largely use independent. Ni (0. 5 mM) induced a positive shift (4 to 6 mV) in the activation curve of I(Ca,L). The block of I(Ca,L) by 0.5 mM Ni was independent of prepulse membrane potential (over the range of -120 to -40 mV). Ni (0.5 mM) also induced a significant shift in I(Ca,L) inactivation: by 6 mV negative in cAMP-free solution and by 4 mV positive in cells dialyzed with 100 microM cAMP. These data suggest that, in addition to blocking channel conductance by binding to a site in the channel pore, Ni may bind to a second site that influences the voltage-dependent gating of the L-type Ca channel. They also suggest that Ca channel phosphorylation causes a conformational change that alters some effects of Ni. The results may be relevant to excitation-contraction coupling studies, which have employed internal cAMP dialysis, and where Ni has been used to block I(Ca,L) and Ca entry into cardiac cells.

  13. 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.

  14. Inhibition of Na/Ca exchange by external Ni in guinea-pig ventricular myocytes at 37 degrees C, dialysed internally with cAMP-free and cAMP-containing solutions.

    Science.gov (United States)

    Hinde, A K; Perchenet, L; Hobai, I A; Levi, A J; Hancox, J C

    1999-04-01

    In many mammalian tissue types an integral membrane protein--the sodium/calcium (Na/Ca) exchanger--plays a key role in intracellular Ca homeostasis, and evidence suggests that Na/Ca exchange function can be modulated by cAMP-dependent phosphorylation. External Nickel (Ni) ions are used widely to inhibit the exchange but little is known about the mode of Ni action. In guinea-pig ventricular myocytes, we investigated inhibition of Na/Ca exchange by external Ni under phosphorylated (cells dialysed with cAMP) and non-phosphorylated conditions. Ventricular myocytes were isolated from adult guinea-pig hearts, recordings were made at 37 degrees C using the whole-cell patch clamp technique. Internal and external solutions were used which allowed Na/Ca exchange current (INaCa) to be measured during a descending voltage ramp protocol (+80 to -120 mV) applied from a holding potential of -40 mV. The application of 10 mM Ni caused a maximal block of INaCa since inhibition was identical to that when a Na- and Ca-free (0Na/0Ca) solution was superfused externally. Kinetics of Ni-block of INaCa were assessed using applications of different external [Ni] to cells dialysed internally with cAMP-free and 100 microM cAMP-containing solutions. At +60 mV, Ni inhibited INaCa in cells dialysed with a cAMP-free solution with a dissociation constant (KD) of 0.29 +/- 0.03 mM and the data were fitted with a Hill coefficient of 0.89 +/- 0.07 (n = 9 cells). In cells dialysed with 100 microM cAMP the exchange was inhibited by Ni with a KD of 0.16 +/- 0.05 mM, the Hill coefficient was 0.82 +/- 0.16 (n = 6-7 cells). The KD and Hill coefficient values obtained in cells dialysed with cAMP-free and cAMP-containing solutions were not significantly different. Inhibition of INaCa by Ni did not appear to be voltage-dependent, was maximal within 3-4 s of application and was rapidly reversible. With cAMP-free internal dialysate, inhibition was 'mixed' showing competition with external Ca and a degree of non

  15. Single sodium channels from human ventricular muscle in planar lipid bilayers

    NARCIS (Netherlands)

    Wartenberg, H. C.; Wartenberg, J. P.; Urban, B. W.

    2001-01-01

    Sodium channels from human ventricular muscle membrane vesicles were incorporated into planar lipid bilayers and the steady-state behavior of single sodium channels were examined in the presence of batrachotoxin. In symmetrical 500 mM NaCl the averaged single channel conductance was 24.7 +/- 1.3 pS

  16. 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

    Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current (Im) and compared membrane potentials recorded in isolated...... cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of -87 ± 2 mV and -83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We...... 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...

  17. The feasibility of repeated left ventricular ejection fraction analysis with sequential single-dose radionuclide ventriculography

    NARCIS (Netherlands)

    van der Vleuten, PA; Slart, RHJA; Tio, RA; van der Horst, ICC; van Veldhuisen, DJ; Dierckx, RA; Zijlstra, F

    Objective Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement

  18. Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle.

    Science.gov (United States)

    Mital, Seema; Chung, Wendy K; Colan, Steven D; Sleeper, Lynn A; Manlhiot, Cedric; Arrington, Cammon B; Cnota, James F; Graham, Eric M; Mitchell, Michael E; Goldmuntz, Elizabeth; Li, Jennifer S; Levine, Jami C; Lee, Teresa M; Margossian, Renee; Hsu, Daphne T

    2011-05-31

    We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle. Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those with SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (PSCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact. http://www.clinicaltrials.gov. Unique identifier: NCT00113087.

  19. Ultrastructure of right ventricular myocardium subjected to acute pressure load.

    Science.gov (United States)

    Mühlfeld, C; Coulibaly, M; Dörge, H; Sellin, C; Liakopoulos, O; Ballat, C; Richter, J; Schoendube, F

    2004-12-01

    Ultrastructural data on acute right ventricular pressure load in pigs are rare. In control (n = 7) and banding groups (n = 6), right ventricular pressure (micromanometry) and function (sonomicrometry) were measured. Right ventricular pressure was increased 2.5-fold in the banding group by pulmonary artery constriction. Right ventricular biopsies were taken at baseline and after 6 h and processed for electron microscopy. Parameters of cellular injury were determined stereologically. Three perfusion -fixed hearts were investigated qualitatively in each group. Stereology revealed an increase in the sarcoplasmic volume fraction and the cellular edema index in the banding group ( p < 0.05). Mitochondrial surface-to-volume ratio and volume fraction did not show significant alterations. Subendocardial edema and small amounts of severely injured myocytes were observed in the perfusion-fixed hearts after banding. Ultrastructure was normal in controls. After an initial increase, the right ventricular work index declined progressively in the banding group but remained unchanged in controls. Ultrastructural alterations resulting from acute right ventricular pressure load were characterized by edema of subendocardial myocytes and single cell necrosis. Focal adrenergic overstimulation and mechanical stress are probably more relevant in the pathogenesis of these lesions than ischemia.

  20. Comparison of the Effects of a Transient Outward Potassium Channel Activator on Currents Recorded from Atrial and Ventricular Cardiomyocytes

    DEFF Research Database (Denmark)

    Callø, Kirstine; Nof, Eyal; Jespersen, Thomas

    2011-01-01

    NS5806 activates the transient outward potassium current (I(to) ) in canine ventricular cells. We compared the effects of NS5806 on canine atrial versus ventricular tissues and myocytes.......NS5806 activates the transient outward potassium current (I(to) ) in canine ventricular cells. We compared the effects of NS5806 on canine atrial versus ventricular tissues and myocytes....

  1. Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion.

    Science.gov (United States)

    Brunetti, Tonya M; Fremin, Brayon J; Cripps, Richard M

    2015-05-15

    In Drosophila, myoblast fusion is a conserved process in which founder cells (FCs) and fusion competent myoblasts (FCMs) fuse to form a syncytial muscle fiber. Mutants for the myogenic regulator Myocyte enhancer factor-2 (MEF2) show a failure of myoblast fusion, indicating that MEF2 regulates the fusion process. Indeed, chromatin immunoprecipitation studies show that several genes involved in myoblast fusion are bound by MEF2 during embryogenesis. Of these, the MARVEL domain gene singles bar (sing), is down-regulated in MEF2 knockdown pupae, and has five consensus MEF2 binding sites within a 9000-bp region. To determine if MEF2 is an essential and direct regulator of sing during pupal muscle development, we identified a 315-bp myoblast enhancer of sing. This enhancer was active during myoblast fusion, and mutation of two MEF2 sites significantly decreased enhancer activity. We show that lack of sing expression resulted in adult lethality and muscle loss, due to a failure of fusion during the pupal stage. Additionally, we sought to determine if sing was required in either FCs or FCMs to support fusion. Interestingly, knockdown of sing in either population did not significantly affect fusion, however, knockdown in both FCs and FCMs resulted in muscles with significantly reduced nuclei numbers, provisionally indicating that sing function is required in either cell type, but not both. Finally, we found that MEF2 regulated sing expression at the embryonic stage through the same 315-bp enhancer, indicating that sing is a MEF2 target at both critical stages of myoblast fusion. Our studies define for the first time how MEF2 directly controls fusion at multiple stages of the life cycle, and provide further evidence that the mechanisms of fusion characterized in Drosophila embryos is also used in the formation of the more complex adult muscles. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Single-site ventricular pacing via the coronary sinus in patients with tricuspid valve disease.

    Science.gov (United States)

    Noheria, Amit; van Zyl, Martin; Scott, Luis R; Srivathsan, Komandoor; Madhavan, Malini; Asirvatham, Samuel J; McLeod, Christopher J

    2017-03-01

    To evaluate coronary sinus single-site (CSSS) left ventricular pacing in adult patients with normal left ventricular ejection fraction (LVEF) when traditional right ventricular lead implantation is not feasible or is contraindicated. We performed a retrospective analysis of 23 patients with tricuspid valve surgery/disease who received a CSSS ventricular pacing lead to avoid crossing the tricuspid valve. Two matched control populations were obtained from patients receiving (i) conventional right ventricular single-site (RVSS) leads and (ii) coronary sinus leads for cardiac resynchronization therapy (CSCRT). Main outcomes of interest were lead stability, electrical lead parameters and change in LVEF during long-term follow-up. Successful CSSS pacing was accomplished in all 23 patients without any procedural complications. During the 5.3 ± 2.8-year follow-up 22/23 (95.7%) leads were functional with stable pacing and sensing parameters, and 1/23 (4.3%) was extracted for unrelated reasons. Compared to CSSS leads, the lead revision/abandonment was similar with RVSS leads (Hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.03, 22.0), but was higher with CSCRT leads (HR 7.41, 95% CI 1.30, 139.0). There was no difference in change in LVEF between CSSS and RVSS groups (-2.4 ± 11.0 vs. 1.5 ± 12.8, P = 0.76), but LVEF improved in CSCRT group (11.2 ± 16.5%, P = 0.002). Fluoroscopy times were longer during implantation of CSSS compared to RVSS leads (25.6 ± 24.6 min vs. 12.3 ± 18.6 min, P = 0.049). In patients with normal LVEF, single-site ventricular pacing via the coronary sinus is a feasible, safe and reliable alternative to right ventricular pacing. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-03

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

  4. Ventricular Assist Device in Single-Ventricle Heart Disease and a Superior Cavopulmonary Anastomosis.

    Science.gov (United States)

    Niebler, Robert A; Shah, Tejas K; Mitchell, Michael E; Woods, Ronald K; Zangwill, Steven D; Tweddell, James S; Berger, Stuart; Ghanayem, Nancy S

    2016-02-01

    Our objective is to describe the use of a ventricular assist device (VAD) in single-ventricle patients with circulatory failure following superior cavopulmonary anastomosis (SCPA). We performed a retrospective chart review of all single-ventricle patients supported with a VAD following SCPA. Implantation techniques, physiologic parameters while supported, medical and surgical interventions postimplant, and outcomes were reviewed. Four patients were supported with an EXCOR Pediatric (Berlin Heart Inc., The Woodlands, TX, USA) following SCPA for a median duration of 10.5 days (range 9-312 days). Selective excision of trabeculae and chords facilitated apical cannulation in all patients without inflow obstruction. There were two pump exchanges in the one patient supported for 312 days. Two patients were evaluated by cardiac catheterization while supported. Three of four patients were successfully bridged to transplantation. One patient died while supported. All patients had significant bleeding at the time of transplantation, and one required posttransplant extracorporeal membrane oxygenation with subsequent full recovery. VAD support can provide a successful bridge to transplantation in patients with single-ventricle circulation following SCPA. A thorough understanding of the challenges encountered during this support is necessary for successful outcomes. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  5. A Novel Nicotinamide Adenine Dinucleotide Correction Method for Mitochondrial Ca(2+) Measurement with FURA-2-FF in Single Permeabilized Ventricular Myocytes of Rat.

    Science.gov (United States)

    Lee, Jeong Hoon; Ha, Jeong Mi; Leem, Chae Hun

    2015-07-01

    Fura-2 analogs are ratiometric fluoroprobes that are widely used for the quantitative measurement of [Ca(2+)]. However, the dye usage is intrinsically limited, as the dyes require ultraviolet (UV) excitation, which can also generate great interference, mainly from nicotinamide adenine dinucleotide (NADH) autofluorescence. Specifically, this limitation causes serious problems for the quantitative measurement of mitochondrial [Ca(2+)], as no available ratiometric dyes are excited in the visible range. Thus, NADH interference cannot be avoided during quantitative measurement of [Ca(2+)] because the majority of NADH is located in the mitochondria. The emission intensity ratio of two different excitation wavelengths must be constant when the fluorescent dye concentration is the same. In accordance with this principle, we developed a novel online method that corrected NADH and Fura-2-FF interference. We simultaneously measured multiple parameters, including NADH, [Ca(2+)], and pH/mitochondrial membrane potential; Fura-2-FF for mitochondrial [Ca(2+)] and TMRE for Ψm or carboxy-SNARF-1 for pH were used. With this novel method, we found that the resting mitochondrial [Ca(2+)] concentration was 1.03 µM. This 1 µM cytosolic Ca(2+) could theoretically increase to more than 100 mM in mitochondria. However, the mitochondrial [Ca(2+)] increase was limited to ~30 µM in the presence of 1 µM cytosolic Ca(2+). Our method solved the problem of NADH signal contamination during the use of Fura-2 analogs, and therefore the method may be useful when NADH interference is expected.

  6. 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.

  7. Ventricular outflow tract reconstructions with cryopreserved cardiac valve homografts. A single surgeon's 10-year experience.

    Science.gov (United States)

    Hopkins, R A; Reyes, A; Imperato, D A; Carpenter, G A; Myers, J L; Murphy, K A

    1996-01-01

    OBJECTIVE: From January 1, 1985 through December 31, 1994, one surgeon implanted cryopreserved valved homografts into 149 patients--65 since December 1988. This latter series (II) was accomplished in a single hospital, facilitating patient follow-up with biannual echocardiograms. Analysis of these 65 patients is the primary focus of this report; the indications and early surgical results for the two parts of the series (I and II) are compared to assess the evolution of a single surgeon's use of homografts in a mixed pediatric and adult practice. METHODS: Fifty-one variables for each patient (series II) were entered into a computerized database and analyzed (multivariate and univariate) using SPSS 6.1 software (Statistical Products and Service Solutions, Chicago, IL). Cox proportional hazard model was used to identify the independent contribution of each variable for patient mortality and homograft failure. Cumulative survival estimates were made using Kaplan-Meier analysis. Homograft failure was defined as requirement for replacement or death. In series I, there were 41 left ventricular outflow tract (LVOT) reconstructions (31 adult) and 43 right ventricular outflow tract (RVOT) reconstructions (42 pediatric). In series II, there were 55 RVOT reconstructions (52 pediatric) and 10 LVOT reconstructions (7 adult). RESULTS: There were no technical surgical failures. Total surgical mortality rate was 6% (5/84) in series I (3 LVOT, 2 RVOT) and 15% (10/65) in series II (2 LVOT, 8 RVOT) (I vs. II NS; p = 0.11, two-tailed Fisher exact test). By the Cox analysis, only age 120 minutes (p < 0.05) were significant predictors for death. Age-based survival curves were compared in a sequential bivariate analyses (log rank test) and age < 2 years again was a significant predictor of decreased patient survival (p < 0.006). Actuarial freedom from patient death or reoperation for homograft failure was 82% +/- 7% at 1000 days and 77% +/- 10% at 2000 days. Three patients required re

  8. 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

  9. HeartMate II Left Ventricular Assist Device Pump Exchange: A Single-Institution Experience.

    Science.gov (United States)

    Shaikh, Asad F; Joseph, Susan M; Lima, Brian; Hall, Shelley A; Malyala, Rajasekhar; Rafael, Aldo E; Gonzalez-Stawinski, Gonzalo V; Chamogeorgakis, Themistokles

    2017-08-01

    Background  Left ventricular assist devices (LVADs) have revolutionized the treatment of patients with end-stage heart failure. These devices are replaced when pump complications arise if heart transplant is not possible. We present our experience with HeartMate II (HMII (Thoratec, Plesanton, California, United States)) LVAD pump exchange. Materials and Methods  We retrospectively reviewed all cases that required pump exchange due to LVAD complication from November 2011 until June 2016 at a single high-volume institution. The indications, demographics, and outcome were extracted and analyzed. Results  Of 250 total patients with implanted HMII LVADs, 16 (6%) required pump exchange during the study period. The initial indications for LVAD placement in these patients were bridge to transplantation ( n  = 6 [37.5%]) or destination therapy ( n  = 10 [62.5%]). Fifteen patients (93.8%) required pump exchange due to pump thrombosis and 1 (6.2%) due to refractory driveline infection. Nine patients (56.2%) underwent repeat median sternotomy while a left subcostal approach was used in the remaining seven patients. Fifteen patients (93.7%) survived until hospital discharge. During the follow-up period (median, 155 days), 11 patients remained alive and 4 of these underwent successful cardiac transplantation. Conclusion  HMII LVAD pump exchange can be safely performed for driveline infection or pump thrombosis when heart transplantation is not an option. Georg Thieme Verlag KG Stuttgart · New York.

  10. Rapid MR assessment of left ventricular systolic function after acute myocardial infarction using single breath-hold cine imaging with the temporal parallel acquisition technique (TPAT) and 4D guide-point modelling analysis of left ventricular function

    International Nuclear Information System (INIS)

    Eberle, Holger C.; Jensen, Christoph J.; Sabin, Georg V.; Naber, Christoph K.; Bruder, Oliver; Nassenstein, Kai; Schlosser, Thomas

    2010-01-01

    We compared four-dimensional guide-point modelling left ventricular function analysis (4DVF) results of cine images in four short-axis and two long-axis slices acquired in a single breath-hold, obtained with the temporal parallel acquisition technique (TPAT), with standard left ventricular function (LVF) analysis results determined by the summation of discs method, in patients who had recently suffered myocardial infarction. Despite wall motion abnormalities, 4DVF yields results for left ventricular ejection fractions and end-diastolic and end-systolic volumes that are in excellent agreement with standard LVF analysis results in these patients. A shortened cardiac magnetic resonance (CMR) protocol using single breath-hold cine image acquisition could facilitate the assessment of left ventricular function soon after myocardial infarction in critically ill patients who are unable to comply with the multiple breath-holds required for standard LVF analysis. (orig.)

  11. Ventricular assist device support in patients with single ventricles: the Melbourne experience.

    Science.gov (United States)

    Poh, Chin L; Chiletti, Roberto; Zannino, Diana; Brizard, Christian; Konstantinov, Igor E; Horton, Stephen; Millar, Johnny; d'Udekem, Yves

    2017-08-01

    The capacity and limitations of ventricular assist device (VAD) support in single-ventricle physiology remains poorly understood. We aimed to review our experience in the use of VAD support in the single-ventricle circulation to determine its feasibility in this population. We reviewed our experience with VAD support in patients with single ventricles over the past 25 years. Fifty-seven patients received 64 runs of VAD support between 1990 and 2015 at a median age of 13 days [interquartile range (IQR) 4.1-99.4 days], of which 55 were supported for post-cardiotomy failure. The majority of patients received short-term VAD support, while 4 patients were either directly supported (1) or transitioned onto the Berlin Heart EXCOR (3). The median duration of support was 3.5 days (IQR 2.8-5.2 days). Twelve patients suffered significant neurological complications, and thromboembolic events occurred in 8 patients. Twenty-nine of the 55 patients were successfully weaned off support (53%). There were 37 inpatient deaths, with a survival-to-hospital discharge rate of 33% (18 of 55). Of the 4 patients supported after early Fontan failure, 3 died. Having a higher mean arterial blood pressure on initiation of VAD support was the only significant predictor of death (hazards ratio 1.08; 95% confidence interval 1.03-1.14; P = 0.002). Patients who required a second run of support had higher hospital mortality (83% vs 63%; P = 0.84). Of the hospital survivors, 12 patients (63%) remain alive without heart transplantation at median 7.2 years (IQR 3.5-14.0) post VAD support. VAD support in patients with a single ventricle has a high hospital mortality, with 1 of 3 patients surviving to discharge. Systemic VAD support is likely futile in the setting of early Fontan failure or when re-initiation of support is required. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  12. 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

  13. Isolation of cardiac myocytes and fibroblasts from neonatal rat pups.

    Science.gov (United States)

    Golden, Honey B; Gollapudi, Deepika; Gerilechaogetu, Fnu; Li, Jieli; Cristales, Ricardo J; Peng, Xu; Dostal, David E

    2012-01-01

    Neonatal rat ventricular myocytes (NRVM) and fibroblasts (FBs) serve as in vitro models for studying fundamental mechanisms underlying cardiac pathologies, as well as identifying potential therapeutic targets. Both cell types are relatively easy to culture as monolayers and can be manipulated using molecular and pharmacological tools. Because NRVM cease to proliferate after birth, and FBs undergo phenotypic changes and senescence after a few passages in tissue culture, primary cultures of both cell types are required for experiments. Below we describe methods that provide good cell yield and viability of primary cultures of NRVM and FBs from 0 to 3-day-old neonatal rat pups.

  14. 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.

  15. Automaticity in acute ischemia: Bifurcation analysis of a human ventricular model

    Science.gov (United States)

    Bouchard, Sylvain; Jacquemet, Vincent; Vinet, Alain

    2011-01-01

    Acute ischemia (restriction in blood supply to part of the heart as a result of myocardial infarction) induces major changes in the electrophysiological properties of the ventricular tissue. Extracellular potassium concentration ([Ko+]) increases in the ischemic zone, leading to an elevation of the resting membrane potential that creates an “injury current” (IS) between the infarcted and the healthy zone. In addition, the lack of oxygen impairs the metabolic activity of the myocytes and decreases ATP production, thereby affecting ATP-sensitive potassium channels (IKatp). Frequent complications of myocardial infarction are tachycardia, fibrillation, and sudden cardiac death, but the mechanisms underlying their initiation are still debated. One hypothesis is that these arrhythmias may be triggered by abnormal automaticity. We investigated the effect of ischemia on myocyte automaticity by performing a comprehensive bifurcation analysis (fixed points, cycles, and their stability) of a human ventricular myocyte model [K. H. W. J. ten Tusscher and A. V. Panfilov, Am. J. Physiol. Heart Circ. Physiol.AJPHAP0363-613510.1152/ajpheart.00109.2006 291, H1088 (2006)] as a function of three ischemia-relevant parameters [Ko+], IS, and IKatp. In this single-cell model, we found that automatic activity was possible only in the presence of an injury current. Changes in [Ko+] and IKatp significantly altered the bifurcation structure of IS, including the occurrence of early-after depolarization. The results provide a sound basis for studying higher-dimensional tissue structures representing an ischemic heart.

  16. Estimation of right ventricular pressure in children by thallium-201 myocardial imaging using single-photon emission computed tomography.

    Science.gov (United States)

    Akiba, T; Yoshikawa, M; Otaki, S; Nakasato, M; Suzuki, H; Sato, S; Sato, T

    1992-03-01

    Thallium-201 myocardial imaging using single-photon emission computed tomography was performed to estimate right ventricular (RV) systolic pressure in 34 children (aged 4.1 to 16.1 years, mean 7.9 +/- 2.9). Acquisition of the images was performed using a semicircular arc of 180 degrees. On a short-axis slice, a line drawn perpendicular to the ventricular septum so as to cross the RV free wall showing maximum uptake was defined as the region of interest. Thallium-201 counts in regions of interest over both RV and left ventricular (LV) free walls were measured. The ratio of RV-to-LV peak thallium-201 counts was compared with RV peak systolic pressure and the ratio of RV-to-LV peak systolic pressure measured at cardiac catheterization. Both RV peak systolic pressure and the ratio of RV-to-LV peak systolic pressure correlated well with the ratio of RV-to-LV peak thallium-201 counts (r = 0.95 and 0.96, respectively). The ratio of RV-to-LV peak thallium-201 counts greater than or equal to 0.45 could predict RV pressure overloading with a sensitivity of 92%, and a specificity of 88%. Thus, the quantitative analysis of thallium-201 myocardial imaging using single-photon emission computed tomography permits the noninvasive and accurate estimation of RV systolic pressure in children.

  17. A novel non invasive measurement of hemodynamic parameters: Comparison of single-chamber ventricular and dual-chamber pacemaker

    Directory of Open Access Journals (Sweden)

    Ingrid M. Pardede

    2008-03-01

    Full Text Available We carried out a cross sectional study to analyze hemodynamic parameters of single-chamber ventricular pacemaker compared with dual-chamber pacemaker by using thoracic electrical bioimpedance monitoring method (Physio Flow™ - a novel simple non-invasive measurement. A total of 48 consecutive outpatients comprised of 27 single chamber pacemaker and 21 dual chamber were analyzed. We measured cardiac parameters: heart rate, stroke volume index, cardiac output index, estimated ejection fraction, end diastolic volume, early diastolic function ratio, thoracic fluid index, and systemic parameters: left cardiac work index and systemic vascular resistance index. Baseline characteristic and pacemaker indication were similar in both groups. Cardiac parameters assessment revealed no significant difference between single-chamber pacemaker and dual-chamber pacemaker in heart rate, stroke volume index, cardiac index, estimated ejection fraction, end-diastolic volume, thoracic fluid index. There was significantly higher early diastolic function ratio in single-chamber pacemaker compared to dual-chamber pacemaker: 92% (10.2-187.7% vs. 100.6% (48.7-403.2%; p=0.006. Systemic parameters assessment revealed significantly higher left cardiac work index in single-chamber group than dual-chamber group 4.9 kg.m/m² (2.8-7.6 kg.m/m² vs. 4.3 kg.m/m² (2.9-7.2 kg.m/m²; p=0.004. There was no significant difference on systemic vascular resistance in single-chamber compared to dual-chamber pacemaker. Single-chamber ventricular pacemaker provides similar stroke volume, cardiac output and left cardiac work, compared to dual-chamber pacemaker. A non-invasive hemodynamic measurement using thoracic electrical bioimpedance is feasible for permanent pacemaker outpatients. (Med J Indones 2008; 17: 25-32Keywords: Permanent pacemaker, single chamber, dual chamber, thoracic electrical bioimpedance, hemodynamic parameter

  18. 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.

  19. Two different cardiomyopathies in a single patient : hypertrophic cardiomyopathy and left ventricular noncompaction.

    Science.gov (United States)

    Sunbul, M; Ozben, B; Mutlu, B

    2013-05-01

    Hypertrophic cardiomyopathy is a complex and relatively common genetic disorder characterized by left ventricular (LV) hypertrophy, usually associated with a nondilated and hyperdynamic chamber with heterogeneous phenotypic expression and clinical course. On the other hand, LV noncompaction is an uncommon cardiomyopathy characterized by the persistence of fetal myocardium with a pattern of prominent trabecular meshwork and deep intertrabecular recesses, systolic dysfunction, and LV dilatation. We report a 29-year-old man with these two different inherent conditions. Our case raises the possibility of a genetic mutation common to these two clinical entities or different gene mutations existing in the same individual.

  20. Longitudinal shortening of sub-epicardial myocytes in severe ischaemic cardiomyopathy

    DEFF Research Database (Denmark)

    Bjerre, Jenny; Kyhl, Kasper; Gustafsson, Finn

    2017-01-01

    We present two patients with three-vessel disease and severely depressed left ventricular (LV) systolic function where viability analysis by cardiac magnetic resonance imaging demonstrated areas of near-transmural sub-endocardial fibrosis and hence little chance of regaining systolic function as ....... The cases highlight that sub-epicardial, longitudinally oriented myocytes can contribute to overall LV systolic function and suggest taking their 'piston-function' into consideration when analysing viability....

  1. Single-Center Experience With HeartMate II Left Ventricular Assist Device Explantation.

    Science.gov (United States)

    Tchantchaleishvili, Vakhtang; Cheyne, Christina; Sherazi, Saadia; Melvin, Amber L; Hallinan, William; Chen, Leway; Todd Massey, Howard

    2016-12-01

    In patients with continuous flow left ventricular assist devices (CF-LVADs) myocardial recovery is uncommon. Given the heterogeneity of the population implanted and low incidence of recovery, the discovery of native left ventricular (LV) recovery and criteria for explantation of CF-LVAD system is not clearly determined. We sought to analyze the characteristics of the patients who underwent CF-LVAD explantation at our institution. Prospectively collected data on patients supported with CF-LVADs were reviewed retrospectively. Patients who underwent CF-LVAD explants were identified and their characteristics were analyzed with a focus on patient presentation and determinants of explantability. From November 2006 to June 2014, 223 patients (181 male, 42 female) underwent implantation of HeartMate II LVAD. Seven female (16.7%) and one male (0.6%) patients were explanted (P < 0.001). Mean age was 43 ± 9 years and etiology for cardiomyopathy was ischemic in three (37.5%) patients, nonischemic in four (50%) patients, and mixed in the one (12.5%) male patient of the cohort. Five (62.5%) patients presented acutely with significant hemolysis, and were found to have LV improvement as well as reduced, absent, or reversed diastolic flow velocities on echocardiography. Overall, mean lactate dehydrogenase level before explantation was 1709 ± 1168 U/L compared to the mean baseline level of 601 ± 316 U/L (P = 0.048). Mean LV ejection fraction (LVEF) improved from 17 ± 7% preimplant to 56 ± 11% pre-explantation (P < 0.001). Median number of days on CF-LVAD support was 870 (interquartile range, 209-975) while mean duration of follow-up after the CF-LVAD explantation was 276 ± 240 days. Mean LVEF dropped from 46 ± 19% postexplantation to 34 ± 10% during the most recent follow-up (P = 0.015). At our institution, patients who underwent LVAD explants were predominantly women with nonischemic cardiomyopathy. Clinical evidence of

  2. Microdomain heterogeneity in 3D affects the mechanics of neonatal cardiac myocyte contraction

    Science.gov (United States)

    Curtis, Matthew W.; Budyn, Elisa; Desai, Tejal A.; Samarel, Allen M.

    2012-01-01

    Cardiac muscle cells are known to adapt to their physical surroundings, optimizing intracellular organization and contractile function for a given culture environment. A previously developed in vitro model system has shown that the inclusion of discrete microscale domains (or microrods) in three dimensions (3D) can alter long-term growth responses of neonatal ventricular myocytes. The aim of this work was to understand how cellular contact with such a domain affects various mechanical changes involved in cardiac muscle cell remodeling. Myocytes were maintained in 3D gels over 5 days in the presence or absence of 100 – μm-long microrods, and the effect of this local heterogeneity on cell behavior was analyzed via several imaging techniques. Microrod abutment resulted in approximately twofold increases in the maximum displacement of spontaneously beating myocytes, as based on confocal microscopy scans of the gel xy-plane or the myocyte long axis. In addition, microrods caused significant increases in the proportion of aligned myofibrils (≤20° deviation from long axis) in fixed myocytes. Microrod-related differences in axial contraction could be abrogated by long-term interruption of certain signals of the RhoA-/Rho-associated kinase (ROCK) or protein kinase C (PKC) pathway. Furthermore, microrod-induced increases in myocyte size and protein content were prevented by ROCK inhibition. In all, the data suggest that microdomain heterogeneity in 3D appears to promote the development of axially aligned contractile machinery in muscle cells, an observation that may have relevance to a number of cardiac tissue engineering interventions. PMID:22407215

  3. Diesterified nitrone rescues nitroso-redox levels and increases myocyte contraction via increased SR Ca(2+ handling.

    Directory of Open Access Journals (Sweden)

    Christopher J Traynham

    Full Text Available Nitric oxide (NO and superoxide (O(2 (- are important cardiac signaling molecules that regulate myocyte contraction. For appropriate regulation, NO and O(2 (.- must exist at defined levels. Unfortunately, the NO and O(2 (.- levels are altered in many cardiomyopathies (heart failure, ischemia, hypertrophy, etc. leading to contractile dysfunction and adverse remodeling. Hence, rescuing the nitroso-redox levels is a potential therapeutic strategy. Nitrone spin traps have been shown to scavenge O(2 (.- while releasing NO as a reaction byproduct; and we synthesized a novel, cell permeable nitrone, 2-2-3,4-dihydro-2H-pyrrole 1-oxide (EMEPO. We hypothesized that EMEPO would improve contractile function in myocytes with altered nitroso-redox levels. Ventricular myocytes were isolated from wildtype (C57Bl/6 and NOS1 knockout (NOS1(-/- mice, a known model of NO/O(2 (.- imbalance, and incubated with EMEPO. EMEPO significantly reduced O(2 (.- (lucigenin-enhanced chemiluminescence and elevated NO (DAF-FM diacetate levels in NOS1(-/- myocytes. Furthermore, EMEPO increased NOS1(-/- myocyte basal contraction (Ca(2+ transients, Fluo-4AM; shortening, video-edge detection, the force-frequency response and the contractile response to β-adrenergic stimulation. EMEPO had no effect in wildtype myocytes. EMEPO also increased ryanodine receptor activity (sarcoplasmic reticulum Ca(2+ leak/load relationship and phospholamban Serine16 phosphorylation (Western blot. We also repeated our functional experiments in a canine post-myocardial infarction model and observed similar results to those seen in NOS1(-/- myocytes. In conclusion, EMEPO improved contractile function in myocytes experiencing an imbalance of their nitroso-redox levels. The concurrent restoration of NO and O(2 (.- levels may have therapeutic potential in the treatment of various cardiomyopathies.

  4. Feasibility of single breath-hold left ventricular function with 3 Tesla TSENSE acquisition and 3D modeling analysis.

    Science.gov (United States)

    Young, Alistair A; Cowan, Brett R; Schoenberg, Stefan O; Wintersperger, Bernd J

    2008-05-21

    A single breath-hold evaluation of ventricular function would allow assessment in cases where scan time or patient tolerance is limited. Spatiotemporal acceleration techniques such as TSENSE decrease cardiovascular MR acquisition time, but standard slice summation analysis requires enough short axis slices to cover the left ventricle (LV). By reducing the number of short axis slices, incorporating long axis slices, and applying a 3D model based analysis, it may be possible to obtain accurate LV mass and volumes. We evaluated LV volume, mass and ejection fraction at 3.0 T using a 3D modeling analysis in 9 patients with a history of myocardial infarction and one healthy volunteer. Acquisition consisted of a standard short axis SSFP stack and a 15 heart-beat single breath-hold six slice multi-planar (4 short and 2 long axis) TSENSE SSFP protocol with an acceleration factor of R = 4. Differences (standard minus accelerated protocol mean +/- s.d.) and coefficients of variation (s.d. of differences as a percentage of the average estimate) were 7.5 +/- 9.6 mL and 6% for end-diastolic volume (p = 0.035), 0.4 +/- 5.1 mL and 7% for end-systolic volume (p = NS), 7.1 +/- 8.1 mL and 9% for stroke volume (p = 0.022), 2.2 +/- 2.8% and 5% for ejection fraction (p = 0.035), and -7.1 +/- 6.2 g and 4% for LV mass (p = 0.005), respectively. Intra- and inter-observer errors were similar for both protocols (p = NS for all measures). These results suggest that clinically useful estimates of LV function can be obtained in a TSENSE accelerated single breath-hold reduced slice acquisition at 3T using 3D modeling analysis techniques.

  5. Correlation of abnormal response of left ventricular ejection fraction after exercise and left ventricular cavity-to-myocardium count ratio of technetium-99m-tetrofosmin single photon emission computed tomography in patients with coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Hueisch-J [Kaohsiung Medical Univ., Taiwan (China). School of Technology for Medical Science; Lin, Ching-C; Wang, Jhi-J [Chi-Mei Medical Center, Tainan, Taiwan (China); Ho, Shung-T [National Defense Medical Center, Taipei, Taiwan (China). School of Medicine; Kao, Albert [China Medical Coll., Taichung, Taiwan (China). Hospital

    2002-09-01

    The aim of this study was to assess the value of the left ventricular cavity-to-myocardium count ratio (C/M ratio) of technetium-99m (Tc-99m) tetrofosmin single photon emission computed tomography (SPECT) to identify abnormal left ventricular ejection fraction (LVEF) responses after exercise in patients with coronary artery diseases (CAD). We studied 50 patients with recent CAD undergoing rest and exercise first-pass ventriculography to calculate LVEF and rest and exercise Tc-99m tetrofosmin myocardial perfusion SPECT to calculate left ventricular C/M ratios. Group A, consisting of 25 CAD patients with normal responses (increased LVEF{>=}5% after exercise), had significantly higher rest and exercise C/M ratios than those of the group B, consisting of 25 CAD patients with abnormal responses (increased LVEF <5% after exercise) after exercise. However, the C/M ratios between exercise and rest did not differ significantly between groups A and B. In addition, there was significant correlation between LVEF and C/M ratios in all of the patients. C/M ratios of Tc-99m tetrofosmin myocardial perfusion SPECT are useful parameters for identifying patients with abnormal LVEF responses among patients with CAD. (author)

  6. Hypoxia inducible factor-1 improves the negative functional effects of natriuretic peptide and nitric oxide signaling in hypertrophic cardiac myocytes.

    Science.gov (United States)

    Tan, Tao; Scholz, Peter M; Weiss, Harvey R

    2010-07-03

    Both natriuretic peptides and nitric oxide may be protective in cardiac hypertrophy, although their functional effects are diminished in hypertrophy. Hypoxia inducible factor-1 (HIF-1) may also protect in cardiac hypertrophy. We hypothesized that upregulation of HIF-1 would protect the functional effects of cyclic GMP (cGMP) signaling in hypertrophied ventricular myocytes. A cardiac hypertrophy model was created in mice by transverse aorta constriction. HIF-1 was increased by deferoxamine (150 mg/kg for 2 days). HIF-1alpha protein levels were examined. Functional parameters were measured (edge detector) on freshly isolated myocytes at baseline and after BNP (brain natriuretic peptide, 10(-8)-10(-7)M) or CNP (C-type natriuretic peptide, 10(-8)-10(-7)M) or SNAP (S-nitroso-N-acetyl-penicillamine, a nitric oxide donor, 10(-6)-10(-5)M) followed by KT5823 (a cyclic GMP-dependent protein kinase (PKG) inhibitor, 10(-6)M). We also determined PKG expression levels and kinase activity. We found that under control conditions, BNP (-24%), CNP (-22%) and SNAP (-23%) reduced myocyte shortening, while KT5823 partially restored function. Deferoxamine treated control myocytes responded similarly. Baseline function was reduced in the myocytes from hypertrophied heart. BNP, CNP, SNAP and KT5823 also had no significant effects on function in these myocytes. Deferoxamine restored the negative functional effects of BNP (-22%), CNP (-18%) and SNAP (-19%) in hypertrophic cardiac myocytes and KT5823 partially reversed this effect. Additionally, deferoxamine maintained PKG expression levels and activity in hypertrophied heart. Our results indicated that the HIF-1 protected the functional effects of cGMP signaling in cardiac hypertrophy through preservation of PKG. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  7. Toward improved myocardial maturity in an organ-on-chip platform with immature cardiac myocytes.

    Science.gov (United States)

    Sheehy, Sean P; Grosberg, Anna; Qin, Pu; Behm, David J; Ferrier, John P; Eagleson, Mackenzie A; Nesmith, Alexander P; Krull, David; Falls, James G; Campbell, Patrick H; McCain, Megan L; Willette, Robert N; Hu, Erding; Parker, Kevin K

    2017-11-01

    In vitro studies of cardiac physiology and drug response have traditionally been performed on individual isolated cardiomyocytes or isotropic monolayers of cells that may not mimic desired physiological traits of the laminar adult myocardium. Recent studies have reported a number of advances to Heart-on-a-Chip platforms for the fabrication of more sophisticated engineered myocardium, but cardiomyocyte immaturity remains a challenge. In the anisotropic musculature of the heart, interactions between cardiac myocytes, the extracellular matrix (ECM), and neighboring cells give rise to changes in cell shape and tissue architecture that have been implicated in both development and disease. We hypothesized that engineered myocardium fabricated from cardiac myocytes cultured in vitro could mimic the physiological characteristics and gene expression profile of adult heart muscle. To test this hypothesis, we fabricated engineered myocardium comprised of neonatal rat ventricular myocytes with laminar architectures reminiscent of that observed in the mature heart and compared their sarcomere organization, contractile performance characteristics, and cardiac gene expression profile to that of isolated adult rat ventricular muscle strips. We found that anisotropic engineered myocardium demonstrated a similar degree of global sarcomere alignment, contractile stress output, and inotropic concentration-response to the β-adrenergic agonist isoproterenol. Moreover, the anisotropic engineered myocardium exhibited comparable myofibril related gene expression to muscle strips isolated from adult rat ventricular tissue. These results suggest that tissue architecture serves an important developmental cue for building in vitro model systems of the myocardium that could potentially recapitulate the physiological characteristics of the adult heart. Impact statement With the recent focus on developing in vitro Organ-on-Chip platforms that recapitulate tissue and organ-level physiology

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

    Directory of Open Access Journals (Sweden)

    Robert D. Johnson

    2018-03-01

    Full Text Available 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.

  9. Effects of magnesium supplementation on electrophysiological remodeling of cardiac myocytes in L-NAME induced hypertensive rats.

    Science.gov (United States)

    Ozturk, Nihal; Olgar, Yusuf; Aslan, Mutay; Ozdemir, Semir

    2016-08-01

    Hypertension is one of the major risk factors of cardiac hypertrophy and magnesium deficiency is suggested to be a contributing factor in the progression of this complication. In this study, we aimed to investigate the relationship between intracellular free Mg(2+) levels and electrophysiological changes developed in the myocardium of L-NAME induced hypertensive rats. Hypertension was induced by administration of 40 mg/kg of L-NAME for 6 weeks, while magnesium treated rats fed with a diet supplemented with 1 g/kg of MgO for the same period. L-NAME administration for 6 weeks elicited a significant increase in blood pressure which was corrected with MgO treatment; thereby cardiac hypertrophy developing secondary to hypertension was prevented. Cytosolic free magnesium levels of ventricular myocytes were significantly decreased with hypertension and magnesium administration restored these changes. Hypertension significantly decreased the fractional shortening with slowing of shortening kinetics in left ventricular myocytes whereas magnesium treatment was capable of restoring hypertension-induced contractile dysfunction. Long-term magnesium treatment significantly restored the hypertension-induced prolongation in action potentials of ventricular myocytes and suppressed Ito and Iss currents. In contrast, hypertension dependent decrement in intracellular Mg(2+) level did not cause a significant change in L-type Ca(2+) currents, SR Ca(2+) content and NCX activity. Nevertheless, hypertension mediated increase in superoxide anion, hydrogen peroxide and protein oxidation mitigated with magnesium treatment. In conclusion, magnesium administration improves mechanical abnormalities observed in hypertensive rat ventricular myocytes due to reduced oxidative stress. It is likely that, changes in intracellular magnesium balance may contribute to the pathophysiology of chronic heart diseases.

  10. 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.

  11. Assessment of left ventricular diastolic function by gated single-photon emission tomography: comparison with Doppler echocardiography

    International Nuclear Information System (INIS)

    Yamano, Tetsuhiro; Sakamoto, Kenzo; Hikosaka, Takato; Zen, Kan; Nakamura, Takeshi; Sawada, Takahisa; Azuma, Akihiro; Nakagawa, Masao; Nakamura, Tomoki; Nishimura, Tsunehiko

    2003-01-01

    Gated single-photon emission tomography (SPET) is not yet an established procedure for the evaluation of left ventricular (LV) diastolic function. This study examined diastolic function derived from gated SPET in comparison with an established diagnostic tool, Doppler echocardiography. We examined 37 consecutive patients with normal sinus rhythm who underwent gated technetium-99m tetrofosmin SPET. A gated SPET program was used with a temporal resolution of 32 frames per R-R interval. We obtained the Doppler transmitral flow velocity waveform immediately before gated SPET image acquisition. Patients who showed a ratio of peak early transmitral flow velocity to atrial flow velocity (E/A) of >1 or whose R-R intervals differed by >5% between Doppler echocardiography and gated SPET were excluded from this investigation. We compared diastolic indices and presumed corresponding intervals in diastole using the two methods. The peak filling rate (PFR) derived from gated SPET correlated with the Doppler peak velocity of the early transmitral flow (E) wave (r=0.65) and deceleration of the E wave (r=0.71). The time to PFR and percent atrial contribution to LV filling from gated SPET correlated excellently with the Doppler LV isovolumic relaxation time (r=0.93) and the E/A ratio (r=-0.85), respectively. There was a significant linear correlation in all the intervals from the R wave to the presumed corresponding diastolic points. The point of PFR in gated SPET and the peak of the E wave in Doppler echocardiography generally coincided. The onset of filling in gated SPET tended to be closer to the second heart sound than the start of the E wave in Doppler echocardiography. We conclude that gated SPET permits the assessment of not only myocardial perfusion and LV systolic function but also diastolic function, although there may be some errors in detection of the precise beginning of LV filling. (orig.)

  12. 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.

  13. 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....

  14. Mst1 inhibition rescues β1-adrenergic cardiomyopathy by reducing myocyte necrosis and non-myocyte apoptosis rather than myocyte apoptosis

    Science.gov (United States)

    Lee, Grace J.; Yan, Lin; Vatner, Dorothy E.

    2015-01-01

    It is generally held that inhibition of mammalian sterile 20-like kinase 1 (Mst1) protects the heart through reducing myocyte apoptosis. We determined whether inhibition with a dominant-negative Mst1 (DN-Mst1) would protect against the cardiomyopathy induced by chronic β1-adrenergic receptor (β1-AR) stimulation by preventing myocyte apoptosis. DN-Mst1 mice were mated with β1-AR transgenic (Tg) mice and followed for 20 months. β1-AR Tg mice developed cardiomyopathy as they aged, as reflected by premature mortality and depressed cardiac function, which were rescued in β1-AR × DN-Mst1 bigenic mice. Surprisingly, myocyte apoptosis did not significantly decrease with Mst1 inhibition. Instead, Mst1 inhibition predominantly reduced non-myocyte apoptosis, e.g., fibroblasts, macrophages, neutrophils and endothelial cells. Fibrosis in the hearts with cardiomyopathy increased fivefold and this increase was nearly abolished in the bigenic mice with Mst1 inhibition. Regression analysis showed no correlation between myocyte apoptosis and cardiac function or myocyte number, whereas the latter two correlated significantly, p myocyte necrosis, chronic β-AR stimulation with isoproterenol was induced for 24 h and myocyte necrosis was assessed by 1 % Evans blue dye. Compared to WT, DN-Mst1 mice showed significant inhibition, p myocyte necrosis. We confirmed this result in Mst1-knockout mice, which also showed significant protection, p myocyte necrosis compared to WT. These data indicate that Mst1 inhibition rescued cardiac fibrosis and myocardial dysfunction in β1-AR cardiomyopathy. However, this did not occur through Mst1 inhibition of myocyte apoptosis but rather by inhibition of cardiomyocyte necrosis and non-myocyte apoptosis, features of Mst1 not considered previously. PMID:25600225

  15. 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.

  16. Variable Myocardial Response to Load Stresses in Infants with Single Left Ventricular Anatomy: Influence of Initial Physiology and Surgical Palliative Strategy.

    Science.gov (United States)

    Horriat, Narges L; Deatsman, Sara L; Stelter, Jessica; Frommelt, Peter C; Hill, Garick D

    2016-12-01

    Initial surgical strategies in neonates with single left ventricular (LV) anatomy vary based on adequacy of pulmonary and systemic blood flow. Differing myocardial responses to these strategies, as reflected in indices of systolic function, ventricular size, and mass have not been well defined. We sought to evaluate single LV myocardial response to varied physiology and initial palliation and determine whether the response is consistent and predictable. Infants with single LV physiology were divided based on neonatal palliation: no palliation/PA band (NO); BT shunt only (BT); or Norwood procedure (NP). Echo measures were obtained at presentation, early post-bidirectional Glenn (BDG), late post-BDG follow-up, and post-Fontan procedure. Measures included ejection fraction, LV mass indexed to height 2.7 and end diastolic volume indexed to body surface area, and mass/volume ratio. The cohort included 38 children (13 NO, 13 BT, 12 NP). Ejection fraction was similar but depressed in all groups at all stages. LV mass was higher in the NP group than the BT group at early post-BDG (p = 0.03) and higher than both BT and NO groups (p < 0.01) at late post-BDG, but the difference was resolved by post-Fontan follow-up. The NP group had the most remarkable remodeling in LV size from BDG to Fontan, suggesting that volume unloading is most valuable in this subgroup. Ventricular remodeling can be identified by echocardiography in children with single LV physiology, despite variable initial surgical palliative strategies. Importantly, these initial surgical strategies do not result in significant differences after Fontan palliation during early childhood.

  17. 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

  18. 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.

  19. 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)

  20. 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.

  1. 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 coronary artery stenosis according to the coronary angiogram results were prospectively enrolled. All the patients had no left ventricular regional wall motion abnormality in two-dimensional echocardiography at rest and exercise stress. There was no significant difference in the 16 segmental systolic peak AS at rest between two groups. After exercise stress, the peak systolic AS rest-stress at mid anterior wall (-7.00%±10.90% vs 2.80%±23.69%) and mid anterolateral wall (-4.40%±18.81% vs 8.80%±19.16%) were decreased, while increased at basal inferolateral wall (14.00%±19.27% vs -5.60%±15.94%) in case group compared with control group (Pcoronary artery stenosis, the area strain was decreased at involved segments, while compensatory increased at noninvolved segments after exercise stress. 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.

  2. β1-adrenoceptor Arg389Gly polymorphism confers differential β-arrestin-binding tropism in cardiac myocytes.

    Science.gov (United States)

    McCrink, Katie A; Brill, Ava; Jafferjee, Malika; Valero, Thairy Reyes; Marrero, Christine; Rodriguez, Martha M; Hale, Genevieve M; Lymperopoulos, Anastasios

    2016-10-01

    The β 1 -adrenergic receptor (AR) Arg389Gly polymorphism affects efficacy of its procontractile signaling in cardiomyocytes and carriers' responses to β-blockers. To identify molecular mechanisms underlying functional differences between Arg389 and Gly389 β 1 ARs, we examined their binding to β-arrestins (βarr-1 and -2), which mediate β 1 AR signaling, in neonatal rat ventricular myocytes. We tested the β 1 AR-βarr interaction via β 1 AR immunoprecipitation followed by βarr immunoblotting. βarr1 binds both variants upon isoproterenol, carvedilol or metoprolol treatment in neonatal rat ventricular myocytes. Conversely, the potentially beneficial in the heart βarr2 only interacts with the Arg389 receptor in response to isoproterenol or carvedilol. Arg389 confers unique βarr2-interacting tropism to the β 1 AR in cardiac myocytes, potentially underlying this variant's gain-of-function phenotype and better clinical responses to β-blockers.

  3. 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)

  4. Subcellular structures and function of myocytes impaired during heart failure are restored by cardiac resynchronization therapy.

    Science.gov (United States)

    Sachse, Frank B; Torres, Natalia S; Savio-Galimberti, Eleonora; Aiba, Takeshi; Kass, David A; Tomaselli, Gordon F; Bridge, John H

    2012-02-17

    Cardiac resynchronization therapy (CRT) is an established treatment for patients with chronic heart failure. However, CRT-associated structural and functional remodeling at cellular and subcellular levels is only partly understood. To investigate the effects of CRT on subcellular structures and protein distributions associated with excitation-contraction coupling of ventricular cardiomyocytes. Our studies revealed remodeling of the transverse tubular system (t-system) and the spatial association of ryanodine receptor (RyR) clusters in a canine model of dyssynchronous heart failure (DHF). We did not find this remodeling in a synchronous heart failure model based on atrial tachypacing. Remodeling in DHF ranged from minor alterations in anterior left ventricular myocytes to nearly complete loss of the t-system and dissociation of RyRs from sarcolemmal structures in lateral cells. After CRT, we found a remarkable and almost complete reverse remodeling of these structures despite persistent left ventricular dysfunction. Studies of whole-cell Ca(2+) transients showed that the structural remodeling and restoration were accompanied with remodeling and restoration of Ca(2+) signaling. DHF is associated with regional remodeling of the t-system. Myocytes undergo substantial structural and functional restoration after only 3 weeks of CRT. The finding suggests that t-system status can provide an early marker of the success of this therapy. The results could also guide us to an understanding of the loss and remodeling of proteins associated with the t-system. The steep relationship between free Ca(2+) and contraction suggests that some restoration of Ca(2+) release units will have a disproportionately large effect on contractility.

  5. 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

  6. 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.

  7. 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

  8. Prospective evaluation of where reperfusion ventricular arrhythmia "bursts" fit into optimal reperfusion in STEMI

    NARCIS (Netherlands)

    van der Weg, Kirian; Kuijt, Wichert J.; Tijssen, Jan G. P.; Bekkers, Sebastiaan C. A. M.; Haeck, Joost D. E.; Green, Cynthia L.; Lemmert, Miguel E.; de Winter, Robbert J.; Gorgels, Anton P. M.; Krucoff, Mitchell W.

    2015-01-01

    Early reperfusion of ischemic myocytes is essential for optimal salvage in acute myocardial infarction. VA (ventricular arrhythmia) bursts after recanalization of the culprit vessel have been found to be related to larger infarct size (IS), using SPECT. The hypothesis was tested that this finding

  9. Single breath-hold magnetic resonance cine imaging for fast assessment of global and regional left ventricular function in clinical routine

    International Nuclear Information System (INIS)

    Nassenstein, Kai; Heilmaier, Christina; Schlosser, Thomas; Eberle, Holger; Jensen, Christoph J.; Bruder, Oliver; Maderwald, Stefan

    2010-01-01

    To evaluate a TGRAPPA (temporal parallel acquisition technique)-accelerated, single breath-hold multi-slice cine imaging approach for the assessment of left ventricular (LV) function. One hundred eleven patients were examined at 1.5 T. Cine imaging was performed with single-slice breath-hold acquisitions in short-axis orientation using a SSFP (TR 2.63 ms, TE 1.12 ms, FA 72 ) sequence and a TGRAPPA SSFP (TR 2.66 ms, TE 1.11 ms, FA 72 , AF 3) sequence, which covered the entire LV in multiple short-axis slices during a single breath-hold. End-diastolic (EDV), end-systolic (ESV), stroke volumes (SV), ejection fraction (EF), muscle mass (MM) and regional wall motion were assessed for both data sets. Single breath-hold imaging was feasible in 108 patients. Excellent correlations were observed for all volumetric parameters derived from both data sets (all r > 0.97). While EDV and ESV showed marginally lower values for single breath-hold imaging (EDV: -1.6 ± 7.9 ml; ESV: -1.8 ± 6.0 ml, p < 0.05), no differences were observed for SV, EF, MM and regional wall motion assessment. Single breath-hold imaging required significant shorter acquisition times (28 ± 6 s vs. 335 ± 87 s). TGRAPPA-accelerated multi-slice SSPF imaging allows for fast and accurate assessment of regional and global LV function within a single breath-hold. (orig.)

  10. 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.

  11. 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.

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

    DEFF Research Database (Denmark)

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

    2018-01-01

    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...... acting simultaneously with a dilatory force component. The ratio of constrictive to dilating force varies locally according to the specific mural architecture. Such antagonism acts according to local demands to preserve the ventricular shape, store the elastic energy that drives the fast late systolic...

  13. Vulnerability to ventricular fibrillation

    Science.gov (United States)

    Janse, Michiel J.

    1998-03-01

    One of the factors that favors the development of ventricular fibrillation is an increase in the dispersion of refractoriness. Experiments will be described in which an increase in dispersion in the recovery of excitability was determined during brief episodes of enhanced sympathetic nerve activity, known to increase the risk of fibrillation. Whereas in the normal heart ventricular fibrillation can be induced by a strong electrical shock, a premature stimulus of moderate intensity only induces fibrillation in the presence of regional ischemia, which greatly increases the dispersion of refractoriness. One factor that is of importance for the transition of reentrant ventricular tachycardia to ventricular fibrillation during acute regional ischemia is the subendocardial Purkinje system. After selective destruction of the Purkinje network by lugol, reentrant tachycardias still develop in the ischemic region, but they do not degenerate into fibrillation. Finally, attempts were made to determine the minimal mass of thin ventricular myocardium required to sustain fibrillation induced by burst pacing. This was done by freezing of subendocardial and midmural layers. The rim of surviving epicardial muscle had to be larger than 20 g. Extracellular electrograms during fibrillation in both the intact and the "frozen" left ventricle were indistinguishable, but activation patterns were markedly different. In the intact ventricle epicardial activation was compatible with multiple wavelet reentry, in the "frozen" heart a single, or at most two wandering reentrant waves were seen.

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

    Science.gov (United States)

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

    2003-01-01

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

  15. 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.

  16. Lateral ventricular subependymomas: An analysis of the clinical features of 27 adult cases at a single institute.

    Science.gov (United States)

    Hou, Zonggang; Wu, Zhen; Zhang, Junting; Zhang, Liwei; Tian, Runfa; Liu, Baiyun; Wang, Zhongcheng

    2012-01-01

    To evaluate the unique clinical characteristics and management of lateral ventricular subependymomas (LVSs). Patients and Methods : The case records of 27 adult consecutive patients with LVS admitted between March 1996 and May 2011 were reviewed. The relevant clinical data (including patient age and sex, neuroimaging studies, surgical records and follow up) were collected through a chart review. Patient neurological status was recorded using the Karnofsky Performance Scale (KPS). The gender distribution was 14:13 and the age from 33 to 66 years (median 45 years) at the time of operation. Headache and dizziness were the most common initial symptoms (17/27). Most of these tumours were located at the foramen of Monro (12/27). Magnetic resonance imaging (MRI) (21/27) showed well circumscribed tumours with cystic changes (21/27). The lesions were hypointense on T1-weighted images (19/21), hyperintense on T2-weighted images (21/21), and contrast enhancement was no or minimal (19/21). Gross total resection was performed in 23 patients. Five patients required a ventriculo-peritoneal shunt because of postoperative hydrocephalus. The follow-up period ranged from 6 to 188 months (mean 55.5 months). No recurrence was observed during the follow up. In this study LVSs had equal gender distribution. Tumours around the foramen of Monro were the candidates for aggressive treatment; surgery was the best curative treatment; postoperative hydrocephalus should be attended to.

  17. Pre-emptive intrathecal vancomycin therapy reduces external ventricular drain infection: a single centre retrospective case-control study.

    Science.gov (United States)

    Fu, Richard Z; Anwar, Durria R; Laban, James T; Maratos, Eleni C; Minhas, Pawanjit S; Martin, Andrew J

    2017-02-01

    External ventricular drain (EVD)-related infection is a significant source of morbidity in neurosurgical patients. Recently, there has been a drive to adopt new catheters with bactericidal properties to reduce infection rates. We propose that the use of standard catheters combined with pre-emptive intrathecal vancomycin (ITV) 10 mg daily provides an effective alternative. Retrospective study of all patients with EVDs between 2010 and 2012, comparing infection rates in those who did and did not receive pre-emptive ITV. All EVDs were of the standard silicon catheter type. CSF infection was defined, as per Centre for Disease Control (CDC) guidelines, as clinical suspicion ± positive CSF gram stain/culture or leucocytosis. Infection rates were compared using Pearson's chi-squared test. 262 EVDs were included in the study, of which 111 were managed with pre-emptive ITV. The infection rate was 2.7% in the vancomycin group and 11.9% in the control group (pvancomycin-resistant infection in either group. The use of pre-emptive ITV is associated with a significantly lower EVD infection rate. This compares favourably with those reported in the literature for bactericidal catheters.

  18. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Hassin, D.; Fixler, R.; Shimoni, Y.; Rubinstein, E.; Raz, S.; Gotsman, M.S.; Hasin, Y.

    1987-01-01

    The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by 45 Ca tracer measurements after loading the myocytes with 45 Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect

  19. Separation of Beating Cardiac Myocytes from Suspensions of Heart Cells

    Science.gov (United States)

    Pretlow, Thomas G.; Glick, Melvin R.; Reddy, William J.

    1972-01-01

    Heart cells were obtained in suspension after incubation with collagenase and hyaluronidase in Saline A. Cardiac myocytes were separated by isopycnic centrifugation in 88.6 to 92.4% purity from other heart cells with different densities, and by velocity or rate-zonal sedimentation, in 92.8 to 97.4% purity from heart cells with different diameters. A previously described computer integration of the differential sedimentation equation was used to determine the centrifugal force, duration of centrifugation and gradient design, which would permit the separation of cardiac myocytes from other heart cells by velocity sedimentation. The myocytes continued to contract rhythmically after being recovered from the density gradients. Velocity sedimentation was superior to isopycnic sedimentation for the separation of cardiac myocytes from heart cell suspensions because it gave the most highly purified myocytes, resulted in recovery of the largest proportion of myocytes in purified fractions from the gradient and required lower centrifugal forces for shorter periods of time. The potential significance of the availability of pure cardiac myocytes is discsused. ImagesFig 2Fig 1 PMID:4336547

  20. [Ca2+]i Elevation and Oxidative Stress Induce KCNQ1 Protein Translocation from the Cytosol to the Cell Surface and Increase Slow Delayed Rectifier (IKs) in Cardiac Myocytes*

    Science.gov (United States)

    Wang, Yuhong; Zankov, Dimitar P.; Jiang, Min; Zhang, Mei; Henderson, Scott C.; Tseng, Gea-Ny

    2013-01-01

    Our goals are to simultaneously determine the three-dimensional distribution patterns of KCNQ1 and KCNE1 in cardiac myocytes and to study the mechanism and functional implications for variations in KCNQ1/KCNE1 colocalization in myocytes. We monitored the distribution patterns of KCNQ1, KCNE1, and markers for subcellular compartments/organelles using immunofluorescence/confocal microscopy and confirmed the findings in ventricular myocytes by directly observing fluorescently tagged KCNQ1-GFP and KCNE1-dsRed expressed in these cells. We also monitored the effects of stress on KCNQ1-GFP and endoplasmic reticulum (ER) remodeling during live cell imaging. The data showed that 1) KCNE1 maintained a stable cell surface localization, whereas KCNQ1 exhibited variations in the cytosolic compartment (striations versus vesicles) and the degree of presence on the cell surface; 2) the degree of cell surface KCNQ1/KCNE1 colocalization was positively correlated with slow delayed rectifier (IKs) current density; 3) KCNQ1 and calnexin (an ER marker) shared a cytosolic compartment; and 4) in response to stress ([Ca2+]i elevation, oxidative overload, or AT1R stimulation), KCNQ1 exited the cytosolic compartment and trafficked to the cell periphery in vesicles. This was accompanied by partial ER fragmentation. We conclude that the cellular milieu regulates KCNQ1 distribution in cardiac myocytes and that stressful conditions can increase IKs by inducing KCNQ1 movement to the cell surface. This represents a hitherto unrecognized mechanism by which IKs fulfills its function as a repolarization reserve in ventricular myocytes. PMID:24142691

  1. [Ca2+]i elevation and oxidative stress induce KCNQ1 protein translocation from the cytosol to the cell surface and increase slow delayed rectifier (IKs) in cardiac myocytes.

    Science.gov (United States)

    Wang, Yuhong; Zankov, Dimitar P; Jiang, Min; Zhang, Mei; Henderson, Scott C; Tseng, Gea-Ny

    2013-12-06

    Our goals are to simultaneously determine the three-dimensional distribution patterns of KCNQ1 and KCNE1 in cardiac myocytes and to study the mechanism and functional implications for variations in KCNQ1/KCNE1 colocalization in myocytes. We monitored the distribution patterns of KCNQ1, KCNE1, and markers for subcellular compartments/organelles using immunofluorescence/confocal microscopy and confirmed the findings in ventricular myocytes by directly observing fluorescently tagged KCNQ1-GFP and KCNE1-dsRed expressed in these cells. We also monitored the effects of stress on KCNQ1-GFP and endoplasmic reticulum (ER) remodeling during live cell imaging. The data showed that 1) KCNE1 maintained a stable cell surface localization, whereas KCNQ1 exhibited variations in the cytosolic compartment (striations versus vesicles) and the degree of presence on the cell surface; 2) the degree of cell surface KCNQ1/KCNE1 colocalization was positively correlated with slow delayed rectifier (IKs) current density; 3) KCNQ1 and calnexin (an ER marker) shared a cytosolic compartment; and 4) in response to stress ([Ca(2+)]i elevation, oxidative overload, or AT1R stimulation), KCNQ1 exited the cytosolic compartment and trafficked to the cell periphery in vesicles. This was accompanied by partial ER fragmentation. We conclude that the cellular milieu regulates KCNQ1 distribution in cardiac myocytes and that stressful conditions can increase IKs by inducing KCNQ1 movement to the cell surface. This represents a hitherto unrecognized mechanism by which IKs fulfills its function as a repolarization reserve in ventricular myocytes.

  2. 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)

  3. Relationship between external ventricular drain clamp trials and ventriculoperitoneal shunt insertion following nontraumatic subarachnoid hemorrhage: a single-center study.

    Science.gov (United States)

    Ascanio, Luis C; Gupta, Raghav; Adeeb, Nimer; Moore, Justin M; Griessenauer, Christoph J; Mayeku, Julie; Tachie-Baffour, Yaw; Thomas, Ranjit; Alturki, Abdulrahman Y; Schmalz, Philip G R; Ogilvy, Christopher S; Thomas, Ajith J

    2018-03-16

    OBJECTIVE Currently, there is no established standard regarding the ideal number of external ventricular drain (EVD) clamp trials performed before ventriculoperitoneal (VP) shunt insertion following nontraumatic subarachnoid hemorrhage (SAH). In this study, the authors aimed to evaluate this relationship. METHODS A retrospective review of all patients presenting with SAH between July 2007 and December 2016 was performed. Patients with SAH who had received an EVD within the first 24 hours of hospital admission and had undergone at least 1 clamp trial prior to EVD removal were eligible for inclusion in the study. Patient demographics, clinical presentations, SAH etiologies and grades, clamp trial data, hospital lengths of stay, and functional outcomes were recorded. RESULTS One hundred fourteen patients with nontraumatic SAH complicated by posthemorrhagic hydrocephalus were included in the study. The median patient age was 57 years (range 28-90 years), with a male/female ratio of 1:1.7. A ruptured aneurysm was the underlying etiology of SAH in 79.8% of patients. A majority of patients (69.4%) had a Hunt and Hess grade III-V on admission. The median number of clamp trials performed was 2 (range 1-6). A VP shunt was required in 40.4% of patients. In those who underwent 2 and 3 clamp trials, 60% and 38.9%, respectively, did not require subsequent VP shunt placement. CONCLUSIONS Surgical placement of a VP shunt is associated with complications. Clamp trials are routinely performed before making the decision to insert a shunt. In the present study, the authors found that a significant percentage of patients passed their second and third clamp trials without requiring subsequent shunt insertion. These data support performing multiple clamp trials prior to shunt placement.

  4. Turbulent states and their transitions in mathematical models for ventricular tissue: The effects of random interstitial fibroblasts

    Science.gov (United States)

    Nayak, Alok Ranjan; Pandit, Rahul

    2015-09-01

    We study the dynamical behaviors of two types of spiral- and scroll-wave turbulence states, respectively, in two-dimensional (2D) and three-dimensional (3D) mathematical models, of human, ventricular, myocyte cells that are attached to randomly distributed interstitial fibroblasts; these turbulence states are promoted by (a) the steep slope of the action-potential-duration-restitution (APDR) plot or (b) early afterdepolarizations (EADs). Our single-cell study shows that (1) the myocyte-fibroblast (MF) coupling Gj and (2) the number Nf of fibroblasts in an MF unit lower the steepness of the APDR slope and eliminate the EAD behaviors of myocytes; we explore the pacing dependence of such EAD suppression. In our 2D simulations, we observe that a spiral-turbulence (ST) state evolves into a state with a single, rotating spiral (RS) if either (a) Gj is large or (b) the maximum possible number of fibroblasts per myocyte Nfmax is large. We also observe that the minimum value of Gj, for the transition from the ST to the RS state, decreases as Nfmax increases. We find that, for the steep-APDR-induced ST state, once the MF coupling suppresses ST, the rotation period of a spiral in the RS state increases as (1) Gj increases, with fixed Nfmax, and (2) Nfmax increases, with fixed Gj. We obtain the boundary between ST and RS stability regions in the Nfmax-Gj plane. In particular, for low values of Nfmax, the value of Gj, at the ST-RS boundary, depends on the realization of the randomly distributed fibroblasts; this dependence decreases as Nfmax increases. Our 3D studies show a similar transition from scroll-wave turbulence to a single, rotating, scroll-wave state because of the MF coupling. We examine the experimental implications of our study and propose that the suppression (a) of the steep slope of the APDR or (b) EADs can eliminate spiral- and scroll-wave turbulence in heterogeneous cardiac tissue, which has randomly distributed fibroblasts.

  5. Distinct Effects of Abelson Kinase Mutations on Myocytes and Neurons in Dissociated Drosophila Embryonic Cultures: Mimicking of High Temperature

    Science.gov (United States)

    Liu, Lijuan; Wu, Chun-Fang

    2014-01-01

    Abelson tyrosine kinase (Abl) is known to regulate axon guidance, muscle development, and cell-cell interaction in vivo. The Drosophila primary culture system offers advantages in exploring the cellular mechanisms mediated by Abl with utilizing various experimental manipulations. Here we demonstrate that single-embryo cultures exhibit stage-dependent characteristics of cellular differentiation and developmental progression in neurons and myocytes, as well as nerve-muscle contacts. In particular, muscle development critically depends on the stage of dissociated embryos. In wild-type (WT) cultures derived from embryos before stage 12, muscle cells remained within cell clusters and were rarely detected. Interestingly, abundant myocytes were spotted in Abl mutant cultures, exhibiting enhanced myocyte movement and fusion, as well as neuron-muscle contacts even in cultures dissociated from younger, stage 10 embryos. Notably, Abl myocytes frequently displayed well-expanded lamellipodia. Conversely, Abl neurons were characterized with fewer large veil-like lamellipodia, but instead had increased numbers of filopodia and darker nodes along neurites. These distinct phenotypes were equally evident in both homo- and hetero-zygous cultures (Abl/Abl vs. Abl/+) of different alleles (Abl1 and Abl4) indicating dominant mutational effects. Strikingly, in WT cultures derived from stage 10 embryos, high temperature (HT) incubation promoted muscle migration and fusion, partially mimicking the advanced muscle development typical of Abl cultures. However, HT enhanced neuronal growth with increased numbers of enlarged lamellipodia, distinct from the characteristic Abl neuronal morphology. Intriguingly, HT incubation also promoted Abl lamellipodia expansion, with a much greater effect on nerve cells than muscle. Our results suggest that Abl is an essential regulator for myocyte and neuron development and that high-temperature incubation partially mimics the faster muscle development

  6. 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

  7. 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.

  8. 9-Phenanthrol inhibits recombinant and arterial myocyte TMEM16A channels

    Science.gov (United States)

    Burris, Sarah K; Wang, Qian; Bulley, Simon; Neeb, Zachary P; Jaggar, Jonathan H

    2015-01-01

    Background and Purpose In arterial smooth muscle cells (myocytes), intravascular pressure stimulates membrane depolarization and vasoconstriction (the myogenic response). Ion channels proposed to mediate pressure-induced depolarization include several transient receptor potential (TRP) channels, including TRPM4, and transmembrane protein 16A (TMEM16A), a Ca2+-activated Cl− channel (CaCC). 9-Phenanthrol, a putative selective TRPM4 channel inhibitor, abolishes myogenic tone in cerebral arteries, suggesting that either TRPM4 is essential for pressure-induced depolarization, upstream of activation of other ion channels or that 9-phenanthrol is non-selective. Here, we tested the hypothesis that 9-phenanthrol is also a TMEM16A channel blocker, an ion channel for which few inhibitors have been identified. Experimental Approach Patch clamp electrophysiology was used to measure rat cerebral artery myocyte and human recombinant TMEM16A (rTMEM16A) currents or currents generated by recombinant bestrophin-1, another Ca2+-activated Cl− channel, expressed in HEK293 cells. Key Results 9-Phenanthrol blocked myocyte TMEM16A currents activated by either intracellular Ca2+ or Eact, a TMEM16A channel activator. In contrast, 9-phenanthrol did not alter recombinant bestrophin-1 currents. 9-Phenanthrol reduced arterial myocyte TMEM16A currents with an IC50 of ∼12 μM. Cell-attached patch recordings indicated that 9-phenanthrol reduced single rTMEM16A channel open probability and mean open time, and increased mean closed time without affecting the amplitude. Conclusions and Implications These data identify 9-phenanthrol as a novel TMEM16A channel blocker and provide an explanation for the previous observation that 9-phenanthrol abolishes myogenic tone when both TRPM4 and TMEM16A channels contribute to this response. 9-Phenanthrol may be a promising candidate from which to develop TMEM16A channel-specific inhibitors. PMID:25573456

  9. 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

  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 {sup 99m}Tc-MIBI single-photon emission computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Lipiec, Piotr [Medical University of Lodz, 2nd Department of Cardiology, Lodz (Poland); Medical University of Lodz, 2nd Department of Cardiology, Bieganski Hospital, Lodz (Poland); Krzeminska-Pakula, Maria; Plewka, Michal; Kasprzak, Jaroslaw D. [Medical University of Lodz, 2nd Department of Cardiology, Lodz (Poland); Kusmierek, Jacek; Plachcinska, Anna; Szuminski, Remigiusz [Medical University of Lodz, Department of Nuclear Medicine, Lodz (Poland); Robak, Tadeusz; Korycka, Anna [Medical University of Lodz, Department of Hematology, Lodz (Poland)

    2009-04-15

    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. Effects of low-dose dobutamine on left ventricular function in normal subjects as assessed by gated single-photon emission tomography myocardial perfusion studies

    Energy Technology Data Exchange (ETDEWEB)

    Everaert, H.; Vanhove, C.; Franken, P.R. [Div. of Nuclear Medicine, University Hospital, Free University of Brussels (Belgium)

    1999-10-01

    Electrocardiography gated single-photon emission tomography (gated SPET) allows the assessment of regional perfusion and function simultaneously and in full spatial congruency. In this study changes in global and regional left ventricular function in response to dobutamine infusion were assessed in ten healthy volunteers using sequential gated SPET myocardial perfusion acquisitions. Four consecutive gated SPET images were recorded 60 min after injection of 925 MBq technetium-99m tetrofosmin on a three-head camera equipped with focussing collimators. Two acquisitions were made at rest (baseline 1 and 2), and the third and fourth acquisitions were started 5 min after the beginning of the infusion of 5 and 10 {mu}g kg{sup -1} min{sup -1} dobutamine, respectively. Systolic wall thickening (WT) was quantified using a method based on circumferential profile analysis. Left ventricular ejection fraction (LVEF) and volumes were calculated automatically using the Cedars-Sinai program. Nine of the ten subjects presented a definite increase in WT during dobutamine infusion. WT increased on average from 46%{+-}14% at baseline to 71%{+-}23% (range: 37%-106%; P<0.05) during 5 {mu}g kg{sup -1} min{sup -1} dobutamine infusion and to 85%{+-}25% (range: 62%-123%; P<0.05 with respect to WT at 5 {mu}g kg{sup -1} min{sup -1}) during 10 {mu}g kg{sup -1} min{sup -1} dobutamine infusion. Apical segments showed the largest WT at baseline. The average WT response to dobutamine was similar for all parts of the myocardium. It is concluded that changes in WT induced by infusion of low-dose dobutamine can be assessed by sequential gated SPET myocardial perfusion studies. The ''stress gated SPET'' protocol proposed in this study might be helpful to distinguish viable from scar tissue in patients with coronary artery disease, by demonstrating a preserved inotropic response in hypoperfused myocardium. (orig.)

  12. Left ventricular function assessed by multi-gated blood pool single photon emission computed tomography with [sup 99m]Tc

    Energy Technology Data Exchange (ETDEWEB)

    Murano, Ken-ichi; Narita, Michihiro; Kurihara, Tadashi (Sumitomo Hospital, Osaka (Japan))

    1992-01-01

    To evaluate the usefulness of gated blood pool single photon emission computed tomography with [sup 99m]Tc (gated SPECT) for assessing left ventricular (LV) function, we performed gated SPECT in 2 normal subjects and 18 patients including 13 with ischemic heart disease, 3 with hypertrophic cardiomyopathy and 2 with dilated cardiomyopathy. LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF) and regional wall motion obtained by gated SPECT were compared with the results of contrast left ventriculography (contrast LVG), echocardiography and planar multigated blood pool imaging (planar blood pool). After the patients' red blood cells were labelled with 30 mCi (1,110 MBq) [sup 99m]Tc in vivo, gated SPECT was performed in each of 32 projections through a 360 degree arc for each of the cardiac cycle divided into 16. From these images, the left ventricular vertical long-axis image, the horizontal long-axis and short-axis images were reconstructed. To calculate LVEDV, we used serial short-axis images which were composed of LV. To define LV and left atrial borders, we used amplitude images and cinematic displays of the vertical long-axis image. The level of the optimal cut for delineating the LV border was determined from the volume-cut-level-graph at each background activity, which was constructed by a phantom study. LV wall motion by gated SPECT was compared with the results of contrast LVG according to segmental analysis. LVEDV obtained by gated SPECT showed an excellent linear correlation with LVEDV calculated by echocardiography (r=0.98) and by contrast LVG (r=0.89). LVEF as determined by gated SPECT correlated well with the results obtained by the planar blood pool (r=0.94) and by contrast LVG (r=0.94). The visual interpretation of regional wall motion according to gated SPECT agreed with that determined by contrast LVG. We concluded that gated SPECT is a reliable method for assessing LV function. (author).

  13. Haemodynamic consequences of targeted single- and dual-site right ventricular pacing in adults with congenital heart disease undergoing surgical pulmonary valve replacement

    Science.gov (United States)

    Plymen, Carla M.; Finlay, Malcolm; Tsang, Victor; O'leary, Justin; Picaut, Nathalie; Cullen, Shay; Walker, Fiona; Deanfield, John E; Hsia, T.Y.; Bolger, Aidan P.; Lambiase, Pier D.

    2015-01-01

    Aims The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity—little is known regarding the potential benefits of CRT in this setting. Methods and results Sixteen adults (age = 32 ± 8 years; 6 M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m2 and RVEDV 183 ± 89 mL/min/m2 on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02). Conclusion Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term. PMID:25371427

  14. ATX-II effects on the apparent location of M cells in a computational model of a human left ventricular wedge.

    Science.gov (United States)

    Dos Santos, Rodrigo Weber; Otaviano Campos, Fernando; Neumann Ciuffo, Leandro; Nygren, Anders; Giles, Wayne; Koch, Hans

    2006-05-01

    The apparent location of the myocytes (M cells) with the longest action potential duration (APD) in a canine left ventricular (LV) wedge have been reported to shift after application of a sea anemone toxin, ATX-II. This toxin slows inactivation of I(Na) and thus prolongs APD. Thus, M cells may exhibit dynamic functional states, rather than being a static, anatomically discrete, myocyte population. In this study, we attempted to further define and understand this phenomenon using a mathematical model of the human ventricular myocyte action potential incorporated into an in silico "wedge" preparation. Our simulations demonstrate that even under conditions of a fixed population and ratio of epicardial, M, and endocardial myocytes, the apparent anatomical position (transmural location) of the myocytes with the longest APD can shift following ATX-II treatment. This arises because the ATX-II effect, modeled as a small increase in the late or persistent Na(+) current, and consequent prolongation of APD significantly changes the electrotonic interactions between ventricular myocytes in this LV wedge preparation. This LV wedge model is based on bidomain equations. It corresponds to a rectangular tissue immersed in a passive and isotropic medium that represents the superfusion bath. In this theoretical work, the three known different and discrete populations of myocytes in the human left ventricle have been included: the epicardial, M, and endocardial cells. The effects of ATX-II on I(Na) were simulated by altering the voltage-dependent steady-state inactivation of the parameters h (fast gate) and j (slow gate). As a result, in these ATX-II simulations a persistent late Na(+) current was generated in all three types of ventricular myocytes. However, the APDs were prolonged in a heterogeneous pattern. Our simulations demonstrate that after the ATX-II effects develop, alterations in transmural electrotonic interactions can produce changes in the transmural location of myocytes

  15. Automatic detection of the left ventricular myocardium long axis and center in thallium-201 single photon emission computed tomography

    International Nuclear Information System (INIS)

    Cauvin, J.C.; Boire, J.Y.; Maubliant, J.C.; Bonny, J.M.; Zanca, M.; Veyre, A.

    1992-01-01

    A new method for centering and reorienting automatically the left ventricle in thallium-201 myocardial single photon emission tomography (SPECT) is proposed. The processing involves the following steps: (a) The transverse sections of the left ventricle are segmented, (b) the three-dimensional skeleton of the left ventricle is extracted using tools of mathematical morphology, (c) the skeleton is fitted to a quadratic surface by the least-squares method, (d) the left ventricle is reoriented and centered using the long axis and the coordinates of the centre of the quadratic surface. A series of 30 consecutive exercise and redistribution 201 Tl SPECT studies were centered and reoriented by two operators twice with this method, and twice manually. There was no significant difference in the mean realignment performed by the automatic and the manual methods while centering differed moderately in some instances. In all cases and for all parameters, the reproducibility of the automatic method was 1.00, while it ranged between 0.74 and 0.98 with the manual centering and reorientation. This automatic approach provides a fast and highly reproducible method for the reconstruction of short- and long-axis sections of the left ventricle in 201 Tl SPECT. (orig.)

  16. Single-beat versus multibeat real-time 3D echocardiography for assessing left ventricular volumes and ejection fraction: a comparison study with cardiac magnetic resonance.

    Science.gov (United States)

    Macron, Laurent; Lim, Pascal; Bensaid, Alexandre; Nahum, Julien; Dussault, Caroline; Mitchell-Heggs, Laurens; Dubois-Randé, Jean-Luc; Deux, Jean-François; Gueret, Pascal

    2010-07-01

    Real-time 3-dimensional echocardiography (RT3DE) is superior to 2D echocardiography in assessing left ventricular (LV) volumes and ejection fraction (EF), but its feasibility is limited by multibeat acquisition, which requires an optimal breath-hold and a regular heart rhythm. We sought to evaluate the accuracy and feasibility of single- and 2-beat RT3DE for LV volume and EF assessment. Sixty-six consecutive patients referred for cardiac magnetic resonance (CMR) underwent RT3DE and CMR on the same day. Of the 50 patients (age, 59+/-18 years; 68%men; 42% coronary artery disease; LVEF=49+/-14%; limits, 14% to 76%) with an adequate RT3DE image quality, accuracy for LV volumes and EF measurements of single- and 2-beat modalities were compared with the conventional 4-beat acquisition and CMR. Correlations with CMR for LV end-diastolic volume (161+/-59 mL, r=0.93 to 0.94) and end-systolic volume (86+/-56 mL, r=0.93 to 0.96) were excellent regardless of the number of cardiac cycles used. However, because of the low temporal resolution (7+/-2 volumes per second), single-beat underestimated LVEF (bias, -5+/-8%) with greater bias than 2-beat (bias, 1+/-6%, P<0.001) and 4-beat (bias, 3+/-7%, P<0.001) modalities. Interestingly, 2-beat provided accuracy similar to 4-beat for end-diastolic volume (bias, -17+/-21 mL versus -15+/-23 mL), end-systolic volume (bias, -9+/-16 mL versus -12+/-17 mL), and LVEF (bias, 1+/-6% versus 3+/-7%) measurements, but fewer stitching artifacts were observed with 2- than 4-beat modalities (3% versus 30%). Compared with conventional multibeat acquisitions, 2-beat modality provides similar accuracy in LV volume and EF measurements and should be preferred due to fewer stitching artifacts. In contrast, the temporal resolution of single-beat modality appears insufficient to provide an accurate estimation of LVEF.

  17. 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.

  18. Jamb and Jamc Are Essential for Vertebrate Myocyte Fusion

    Science.gov (United States)

    Powell, Gareth T.; Wright, Gavin J.

    2011-01-01

    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. PMID:22180726

  19. The evolutionary origin of bilaterian smooth and striated myocytes

    Science.gov (United States)

    Brunet, Thibaut; Fischer, Antje HL; Steinmetz, Patrick RH; Lauri, Antonella; Bertucci, Paola; Arendt, Detlev

    2016-01-01

    The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed and nervous control. Our data suggest that both visceral smooth and somatic striated myocytes were present in the protostome-deuterostome ancestor and that smooth myocytes later co-opted the striated contractile module repeatedly – for example, in vertebrate heart evolution. During these smooth-to-striated myocyte conversions, the core regulatory complex of transcription factors conveying myocyte identity remained unchanged, reflecting a general principle in cell type evolution. DOI: http://dx.doi.org/10.7554/eLife.19607.001 PMID:27906129

  20. 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.

  1. Carvedilol stimulates nitric oxide synthesis in rat cardiac myocytes.

    Science.gov (United States)

    Kurosaki, K; Ikeda, U; Maeda, Y; Shimada, K

    2000-02-01

    The purpose of this study was to investigate the effects of the beta-adrenergic blocker carvedilol on nitric oxide (NO) synthesis in cardiac myocytes. We measured the accumulation of nitrite, a stable oxidation product of NO, and the expression of inducible NO synthase (iNOS) protein in cultured neonatal rat cardiac myocytes. Incubation of the cultures with interleukin 1 beta (IL-1 beta; 10 ng/ml) caused a marked increase in nitrite production. Although carvedilol alone showed no effect on nitrite accumulation, it significantly enhanced IL-1 beta-induced nitrite production by cardiac myocytes. The effect of carvedilol was completely abolished in the presence of aminoguanidine or actinomycin D. The nitrite production enhanced by carvedilol was accompanied by increased iNOS protein expression. Unlike carvedilol, other beta-blockers, namely propranolol, atenolol and arotinolol, did not enhance IL-1 beta-induced nitrite production. Addition of isoproterenol significantly increased nitrite production by IL-1 beta-stimulated cardiac myocytes. Atenolol suppressed this isoproterenol-induced nitrite accumulation, while carvedilol further increased the nitrite accumulation. These findings indicate that carvedilol increases NO synthesis in IL-1 beta-stimulated rat cardiac myocytes by a beta-adrenoceptor-independent mechanism. Copyright 2000 Academic Press.

  2. 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.

  3. Ventricular Arrhythmias in Hypertrophic Cardiomyopathy- Can We Ever Predict Them?

    Directory of Open Access Journals (Sweden)

    Narayanan Namboodiri

    2010-03-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is characterized by gross cardiac and myocyte hypertrophy, myocyte disarray, and interstitial fibrosis. This condition is relatively common, with a prevalence of about 1:500 in the general population. Most patients with HCM are either asymptomatic or have only minimal symptoms. In general, HCM is a relatively benign disease with an annual mortality rate of slightly less than 1% in unselected HCM populations [1,2]. However, sudden cardiac death (SCD may be the first manifestation of the disease. Approximately 60% to 70% of all patients with HCM die suddenly [3], and the fatal event is generally assumed, though not proven so far, due to ventricular arrhythmias.

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

    Energy Technology Data Exchange (ETDEWEB)

    Vourvouri, E.C.; Poldermans, D.; Sianos, G.; Sozzi, F.B.; Schinkel, A.F.L.; Sutter, J. de; Roelandt, J.R.T.C. [Dept. of Cardiology, Erasmus Medical Center Rotterdam (Netherlands); Bax, J.J. [Dept. of Cardiology, Leiden Univ. Medical Center (Netherlands); Parcharidis, G. [Dept. of Cardiology, AHEPA Univ. Hospital, Thessaloniki (Greece); Valkema, R. [Dept. of Nuclear Medicine, Erasmus Medical Center Rotterdam (Netherlands)

    2001-11-01

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Bartram, P.; Hanel, B.; Gustafsson, F.; Mortensen, J.; Hesse, B. [Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital (Denmark); Toft, J. [Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital (Denmark)]|[Copenhagen City Heart Study, Epidemiological Research Unit (Denmark); Ali, S. [Dept. of Cardiology, Copenhagen University Hospital (Denmark)

    1998-09-01

    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.) With 1 fig., 26 tabs., 22 refs.

  6. 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.)

  7. Increased sarcoplasmic reticulum calcium leak but unaltered contractility by acute CaMKII overexpression in isolated rabbit cardiac myocytes.

    Science.gov (United States)

    Kohlhaas, Michael; Zhang, Tong; Seidler, Tim; Zibrova, Darya; Dybkova, Nataliya; Steen, Astrid; Wagner, Stefan; Chen, Lu; Brown, Joan Heller; Bers, Donald M; Maier, Lars S

    2006-02-03

    The predominant cardiac Ca2+/calmodulin-dependent protein kinase (CaMK) is CaMKIIdelta. Here we acutely overexpress CaMKIIdeltaC using adenovirus-mediated gene transfer in adult rabbit ventricular myocytes. This circumvents confounding adaptive effects in CaMKIIdeltaC transgenic mice. CaMKIIdeltaC protein expression and activation state (autophosphorylation) were increased 5- to 6-fold. Basal twitch contraction amplitude and kinetics (1 Hz) were not changed in CaMKIIdeltaC versus LacZ expressing myocytes. However, the contraction-frequency relationship was more negative, frequency-dependent acceleration of relaxation was enhanced (tau(0.5Hz)/tau(3Hz)=2.14+/-0.10 versus 1.87+/-0.10), and peak Ca2+ current (ICa) was increased by 31% (-7.1+/-0.5 versus -5.4+/-0.5 pA/pF, P<0.05). Ca2+ transient amplitude was not significantly reduced (-27%, P=0.22), despite dramatically reduced sarcoplasmic reticulum (SR) Ca2+ content (41%; P<0.05). Thus fractional SR Ca2+ release was increased by 60% (P<0.05). Diastolic SR Ca2+ leak assessed by Ca2+ spark frequency (normalized to SR Ca2+ load) was increased by 88% in CaMKIIdeltaC versus LacZ myocytes (P<0.05; in an multiplicity-of-infection-dependent manner), an effect blocked by CaMKII inhibitors KN-93 and autocamtide-2-related inhibitory peptide. This enhanced SR Ca2+ leak may explain reduced SR Ca2+ content, despite measured levels of SR Ca2+-ATPase and Na+/Ca2+ exchange expression and function being unaltered. Ryanodine receptor (RyR) phosphorylation in CaMKIIdeltaC myocytes was increased at both Ser2809 and Ser2815, but FKBP12.6 coimmunoprecipitation with RyR was unaltered. This shows for the first time that acute CaMKIIdeltaC overexpression alters RyR function, leading to enhanced SR Ca2+ leak and reduced SR Ca2+ content but without reducing twitch contraction and Ca2+ transients. We conclude that this is attributable to concomitant enhancement of fractional SR Ca2+ release in CaMKIIdeltaC myocytes (ie, Ca

  8. 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.

  9. Histamine H1-receptor-mediated increase in the Ca2+ transient without a change in the Ca2+ current in electrically stimulated guinea-pig atrial myocytes

    OpenAIRE

    Yoshimoto, Kimihiro; Hattori, Yuichi; Houzen, Hideki; Kanno, Morio; Yasuda, Keishu

    1998-01-01

    The effects of histamine on the intracellular Ca2+ concentration ([Ca2+]i), action potential and membrane currents were assessed in single atrial myocytes prepared from guinea-pigs.Histamine caused a concentration-dependent increase in the [Ca2+]i transient in indo1/AM loaded myocytes when stimulated electrically at 0.5 Hz. However, the maximum increase in [Ca2+]i transient produced by histamine was less than 50% of that elicited by isoprenaline. The histamine-induced increase in [Ca2+]i tran...

  10. 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.

  11. 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.

  12. 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.

  13. The GSTM2 C-Terminal Domain Depresses Contractility and Ca2+ Transients in Neonatal Rat Ventricular Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Ruwani P Hewawasam

    Full Text Available The cardiac ryanodine receptor (RyR2 is an intracellular ion channel that regulates Ca2+ release from the sarcoplasmic reticulum (SR during excitation-contraction coupling in the heart. The glutathione transferases (GSTs are a family of phase II detoxification enzymes with additional functions including the selective inhibition of RyR2, with therapeutic implications. The C-terminal half of GSTM2 (GSTM2C is essential for RyR2 inhibition, and mutations F157A and Y160A within GSTM2C prevent the inhibitory action. Our objective in this investigation was to determine whether GSTM2C can enter cultured rat neonatal ventricular cardiomyocytes and influence contractility. We show that oregon green-tagged GSTM2C (at 1 μM is internalized into the myocytes and it reduces spontaneous contraction frequency and myocyte shortening. Field stimulation of myocytes evoked contraction in the same percentage of myocytes treated either with media alone or media plus 15 μM GSTM2C. Myocyte shortening during contraction was significantly reduced by exposure to 15 μM GSTM2C, but not 5 and 10 μM GSTM2C and was unaffected by exposure to 15 μM of the mutants Y160A or F157A. The amplitude of the Ca2+ transient in the 15 μM GSTM2C - treated myocytes was significantly decreased, the rise time was significantly longer and the decay time was significantly shorter than in control myocytes. The Ca2+ transient was not altered by exposure to Y160A or F157A. The results are consistent with GSTM2C entering the myocytes and inhibiting RyR2, in a manner that indicates a possible therapeutic potential for treatment of arrhythmia in the neonatal heart.

  14. 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

  15. 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

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

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Nyengaard, Jens Randel

    2005-01-01

    in 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...

  17. 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 Diseases incl. Cardiotharic Surgery Impact factor: 9.721, year: 2007

  18. The functional role of cardiac T-tubules in a model of rat ventricular myocytes

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Šimurda, J.; Christé, G.

    2006-01-01

    Roč. 364, č. 1842 (2006), s. 1187-1206 ISSN 1364-503X Institutional research plan: CEZ:AV0Z20760514 Keywords : accumulation-depletion of ions * transverse tubule * heart Subject RIV: BO - Biophysics Impact factor: 2.282, year: 2006

  19. 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

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

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    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.

  1. Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

    DEFF Research Database (Denmark)

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

    2008-01-01

    Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP(2)) levels and reduced intercellular coupling, we tested the hypothesis...... that agonist-induced changes in PIP(2) can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular coupling was measured by Lucifer Yellow dye transfer in cultured neonatal rat cardiomyocytes. Conduction velocity was measured...... in cardiomyocytes grown on microelectrode arrays. Intercellular coupling was reduced by angiotensin II (43.7 +/- 9.3%, N = 11) and noradrenaline (58.0 +/- 10.7%, N = 11). To test if reduced intercellular coupling after agonist stimulation was caused by PIP(2)-depletion, myocytes were stimulated by angiotensin II...

  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. 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.)

  4. Local stimulation of cultured myocyte cells by femtosecond laser-induced stress wave

    Science.gov (United States)

    Kuo, Yung-En; Wu, Cheng-Chi; Hosokawa, Yoichiroh; Maezawa, Yasuyo; Okano, Kazunori; Masuhara, Hiroshi; Kao, Fu-Jen

    2010-12-01

    When an 800 nm femtosecond laser is tightly focused into cell culture medium a stress wave is generated at the laser focal point. Since the stress wave localizes in a few tens of μm, it is possible to locally stimulate single cells in vitro. In this work, several kinds of cultured mammalian cells, HeLa, PC12, P19CL6, and C2C12, were stimulated by the stress wave and the cell growth after the stress loading with the laser irradiation was investigated. In comparison with the control conditions, cell growth after the laser irradiation was enhanced for the cells of C2C12 and P19CL6, which can differentiate into myocytes, and suppressed for PC12 and HeLa cell lines. These results suggest a possibility of cell growth enhancement due to myogenic cells response to the femtosecond laser-induced stress.

  5. 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.

  6. 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.

  7. Myomaker is required for the fusion of fast-twitch myocytes in the zebrafish embryo.

    Science.gov (United States)

    Zhang, Weibin; Roy, Sudipto

    2017-03-01

    During skeletal muscle development, myocytes aggregate and fuse to form multinucleated muscle fibers. Inhibition of myocyte fusion is thought to significantly derail the differentiation of functional muscle fibers. Despite the purported importance of fusion in myogenesis, in vivo studies of this process in vertebrates are rather limited. Myomaker, a multipass transmembrane protein, has been shown to be the first muscle-specific fusion protein essential for myocyte fusion in the mouse. We have generated loss-of-function alleles in zebrafish myomaker, and found that fusion of myocytes into syncytial fast-twitch muscles was significantly compromised. However, mutant myocytes could be recruited to fuse with wild-type myocytes in chimeric embryos, albeit rather inefficiently. Conversely, overexpression of Myomaker was sufficient to induce hyperfusion among fast-twitch myocytes, and it also induced fusion among slow-twitch myocytes that are normally fusion-incompetent. In line with this, Myomaker overexpression also triggered fusion in another myocyte fusion mutant compromised in the function of the junctional cell adhesion molecule, Jam2a. We also provide evidence that Rac, a regulator of actin cytoskeleton, requires Myomaker activity to induce fusion, and that an approximately 3kb of myomaker promoter sequence, with multiple E-box motifs, is sufficient to direct expression within the fast-twitch muscle lineage. Taken together, our findings underscore a conserved role for Myomaker in vertebrate myocyte fusion. Strikingly, and in contrast to the mouse, homozygous myomaker mutants are viable and do not exhibit discernible locomotory defects. Thus, in the zebrafish, myocyte fusion is not an absolute requirement for skeletal muscle morphogenesis and function. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Myocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish.

    Science.gov (United States)

    Saera-Vila, Alfonso; Kasprick, Daniel S; Junttila, Tyler L; Grzegorski, Steven J; Louie, Ke'ale W; Chiari, Estelle F; Kish, Phillip E; Kahana, Alon

    2015-07-01

    The purpose of this study was to characterize the injury response of extraocular muscles (EOMs) in adult zebrafish. Adult zebrafish underwent lateral rectus (LR) muscle myectomy surgery to remove 50% of the muscle, followed by molecular and cellular characterization of the tissue response to the injury. Following myectomy, the LR muscle regenerated an anatomically correct and functional muscle within 7 to 10 days post injury (DPI). Following injury, the residual muscle stump was replaced by a mesenchymal cell population that lost cell polarity and expressed mesenchymal markers. Next, a robust proliferative burst repopulated the area of the regenerating muscle. Regenerating cells expressed myod, identifying them as myoblasts. However, both immunofluorescence and electron microscopy failed to identify classic Pax7-positive satellite cells in control or injured EOMs. Instead, some proliferating nuclei were noted to express mef2c at the very earliest point in the proliferative burst, suggesting myonuclear reprogramming and dedifferentiation. Bromodeoxyuridine (BrdU) labeling of regenerating cells followed by a second myectomy without repeat labeling resulted in a twice-regenerated muscle broadly populated by BrdU-labeled nuclei with minimal apparent dilution of the BrdU signal. A double-pulse experiment using BrdU and 5-ethynyl-2'-deoxyuridine (EdU) identified double-labeled nuclei, confirming the shared progenitor lineage. Rapid regeneration occurred despite a cell cycle length of 19.1 hours, whereas 72% of the regenerating muscle nuclei entered the cell cycle by 48 hours post injury (HPI). Dextran lineage tracing revealed that residual myocytes were responsible for muscle regeneration. EOM regeneration in adult zebrafish occurs by dedifferentiation of residual myocytes involving a muscle-to-mesenchyme transition. A mechanistic understanding of myocyte reprogramming may facilitate novel approaches to the development of molecular tools for targeted therapeutic

  9. SDF-1 induces TNF-mediated apoptosis in cardiac myocytes.

    Science.gov (United States)

    Jarrah, Andrew A; Schwarskopf, Martina; Wang, Edward R; LaRocca, Thomas; Dhume, Ashwini; Zhang, Shihong; Hadri, Lahouria; Hajjar, Roger J; Schecter, Alison D; Tarzami, Sima T

    2018-01-01

    Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation. One such chemokine, Stromal cell-derived factor-1 (SDF-1) also known as CXCL12, and its receptor, CXCR4, are expressed and functional in cardiac myocytes. SDF-1 both stimulates and enhances the cellular signal which attracts potentially beneficial stem cells for tissue repair within the ischemic heart. Paradoxically however, this chemokine is known to act in concert with the inflammatory cytokines of the innate immune response which contributes to cellular injury through the recruitment of inflammatory cells during ischemia. In the present study, we have demonstrated that SDF-1 has dose dependent effects on freshly isolated cardiomyocytes. Using Tunnel and caspase 3-activation assays, we have demonstrated that the treatment of isolated adult rat cardiac myocyte with SDF-1 at higher concentrations (pathological concentrations) induced apoptosis. Furthermore, ELISA data demonstrated that the treatment of isolated adult rat cardiac myocyte with SDF-1 at higher concentrations upregulated TNF-α protein expression which directly correlated with subsequent apoptosis. There was a significant reduction in SDF-1 mediated apoptosis when TNF-α expression was neutralized which suggests that SDF-1 mediated apoptosis is TNF-α-dependent. The fact that certain stimuli are capable of driving cardiomyocytes into apoptosis indicates that these cells are susceptible to clinically relevant apoptotic triggers. Our findings suggest that the elevated SDF-1 levels seen in a variety of clinical conditions, including ischemic myocardial infarction, may either directly or indirectly contribute to cardiac cell death via a TNF-α mediated pathway. This highlights the importance of this receptor/ligand in regulating the cardiomyocyte response to stress conditions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hallaq, H.; Leaf, A. (Harvard Medical School, Boston, MA (USA)); Sellmayer, A. (Univ. Munchen, (Germany)); Smith, T.W. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-10-01

    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 {mu}M 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 {mu}M eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable {sup 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 {plus minus} 29 and 757 {plus minus} 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.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Kunal Pathak

    2016-09-01

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

  13. 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.

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

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    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.

  15. 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

  16. 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

    Energy Technology Data Exchange (ETDEWEB)

    Morel, O.; Pezard, P.; Le Jeune, J.J.; Denizot, B.; Jallet, P. [Department of Nuclear Medicine, University Hospital, Angers (France); Furber, A. [Department of Cardiology, University Hospital, Angers (France); Vielle, B. [Department of Biostatistics, University Hospital, Angers (France)

    1999-06-01

    The aim of this study was to correlate lung thallium-201 uptake on exercise with {sup 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 {sup 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 <5% likelihood of CAD were used as a reference group. In 44 CAD patients (group II), L/H ratio was compared with {sup 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<0.001) than the group II L/H ratio of 0.45{+-}0.10. An L/H ratio >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 {sup 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

  17. 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...

  18. 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

  19. 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

  20. 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.

  1. Regulation of Myocyte Enhancer Factor-2 Transcription Factors by Neurotoxins

    Science.gov (United States)

    She, Hua; Mao, Zixu

    2011-01-01

    Various isoforms of myocyte enhancer factor-2 (MEF2) constitute a group of nuclear proteins found to play important roles in increasing types of cells. In neurons, MEF2s are required to regulate neuronal development, synaptic plasticity, as well as survival. MEF2s promote the survival of several types of neurons under different conditions. In cellular models, negative regulation of MEF2s by stress and toxic signals contributes to neuronal death. In contrast, enhancing MEF2 activity not only protects cultured primary neurons from death in vitro but also attenuates the loss of dopaminergic neurons in substantia nigra pars compacta in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. In this work, the mechanisms of regulation of MEF2 function by several well-known neurotoxins and their implications in various neurodegenerative diseases are reviewed. PMID:21741404

  2. Regularity of beating of small clusters of embryonic chick ventricular heart-cells: experiment vs. stochastic single-channel population model.

    Science.gov (United States)

    Krogh-Madsen, Trine; Kold Taylor, Louise; Skriver, Anne D; Schaffer, Peter; Guevara, Michael R

    2017-09-01

    The transmembrane potential is recorded from small isopotential clusters of 2-4 embryonic chick ventricular cells spontaneously generating action potentials. We analyze the cycle-to-cycle fluctuations in the time between successive action potentials (the interbeat interval or IBI). We also convert an existing model of electrical activity in the cluster, which is formulated as a Hodgkin-Huxley-like deterministic system of nonlinear ordinary differential equations describing five individual ionic currents, into a stochastic model consisting of a population of ∼20 000 independently and randomly gating ionic channels, with the randomness being set by a real physical stochastic process (radio static). This stochastic model, implemented using the Clay-DeFelice algorithm, reproduces the fluctuations seen experimentally: e.g., the coefficient of variation (standard deviation/mean) of IBI is 4.3% in the model vs. the 3.9% average value of the 17 clusters studied. The model also replicates all but one of several other quantitative measures of the experimental results, including the power spectrum and correlation integral of the voltage, as well as the histogram, Poincaré plot, serial correlation coefficients, power spectrum, detrended fluctuation analysis, approximate entropy, and sample entropy of IBI. The channel noise from one particular ionic current (I Ks ), which has channel kinetics that are relatively slow compared to that of the other currents, makes the major contribution to the fluctuations in IBI. Reproduction of the experimental coefficient of variation of IBI by adding a Gaussian white noise-current into the deterministic model necessitates using an unrealistically high noise-current amplitude. Indeed, a major implication of the modelling results is that, given the wide range of time-scales over which the various species of channels open and close, only a cell-specific stochastic model that is formulated taking into consideration the widely different

  3. 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.

  4. Vector-averaged gravity alters myocyte and neuron properties in cell culture

    Science.gov (United States)

    Gruener, Raphael; Hoeger, Glenn

    1991-01-01

    The effect of changes in the gravitational field of developing neurons and myocytes on the development of these cells was investigated using observations of rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat, in which rotation produces, from the cells' perspective, a 'vector-free' gravity environment by continous averaging of the vector, thus simulating the microgravity of space. It was found that, at rotation rates between 1 and 50 rpm, cellular and nuclear areas of myocytes become significantly enlarged and the number of presumptive nucleoli increase; in neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after the cessation of rotation.

  5. Right ventricular dysfunction affects survival after surgical left ventricular restoration.

    Science.gov (United States)

    Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

    2017-04-01

    Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left

  6. 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.

  7. Premature Ventricular Contractions (PVCs)

    Science.gov (United States)

    ... Premature ventricular contractions (PVCs) Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  8. 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.

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

    NARCIS (Netherlands)

    Chang Liao, Mei-Ling; de Boer, Teun P|info:eu-repo/dai/nl/30481878X; Mutoh, Hiroki; Raad, Nour; Richter, Claudia; Wagner, Eva; Downie, Bryan R; Unsöld, Bernhard; Arooj, Iqra; Streckfuss-Bömeke, Katrin; Döker, Stephan; Luther, Stefan; Guan, Kaomei; Wagner, Stefan; Lehnart, Stephan E; Maier, Lars S; Stühmer, Walter; Wettwer, Erich; van Veen, Toon|info:eu-repo/dai/nl/229701310; Morlock, Michael M; Knöpfel, Thomas; Zimmermann, Wolfram-Hubertus

    2015-01-01

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

  10. Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus

    Science.gov (United States)

    Buchholz, Bettina M.; Shapiro, Richard A.; Vodovotz, Yoram; Billiar, Timothy R.; Sodhi, Chhinder P.; Hackam, David J.

    2015-01-01

    Myocytes are nonhemopoietic in origin and functionally essential in generating gastrointestinal motility. In endotoxemia, a rapid-onset nonhemopoietic mechanism potently triggers early ileus in a Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88)-dependent manner. Moreover, synergistically with hemopoietic cells, nonhemopoietic cells escalate late ileus via an IL-6 receptor-dependent inflammation-driven pathway. We therefore specifically investigated the role of myocytes in TLR4-triggered inflammation and ileus. TLR4+/+, TLR4−/−, bmTLR4+/+/TLR4−/− chimera, SM22-Cre−/−TLR4flox/flox, and selective myocyte TLR4-deficient (SM22-Cre+/−TLR4flox/flox) mice were injected intraperitoneally with purified lipopolysaccharide. SM22-driven Cre recombinase activity was selectively detected in cardiac, gastrointestinal, skeletal, and vascular myocytes, of small-sized vessels in a two-color fluorescent Cre reporter mouse. In contrast to nonhemopoietic TLR4 deficiency, deletion of myocyte TLR4 signaling prevented neither endotoxin-induced suppression of spontaneous jejunal contractility in vitro nor early ileus in vivo at 6 h. Circulating plasma colony-stimulating factor 3 was greatly elevated during endotoxemia, independent of myocyte TLR4 signaling or time. TLR4 activation of myocytes contributed significantly to an early enteric IL-6 mRNA induction and systemic IL-6 release, as well as to a late increase in circulating chemokine (C-X-C motif) ligand 1 (CXCL1) and IL-17. Consequently, inhibition of myocyte TLR4 signaling allowed functional recovery of motility by preventing inflammation-driven late ileus at 24 h. Direct TLR4 activation of myocytes is not responsible for nonhemopoietic-mediated early ileus. However, myocytes are proinflammatory cells that potently drive enteric and systemic inflammation, subsequently fueling late mediator-triggered ileus. Specifically, the myocyte TLR4-dependent inflammatory signature of elevated

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

    Science.gov (United States)

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

    2015-10-15

    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 (Ito) and the molecular correlate, the Kv4.3 channel has not being studied. Here, we describe the mefloquine-induced inhibition of the rat ventricular Ito and of CHO cells co-transfected with human Kv4.3 and its accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat Ito and hKv4.3+KChIP2C currents in a concentration-dependent manner with a limited voltage dependence and similar potencies (IC50=8.9μM and 10.5μM for cardiac myocytes and Kv4.3 channels, respectively). In addition, mefloquine did not affect the activation of either current but significantly modified the hKv4.3 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Berlin heart ventricular assist device as a long-term bridge to transplantation in a Fontan patient with failing single ventricle.

    Science.gov (United States)

    Halaweish, I; Ohye, R G; Si, M S

    2015-12-01

    The use of VADs as a BTT in children with heart failure has increased due to enhanced device design and reliability, leading to improved survival, functional capacity, and quality of life. However, the use of VADs in patients with Fontan physiology as a BTT is rare with few case reports. Here, we describe a case of implantation of the Berlin VAD as a BTT for 179 days, one of the longest reported periods of mechanical support, in a child with failing single ventricle. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    Science.gov (United States)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists

  14. 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.

  15. Decreased inward rectifier potassium current IK1in 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.

  16. 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)

  17. Arritmias ventriculares. Aspectos generales

    OpenAIRE

    Fernando Hornero; Jesús Almendral

    2010-01-01

    La cirugía de la arritmia ventricular ha desaparecido casi por completo en las últimas décadas con la aparición del desfibrilador automático implantable. En la actualidad, conocemos mejor las limitaciones del desfibrilador y los progresos en la ablación por catéter. Avances tecnológicos en el mapeo ventricular y en los sistemas de ablación con catéter están cambiando el planteamiento terapéutico a favor de soluciones más eficaces. A su vez, la actual cirugía de la arritmia ventricular tiene b...

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

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmad

    2011-01-01

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

  19. Dose-dependent apoptotic and necrotic myocyte death induced by the β2-adrenergic receptor agonist, clenbuterol

    Science.gov (United States)

    Burniston, Jatin G; Chester, Neil; Clark, William A; Tan, Lip-Bun; Goldspink, David F

    2007-01-01

    We have investigated the dose- and time-dependency of myocyte apoptosis and necrosis induced by the β2-adrenergic receptor agonist, clenbuterol, with the aim of determining whether myocyte apoptosis and necrosis are two separate processes or a continuum of events. Male Wistar rats were administered subcutaneous injections of clenbuterol, and immunohistochemistry was used to detect myocyte specific apoptosis and necrosis. Myocyte apoptosis peaked 4 h after, and necrosis 12 h after, clenbuterol administration. In the soleus, peak apoptosis (5.8 ± 2.0 %; Pclenbuterol kg-1. Twelve hours after clenbuterol administration, 73 % of damaged myocytes labelled as necrotic, 27 % as apoptotic and necrotic and none labelled as purely apoptotic. Bi-daily administrations of 10 μg of clenbuterol kg-1 induced cumulative myocyte death over 8 days. These data show that the phenotype of myocyte death is dependent on the magnitude of the insult and the time at which it is investigated. Only very low doses induced only apoptosis, in most cases apoptotic myocytes lysed and became necrotic and the magnitude of necrosis was greater than that of apoptosis. Thus, it is important to investigate both apoptotic and necrotic myocyte death, this being contrary to the current trend of only investigating apoptotic cell death. PMID:16007677

  20. Persistence of pro-arrhythmic spatio-temporal calcium patterns in atrial myocytes: a computational study of ping waves

    Directory of Open Access Journals (Sweden)

    Rüdiger eThul

    2012-07-01

    Full Text Available Clusters of ryanodine receptors within atrial myocytes are confined to spatially separated layers. In many species, these layers are not juxtaposed by invaginations of the plasma membrane, so that calcium-induced-calcium signals rely on centripetal propagation rather than voltage-synchronised channel openings to invade the interior of the cell and trigger contraction. The combination of this specific cellular geometry and dynamics of calcium release can lead to novel autonomous spatio-temporal waves, and in particular ping waves. These are waves of calcium release activity that spread as counter-rotating sectors of elevated calcium within a single layer of ryanodine receptors, and can seed further longitudinal calcium waves. Here we show, using a computational model, that these calcium waves can dominate the response of a cell to electrical pacing and hence are pro-arrhythmic. This highlights the importance of modelling internal cellular structures when investigating mechanisms of cardiac dysfunction such as atrial arrhythmia.

  1. Is there a referral bias against catheterization of patients with reduced left ventricular ejection fraction? Influence of ejection fraction and inducible ischemia on post-single-photon emission computed tomography management of patients without a history of coronary artery disease.

    Science.gov (United States)

    Hachamovitch, Rory; Hayes, Sean W; Friedman, John D; Cohen, Ishac; Kang, Xingping; Germano, Guido; Berman, Daniel S

    2003-10-01

    The objective of this work was to define the relationship between left ventricular perfusion/ function measures and referral rates to catheterization and revascularization early after stress gated myocardial perfusion single-photon emission computed tomography (MPS). Although revascularization yields the greatest survival benefit in patients with low ejection fraction (EF) and extensive coronary artery disease, referral patterns to catheterization and revascularization after noninvasive testing are not well defined. We identified 3,369 patients without previous myocardial infarction or revascularization who underwent exercise or adenosine stress MPS and who were followed-up (97% complete) for occurrence of early (stress MPS, 445 catheterizations (13.2%) and 254 revascularizations (7.5%) occurred, including 140 coronary artery bypass graft surgeries (4.1%) and 114 percutaneous coronary interventions (3.4%). Both post-stress gated EF and percent of the myocardium ischemic by stress MPS were independent predictors of revascularization. Logistic regression revealed that the likelihood of catheterization increased with both increasing ischemia and decreasing EF (c-index = 0.94, chi-square = 590). Predicted referral rates to catheterization increased with decreasing EF except in patients with severe ischemia (>15% of myocardium), where rates decreased with decreasing EF. Similar modeling of revascularization (c-index = 0.94, chi-square = 329) revealed that the likelihood of revascularization increased with increasing ischemia but, in general, decreased with decreasing EF. Although post-SPECT referral to both catheterization and revascularization is driven by ischemia, EF has the opposite effect on these two outcomes. Further studies evaluating the appropriateness of these referral patterns are warranted.

  2. 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

  3. 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.

  4. Relationship between right and left ventricular function in candidates for implantable cardioverter defibrillator with low left ventricular ejection fraction.

    Science.gov (United States)

    Jimenez-Juan, Laura; Karur, Gauri R; Connelly, Kim A; Deva, Djeven; Yan, Raymond T; Wald, Rachel M; Singh, Sheldon; Leung, General; Oikonomou, Anastasia; Dorian, Paul; Angaran, Paul; Yan, Andrew T

    2017-04-01

    Indications for the primary prevention of sudden death using an implantable cardioverter defibrillator (ICD) are based predominantly on left ventricular ejection fraction (LVEF). However, right ventricular ejection fraction (RVEF) is also a known prognostic factor in a variety of structural heart diseases that predispose to sudden cardiac death. We sought to investigate the relationship between right and left ventricular parameters (function and volume) measured by cardiovascular magnetic resonance (CMR) among a broad spectrum of patients considered for an ICD. In this retrospective, single tertiary-care center study, consecutive patients considered for ICD implantation who were referred for LVEF assessment by CMR were included. Right and left ventricular function and volumes were measured. In total, 102 patients (age 62±14 years; 23% women) had a mean LVEF of 28±11% and RVEF of 44±12%. The left ventricular and right ventricular end diastolic volume index was 140±42 mL/m 2 and 81±27 mL/m 2 , respectively. Eighty-six (84%) patients had a LVEF right ventricular systolic dysfunction. Although there was a significant and moderate correlation between LVEF and RVEF ( r =0.40, p right ventricular systolic dysfunction (Kappa=0.041). Among patients being considered for an ICD, there is a positive but moderate correlation between LVEF and RVEF. A considerable proportion of patients who qualify for an ICD based on low LVEF have preserved RVEF, and vice versa.

  5. Unresponsive ventricular tachycardia associated with aluminum phosphide poisoning.

    Science.gov (United States)

    Jadhav, Amar P; Nusair, Maein B; Ingole, Apekshe; Alpert, Martin A

    2012-05-01

    Inhalation or ingestion of aluminum phosphide (AP) generates phosphine gas on exposure to moisture, which, in turn, produces widespread organ toxicity primarily involving the lungs, heart, liver, and kidneys. Cardiac manifestations of AP poisoning include toxic myocarditis, refractory heart failure, bradyarrhythmias, and tachyarrhythmias including ventricular tachycardia (VT). A 19-year-old depressed male farm worker ingested ten 500-mg tablets of Celphos in a suicide attempt. Each Celphos tablet contains 56% AP. Over the course of 10 hours, the patient developed heart failure and respiratory failure associated with a rise in serum troponin level to 12.7 ng/mL. Serum electrolytes (including magnesium) and serum creatinine levels were normal throughout. His course was further complicated by acidemia and hypotension. These hemodynamic and metabolic abnormalities were initially corrected by assisted ventilation and continuous veno-venous hemofiltration. However, he developed hemodynamically stable sustained monomorphic VT, which proved unresponsive to treatment with intravenous magnesium sulfate and intravenous amiodarone therapy. After a decline in blood pressure, 6 attempts at electrocardioversion failed to restore sinus rhythm, and he died. Postmortem histologic examination of myocardium showed contraction band necrosis, early coagulation necrosis, edema, hemorrhage, and pyknosis of cardiac myocyte nuclei. Ventricular tachycardia associated with AP poisoning has been successfully treated with magnesium sulfate, amiodarone, and electrocardioversion. This case report documents failure of all 3 of these therapeutic modalities.

  6. 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.

  7. Noninvasive imaging of myocyte apoptosis following application of a stem cell-engineered delivery platform to acutely infarcted myocardium.

    Science.gov (United States)

    Godier-Furnémont, Amandine F G; Tekabe, Yared; Kollaros, Maria; Eng, George; Morales, Alfredo; Vunjak-Novakovic, Gordana; Johnson, Lynne L

    2013-06-01

    The cardioprotective effects of mesenchymal stem cells (MSCs) include reducing myocyte apoptosis, and this effect can be enhanced by preconditioning and encapsulation in a fibrin scaffold. This study aimed to test the hypothesis that apoptosis imaging can detect the cardioprotective effects of a conditioned MSC patch grafted in a rat model of acute myocardial infarction. Cell culture experiments simulating engraftment of fibrin patches onto beating rat ventricular myocytes exposed to hypoxia showed an effect of conditioned cells to reduce apoptosis. Twenty-three nude rats underwent successful left anterior descending coronary artery occlusion and were divided into 3 groups: transforming growth factor β1-conditioned human MSC-laden patches (CP), infarct alone without patch (no patch [NP]), and patch alone (patch only [PO]). Twenty-four hours after myocardial infarction, all rats were injected with (99m)Tc-hydrazinonicotinamide ((99m)Tc-HYNIC) annexin V and (201)Tl and underwent dual-isotope SPECT/CT imaging. Six rats were sacrificed for histology and counting. The remaining rats (n = 17; 1 rat was eliminated) were injected and imaged on day 7; of those, 3 rats were sacrificed for histology and counting, and the remaining 13 rats survived to day 21, when they were sacrificed for histology. Numbers of rats imaged on day 7 in the 3 groups were 7 in the CP group, 5 in the NP, and 5 in the PO. Perfused myocardium, infarct size, and (99m)Tc-HYNIC annexin V uptake were quantified from the scans from days 1 and 7. (99m)Tc-HYNIC annexin V uptake was correlated with quantitative caspase staining, and infarct size as percentage fibrosis was quantified at day 21. (99m)Tc-HYNIC annexin V uptake as percentage injected dose (×10(-4)) decreased between days 1 and 7 by 1.04 ± 0.28 in the CP group, 0.44 ± 0.17 in the NP group, and 0.34 ± 0.27 in the PO group (P = 0.003 for NP vs. CP, P = 0.005 for PO vs. CP, and P = 0.5 for NP vs. CP). The changes in defect size as percentage

  8. 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

  9. 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.

  10. A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse–axial tubular system

    Czech Academy of Sciences Publication Activity Database

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

    2008-01-01

    Roč. 96, 1-3 (2008), s. 258-280 ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : guinea pig * cardiac cell * transverse-axial tubular system * quantitative model Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

  11. 26S Proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-07

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

  12. 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....

  13. β-Adrenergic Receptor-Stimulated Cardiac Myocyte Apoptosis: Role of β1 Integrins

    Directory of Open Access Journals (Sweden)

    Parthiv Amin

    2011-01-01

    Full Text Available Increased sympathetic nerve activity to the myocardium is a central feature in patients with heart failure. Accumulation of catecholamines plays an important role in the pathogenesis of heart disease. Acting via β-adrenergic receptors (β-AR, catecholamines (norepinephrine and isoproterenol increase cardiac myocyte apoptosis in vitro and in vivo. Specifically, β1-AR and β2-AR coupled to Gαs exert a proapoptotic action, while β2-AR coupled to Gi exerts an antiapoptotic action. β1 integrin signaling protects cardiac myocytes against β-AR-stimulated apoptosis in vitro and in vivo. Interaction of matrix metalloproteinase-2 (MMP-2 with β1 integrins interferes with the survival signals initiated by β1 integrins. This paper will discuss background information on β-AR and integrin signaling and summarize the role of β1 integrins in β-AR-stimulated cardiac myocyte apoptosis.

  14. 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.

  15. A Computational Study of the Factors Influencing the PVC-Triggering Ability of a Cluster of Early Afterdepolarization-Capable Myocytes

    Science.gov (United States)

    Zimik, Soling; Nayak, Alok Ranjan; Pandit, Rahul

    2015-01-01

    Premature ventricular complexes (PVCs), which are abnormal impulse propagations in cardiac tissue, can develop because of various reasons including early afterdepolarizations (EADs). We show how a cluster of EAD-generating cells (EAD clump) can lead to PVCs in a model of cardiac tissue, and also investigate the factors that assist such clumps in triggering PVCs. In particular, we study, through computer simulations, the effects of the following factors on the PVC-triggering ability of an EAD clump: (1) the repolarization reserve (RR) of the EAD cells; (2) the size of the EAD clump; (3) the coupling strength between the EAD cells in the clump; and (4) the presence of fibroblasts in the EAD clump. We find that, although a low value of RR is necessary to generate EADs and hence PVCs, a very low value of RR leads to low-amplitude EAD oscillations that decay with time and do not lead to PVCs. We demonstrate that a certain threshold size of the EAD clump, or a reduction in the coupling strength between the EAD cells, in the clump, is required to trigger PVCs. We illustrate how randomly distributed inexcitable obstacles, which we use to model collagen deposits, affect PVC-triggering by an EAD clump. We show that the gap-junctional coupling of fibroblasts with myocytes can either assist or impede the PVC-triggering ability of an EAD clump, depending on the resting membrane potential of the fibroblasts and the coupling strength between the myocyte and fibroblasts. We also find that the triggering of PVCs by an EAD clump depends sensitively on factors like the pacing cycle length and the distribution pattern of the fibroblasts. PMID:26675670

  16. Arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Soni, Roopali; Oade, Yvette

    2011-08-24

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disease of the heart muscle that causes ventricular tachyarrhythmias and sudden death in young people and athletes. It results in fibrofatty replacement of the right ventricle, and the subepicardial region of the left ventricle. It is the most common cause of sudden cardiac death in young people after hypertrophic heart disease. Diagnosis can be difficult and at present there is no cure for ARVC. Prevention of sudden death is the most important management strategy. Paediatricians need to be aware of the possibility of ARVC in adolescents and young adults presenting with palpitations, fatigue, syncope or cardiac arrest. The authors present two cases of apparently healthy teenage boys who died suddenly and unexpectedly. Postmortem examination of the myocardium was strongly suggestive of ARVC in both cases.

  17. 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.

  18. Body-surface QRST integral mapping. Arrhythmogenic righ ventricular dysplasia versus idiopathic right ventricular tachycardia

    NARCIS (Netherlands)

    Peeters, H. A.; SippensGroenewegen, A.; Schoonderwoerd, B. A.; Wever, E. F.; Grimbergen, C. A.; Hauer, R. N.; Rohles de Medina, E. O.

    1997-01-01

    Ventricular tachycardia originating in the right ventricle may arise in the presence or absence of structural heart disease. The two main causes of right ventricular tachycardia are arrhythmogenic right ventricular dysplasia (ARVD) and idiopathic right ventricular tachycardia (IRVT) originating from

  19. 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.

  20. The transcription factor myocyte enhancer factor-2 (MEF2) in cardiac hypertrophy and heart failure

    NARCIS (Netherlands)

    Oort, R.J. van

    2007-01-01

    The heart responds to stress signals by hypertrophic growth, which is the first step towards heart failure (HF). The genetic pattern underlying HF remains largely elusive. Although the transcription factor Myocyte Enhancer Factor-2 (MEF2) is known to be a common endpoint for several hypertrophic

  1. Effects of phytoestrogens on protein turnover in rainbow trout primary myocytes

    Science.gov (United States)

    Soybean-derived ingredients used in aquaculture feeds may contain phytoestrogens, but it is unknown if these compounds can mimic the catabolic effects of estradiol in fish muscle. Six day-old rainbow trout primary myocytes were exposed to increasing concentrations (10 nM – 100 µM) of either geniste...

  2. Myocyte-Fibroblast Communication in Cardiac Fibrosis and Arrhythmias: Mechanisms and Model Systems

    Science.gov (United States)

    Pellman, Jason; Zhang, Jing; Sheikh, Farah

    2016-01-01

    Development of cardiac fibrosis and arrhythmias is controlled by the activity of and communication between cardiomyocytes and fibroblasts in the heart. Myocyte-fibroblast interactions occur via both direct and indirect means including paracrine mediators, extracellular matrix interactions, electrical modulators, mechanical junctions, and membrane nanotubes. In the diseased heart, cardiomyocyte and fibroblast ratios and activity, and thus myocyte-fibroblast interactions, change and are thought to contribute to the course of disease including development of fibrosis and arrhythmogenic activity. Fibroblasts have a developing role in modulating cardiomyocyte electrical and hypertrophic activity, however gaps in knowledge regarding these interactions still exist. Research in this field has necessitated the development of unique approaches to isolate and control myocyte-fibroblast interactions. Numerous methods for 2D and 3D co-culture systems have been developed, while a growing part of this field is in the use of better tools for in vivo systems including cardiomyocyte and fibroblast specific Cre mouse lines for cell type specific genetic ablation. This review will focus on (i) mechanisms of myocyte-fibroblast communication and their effects on disease features such as cardiac fibrosis and arrhythmias as well as (ii) methods being used and currently developed in this field. PMID:26996756

  3. 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...

  4. 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

  5. Endogenous nitric oxide formation in cardiac myocytes does not control respiration during β-adrenergic stimulation.

    Science.gov (United States)

    Kohlhaas, Michael; Nickel, Alexander G; Bergem, Stefanie; Casadei, Barbara; Laufs, Ulrich; Maack, Christoph

    2017-06-15

    In the heart, endothelial nitric oxide (NO) controls oxygen consumption in the working heart through paracrine mechanisms. While cardiac myocytes contain several isoforms of NO synthases, it is unclear whether these can control respiration in an intracrine fashion. A long-standing controversy is whether a NOS exists within mitochondria. By combining fluorescence technologies with electrical field stimulation or the patch-clamp technique in beating cardiac myocytes, we identified a neuronal NO synthase (nNOS) as the most relevant source of intracellular NO during β-adrenergic stimulation, while no evidence for a mitochondria-located NOS was obtained. The amounts of NO produced by non-mitochondrial nNOS were insufficient to regulate respiration during β-adrenergic stimulation, arguing against intracrine control of respiration by NO within cardiac myocytes. Endothelial nitric oxide (NO) controls cardiac oxygen (O 2 ) consumption in a paracrine way by slowing respiration at the mitochondrial electron transport chain. While NO synthases (NOSs) are also expressed in cardiac myocytes, it is unclear whether they control respiration in an intracrine way. Furthermore, the existence of a mitochondrial NOS is controversial. Here, by combining fluorescence imaging with electrical field stimulation, the patch-clamp method and knock-out technology, we determined the sources and consequences of intracellular NO formation during workload transitions in isolated murine and guinea pig cardiac myocytes and mitochondria. Using 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) as a fluorescent NO-sensor that locates to the cytosol and mitochondria, we observed that NO increased by ∼12% within 3 min of β-adrenergic stimulation in beating cardiac myocytes. This NO stems from neuronal NOS (nNOS), but not endothelial (eNOS). After patch clamp-mediated dialysis of cytosolic DAF, the remaining NO signals (mostly mitochondrial) were blocked by nNOS deletion, but not by

  6. Ventricular assist device in univentricular heart physiology.

    Science.gov (United States)

    Brancaccio, Gianluca; Gandolfo, Fabrizio; Carotti, Adriano; Amodeo, Antonio

    2013-04-01

    The use of mechanical cardiac assistance is well established as a bridge to orthotopic heart transplantation (OHT) or to recovery for patients with congestive heart failure, however, the experience in single ventricle (SV) physiology is still limited. We report two cases of mechanical assistance in patients with SV physiology: a 2-year old male with hypoplastic left heart syndrome who underwent Norwood Stage I and II followed by HF and a 4-year old female with a univentricular heart who developed a severe right ventricular dysfunction 2 years after a cavopulmonary shunt. Mechanical support utilizing ventricular assist devices (VADs) is considered a valid tool to bridge patients with congestive heart failure to either OHT or to recovery. Increasing experience and improved outcomes utilizing this technology in children with biventricular hearts have led to considering employing these devices in failing SV treatment. We present 2 cases of terminally ill children with SV who were assisted with a VAD.

  7. TNF-α- mediated-p38-dependent signaling pathway contributes to myocyte apoptosis in rats subjected to surgical trauma.

    Science.gov (United States)

    Wu, Huaxing; Wang, Guonian; Li, Shuai; Zhang, Mingyue; Li, Hulun; Wang, Kun

    2015-01-01

    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. 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. 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. 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. © 2015 S. Karger AG, Basel.

  8. 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.

  9. 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.

  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. Left ventricular hypertrophy in athletes.

    Science.gov (United States)

    Douglas, P S; O'Toole, M L; Katz, S E; Ginsburg, G S; Hiller, W D; Laird, R H

    1997-11-15

    Left ventricular wall thickness >1.3 cm, septal-to-posterior wall ratios > 1.5, diastolic left ventricular size >6.0 cm, and eccentric or concentric remodeling are rare in athletes. Values outside of these cutoffs in an athlete of any age probably represent a pathologic state.

  12. Arrhythmogenic right ventricular dysplasia: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Wall, E.E. van der; Bootsma, M.M.; Schalij, M.J. [Dept. of Cardiology, Leiden Univ. Medical Center, Leiden (Netherlands); Kayser, H.W.M.; Roos, A. de [Dept. of Radiology, Leiden Univ. Medical Center, Leiden (Netherlands)

    2000-06-01

    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.) [German] Die arrhythmogene rechtsventrikulaere Dysplasie (ARVD), eine Herzmuskelerkrankung unklarer Aetiologie, ist pathologisch durch fettige Degeneration des rechtsventrikulaeren Myokards gekennzeichnet. Die klinischen Symptome

  13. [Application of recording SK2 current in human atrial myocytes by perforated patch clamp techniques with the mix of beta-escin and amphotericin B].

    Science.gov (United States)

    Wang, Hua; Li, Tao; Lei, Ming; Li, Miao-ling; Ding, Yin-yuan; Yang, Yan; Zeng, Xiao-rong

    2012-05-01

    To establish a perforated patch-clamp technology with amphotericin B and beta-escin and to research the regulation of small conductance calcium-activated potassium channel SK2 currents by calcium ions. Single human atrial myocytes were enzymatically isolated from the right atrial appendage. Amphotericin B and / or beta-escin were used by perforated electrode liquid. The regulation of SK2 current by calcium ions in human atrial myocytes was performed with the perforated patch-clamp technique. The intracellular calcium changes were measured by the intracellular calcium test system. Mixed perforated electrode liquid compared with 150 microg/ml amphotericin B or 6.88 microg/ml beta-escin alone, it was easy to seal cells and activate SK2 current by the former method. Moreover, the ration of F340/380 was consistent with the change of intracellular free calcium ion concentration increase after the formation of perforation. The ration of F340/380 was measured by intracellular calcium test system. The appropriate concentration of amphotericin B mixed with beta-escin can form a stable whole-cell patch recording technology that is appropriate for the research of SK2 current regulation by intracellular calcium.

  14. 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.

  15. 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

  16. 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

  17. S100A1 in human heart failure: lack of recovery following left ventricular assist device support.

    Science.gov (United States)

    Bennett, Mosi K; Sweet, Wendy E; Baicker-McKee, Sara; Looney, Elizabeth; Karohl, Kristen; Mountis, Maria; Tang, W H Wilson; Starling, Randall C; Moravec, Christine S

    2014-07-01

    We hypothesized that S100A1 is regulated during human hypertrophy and heart failure and that it may be implicated in remodeling after left ventricular assist device. S100A1 is decreased in animal and human heart failure, and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling. We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, phospholamban, and ryanodine receptor proteins, as well as β-adrenergic receptor density in nonfailing, hypertrophied (left ventricular hypertrophy), failing, and failing left ventricular assist device-supported hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, sarcoplasmic endoplasmic reticulum Ca(2+)ATPase and phospholamban were normal in left ventricular hypertrophy, but decreased in failing hearts, while ryanodine receptor was unchanged in either group. Baseline muscle contraction was not altered in left ventricular hypertrophy or failing hearts. β-Adrenergic receptor and inotropic response were decreased in failing hearts. In failing left ventricular assist device-supported hearts, S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase showed no recovery, while phospholamban, β-adrenergic receptor, and the inotropic response fully recovered. S100A1 and sarcoplasmic endoplasmic reticulum Ca(2+)ATPase, both key Ca(2+)-regulatory proteins, are decreased in human heart failure, and these changes are not reversed after left ventricular assist device. The clinical significance of these findings for cardiac recovery remains to be addressed. © 2014 American Heart Association, Inc.

  18. Corticosteroids and redox potential modulate spontaneous contractions in isolated rat ventricular cardiomyocytes.

    Science.gov (United States)

    Rossier, Michel F; Lenglet, Sébastien; Vetterli, Laurène; Python, Magaly; Maturana, Andrés

    2008-10-01

    The mineralocorticoid receptor has been implicated in the development of several cardiac pathologies and could participate in the high incidence of lethal ventricular arrhythmias associated with hyperaldosteronism. We have observed previously that aldosterone markedly increases in vitro the rate of spontaneous contractions of isolated neonate rat ventricular myocytes, a putative proarrhythmogenic condition if occurring in vivo. In the present study, we investigated the effect of glucocorticoids, the involvement of the glucocorticoid receptor, and the modulation of their action by redox agents. Aldosterone and glucocorticoids exerted in vitro a similar, concentration-dependent chronotropic action on cardiomyocytes, which was mediated by both the mineralocorticoid and glucocorticoid receptors. However, the relative contribution of each receptor was different for each agonist, at each concentration. Angiotensin II induced a similar response that was entirely dependent on the activity of the glucocorticoid receptor. Corticosteroid action was modulated by the redox state of the cells, with oxidation increasing the response while reducing conditions partially preventing it. When only the mineralocorticoid receptor was functionally present in the cells, oxidation was necessary to reveal glucocorticoid action, but no obvious competition with mineralocorticoids was observed when both agonists where simultaneously present. In conclusion, corticosteroids exert a strong chronotropic action in ventricular cardiomyocytes, mediated by both the mineralocorticoid and glucocorticoid receptors and modulated by the redox state of the cell. This phenomenon is believed to be because of cell electric remodeling and could contribute in vivo to the deleterious consequence of inappropriate receptor activation, leading to increased susceptibility of patients to arrhythmias.

  19. Molecular changes after left ventricular assist device support for heart failure.

    Science.gov (United States)

    Birks, Emma J

    2013-08-30

    Heart failure is associated with remodeling that consists of adverse cellular, structural, and functional changes in the myocardium. Until recently, this was thought to be unidirectional, progressive, and irreversible. However, irreversibility has been shown to be incorrect because complete or partial reversal can occur that can be marked after myocardial unloading with a left ventricular assist device (LVAD). Patients with chronic advanced heart failure can show near-normalization of nearly all structural abnormalities of the myocardium or reverse remodeling after LVAD support. However, reverse remodeling does not always equate with clinical recovery. The molecular changes occurring after LVAD support are reviewed, both those demonstrated with LVAD unloading alone in patients bridged to transplantation and those occurring in the myocardium of patients who have recovered enough myocardial function to have the device removed. Reverse remodeling may be attributable to a reversal of the pathological mechanisms that occur in remodeling or the generation of new pathways. A reduction in cell size occurs after LVAD unloading, which does not necessarily correlate with improved cardiac function. However, some of the changes in both the cardiac myocyte and the matrix after LVAD support are specific to myocardial recovery. In the myocyte, increases in the cytoskeletal proteins and improvements in the Ca²⁺ handling pathway seem to be specifically associated with myocardial recovery. Changes in the matrix are complex, but excessive scarring appears to limit the ability for recovery, and the degree of fibrosis in the myocardium at the time of implantation may predict the ability to recover.

  20. Hemodynamic effects of ventricular defibrillation

    Science.gov (United States)

    Pansegrau, Donald G.; Abboud, François M.

    1970-01-01

    Hemodynamic responses to ventricular defibrillation were studied in anesthetized dogs. Observations were made on arterial, right atrial and left ventricular end-diastolic pressures, on cardiac output (dye dilution), heart rate, and right atrial electrocardiogram. Ventricular fibrillation was induced electrically with a bipolar electrode catheter placed in the right ventricle. Fibrillation was maintained for 15 or 30 sec and terminated with a 400 w sec capacitor discharge across the thoracic cage. Responses lasted 1-10 min after conversion and included a cholinergic and an adrenergic component. The cholinergic component was characterized by sinus bradycardia, periods of sinus arrest, atrioventricular block, and ventricular premature beats. The adrenergic component included increases in arterial pressure, in cardiac output, and in left ventricular stroke work at a time when left ventricular end-diastolic pressure was normal; there was no change in total peripheral resistance. The pH of arterial blood decreased slightly and pCO2 increased but pO2 and the concentration of lactate were unchanged. Bilateral vagotomy and intravenous administration of atropine blocked the cholinergic component, unmasked a sinus tachycardia, and accentuated the adrenergic component of the response. The latter was blocked by intravenous administration of propranolol and phenoxybenzamine. These responses were related primarily to conversion of ventricular fibrillation rather than to the electrical discharge of countershock because countershock without ventricular fibrillation caused more transient and smaller responses than those observed with defibrillation: furthermore, the hemodynamic effects of defibrillation were augmented by prolongation of the duration of fibrillation. The results suggest that the cholinergic component of the response may be detrimental in that it favors spontaneous recurrence of fibrillation; on the other hand, the adrenergic component may be essential for conversion

  1. Speckle based configuration for simultaneous in vitro inspection of mechanical contractions of cardiac myocyte cells

    Science.gov (United States)

    Golberg, Mark; Fixler, Dror; Shainberg, Asher; Zlochiver, Sharon; Micó, Vicente; Garcia, Javier; Beiderman, Yevgeny; Zalevsky, Zeev

    2013-04-01

    In this manuscript we propose optical lensless configuration for a remote non-contact measuring of mechanical contractions of vast number of cardiac myocytes. All the myocytes were taken from rats, and the measurements were done in an in vitro mode. The optical method is based on temporal analysis of secondary reflected speckle patterns generated in lensless microscope configuration. The processing involves analyzing the movement and the change in the statistics of the generated secondary speckle patterns that are created on top of the cell culture when it is illuminated by a spot of laser beam. The main advantage of the proposed system is the ability to measure many cells simultaneously (approximately one thousand cells) and to extract the statistical data of their movement at once. The presented experimental results also include investigation the effect of isoproteranol on cells contraction process.

  2. 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

    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.......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...... on genome-wide transcription. This setup enabled us to identify intrinsic properties, originating from muscle precursor cells and retained in the corresponding myocytes. Bioinformatic and statistical methods, including differential expression analysis, gene-set analysis, and metabolic network analysis, were...

  3. 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...

  4. RYR2 sequencing reveals novel missense mutations in a Kazakh idiopathic ventricular tachycardia study cohort.

    Directory of Open Access Journals (Sweden)

    Ainur Akilzhanova

    Full Text Available Channelopathies, caused by disturbed potassium or calcium ion management in cardiac myocytes are a major cause of heart failure and sudden cardiac death worldwide. The human ryanodine receptor 2 (RYR2 is one of the key players tightly regulating calcium efflux from the sarcoplasmic reticulum to the cytosol and found frequently mutated (T; p.D4631V in a CPVT patient and a novel rare variant (c5428G>C; p.V1810L of uncertain significance in a patient with VT of idiopathic origin which we suggest represents a low-penetrance or susceptibility variant. In addition we identified a known variant previously associated with arrhythmogenic right ventricular dysplasia type2 (ARVD2. Combining sets of prediction scores and reference databases appeared fundamental to predict the pathogenic potential of novel and rare missense variants in populations where genotype data are rare.

  5. Giant Cell Myocarditis with Incessant Ventricular Arrhythmias Treated Successfully with Methylprednisolone and Rat Antithymocyte Globulin

    Directory of Open Access Journals (Sweden)

    Mudassar Baig

    2011-01-01

    Full Text Available Giant cell myocarditis is an aggressive form of this condition that is typically progressive and unresponsive to usual medical treatment. Here, we describe a 34-year-old patient presenting with incessant ventricular arrhythmias with hemodynamic compromise who required prolonged support in intensive care with an intra-aortic balloon pump (IABP. His Coronary arteries were normal and LV endomyocardial biopsy revealed myocyte necrosis with inflammatory infiltrate of lymphocytes, eosinophils, and giant cells suggestive of giant cell myocarditis. He was successfully treated with pulsed intravenous methylprednisolone and rat antithymocyte globulin (RATG. Despite a good functional cardiac recovery, some months later he developed a fluctuant neck swelling which fine needle aspiration confirmed as tuberculosis.

  6. MicroRNA-208a Silencing Attenuates Doxorubicin Induced Myocyte Apoptosis and Cardiac Dysfunction

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    Hasahya Tony

    2015-01-01

    Full Text Available Aims. GATA4 depletion is a distinct mechanism by which doxorubicin leads to cardiomyocyte apoptosis, and preservation of GATA4 mitigates doxorubicin induced myocyte apoptosis and cardiac dysfunction. We investigated a novel approach of attenuating doxorubicin induced cardiac toxicity by silencing miR-208a, a heart specific microRNA known to target GATA4. Methods and Results. Eight-week-old female Balb/C mice were randomly assigned to sham, antagomir, and control groups. Antagomir group were pretreated with miR-208a antagomir 4 days before doxorubicin administration. At day 0, control and antagomir groups received 20 mg/kg of doxorubicin, while sham mice received phosphate buffered solution. Echocardiography was done at day 7, after which animals were sacrificed and hearts harvested and assessed for apoptosis and expression of miR-208a, GATA4, and BCL-2. Doxorubicin significantly upregulated miR-208a, downregulated GATA4, and increased myocyte apoptosis, with resulting decrease in cardiac function. In contrast, therapeutic silencing of miR-208a salvaged GATA4 and BCL-2 and decreased apoptosis, with improvement in cardiac function. Conclusion. Doxorubicin upregulates miR-208a and promotes cardiomyocyte apoptosis, while therapeutic silencing of miR-208a attenuates doxorubicin induced myocyte apoptosis with subsequent improvement in cardiac function. These novel results highlight the therapeutic potential of targeting miR-208a to prevent doxorubicin cardiotoxicity.

  7. c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration.

    Science.gov (United States)

    Webster, Micah T; Fan, Chen-Ming

    2013-01-01

    Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.

  8. 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.

  9. A computationally efficient electrophysiological model of human ventricular cells

    NARCIS (Netherlands)

    Bernus, O.; Wilders, R.; Zemlin, C. W.; Verschelde, H.; Panfilov, A. V.

    2002-01-01

    Recent experimental and theoretical results have stressed the importance of modeling studies of reentrant arrhythmias in cardiac tissue and at the whole heart level. We introduce a six-variable model obtained by a reformulation of the Priebe-Beuckelmann model of a single human ventricular cell. The

  10. 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.)

  11. Dabigatran for left ventricular thrombus

    Directory of Open Access Journals (Sweden)

    Satishkumar Kolekar

    2015-09-01

    Dabigatran is a reversible direct thrombin inhibitor and currently approved for the prevention of thromboembolic episodes in non-valvar atrial fibrillation. This case demonstrates possible thrombolytic properties of dabigatran in resolution of left ventricular thrombus.

  12. Catch 22: a case of incessant ventricular tachycardia post-left ventricular assist device resulting in right ventricular failure, left ventricular cavity obliteration and failure of endocardial ventricular tachycardia ablation.

    Science.gov (United States)

    Thosani, Amit J; Bailey, Stephen H; Raina, Amresh

    2017-06-01

    Ventricular tachycardia (VT) in the setting of left ventricular assist device (LVAD) therapy has been well described. We present a case of incessant ventricular tachycardia resulting in severe right ventricular (RV) failure and subsequent left ventricular (LV) cavity obliteration, which in turn diminished the feasibility of initial attempt at VT ablation.

  13. Usefulness of immunostaining for plakoglobin as a diagnostic marker of arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Munkholm, Julie; Christensen, Alex H; Svendsen, Jesper H

    2012-01-01

    The clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging due to phenotypic variation, reduced/age-related penetrance, and lack of a diagnostic test. A single report has suggested quantitative myocardial immunoanalysis for the desmosomal protein...

  14. [Signaling indicator of ventricular fibrillation].

    Science.gov (United States)

    Agizim, G M; Pasichnik, T V; Sherman, A M

    1976-01-01

    The purpose of the work was to design an appliance for reliable detection of ventricular fibrillation. Frequency-amplitude spectrum of electrocardiograms taken in dogs with normal rhythm and fibrillation, as well as the impulse ratio in normalcy, tachycardia and in fibrillation were investigated. An appliance for automatic separation of ventricular fibrillation by referring to pulse ratio is described. The designed device is shown to have a high degree of discrimination and noise-immunity.

  15. 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)

  16. 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.

  17. 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

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Eric Y Zhang

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

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

    Directory of Open Access Journals (Sweden)

    Koji Isodono

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

  1. 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

  2. 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

  3. 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.

  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. Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.

    Science.gov (United States)

    Chan, Yi-Hsin; Tsai, Wei-Chung; Ko, Jum-Suk; Yin, Dechun; Chang, Po-Cheng; Rubart, Michael; Weiss, James N; Everett, Thomas H; Lin, Shien-Fong; Chen, Peng-Sheng

    2015-10-13

    Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038). Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction. © 2015 American Heart Association, Inc.

  6. 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

  7. Inhibition of angiotensin II-induced cardiac hypertrophy and associated ventricular arrhythmias by a p21 activated kinase 1 bioactive peptide.

    Science.gov (United States)

    Wang, Rui; Wang, Yanwen; Lin, Wee K; Zhang, Yanmin; Liu, Wei; Huang, Kai; Terrar, Derek A; Solaro, R John; Wang, Xin; Ke, Yunbo; Lei, Ming

    2014-01-01

    Cardiac hypertrophy increases the risk of morbidity and mortality of cardiovascular disease and thus inhibiting such hypertrophy is beneficial. In the present study, we explored the effect of a bioactive peptide (PAP) on angiotensin II (Ang II)-induced hypertrophy and associated ventricular arrhythmias in in vitro and in vivo models. PAP enhances p21 activated kinase 1 (Pak1) activity by increasing the level of phosphorylated Pak1 in cultured neonatal rat ventricular myocytes (NRVMs). Such PAP-induced Pak1 activation is associated with a significant reduction of Ang II-induced hypertrophy in NRVMs and C57BL/6 mice, in vitro and in vivo, respectively. Furthermore, PAP antagonizes ventricular arrhythmias associated with Ang II-induced hypertrophy in mice. Its antiarrhythmic effect is likely to be involved in multiple mechanisms to affect both substrate and trigger of ventricular arrhythmogenesis. Thus our results suggest that Pak1 activation achieved by specific bioactive peptide represents a potential novel therapeutic strategy for cardiac hypertrophy and associated ventricular arrhythmias.

  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. 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.

  10. Myocyte-Derived Hsp90 Modulates Collagen Upregulation via Biphasic Activation of STAT-3 in Fibroblasts during Cardiac Hypertrophy

    Science.gov (United States)

    Datta, Ritwik; Bansal, Trisha; Rana, Santanu; Datta, Kaberi; Datta Chaudhuri, Ratul; Chawla-Sarkar, Mamta

    2016-01-01

    ABSTRACT Signal transducer and activator of transcription 3 (STAT-3)-mediated signaling in relation to upregulated collagen expression in fibroblasts during cardiac hypertrophy is well defined. Our recent findings have identified heat shock protein 90 (Hsp90) to be a critical modulator of fibrotic signaling in cardiac fibroblasts in this disease milieu. The present study was therefore intended to analyze the role of Hsp90 in the STAT-3-mediated collagen upregulation process. Our data revealed a significant difference between in vivo and in vitro results, pointing to a possible involvement of myocyte-fibroblast cross talk in this process. Cardiomyocyte-targeted knockdown of Hsp90 in rats (Rattus norvegicus) in which the renal artery was ligated showed downregulated collagen synthesis. Furthermore, the results obtained with cardiac fibroblasts conditioned with Hsp90-inhibited hypertrophied myocyte supernatant pointed toward cardiomyocytes' role in the regulation of collagen expression in fibroblasts during hypertrophy. Our study also revealed a novel signaling mechanism where myocyte-derived Hsp90 orchestrates not only p65-mediated interleukin-6 (IL-6) synthesis but also its release in exosomal vesicles. Such myocyte-derived exosomes and myocyte-secreted IL-6 are responsible in unison for the biphasic activation of STAT-3 signaling in cardiac fibroblasts that culminates in excess collagen synthesis, leading to severely compromised cardiac function during cardiac hypertrophy. PMID:28031326

  11. follow-up of patients with arrhythmogenic right ventricular

    African Journals Online (AJOL)

    Patient suffered from arterial hypertension. § Non-sustained monomorphic ventricular tachycardia. VT = sustained ventricular tachycardia documented; EPS = electrophysiological study perfonned; VTIEPS = ventricular tachycardia induced during electrophysiological study; VPCS = ventricular premature contractions; morph ...

  12. Dynamics of Muscle Microcirculatory and Blood-myocyte O2 Flux During Contractions

    Science.gov (United States)

    Poole, David C.; Copp, Steven W.; Hirai, Daniel M.; Musch, Timothy I.

    2011-01-01

    The O2 requirements of contracting skeletal muscle may increase 100-fold above rest. In 1919 August Krogh’s brilliant insights recognized the capillary as the principal site for this increased blood-myocyte O2 flux. Based on the premise that most capillaries did not sustain RBC flux at rest Krogh proposed that capillary recruitment (i.e., initiation of red blood cell (RBC) flux in previously non-flowing capillaries) increased the capillary surface area available for O2 flux and reduced mean capillary-to-mitochondrial diffusion distances. More modern experimental approaches reveal that most muscle capillaries may support RBC flux at rest. Thus, rather than contraction-induced capillary recruitment per se, increased RBC flux and hematocrit within already-flowing capillaries likely elevate perfusive and diffusive O2 conductances and hence blood-myocyte O2 flux. Additional surface area for O2 exchange is recruited but, crucially, this may occur along the length of already-flowing capillaries (i.e. longitudinal recruitment). Today, the capillary is still considered the principal site for O2 and substrate delivery to contracting skeletal muscle. Indeed, the presence of very low intramyocyte O2 partial pressures (PO2’s) and the absence of PO2 gradients, whilst refuting the relevance of diffusion distances, place an even greater importance on capillary hemodynamics. This emergent picture calls for a paradigm-shift in our understanding of the function of capillaries by de-emphasizing de novo ‘capillary recruitment.’ Diseases such as heart failure impair blood-myocyte O2 flux, in part, by decreasing the proportion of RBC-flowing capillaries. Knowledge of capillary function in healthy muscle is requisite for identification of pathology and efficient design of therapeutic treatments. PMID:21199399

  13. 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.

  14. Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes.

    Science.gov (United States)

    Kohlhaas, Michael; Liu, Ting; Knopp, Andreas; Zeller, Tanja; Ong, Mei Fang; Böhm, Michael; O'Rourke, Brian; Maack, Christoph

    2010-04-13

    Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart failure, elevated cytosolic Na(+) ([Na(+)](i)) reduces mitochondrial Ca(2+) ([Ca(2+)](m)) by accelerating Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by [Ca(2+)](m), we speculated that in failing myocytes, elevated [Na(+)](i) promotes oxidative stress. We used a patch-clamp-based approach to simultaneously monitor cytosolic and mitochondrial Ca(2+) and, alternatively, mitochondrial H(2)O(2) together with NAD(P)H in guinea pig cardiac myocytes. Cells were depolarized in a voltage-clamp mode (3 Hz), and a transition of workload was induced by beta-adrenergic stimulation. During this transition, NAD(P)H initially oxidized but recovered when [Ca(2+)](m) increased. The transient oxidation of NAD(P)H was closely associated with an increase in mitochondrial H(2)O(2) formation. This reactive oxygen species formation was potentiated when mitochondrial Ca(2+) uptake was blocked (by Ru360) or Ca(2+) efflux was accelerated (by elevation of [Na(+)](i)). In failing myocytes, H(2)O(2) formation was increased, which was prevented by reducing mitochondrial Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Besides matching energy supply and demand, mitochondrial Ca(2+) uptake critically regulates mitochondrial reactive oxygen species production. In heart failure, elevated [Na(+)](i) promotes reactive oxygen species formation by reducing mitochondrial Ca(2+) uptake. This novel mechanism, by which defects in ion homeostasis induce oxidative stress, represents a potential drug target to reduce reactive oxygen species production in the failing heart.

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

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    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 [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2004-07-01

    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.

  16. 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

  17. Theory of arrhythmia based on mechano-electric feedback between cardiac myocytes and cardiac fibroblasts

    Directory of Open Access Journals (Sweden)

    Sergey V. Kolmakow

    2016-05-01

    Full Text Available When analyzing the articles submitted to our current issue, we involved into the preparation processing some relevant papers deserving special attention. The papers reveal the mechano-electric mechanism of the feedback between cardiac myocytes and cardiac fibroblasts that is capable of directly initiating cardiac arrhythmia. In the meantime, unfortunately, direct communication with Russian researchers Kamkin A.G., Kiseleva I.S. and Yarygin V.N. was not possible, but nevertheless, we are of the opinion that it is reasonable to review their articles, which discuss this interesting and logically justified mechanism of arrhythmia.

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

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    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

  19. Regulation of PTEN/Akt pathway enhances cardiomyogenesis and attenuates adverse left ventricular remodeling following thymosin β4 Overexpressing embryonic stem cell transplantation in the infarcted heart.

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    Binbin Yan

    Full Text Available Thymosin β4 (Tβ4, a small G-actin sequestering peptide, mediates cell proliferation, migration, and angiogenesis. Whether embryonic stem (ES cells, overexpressing Tβ4, readily differentiate into cardiac myocytes in vitro and in vivo and enhance cardioprotection following transplantation post myocardial infarction (MI remains unknown. Accordingly, we established stable mouse ES cell lines, RFP-ESCs and Tβ4-ESCs, expressing RFP and an RFP-Tβ4 fusion protein, respectively. In vitro, the number of spontaneously beating embryoid bodies (EBs was significantly increased in Tβ4-ESCs at day 9, 12 and 15, compared with RFP-ESCs. Enhanced expression of cardiac transcriptional factors GATA-4, Mef2c and Txb6 in Tβ4-EBs, as confirmed with real time-PCR analysis, was accompanied by the increased number of EB areas stained positive for sarcomeric α-actin in Tβ4-EBs, compared with the RFP control, suggesting a significant increase in functional cardiac myocytes. Furthermore, we transplanted Tβ4-ESCs into the infarcted mouse heart and performed morphological and functional analysis 2 weeks after MI. There was a significant increase in newly formed cardiac myocytes associated with the Notch pathway, a decrease in apoptotic nuclei mediated by an increase in Akt and a decrease in levels of PTEN. Cardiac fibrosis was significantly reduced, and left ventricular function was significantly augmented in the Tβ4-ESC transplanted group, compared with controls. It is concluded that genetically modified Tβ4-ESCs, potentiates their ability to turn into cardiac myocytes in vitro as well as in vivo. Moreover, we also demonstrate that there was a significant decrease in both cardiac apoptosis and fibrosis, thus improving cardiac function in the infarcted heart.

  20. 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)

  1. Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine

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    Brian R. Weil, PhD

    2017-04-01

    Full Text Available Summary: In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cardiac troponin I (cTnI that exceeded the 99th percentile for normal animals 60 min after reperfusion and rose to readily detectable levels 24 h later. Although tissue analysis at 60 min showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24 h. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with apoptosis in the absence of pathological evidence of infarction. Key Words: cardiac troponin I, cardiomyocyte apoptosis, myocardial ischemia, myocardial stunning

  2. Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability.

    Science.gov (United States)

    Campbell, Matthew D; Witcher, Marc; Gopal, Anoop; Michele, Daniel E

    2016-05-01

    Delta-sarcoglycan is a component of the sarcoglycan subcomplex within the dystrophin-glycoprotein complex located at the plasma membrane of muscle cells. While recessive mutations in δ-sarcoglycan cause limb girdle muscular dystrophy 2F, dominant mutations in δ-sarcoglycan have been linked to inherited dilated cardiomyopathy (DCM). The purpose of this study was to investigate functional cellular defects present in adult cardiac myocytes expressing mutant δ-sarcoglycans harboring the dominant inherited DCM mutations R71T or R97Q. This study demonstrates that DCM mutant δ-sarcoglycans can be stably expressed in adult rat cardiac myocytes and traffic similarly to wild-type δ-sarcoglycan to the plasma membrane, without perturbing assembly of the dystrophin-glycoprotein complex. However, expression of DCM mutant δ-sarcoglycan in adult rat cardiac myocytes is sufficient to alter cardiac myocyte plasma membrane stability in the presence of mechanical strain. Upon cyclical cell stretching, cardiac myocytes expressing mutant δ-sarcoglycan R97Q or R71T have increased cell-impermeant dye uptake and undergo contractures at greater frequencies than myocytes expressing normal δ-sarcoglycan. Additionally, the R71T mutation creates an ectopic N-linked glycosylation site that results in aberrant glycosylation of the extracellular domain of δ-sarcoglycan. Therefore, appropriate glycosylation of δ-sarcoglycan may also be necessary for proper δ-sarcoglycan function and overall dystrophin-glycoprotein complex function. These studies demonstrate that DCM mutations in δ-sarcoglycan can exert a dominant negative effect on dystrophin-glycoprotein complex function leading to myocardial mechanical instability that may underlie the pathogenesis of δ-sarcoglycan-associated DCM. Copyright © 2016 the American Physiological Society.

  3. Transapical miniaturized ventricular assist device: Design and initial testing

    Science.gov (United States)

    Slaughter, Mark S.; Giridharan, Guruprasad A.; Tamez, Dan; LaRose, Jeff; Sobieski, Mike A.; Sherwood, Leslie; Koenig, Steven C.

    2013-01-01

    Background Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure. Methods HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated. Results The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5–6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0–30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs. Conclusions We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis. PMID:21320708

  4. 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.

  5. 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

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

    Science.gov (United States)

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

    2016-01-01

    Cardiac hypertrophy is the most potent cardiovascular risk factor after age, and relative mortality risk linked with cardiac hypertrophy is greater in women. Ischemic heart disease is the most common form of cardiovascular pathology for both men and women, yet significant differences in incidence and outcomes exist between the sexes. Cardiac hypertrophy and ischemia are frequently occurring dual pathologies. Whether the cellular (cardiomyocyte) mechanisms underlying myocardial damage differ in women and men remains to be determined. In this study, utilizing an in vitro experimental approach, our goal was to examine the proposition that responses of male/female cardiomyocytes to ischemic (and adrenergic) stress may be differentially modulated by the presence of pre-existing cardiac hypertrophy. We used a novel normotensive custom-derived hypertrophic heart rat (HHR; vs control strain normal heart rat (NHR)). Cardiomyocyte morphologic and electromechanical functional studies were performed using microfluorimetric techniques involving simulated ischemia/reperfusion protocols. HHR females exhibited pronounced cardiac/cardiomyocyte enlargement, equivalent to males. Under basal conditions, a lower twitch amplitude in female myocytes was prominent in normal but not in hypertrophic myocytes. The cardiomyocyte Ca(2+) responses to β-adrenergic challenge differed in hypertrophic male and female cardiomyocytes, with the accentuated response in males abrogated in females-even while contractile responses were similar. In simulated ischemia, a marked and selective elevation of end-ischemia Ca(2+) in normal female myocytes was completely suppressed in hypertrophic female myocytes-even though all groups demonstrated similar shifts in myocyte contractile performance. After 30 min of simulated reperfusion, the Ca(2+) desensitization characterizing the male response was distinctively absent in female cardiomyocytes. Our data demonstrate that cardiac hypertrophy produces dramatically

  7. Changes in the transcriptional profile of cardiac myocytes following green fluorescent protein expression.

    Science.gov (United States)

    Badrian, Bahareh; Bogoyevitch, Marie A

    2007-10-01

    Green fluorescent protein (GFP) and its multiple forms, such as enhanced GFP (EGFP), have been widely used as marker proteins and for tracking purposes in many biological systems, including the heart and cardiac cell systems. Despite some concerns on its toxicity under certain circumstances, GFP remains amongst the most reliable and easy-to-use markers available. Using rat full genome DNA microarrays, we have investigated the broader consequences of adenoviral-driven GFP expression in cardiac myocytes. In our transcriptional profiling analysis, we set a threshold of a twofold change. We removed possible changes resulting from adenoviral infection by comparison with transcriptional profiles of cardiac myocytes with adenoviral-driven expression of an unrelated protein, the kinase MEK. Our analysis revealed changes in the expression of 212 genes. Of these genes, 174 were upregulated and 38 were downregulated following GFP expression. Many of these genes remain unannotated, but an evaluation of those with described functions for their resulting proteins indicated that many were involved in processes, including responses to stimuli/stress and signal transduction. Our analysis thus indicates the broader consequences of GFP expression in altering gene expression profiles in cardiac cells. Care should therefore be taken when using GFP expression as a control in gene expression studies.

  8. High frequency stimulation of cardiac myocytes: A theoretical and computational study

    Science.gov (United States)

    Weinberg, Seth H.

    2014-12-01

    High-frequency stimulation (HFS) has recently been identified as a novel approach for terminating life-threatening cardiac arrhythmias. HFS elevates myocyte membrane potential and blocks electrical conduction for the duration of the stimulus. However, low amplitude HFS can induce rapidly firing action potentials, which may reinitiate an arrhythmia. The cellular level mechanisms underlying HFS-induced electrical activity are not well understood. Using a multiscale method, we show that a minimal myocyte model qualitatively reproduces the influence of HFS on cardiac electrical activity. Theoretical analysis and simulations suggest that persistent activation and de-inactivation of ionic currents, in particular a fast inward window current, underlie HFS-induced action potentials and membrane potential elevation, providing hypotheses for future experiments. We derive analytical expressions to describe how HFS modifies ionic current amplitude and gating dynamics. We show how fast inward current parameters influence the parameter regimes for HFS-induced electrical activity, demonstrating how the efficacy of HFS as a therapy for terminating arrhythmias may depend on the presence of pathological conditions or pharmacological treatments. Finally, we demonstrate that HFS terminates cardiac arrhythmias in a one-dimensional ring of cardiac tissue. In this study, we demonstrate a novel approach to characterize the influence of HFS on ionic current gating dynamics, provide new insight into HFS of the myocardium, and suggest mechanisms underlying HFS-induced electrical activity.

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

    International Nuclear Information System (INIS)

    Ballester-Rodes, M.; Carrio-Gasset, I.; Abadal-Berini, L.; Obrador-Mayol, D.; Berna-Roqueta, L.; Caralps-Riera, J.M.

    1988-01-01

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

  10. 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

  11. Ventricular tachycardia following tube thoracotomy.

    Science.gov (United States)

    Hibbert, Benjamin; Lim, Toon Wei; Hibbert, Rebecca; Green, Martin; Gollob, Michael H; Davis, Darryl R

    2010-10-01

    Arrhythmias provoked by tube thoracotomy are a rare complication. We report a ventricular tachycardia after chest tube insertion for a device-related pneumothorax. Sinus rhythm was restored only by removal of the chest tube and insertion of a pliable pleural drain. Identification of the chest tube as an arrhythmic trigger following tube thoracotomy is essential in definitive management of refractory arrhythmias.

  12. Asymptomatic Left Ventricular Myxoma in a 12-Year-Old Male.

    Science.gov (United States)

    Chlebowski, Meghan; O'Brien, James; Hertzenberg, Casey; Wagner, Jonathan

    2016-06-01

    Cardiac myxoma is the most common cardiac tumor in patients of all ages; the majority are encountered as single left atrial tumors. Left ventricular myxomas are exceedingly rare, having been recorded in a small number of case reports involving children worldwide. We report a case of a left ventricular myxoma with left ventricular outflow tract obstruction in a previously healthy, asymptomatic adolescent black male. Transthoracic echocardiograms revealed a single, large (2.5 × 5-cm), lobulated, mobile mass within the left ventricular cavity that oscillated into the outflow tract, thereby causing moderate obstruction during systole. Advanced images delineated the location and tissue composition of the mass, characterizing it as a myxoma. Complete surgical excision of the mass was accomplished via aortotomy. Gross examination and histology confirmed the diagnosis of myxoma.

  13. Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Tang, Chun-Mei; Liu, Fang-Zhou; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Deng, Chun-Yu; Hu, Zhi-Qin; Yang, Hui; Zheng, Xi-Long; Cheng, Jian-Ding; Wu, Shu-Lin; Shan, Zhi-Xin

    2016-10-31

    The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.

  14. 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.

  15. 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.)

  16. Left ventricular diastolic performance of left ventricular hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ikezono, Tohru; Ozaki, Masaharu; Yamagishi, Takashi; Shimizu, Tatsuro; Furutani, Yuji; Kusukawa, Reizo

    1987-02-01

    To study left ventricular diastolic performance in different forms of left ventricular hypertrophy, ECG gated cardiac blood pool scan was performed in 11 patients with hypertrophic nonobstructive cardiomyopathy (HCM) and in 19 patients with hypertension (HT), and left ventricular volume curve (LVVC) was analyzed and compared with those of 13 normal subjects (N). Ejection fraction (EF) and early filling volume ratio (the ratio of volume increment of 100 msec later than the zero point in the first derivative of LVVC to the end diastolic volume) (%EFV) were computed from LVVC. Peak ejection rate (PER) and peak filling rate (PFR) were obtained from the first derivative of LVVC. Peak ejection acceleration (PEA) and peak filling acceleration (PFA) were calculated from the second derivative of LVVC. EF, PER and PEA did not show any difference between these 3 groups. PFR was lower in HT (2.6 +- 0.5) compared with those in HCM (3.0 +- 0.5) (p < 0.05) and in N (3.4 +- 0.5) (p < 0.001), but the %EFV in HCM (4.9 +- 1.8) was lower than those in HT (6.9 +- 1.9) (p < 0.01) and in N (11.4 +- 1.4) (p < 0.001). Moreover, PFA in HCM (27.9 +- 7.2) was increased than those in HT (20.2 +- 5.4) (p < 0.01) with no differences between HCM and N (29.4 +- 8.1). Significant correlation was observed between PFR and PFA (Y = 0.06X + 1.4. r = 0.856. p < 0.001). These result indicate that, in HCM, reduced increase in early left ventricular volume is compensated by a greater filling acceleration. In contrast, there is no compensation by filling acceleration in HT.

  17. Bidirectional Ventricular Tachycardia: A Hallmark of Catecholaminergic Polymorphic Ventricular Tachycardia

    Directory of Open Access Journals (Sweden)

    Dr. Francisco Femenia, MD

    2012-03-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion triggered syncope and sudden cardiac death. We present a 13 year-old girl with recurrent episodes of exercise-related syncope and prior history of sudden death in a first degree relative.

  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. Calpain inhibition prevents pacing-induced cellular remodeling in a HL-1 myocyte model for atrial fibrillation

    NARCIS (Netherlands)

    Brundel, BJJM; Kampinga, HH; Henning, RH

    2004-01-01

    Objective: Atrial fibrillation (AF) is a progressive disease. Previously, clinical and animal experimental studies in AF revealed a variety of myocyte remodeling processes including L-type Ca(2+) channel reduction and structural changes, which finally result in electrical remodeling and contractile

  20. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  2. [Posterior ventricular septal perforation successfully repaired through right ventricular approach].

    Science.gov (United States)

    Takeuchi, Kazuma; Morishige, N; Iwahashi, H; Hayashida, Y; Teshima, H; Ito, N; Tashiro, T

    2006-12-01

    A 65-year-old man underwent a successful repair of a posterior ventricular septal perforation (VSP) 9 days after suffering an acute inferior myocardial infarction. After hospitalization, his hemodynamic condition gradually worsened, in spite of administering intensive medical therapy. Emergent operation was performed on the 4th day after onset. An equine pericardial patch was sutured around the VSP through the right ventricular side of the septum using the double-patch repair method and the right ventricular wall was closed as using the standard extracorporeal perfusion technique. The dimensions of the VSP measured 5 mm in diameter. Transesophageal echocardiography was performed on the 14th postoperative day. Cardiac catheter examination was done on the 18th postoperative day. No residual shunt was recognized and cardiac function was good. He was discharged on the 20th postoperative day. The occurrence of a posterior VSP is comparatively rare, and repair of VSP is difficult to perform during an acute period. Therefore, the operative results of VSP cases remain poor.

  3. Effects of a pure alpha/beta-adrenergic receptor blocker on monocrotaline-induced pulmonary arterial hypertension with right ventricular hypertrophy in rats.

    Science.gov (United States)

    Ishikawa, Masaya; Sato, Naoki; Asai, Kuniya; Takano, Teruo; Mizuno, Kyoichi

    2009-12-01

    It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 +/-9 vs 21 +/-2 mmHg in the control (n=6); Parotinolol group (41 +/-3 vs 91 +/-14 mmHg in the control, Parotinolol group. The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH.

  4. Cardio-protecteffect of qiliqiangxin capsule on left ventricular remodeling, dysfunction and apoptosis in heart failure rats after chronic myocardial infarction.

    Science.gov (United States)

    Liang, Tuo; Zhang, Yuhui; Yin, Shijie; Gan, Tianyi; An, Tao; Zhang, Rongcheng; Wang, Yunhong; Huang, Yan; Zhou, Qiong; Zhang, Jian

    2016-01-01

    Qiliqiangxin (QL) capsule is a traditional Chinese medicine which has been approved for the treatment of chronic heart failure. Evidences proved that QL capsules further reduced the NT-proBNP levels and improved left ventricular ejection fraction in CHF patients but the evidence supporting its underlying mechanism is still unclear. Myocardial infarction (MI) -Heart failure (HF) Sprague-Dawley ratsmodel and neonatal rat cardiac myocytes (NRCMs) were used. Animals were assigned into 4 groups, normal group (n=6), shame-operation group (n=6), MI rats 4 weeks after left anterior descending coronary artery ligation were randomized into vehicle group (n=8), QL group (n=8). QL significantly attenuated cardiac dysfunction and ventricle remodeling as echocardiography and hemodynamic measurements showed improvement in left ventricular ejection fraction, fractional shortening, ±dp/dt and left ventricular end diastolic and systolic diameters in QL treated group compared with the vehicle group. Improvements ininterstitial fibrosisand mitochondrial structures were also exhibited by Sirius Red staining, RT-PCR and electron microscopy. QL treatment improved apoptosis and VEGF expression in rats marginal infract area. Complementary experiments analyzed the improved apoptosis and up-regulate of VEGF in ischemia-hypoxia cultivated NRCMs is in an Akt dependent manner and can be reversed by Akt inhibitor. QL capsule can improve cardiac dysfunction and ventricular remodeling in MI-HF ratsmodel, this cardiac protective efficacy may be concerned with attenuated apoptosis and cardiac fibrosis. Up-regulated VEGF expression and Akt phosphorylation may take part in this availability.

  5. 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.

  6. 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.

  7. Ventricular androgenic-anabolic steroid-related remodeling: an immunohistochemical study.

    Science.gov (United States)

    Cecchi, Rossana; Muciaccia, Barbara; Ciallella, Costantino; Di Luca, Natale Mario; Kimura, Akihiko; Sestili, Cristina; Nosaka, Mizuho; Kondo, Toshikazu

    2017-11-01

    Several fatal cases of bodybuilders, following a myocardial infarction after long exposure to androgenic-anabolic steroids (AAS), are reported. In recent years, evidence has emerged of cases of heart failure related to AAS consumption, with no signs of coronary or aorta atherosclerosis. This study aims to further investigate the pathogenesis of the ventricular AAS-related remodeling performing immunohistochemistry (IHC). In order to examine innate immunity activity and myocytes and endothelial cell apoptosis, IHC analyses were performed on heart tissue of two cases of bodybuilders who died after years of supratherapeutic use of metelonone and nandrolone and where no atherosclerosis or thrombosis were found, using the following antibodies: anti-CD68, anti-iNOS, anti-CD163, anti-CD 15, anti-CD8, anti-CD4, anti-HIF1 α, and in situ TUNEL staining. Results confirm the experimental findings of recent research that, in the absence of other pathological factors, if intensive training is combined with AAS abuse, myocytes and endothelial cells undergo apoptotic alterations. The absence of inflammatory reactions and the presence of an increased number of M2 macrophages in the areas of fibrotic remodeling confirm that the fibrotic changes in the heart are apoptosis-related and not necrosis-related. In conclusion, the study indicates that, in very young subjects with chronic hypoxia-related alterations of the heart, signs of a heart failure in the other organs and a history of AAS abuse, death can be ascribed to progressive heart failure due to the direct apoptotic cardiac and endothelial changes produced by AAS.

  8. Prophylactic amiodarone in patients with severe aortic stenosis and left ventricular hypertrophy undergoing aortic valve replacement: Silencing the rebels

    Directory of Open Access Journals (Sweden)

    Mohammed Abd Al Jawad

    2017-12-01

    Conclusions: Prophylactic use of a single dose amiodarone through the pump circuit before cross clamp release reduces the incidence of reperfusion induced ventricular fibrillation and subsequent defibrillation therapy needed.

  9. 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

  10. Estereologia do miocárdio de ratos jovens e idosos Stereology of the myocytes in young and aged rats

    Directory of Open Access Journals (Sweden)

    Márcia Barbosa Águila

    1998-02-01

    group we counted 15 random microscopic fields. The following parameters were studied: Vv(myocyte and Vv(interstitium(% (the volume densities of the cardiac myocyte and interstitium, determined by the point-counting method, and Nv(myocyte (1/mm³ (the numerical density of the cardiac myocytes, determined with the disector method. The total number of myocytes (N[myocyte] and the mean volume of the myocytes (V[myocytes] were also determined. The differences were tested by the Mann-Whitney test.RESULTS: Cardiac weight increased from 1.1 to 1.7g, the Vv(myocyte decreased from 76.7 to 72.2%, the Vv(interstitium increased from 23.3 to 27.8%. The Nv(myocyte and the N(myocyte decreased from 14.76x10(4 to 6.19x10(4/mm³ and 15.64x10(4 to 10.72x10(4 myocytes, respectively. Simultaneously, the V(myocyte increased from 5.42x10³ to 13.26x10³mm³. These differences were statistically significant (p<0.05. CONCLUSION: Myocardial changes, comparing young rats with aged ones suggest loss of myocytes (increased apoptosis? with simultaneous myocyte hypertrophy.

  11. BDNF-Induced Potentiation of Spontaneous Twitching in Innervated Myocytes Requires Calcium Release From Intracellular Stores

    Science.gov (United States)

    KLEIMAN, ROBIN J.; TIAN, NING; KRIZAJ, DAVID; HWANG, THOMAS N.; COPENHAGEN, DAVID R.; REICHARDT, LOUIS F.

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) can potentiate synaptic release at newly developed frog neuromuscular junctions. Although this potentiation depends on extracellular Ca2+ and reflects changes in acetylcholine release, little is known about the intracellular transduction or calcium signaling pathways. We have developed a video assay for neurotrophin-induced potentiation of myocyte twitching as a measure of potentiation of synaptic activity. We use this assay to show that BDNF-induced synaptic potentiation is not blocked by cadmium, indicating that Ca2+ influx through voltage-gated Ca2+ channels is not required. TrkB autophosphorylation is not blocked in Ca2+-free conditions, indicating that TrkB activity is not Ca2+ dependent. Additionally, an inhibitor of phospholipase C interferes with BDNF-induced potentiation. These results suggest that activation of the TrkB receptor activates phospholipase C to initiate intracellular Ca2+ release from stores which subsequently potentiates transmitter release. PMID:10899220

  12. miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D.

    Science.gov (United States)

    Cao, Quanxing; Dong, Pingshuan; Wang, Yanyu; Zhang, Junwei; Shi, Xinge; Wang, Yongsheng

    2015-05-01

    Cardiac myxoma is the most common type of human heart tumor, yet the molecular mechanism is still poorly understood. In the present study, we found that the level of myocyte enhancer factor 2D (MEF2D), a key regulatory protein for cardiac development, was elevated in specimens of cardiac myxoma, and was positively associated with the proliferation of myxoma cells. MEF2D suppression reduced the proliferation of myxoma cells and its tumorigenicity. Cell cycle progression was also inhibited by MEF2D suppression. miR-218, which is downregulated in myxoma, suppressed MEF2D expression by targeting its mRNA 3'UTR. Altogether, we found that miR-218/MEF2D may be an effective target for myxoma treatment.

  13. Cellular Trafficking of Phospholamban and Formation of Functional Sarcoplasmic Reticulum During Myocyte DIfferentiation

    Energy Technology Data Exchange (ETDEWEB)

    Stenoien, David L.; Knyushko, Tatyana V.; Londono, Monica P.; Opresko, Lee; Mayer, M. Uljana; Brady, Scott T.; Squier, Thomas C.; Bigelow, Diana J.

    2007-06-01

    The sarco/endoplasmic reticulum Ca-ATPase (SERCA) family members are transmembrane proteins that play an essential role in regulating intracellular calcium levels. Phospholamban (PLB), a 52 amino acid phosphoprotein, regulates SERCA activity in adult heart and skeletal muscle. Using the C2C12 myocyte cell line, we find endogenous PLB constitutively expressed in both myoblasts and myotubes, whereas SERCA expression coincides with activation of the differentiation program. PLB has a punctuate distribution in myoblasts changing to a reticular distribution in myotubes where it colocalizes with SERCAs. To examine the distribution and dynamics of PLB and SERCA, we expressed fluorescent fusion proteins (GFP, CFP, and YFP) of PLB and SERCA in myoblasts. Coexpressed PLB and SERCA localize to distinct cellular compartments in myoblasts but begin to colocalize as cells differentiate. Fluorescence Recovery After Photobleaching (FRAP) studies show different recovery patterns for each protein in myoblasts confirming their localization to distinct compartments. To extend these studies, we created stable cell lines expressing O6-alkylguanine-DNA alkyltransferase (AGT) fusions with PLB or SERCA to track their localization as myocytes differentiate. These experiments demonstrate that PLB localizes to punctate vesicles in myoblasts and adopts a reticular distribution that coincides with SERCA distribution after differentiation. Colocalization experiments indicate that a subset of PLB in myoblasts colocalizes with endosomes, Golgi, and the plasma membrane however PLB also localizes to other, as yet unidentified vesicles. Our results indicate that differentiation plays a critical role in regulating PLB distribution to ensure its colocalization within the same cellular compartment as SERCA in differentiated cells. The presence and altered distribution of PLB in undifferentiated myoblasts raises the possibility that this protein has additional functions distinct from SERCA regulation.

  14. Dissociation of insulin receptor phosphorylation and stimulation of glucose transport in BC3H-1 myocytes

    International Nuclear Information System (INIS)

    Mojsilovic, L.P.; Standaert, M.L.; Rosic, N.K.; Pollet, R.J.

    1986-01-01

    The authors have investigated insulin receptor phosphorylation in differentiated cultured BC3H-1 myocytes. As for other insulin-responsive cell systems in partially purified wheat germ agglutinin receptor preparations, insulin stimulates the phosphorylation of its own receptor (95K β-subunits) in a dose dependent manner (0-400 nM), as identified by immunoprecipitation with antiinsulin receptor antibodies and SDS-PAGE. In the same preparations they show that 12-0-tetradecanyl phorbol acetate (TPA), which in many respect β-subunits in the same dose dependent manner (0-5 μM). In addition, antiinsulin receptor antibodies (B-10) also induced phosphorylation of mimics insulin action, also induced phosphorylation of the insulin receptor and HPLC tryptic maps of the 32 P-labeled β-subunit were identical to those for insulin-induced receptor phosphorylation. However, while insulin and TPA are potent stimulators of glucose transport in these muscle cells, the antireceptor antibodies alone failed to provoke glucose transport at any concentration. The specificity and activity of these antibodies were confirmed in their system by their ability to inhibit insulin binding and insulin-stimulated glucose transport in a concentration-dependent manner. Their results indicate that phosphorylation of insulin receptor is not a crucial event in mediating insulin action, at least with respect to glucose transport. While the effects of the B-10 antibody in the BC3H-1 myocyte differ from those in the adipocyte, their results provide independent confirmation of their essential conclusion that phosphorylation of the insulin receptor may not be necessary nor sufficient for its acute action in promoting glucose transport

  15. Beneficial effect of methylprednisolone on cardiac myocytes in a rat model of severe brain injury.

    Science.gov (United States)

    Emir, Mustafa; Ozisik, Kanat; Cagli, Kerim; Ozisik, Pinar; Tuncer, Serdar; Bakuy, Vedat; Yildirim, Erkan; Kilinc, Kamer; Gol, Kamil

    2005-10-01

    Cardiac injury, occurred after traumatic brain injury (TBI), has been recognized for more than a century. Bcl-2 is a key regulatory component of the mitochondrial cell death pathway, and its overexpression is cytoprotective in many cell types. The therapeutic agents, which induce the expression of bcl-2 protein, might provide a new therapy to prevent cardiac myocyte damage following TBI. In this study, we investigated whether methylprednisolone sodium succinate (MPSS) influences the expression of bcl-2 in the heart. Wistar-Albino female rats underwent TBI (300 g/cm) generated by the weight-drop method, and were left untreated (n = 6) or treated with either MPSS (30 mg/kg) (n = 6) or vehicle (albumin solution) (n = 6). The heart was isolated from each animal with TBI. For comparison, the hearts were isolated from sham-operated (n = 6) and control rats (n = 6). The relative expression of bcl-2 mRNA in the heart was quantitated by real-time polymerase chain reaction. We also assessed lipid peroxidation in the heart tissue by determining the concentration of thiobarbituric acid-reactive substances (TBARs) as an indicator of tissue damage. The bcl-2 expression level was significantly higher in the hearts of MPSS-treated rats compared to that of other TBI groups (p < 0.0001). Moreover, TBI increased the lipid peroxidation in the heart, which was significantly reduced by the treatment with MPSS (p < 0.0001). These findings provide evidence for the efficacy of MPSS in protection of cardiac myocytes to achieve optimal heart donation after TBI in heart transplantation.

  16. 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.

  17. HDAC1 localizes to the mitochondria of cardiac myocytes and contributes to early cardiac reperfusion injury.

    Science.gov (United States)

    Herr, Daniel J; Baarine, Mauhamad; Aune, Sverre E; Li, Xiaoyang; Ball, Lauren E; Lemasters, John J; Beeson, Craig C; Chou, James C; Menick, Donald R

    2018-01-01

    Recent evidence indicates that histone deacetylase enzymes (HDACs) contribute to ischemia reperfusion (I/R) injury, and pan-HDAC inhibitors have been shown to be cardioprotective when administered either before an ischemic insult or during reperfusion. We have shown previously that selective inhibition of class I HDACs provides superior cardioprotection when compared to pan-HDAC inhibition in a pretreatment model, but selective class I HDAC inhibition has not been tested during reperfusion, and specific targets of class I HDACs in I/R injury have not been identified. We hypothesized that selective inhibition of class I HDACs with the drug MS-275 (entinostat) during reperfusion would improve recovery from I/R injury in the first hour of reperfusion. Hearts from male Sprague-Dawley rats were subjected to ex vivo I/R injury±MS-275 class I HDAC inhibition during reperfusion alone. MS-275 significantly attenuated I/R injury, as indicated by improved LV function and tissue viability at the end of reperfusion. Unexpectedly, we observed that HDAC1 is present in the mitochondria of cardiac myocytes, but not fibroblasts or endothelial cells. We then designed mitochondria-restricted and mitochondria-excluded HDAC inhibitors, and tested both in our ex vivo I/R model. The selective inhibition of mitochondrial HDAC1 attenuated I/R injury to the same extent as MS-275, whereas the mitochondrial-excluded inhibitor did not. Further assays demonstrated that these effects are attributable to a decrease in SDHA activity and subsequent metabolic ROS production in reperfusion. We demonstrate for the first time that HDAC1 is present within the mitochondria of cardiac myocytes, and mitochondrial HDAC1 contributes significantly to I/R injury within the first hour of reperfusion. Copyright © 2017. Published by Elsevier Ltd.

  18. The impact of atrio-biventricular pacing on hemodynamics and left ventricular dyssynchrony compared with atrio-right ventricular pacing alone in the postoperative period after cardiac surgery.

    Science.gov (United States)

    Cannesson, Maxime; Farhat, Fadi; Scarlata, Maria; Cassar, Emmanuel; Lehot, Jean-Jacques

    2009-06-01

    The aims of this study were to test the hypotheses that in the postoperative period after coronary artery bypass graft surgery (1) atrio-right ventricular (RA-RV) pacing induces a decrease in cardiac output compared with RA pacing alone and (2) atrio-biventricular (RA-BiV) pacing improves CO compared with RA-RV pacing. A prospective observational study. A single-center university hospital. Patients referred for coronary artery bypass graft surgery. Patients were studied during atrial, RA-RV, and RA-BiV pacing. Cardiac output (echocardiography) and left ventricular dyssynchrony were assessed at each step. RA-RV pacing induced a significant decrease in cardiac output (4.3 +/- 1.0 to 3.7 +/- 0.8 L/min, p < 0.01) and a significant increase in left ventricular dyssynchrony (13 +/- 12 to 80 +/- 25 milliseconds, p < 0.01). Biventricular pacing induced a significant increase in cardiac output (3.7 +/- 0.8 to 4.5 +/- 1.0 L/min, p < 0.01) and a significant decrease in left ventricular dyssynchrony compared with right ventricular pacing (80 +/- 25 to 21 +/- 16 milliseconds, p < 0.05). RA-BiV pacing improves cardiac output compared with RA-RV pacing in the postoperative period after coronary artery bypass graft surgery. This improvement is related to an improvement in left ventricular synchronicity.

  19. 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.)

  20. Comparison between tagged MRI and standard cine MRI for evaluation of left ventricular ejection fraction

    Energy Technology Data Exchange (ETDEWEB)

    Dornier, Christophe; Ivancevic, Marko K.; Didier, Dominique; Vallee, Jean-Paul [Departement de Radiologie et d' Informatique Medicale, Hopitaux Universitaires de Geneve, 24 rue Micheli-du-Crest, 1211, Geneva (Switzerland); Somsen, G. Aernout; Righetti, Alberto [Div. de Cardiologie, Departement de Medecine Interne, Hopitaux Universitaires de Geneve, 24 rue Micheli-du-Crest, 1211, Geneva (Switzerland); Osman, Nael F. [Department of Radiology, Johns Hopkins University, 600 North Wolfe Street, 21287, Baltimore, MD (United States)

    2004-08-01

    Global left ventricular function is a prognostic indicator and is used to evaluate therapeutical interventions in patients with heart failure. Regional left ventricular function can be determined with tagged MRI. Assessment of global left ventricular function using the tagging data may have additional clinical value without incurring extra scanning time, which is currently a limiting factor in cardiac imaging. Direct determination of end-diastolic volume is not possible with conventional tagged MRI. However, end-systolic volume can be directly measured because myocardium-blood contrast improves through a tagged image series. We investigated the potential of tagged MRI using frequency-domain analysis software to retrospectively track end-diastolic contour from end-systolic contour and subsequently calculate the ejection fraction. Tagged MRI was compared with the standard bright-blood cine MRI in healthy volunteers (n=20) and patients with previous myocardial infarction (n=8). Left ventricular ejection fraction derived from tagged MRI is linearly correlated to left ventricular ejection fraction obtained by standard cardiac cine MRI (y=1.0x+1.31, r>0.98, p=0.014). In addition, the inter-observer and intra-observer coefficient of variation for left ventricular ejection fraction measurements was low (CV{sub intra}=0.4%, CV{sub inter}=1.3%). With tagged MRI, only end-systolic volume needs to be manually determined, and accurate estimation of left ventricular ejection fraction is obtained because end-diastolic and end-systolic volumes are determined using identical anatomical points. Our data indicate that tagged MRI can be used to quantitatively assess both regional and global left ventricular function. Therefore, tagged MRI may be a valuable clinical tool for determining the prognosis and evaluating the effect of therapeutical intervention using a single imaging session in patients with left ventricular dysfunction. (orig.)

  1. Successful Right Ventricular Tachycardia Ablation in a Patient with Left Ventricular Non-compaction Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Shohreh Honarbakhsh, MBBS, BSc, MRCP

    2013-09-01

    Full Text Available We report a case of a 67-year old male with a recent diagnosis of left ventricular noncompaction (LVNC, initially presenting with symptomatic ventricular ectopy and runs of non-sustained ventricular tachycardia (VT. This ventricular arrhythmia originated in a structurally normal right ventricle (RV and was successfully localized and ablated with the aid of the three-dimensional mapping and remote magnetic navigation.

  2. 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 My46 Trait Profile Orphanet: Arrhythmogenic right ventricular cardiomyopathy Orphanet: Familial isolated ...

  3. 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.

  4. Early surgical removal of membranous ventricular septal device might allow recovery of atrio-ventricular block.

    Science.gov (United States)

    Ovaert, Caroline; Dragulescu, Andreea; Sluysmans, Thierry; Carminati, Mario; Fraisse, Alain

    2008-09-01

    Complete atrio-ventricular heart block is a well-reported complication after percutaneous closure of perimembranous ventricular septal defects. The incidence seems to be higher than after surgical closure. Early heart block can be transient and pacemaker implantation is not always required. Late heart block is also described. We describe two patients who both presented with complete atrio-ventricular block 4 days after device insertion. Surgical device removal was followed by a rapid and complete recovery of the atrio-ventricular conduction. Surgical device removal should be considered in cases of subacute heart block, as removal might result in recovery of the atrio-ventricular conduction.

  5. 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

  6. Bidirectional ventricular tachycardia of unusual etiology

    Directory of Open Access Journals (Sweden)

    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.

  7. Ventricular dilatation in aging and dementia

    NARCIS (Netherlands)

    Palm, Walter Miguel

    2015-01-01

    The general objective of this thesis was to study the causes and consequences of ventricular dilatation in aging and dementia. For this purpose, we used ventricular shape analysis to study potential new MRI markers of cognitive decline in aging, subjective memory complaints, mild cognitive

  8. Left ventricular hypertrophy, geometric patterns and clinical ...

    African Journals Online (AJOL)

    Background: Left ventricular hypertrophy can be due to various reasons including hypertension. It constitutes an increased cardiovascular risk. Various left ventricular geometric patterns occur in hypertension and may affect the cardiovascular risk profile of hypertensive subjects. Methods: One hundred and eighty eight ...

  9. 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

  10. 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.

  11. Acute simvastatin inhibits K ATP channels of porcine coronary artery myocytes.

    Directory of Open Access Journals (Sweden)

    Sai Wang Seto

    Full Text Available Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.Pig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca(2+]i, [ATP]i and [glucose]o uptake measurements.The cromakalim (10 nM to 10 µM- and pinacidil (10 nM to 10 µM-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM. Simvastatin (1, 3 and 10 µM suppressed (in okadaic acid (10 nM-sensitive manner cromakalim (10 µM- and pinacidil (10 µM-mediated opening of whole-cell KATP channels of arterial myocytes. Simvastatin (10 µM and AICAR (1 mM elicited a time-dependent, compound C (1 µM-sensitive [(3H]-2-deoxy-glucose uptake and an increase in [ATP]i levels. A time (2-30 min- and concentration (0.1-10 µM-dependent increase by simvastatin of p-AMPKα-Thr(172 and p-PP2A-Tyr(307 expression was observed. The enhanced p-AMPKα-Thr(172 expression was inhibited by compound C, ryanodine (100 µM and KN93 (10 µM. Simvastatin-induced p-PP2A-Tyr(307 expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM, ouabain (10 µM, and in [glucose]o-free or [Na(+]o-free conditions.Simvastatin causes ryanodine-sensitive Ca(2+ release which is important for AMPKα-Thr(172 phosphorylation via Ca(2+/CaMK II. AMPKα-Thr(172 phosphorylation causes [glucose]o uptake (and an [ATP]i increase, closure of KATP channels, and phosphorylation of AMPKα-Thr(172 and PP2A-Tyr(307 resulted. Phosphorylation of PP2A-Tyr(307 occurs at a site downstream of AMPKα-Thr(172 phosphorylation.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    1999-01-01

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

  14. Evidence of cell-mediated cardiac myocyte injury involved in the heart failure of a patient with progressive systemic sclerosis.

    Science.gov (United States)

    Takahashi, N; Seko, Y; Azuma, M; Yagita, H; Okumura, K; Yazaki, Y

    1999-01-01

    A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 24%). Methylprednisolone, heparin, and diuretics were administered, without benefit. Anemia, thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart failure on the 14th hospital day. Immunohistochemical study of the myocardial tissue showed mild to moderate cell infiltration, mainly consisting of natural killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper cells. Perforin, a cytolytic factor, was expressed in the infiltrating CTLs and NK cells, indicating that these cells were activated killer cells. Furthermore, human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not to be expressed in cardiac myocytes under normal conditions, were moderately to strongly expressed in cardiac myocytes. There was no detectable level of enterovirus genomes in the polymerase chain reaction products from the myocardial tissue of this patient. These findings strongly suggest that the infiltrating killer cells recognized cardiac myocytes as target cells and directly damaged them by releasing perforin. Enhanced expression of these antigens may have played an important role in the activation and cytotoxicity of the infiltrating killer cells. Absence of enterovirus genomes in the myocardial tissue may suggest that this autoimmune process is primarily induced by PSS.

  15. Hydralazine decreases sodium nitroprusside-induced rat aortic ring relaxation and increased cGMP production by rat aortic myocytes.

    Science.gov (United States)

    Vidrio, Horacio; González-Romo, Pilar; Alvarez, Ezequiel; Alcaide, Carlos; Orallo, Francisco

    2005-10-28

    Association of hydralazine with nitrova-sodilators has long been known to be beneficial in the vasodilator treatment of heart failure. We previously found that hydralazine appeared to reduce the increase in cGMP induced by sodium nitroprusside in cultured rat aortic myocytes. In order to further explore this seemingly paradoxical interaction, we extended our initial observations in rat aortic myocytes and also determined the influence of hydralazine on sodium nitroprusside-induced relaxation of rat aortic rings. Hydralazine produced a concentration-dependent inhibition of sodium nitroprusside stimulation of cGMP production and caused a rightward shift of concentration-relaxation curves in aortic rings. A possible mechanism of the hydralazine-nitroprusside interaction could be the interference with bioactivation of the nitro-vasodilator to release nitric oxide. Recent evidence indicates that vascular NADH oxidase, an enzyme known to be inhibited by hydralazine, could be involved in this process. Accordingly, hydralazine was found to inhibit NADH oxidase activity in rat aortic myocytes at concentrations similar to those reducing sodium nitroprusside responses. It was concluded that antagonism of sodium nitroprusside action by hydralazine could be a consequence of interference with bioactivation of the former, apparently through inhibition of vascular NADH oxidase.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Comparative significance in systolic ventricular interaction.

    Science.gov (United States)

    Yamaguchi, S; Harasawa, H; Li, K S; Zhu, D; Santamore, W P

    1991-09-01

    The aim was to measure the systolic coupling between the ventricles and to determine the relative importance of ventricular interaction in the pressure development of each ventricle. Acute studies were done in dogs to measure the changes in right and left ventricular pressures (dPr, dPl) caused by sudden changes in left ventricular pressure (dPl') with release of an aortic constriction, and sudden changes in right ventricular pressure (dPr') with release of a pulmonary artery constriction, respectively. The instantaneous cross talk gain [dPr/dPl' (Klr) or dPl/dPr' (Krl)] was calculated during the ejection phase. The potential systolic pressure generated by the contralateral ventricle was evaluated as the cross talk gain multiplied by the contralateral systolic developed pressure. Studies were done in eight random source dogs (12-18 kg), anaesthetised with sodium pentobarbitone. The maximal Klr was lower than the maximal Krl, at 0.09 (SD 0.05) v 0.25 (0.06), and the mean Klr also was lower than the mean Krl, at 0.04 (0.02) v 0.10 (0.03), p less than 0.05. The potential right ventricular pressures developed by the left ventricle [maximum 10.3(5.6), mean 4.8(2.7) mm Hg] were not significantly different from the potential left ventricular pressures developed by the right ventricle [maximum 8.8(2.7), mean 3.4(0.7) mm Hg]. However, the ratio between the potential transmitted pressure and the measured developed pressure was greater in the right ventricle [maximum 39.0(21.1), mean 17.8(8.9)%] than in the left ventricle [maximum 11.1(7.1)%, p less than 0.05; mean 3.9(1.5)%, p less than 0.01]. This suggests that about 20-40% of the right ventricular systolic pressure may result from the left ventricle and about 4-10% of the left ventricular systolic pressure may result from right ventricle. Although the pressure coupling was greater in right to left ventricular interaction, right ventricular pressure generation may be more dependent on the left ventricle. Systolic

  1. 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.

  2. SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes.

    Science.gov (United States)

    Berdeaux, Rebecca; Goebel, Naomi; Banaszynski, Laura; Takemori, Hiroshi; Wandless, Thomas; Shelton, G Diane; Montminy, Marc

    2007-05-01

    During physical exercise, increases in motor neuron activity stimulate the expression of muscle-specific genes through the myocyte enhancer factor 2 (MEF2) family of transcription factors. Elevations in intracellular calcium increase MEF2 activity via the phosphorylation-dependent inactivation of class II histone deacetylases (HDACs). In studies to determine the role of the cAMP responsive element binding protein (CREB) in skeletal muscle, we found that mice expressing a dominant-negative CREB transgene (M-ACREB mice) exhibited a dystrophic phenotype along with reduced MEF2 activity. Class II HDAC phosphorylation was decreased in M-ACREB myofibers due to a reduction in amounts of Snf1lk (encoding salt inducible kinase, SIK1), a CREB target gene that functions as a class II HDAC kinase. Inhibiting class II HDAC activity either by viral expression of Snf1lk or by the administration of a small molecule antagonist improved the dystrophic phenotype in M-ACREB mice, pointing to an important role for the SIK1-HDAC pathway in regulating muscle function.

  3. Genome-wide association identifies a deletion in the 3' untranslated region of striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Meurs, Kathryn M; Mauceli, Evan; Lahmers, Sunshine; Acland, Gregory M; White, Stephen N; Lindblad-Toh, Kerstin

    2010-09-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease characterized by ventricular arrhythmias and sudden cardiac death. It is most frequently inherited as an autosomal dominant trait with incomplete and age-related penetrance and variable clinical expression. The human disease is most commonly associated with a causative mutation in one of several genes encoding desmosomal proteins. We have previously described a spontaneous canine model of ARVC in the boxer dog. We phenotyped adult boxer dogs for ARVC by performing physical examination, echocardiogram and ambulatory electrocardiogram. Genome-wide association using the canine 50k SNP array identified several regions of association, of which the strongest resided on chromosome 17. Fine mapping and direct DNA sequencing identified an 8-bp deletion in the 3' untranslated region (UTR) of the Striatin gene on chromosome 17 in association with ARVC in the boxer dog. Evaluation of the secondary structure of the 3' UTR demonstrated that the deletion affects a stem loop structure of the mRNA and expression analysis identified a reduction in Striatin mRNA. Dogs that were homozygous for the deletion had a more severe form of disease based on a significantly higher number of ventricular premature complexes. Immunofluorescence studies localized Striatin to the intercalated disc region of the cardiac myocyte and co-localized it to three desmosomal proteins, Plakophilin-2, Plakoglobin and Desmoplakin, all involved in the pathogenesis of ARVC in human beings. We suggest that Striatin may serve as a novel candidate gene for human ARVC.

  4. Electrohydraulic ventricular assist device development.

    Science.gov (United States)

    Diegel, P D; Mussivand, T; Holfert, J W; Nahon, D; Miller, J; Maclean, G K; Santerre, J P; Bearnson, G B; Juretich, J; Hansen, A C

    1991-01-01

    A 64 ml (effective stroke volume) in vitro electrohydraulic ventricular assist device (VAD) prototype has been built. The energy converter is an axial flow pump driven by a brushless direct current (DC) motor. Systole begins as silicone oil is pumped from the volume displacement chamber (VDC) into the ventricle, displacing the flexing diaphragm separating the oil and the blood. In diastole, the motor reverses, providing active filling by pumping oil from the ventricle into the VDC. The surface mount electronic internal controller provides motor commutator, energy management, telemetry, and physiologic control functions. Energy is supplied externally by either a 12 V DC power supply or a 12 V DC rechargeable battery and is transmitted through the skin by a transcutaneous energy transformer (TET). Energy can also be supplied by a 12 V DC rechargeable internal battery. Bidirectional infrared telemetry is used to transmit information between the internal and external controllers.

  5. Antiandrogenic therapy with finasteride attenuates cardiac hypertrophy and left ventricular dysfunction.

    Science.gov (United States)

    Zwadlo, Carolin; Schmidtmann, Elisa; Szaroszyk, Malgorzata; Kattih, Badder; Froese, Natali; Hinz, Hebke; Schmitto, Jan Dieter; Widder, Julian; Batkai, Sandor; Bähre, Heike; Kaever, Volkhard; Thum, Thomas; Bauersachs, Johann; Heineke, Joerg

    2015-03-24

    In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure. We found a strongly induced expression of all 3 isoforms of the 5-α-reductase (Srd5a1 to Srd5a3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of dihydrotestosterone. Starting 1 week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for 2 weeks. Cardiac function, hypertrophy, dilation, and fibrosis were markedly improved in response to finasteride treatment in not only male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride, by decreasing dihydrotestosterone, potently inhibited hypertrophy and Akt-dependent prohypertrophic signaling in isolated cardiac myocytes, whereas the introduction of constitutively active Akt blunted these effects of finasteride. Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice and might be a therapeutic option for heart failure. © 2015 American Heart Association, Inc.

  6. 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.

  7. 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.

  8. Incidence of ventricular arrhythmias, brady-arrhythmias and sudden ...

    African Journals Online (AJOL)

    Ventricular arrhythmias (VAS), Including ventricular tachycardia (VT), ventricular fibrillation (VF) and Brady-arrhythmias, are life-threatening complications of acute myocardial infarction (MI). Objective: To study the incidence of ventricular arrhythmias, brady-arrhythmias and Sudden Cardiac Death (SCD) in Sudanese ...

  9. Late potentials and their correlation with ventricular structure in patients with ventricular arrhythmias

    DEFF Research Database (Denmark)

    Marstrand, Peter; Axelsson, Anna; Thune, Jens Jakob

    2017-01-01

    arrhythmias. METHODS: We included 42 patients admitted with ventricular tachycardia or fibrillation who had undergone both signal-averaged ECG recording and CMR imaging. Clinical data and CMR findings were compared in patients with and without LP. RESULTS: The majority, 26 (62%) patients, were sudden cardiac...... death survivors and the remaining 16 (38%) were admitted with ventricular tachycardia. After full diagnostic work-up, the most common diagnoses in the cohort were idiopathic ventricular tachycardia/ventricular fibrillation (25 patients, 60%) or cardiomyopathies (11 patients, 26%). LPs were positive......INTRODUCTION: The presence of late potentials (LP) may indicate a predisposition to ventricular arrhythmias and sudden cardiac death. We investigated the association between presence of LP and structural cardiac anomalies assessed by magnetic resonance (CMR) in patients presenting with ventricular...

  10. Apical left ventricular hypertrophy and mid-ventricular obstruction in fabry disease.

    Science.gov (United States)

    Cianciulli, Tomás F; Saccheri, María C; Fernández, Segundo P; Fernández, Cinthia C; Rozenfeld, Paula A; Kisinovsky, Isaac

    2015-05-01

    We report the case of a rare cardiac presentation of Fabry disease. Although concentric left ventricular hypertrophy is a major cardiac finding in Fabry disease, there is no case report of dynamic obstruction at mid-left ventricular level. We describe a 59-year-old-woman suffering from a severe form of Fabry disease, mimicking an apical hypertrophic cardiomyopathy with mid-ventricular obstruction. Differentiation of Fabry disease from hypertrophic cardiomyopathy is crucial given the therapeutic and prognostic differences. Fabry disease should always be suspected in an adult, independently of the pattern of left ventricular hypertrophy. © 2015, Wiley Periodicals, Inc.

  11. 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

  12. Rest and exercise ventricular function in adults with congenital ventricular septal defects

    Energy Technology Data Exchange (ETDEWEB)

    Jablonsky, G.; Hilton, J.D.; Liu, P.P.; Morch, J.E.; Druck, M.N.; Bar-Shlomo, B.Z.; McLaughlin, P.R.

    1983-01-15

    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.

  13. 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.

  14. 21 CFR 882.4060 - Ventricular cannula.

    Science.gov (United States)

    2010-04-01

    ... for injection. This device is frequently referred to as a ventricular needle. (b) Classification. Class I (general controls). When made only of surgical grade stainless steel, the device is exempt from...

  15. Electrocardiographic features suggestive of a left. ventricular ...

    African Journals Online (AJOL)

    Abstract. Electrocardiographic features suggestive of a transmural anterior myocardial infarction with resultant left ventricular aneurysm formation were found in a 22-year-old man who had sustained a ballistic missile injury to his chest.

  16. Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding

    Science.gov (United States)

    Urashima, Takashi; Shimura, Daisuke; Amemiya, Erika; Miyasaka, Genki; Yokota, Shunsuke; Fujimoto, Yoshitaka; Akaike, Toru; Inoue, Takahiro; Minamisawa, Susumu

    2017-01-01

    Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling) has not yet been clarified. We developed an animal model of right ventricular (RV) hypertrophy with fibrosis by pulmonary artery (PA) banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca2+ concentration of RV papillary muscles were simultaneously measured (n = 33). The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca2+ responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca2+ had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca2+ responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1) the decrease in Ca2+ responsiveness and 2) the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication. PMID:28068381

  17. 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.

  18. Association of common genetic variants related to atrial fibrillation and the risk of ventricular fibrillation in the setting of first ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jabbari, Reza; Jabbari, Javad; Glinge, Charlotte

    2017-01-01

    Background: Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). In this study, we hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated...

  19. 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

  20. Safety Testing of Left Ventricular Vent Valves

    OpenAIRE

    Gavin, Caroline; Coblentz, John; Acsell, Jeffrey R.; Shackelford, Anthony G.; Sistino, Joseph J.

    2015-01-01

    Vent vacuum relief valves (VRVs) are used to limit the negative pressure at the ventricular vent catheter tip as well as prevent reversal of blood flow and prevention of air embolism. The purpose of this study was to evaluate the performance of three commercially available ventricular vent valves. The negative pressure at which the vent valve opened was measured at the valve inlet using high-fidelity pressure transducers. Also, the flow rate at which air entrainment occurred due to valve open...

  1. 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....

  2. Right ventricular ischemia evaluated by radionuclide ventriculography

    International Nuclear Information System (INIS)

    Yamamuro, Masashi; Yada, Takashi; Ichikawa, Takehiko; Futagami, Yasuo; Konishi, Tokuji; Nakano, Takeshi; Takezawa, Hideo

    1986-01-01

    The subjects consisted of 25 patients with acute inferior myocardial infarction, 19 patients with old myocardial infarction and six patients with angina pectoris who had severe stenosis of the right coronary artery. In patients with acute inferior myocardial infarction, follow-up radionuclide studies were performed during the recovery periods on the first, 7th ∼ 14th, and 30th hospital day. Fifteen of the 25 patients initially had decreased right ventricular ejection fractions (evidence of right ventricular infarction). The mean value was 28 ± 8 % on the initial day, but 7 - 14 days and 30 days after the acute attack, it improved markedly to 36 ± 9 % and 39 ± 9 %, respectively. In 25 patients with old myocardial infarction or with angina pectoris, RNV was performed at rest and during supine exercise to determine the influence of right coronary artery disease. Right ventricular ejection fraction was changed by exercise from 42 ± 7 % to 44 ± 10 % in patients with proximal artery lesions, and from 45 ± 7 % to 50 ± 10 % in patients with distal artery lesions. Right ventricular ejection fraction increased in patients with isolated right coronary artery disease (rest: 44 ± 8 %, exercise: 49 ± 9 %), decreased in patients with combined left anterior descending artery disease (rest: 40 ± 6 %, exercise: 38 ± 11 %) and increased in patients with combined circumflex artery disease (rest: 43 ± 5 %, exercise: 47 ± 6 %). We concluded that right ventricular infarction is a frequent complication in patients with inferior myocardial infarction. However, right ventricular ejection fraction and right ventricular regional wall motion abnormality improve dramatically within one month. Stress-induced ischemia would be rare in patients with isolated right coronary artery disease. The above findings support the notion that the right ventricular myocardium has peculiar coronary perfusions. (J.P.N.)

  3. Cardiac Body Surface Potentials in Rats with Experimental Pulmonary Hypertension during Ventricular Depolarization.

    Science.gov (United States)

    Suslonova, O V; Smirnova, S L; Roshchevskaya, I M

    2016-11-01

    The spatial and the amplitude-temporal parameters of cardiac body surface potentials were examined in female Wistar rats with experimental pulmonary hypertension during ventricular depolarization. The cardiac body surface potentials have been led from 64 subcutaneous electrodes evenly distributed across the chest surface prior to and 4 weeks after subcutaneous injection of a single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and electrophysiological remodeling of the heart developed in rats with experimental pulmonary hypertension in 4 weeks after monocrotaline injection; these changes led to a significant increase in amplitude and temporal characteristics of the cardioelectric field on the body surface in comparison with the initial state.

  4. 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

    2018-04-16

    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.

  5. Electrophysiologic features of protected channels in late postinfarction patients with and without spontaneous ventricular tachycardia.

    Science.gov (United States)

    Nayyar, Sachin; Wilson, Lauren; Ganesan, Anand; Sullivan, Thomas; Kuklik, Pawel; Young, Glenn; Sanders, Prashanthan; Roberts-Thomson, Kurt C

    2018-01-01

    Protected channels of surviving myocytes in late postinfarction ventricular scar predispose to ventricular tachycardia (VT). However, only a few patients develop VT spontaneously. We studied differences in electric remodeling and protected channels in late postinfarction patients with and without spontaneous VT. Patients with ischemic cardiomyopathy (ICM) with recurrent sustained monomorphic VT (n = 22) were compared with stable ICM patients without spontaneous VT (control group; n = 5). Left ventricular mapping was performed with a 20-pole catheter. Detailed pace mapping was used to identify channels of protected conduction, and confirmed, when feasible, by entrainment. Anatomical and electrophysiological properties of VT channels and non-VT channels in VT patients and channels in controls were evaluated. Seventy-three (median 3) VTs were inducible in VT patients compared to two (median 0) in controls. The VT channels in VT patients (n = 57, 3 ± 1 per patient) were lengthier (mean ± SEM 53 ± 5 vs. 33 ± 4 vs. 24 ± 8 mm), had longer S-QRS (73 ± 4 vs. 63 ± 3 vs. 44 ± 8 ms), longer conduction time (103 ± 13 vs. 33 ± 4 vs. 24 ± 8 ms), and slower conduction velocity (CV) (0.85 ± 0.21 vs. 1.39 ± 0.20 vs. 1.31 ± 0.41 m/s) than non-VT channels in VT patients (n = 183, 8 ± 6 per patient) (p ≤ 0.01) and channels in controls (n = 46, 9 ± 8 per patient) (p ≤ 0.01). Additionally, non-VT channels in VT patients had longer S-QRS (p = 0.02); however, they were similar in length, conduction time, and CV compared to channels in controls. Channels supporting VT are lengthier, with longer conduction times and slower CV compared to channels in patients without spontaneous VT. These observations may explain why some ICM patients have spontaneous VT and others do not.

  6. Cardiac FKBP12.6 overexpression protects against triggered ventricular tachycardia in pressure overloaded mouse hearts.

    Science.gov (United States)

    Vinet, Laurent; Pezet, Mylène; Bito, Virginie; Briec, François; Biesmans, Liesbeth; Rouet-Benzineb, Patricia; Gellen, Barnabas; Prévilon, Miresta; Chimenti, Stefano; Vilaine, Jean-Paul; Charpentier, Flavien; Sipido, Karin R; Mercadier, Jean-Jacques

    2012-03-01

    Alterations in RyR2 function have been proposed as a major pathophysiological mechanism of arrhythmias and heart failure (HF). Cardiac FKBP12.6 overexpression protects against myocardial infarction-induced HF and catecholamine-promoted ventricular arrhythmias. We tested the hypothesis that FKBP12.6 overexpression protects against maladaptive LVH and triggered ventricular arrhythmias following transverse aorta constriction (TAC) in the mouse. The TAC-associated mortality rate was significantly lower in male transgenic (DT) than in Ctr mice (p < 0.05). TAC-associated maladaptive hypertrophy was blunted in DT mice especially 1 month post-TAC and their SERCA2a/PLB ratio remained unchanged 1 and 2 months post-TAC. Two months after TAC, trains of 30 stimuli (burst pacing) performed following isoproterenol injection (0.2 mg/kg, ip), induced VT in 50% of the TAC-Ctr and in none of the TAC-DT mice (p = 0.022). The increase in myocyte shortening and Ca(2+) spark frequency observed in sham-operated Ctr mice in response to 50 nM isoproterenol was reduced in DT mice, and abolished in TAC-DT mice. NCX1 function was reduced in Sham-DT and TAC-DT compared with Sham-Ctr and TAC-Ctr mice, respectively (p < 0.05 for the 2 comparisons). In mice killed after isoproterenol injection and burst pacing, RyR2 S2814 phosphorylation was decreased by 50% in TAC-DT versus TAC-Ctr mice (p < 0.05), with no change in RyR2 S2808 and PLB S16 and T17 phosphorylation. Cardiac FKBP12.6 overexpression in the mouse blunts pressure overload-induced maladaptive LV remodelling and protects against catecholamine-promoted burst pacing-induced ventricular tachycardia by decreasing cardiac sensitivity to adrenergic stress and RyR2 S2814 phosphorylation, and decreasing NCX1 activity.

  7. Clinical sustained uniform ventricular tachycardia in hypertrophic cardiomyopathy: association with left ventricular apical aneurysm.

    OpenAIRE

    Alfonso, F; Frenneaux, M P; McKenna, W J

    1989-01-01

    Of 51 patients with hypertrophic cardiomyopathy who had episodes of ventricular tachycardia detected during ambulatory electrocardiographic monitoring only two had clinical sustained uniform ventricular tachycardia that required medical treatment because of worsening symptoms. In both patients the arrhythmia was associated with the uncommon finding of an apical aneurysm with angiographically normal coronary arteries.

  8. Cardiac Metastasis of Leiomyosarcoma Complicated with Complete Atrio-Ventricular Block and Ventricular Tachycardia.

    Science.gov (United States)

    Park, Yae Min; Shin, Jae Ouk; Kim, Minsu; Kang, Woong Chol; Moon, Jeonggeun; Chung, Wook-Jin; Sung, Yon Mi

    2016-03-01

    We described a case of a 54-year-old male who presented with dizziness and dyspnea due to cardiac metastasis of leiomyosarcoma. Cardiac metastasis of leiomyosarcoma caused both bradyarrhythmia and tachyarrhythmia in the patient. He was treated with implantation of a permanent pacemaker for management of complete atrio-ventricular block and anti-arrhythmic drug that suppressed ventricular tachycardia successfully.

  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. 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.)

  11. 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....

  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. 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

  14. Right ventricular assist device with membrane oxygenator support for right ventricular failure following implantable left ventricular assist device placement.

    Science.gov (United States)

    Leidenfrost, Jeremy; Prasad, Sunil; Itoh, Akinobu; Lawrance, Christopher P; Bell, Jennifer M; Silvestry, Scott C

    2016-01-01

    Cardiogenic shock from refractory right ventricular (RV) failure during left ventricular assist device placement is associated with high morbidity and mortality. The addition of extracorporeal membrane oxygenation to RV mechanical assistance may help RV recovery and lead to improved outcomes. We retrospectively reviewed all implanted continuous-flow left ventricular assist devices from April 2009 to June 2013. RV mechanical support was utilized for RV failure defined as haemodynamic instability despite vasopressors, pulmonary vascular dilators and inotropic therapy. RV assist devices were utilized with and without in-line membrane oxygenation. During the study period, 267 continuous-flow left ventricular assist devices were implanted. RV mechanical support was utilized in 27 (10%) patients; 12 (46%) had the addition of in-line extracorporeal membrane oxygenation. The mean age of patients with a right ventricular assist device with membrane oxygenation was lower than that in patients with a right ventricular assist device alone (45.6 ± 15.9 vs 64.6 ± 6.5, P = 0.001). Support was weaned in 66% (10 of 15) of patients with right ventricular assist device (RVAD) alone vs 83% (10 of 12) of those with RVAD with membrane oxygenation (P = 0.42). The RVAD was removed after 10.4 ± 9.4 vs 5 ± 2.99 days for patients with a RVAD with membrane oxygenation (P = 0.1). Patients with RVAD with membrane oxygenation had a 30-day mortality rate of 8 vs 47% for those with RVAD alone (P = 0.04). The survival rate after discharge was 86, 63 and 54% at 3, 6 and 12 months for both groups combined. Patients with a RVAD with membrane oxygenation support for acute RV failure after continuous-flow left ventricular assist device implantation had a lower 30-day mortality than those with a RVAD alone. Patients who survive to discharge have a reasonable 1-year survival. Combining membrane oxygenation with RVAD support appears to offer a short-term survival benefit in patients with RV failure

  15. Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling.

    Science.gov (United States)

    Mollenhauer, Martin; Friedrichs, Kai; Lange, Max; Gesenberg, Jan; Remane, Lisa; Kerkenpaß, Christina; Krause, Jenny; Schneider, Johanna; Ravekes, Thorben; Maass, Martina; Halbach, Marcel; Peinkofer, Gabriel; Saric, Tomo; Mehrkens, Dennis; Adam, Matti; Deuschl, Florian G; Lau, Denise; Geertz, Birgit; Manchanda, Kashish; Eschenhagen, Thomas; Kubala, Lukas; Rudolph, Tanja K; Wu, Yuping; Tang, W H Wilson; Hazen, Stanley L; Baldus, Stephan; Klinke, Anna; Rudolph, Volker

    2017-06-23

    Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin-deficient (CD11b -/- ) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo -/- ) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo -/- mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H 2 O 2 incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo -/- mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable

  16. 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

  17. Left ventricular wall stress compendium.

    Science.gov (United States)

    Zhong, L; Ghista, D N; Tan, R S

    2012-01-01

    Left ventricular (LV) wall stress has intrigued scientists and cardiologists since the time of Lame and Laplace in 1800s. The left ventricle is an intriguing organ structure, whose intrinsic design enables it to fill and contract. The development of wall stress is intriguing to cardiologists and biomedical engineers. The role of left ventricle wall stress in cardiac perfusion and pumping as well as in cardiac pathophysiology is a relatively unexplored phenomenon. But even for us to assess this role, we first need accurate determination of in vivo wall stress. However, at this point, 150 years after Lame estimated left ventricle wall stress using the elasticity theory, we are still in the exploratory stage of (i) developing left ventricle models that properly represent left ventricle anatomy and physiology and (ii) obtaining data on left ventricle dynamics. In this paper, we are responding to the need for a comprehensive survey of left ventricle wall stress models, their mechanics, stress computation and results. We have provided herein a compendium of major type of wall stress models: thin-wall models based on the Laplace law, thick-wall shell models, elasticity theory model, thick-wall large deformation models and finite element models. We have compared the mean stress values of these models as well as the variation of stress across the wall. All of the thin-wall and thick-wall shell models are based on idealised ellipsoidal and spherical geometries. However, the elasticity model's shape can vary through the cycle, to simulate the more ellipsoidal shape of the left ventricle in the systolic phase. The finite element models have more representative geometries, but are generally based on animal data, which limits their medical relevance. This paper can enable readers to obtain a comprehensive perspective of left ventricle wall stress models, of how to employ them to determine wall stresses, and be cognizant of the assumptions involved in the use of specific models.

  18. Diastolic And Systolic Right Ventricular Dysfunction Precedes Left Ventricular Dysfunction In Patients Paced From Right Ventricular Apex

    Directory of Open Access Journals (Sweden)

    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

  19. Ca2+/Calmodulin-Dependent Protein Kinase II and Androgen Signaling Pathways Modulate MEF2 Activity in Testosterone-Induced Cardiac Myocyte Hypertrophy

    Directory of Open Access Journals (Sweden)

    Javier Duran

    2017-09-01

    Full Text Available Testosterone is known to induce cardiac hypertrophy through androgen receptor (AR-dependent and -independent pathways, but the molecular underpinnings of the androgen action remain poorly understood. Previous work has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII and myocyte-enhancer factor 2 (MEF2 play key roles in promoting cardiac myocyte growth. In order to gain mechanistic insights into the action of androgens on the heart, we investigated how testosterone affects CaMKII and MEF2 in cardiac myocyte hypertrophy by performing studies on cultured rat cardiac myocytes and hearts obtained from adult male orchiectomized (ORX rats. In cardiac myocytes, MEF2 activity was monitored using a luciferase reporter plasmid, and the effects of CaMKII and AR signaling pathways on MEF2C were examined by using siRNAs and pharmacological inhibitors targeting these two pathways. In the in vivo studies, ORX rats were randomly assigned to groups that were administered vehicle or testosterone (125 mg⋅kg-1⋅week-1 for 5 weeks, and plasma testosterone concentrations were determined using ELISA. Cardiac hypertrophy was evaluated by measuring well-characterized hypertrophy markers. Moreover, western blotting was used to assess CaMKII and phospholamban (PLN phosphorylation, and MEF2C and AR protein levels in extracts of left-ventricle tissue from control and testosterone-treated ORX rats. Whereas testosterone treatment increased the phosphorylation levels of CaMKII (Thr286 and phospholambam (PLN (Thr17 in cardiac myocytes in a time- and concentration-dependent manner, testosterone-induced MEF2 activity and cardiac myocyte hypertrophy were prevented upon inhibition of CaMKII, MEF2C, and AR signaling pathways. Notably, in the hypertrophied hearts obtained from testosterone-administered ORX rats, both CaMKII and PLN phosphorylation levels and AR and MEF2 protein levels were increased. Thus, this study presents the first evidence indicating that

  20. 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...

  1. 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

  2. Differing Effects of Younger and Older Human Plasma on C2C12 Myocytes in Vitro

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    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

  3. 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

    2016-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

  4. 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.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    A4 expression primarily colocalizes with markers of fibroblasts. In hypertrophy elicited by aortic banding/stenosis or myocardial infarction, this expression is increased. Moreover, invading macrophages and leucocytes stain strongly for S100A4, further increasing cardiac levels of S100A4 protein...... and immunoblotting that S100A4 mRNA and protein is upregulated in hypertrophic rat and human hearts and show by way of confocal microscopy that S100A4 protein, but not mRNA, appears in cardiac myocytes only in the border zone after an acute ischemic event in rat and human hearts. In normal rat and human hearts, S100...... after injury. Promisingly, recombinant S100A4 protein elicited a robust hypertrophic response and increased the number of viable cells in cardiac myocyte cultures by inhibiting apoptosis. We also found that ERK1/2 activation was necessary for both the hypertrophy and survival effects of S100A4 in vitro...

  6. Ca2+ alternans in a cardiac myocyte model that uses moment equations to represent heterogeneous junctional SR Ca2+.

    Science.gov (United States)

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

    2010-07-21

    Multiscale whole-cell models that accurately represent local control of Ca2+-induced Ca2+ release in cardiac myocytes can reproduce high-gain Ca2+ release that is graded with changes in membrane potential. Using a recently introduced formalism that represents heterogeneous local Ca2+ using moment equations, we present a model of cardiac myocyte Ca2+ cycling that exhibits alternating sarcoplasmic reticulum (SR) Ca2+ release when periodically stimulated by depolarizing voltage pulses. The model predicts that the distribution of junctional SR [Ca2+] across a large population of Ca2+ release units is distinct on alternating cycles. Load-release and release-uptake functions computed from this model give insight into how Ca2+ fluxes and stimulation frequency combine to determine the presence or absence of Ca2+ alternans. Our results show that the conditions for the onset of Ca2+ alternans cannot be explained solely by the steepness of the load-release function, but that changes in the release-uptake process also play an important role. We analyze the effect of the junctional SR refilling time constant on Ca2+ alternans and conclude that physiologically realistic models of defective Ca2+ cycling must represent the dynamics of heterogeneous junctional SR [Ca2+] without assuming rapid equilibration of junctional and network SR [Ca2+]. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. 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.

  8. 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; Laurence, Graham G.; Coleman, Bernell R.; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E.

    2011-01-01

    Summary Background 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. Material/Methods 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. Results 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. Conclusions 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. PMID:21709626

  9. 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.

  10. 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

  11. [Ventricular tachyarrhythmias in patients with cardiomyopathy

    DEFF Research Database (Denmark)

    Henningsen, K.; Christensen, A.H.; Svendsen, Jesper Hastrup

    2008-01-01

    INTRODUCTION: The purpose of this study was to determine the number and distribution of cardiomyopathies as the aetiology of ventricular tachyarrhythmias among patients discharged from the Department of Cardiology, Rigshospitalet. MATERIALS AND METHODS: The study was a retrospective review......), 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...... cardiology department. Implantation of an ICD device has a central position in the treatment of patients with cardiomyopathy and ventricular tachyarrythmias and is primarily used as a prophylactic treatment Udgivelsesdato: 2008/6/16...

  12. Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence

    Science.gov (United States)

    Atluri, Pavan; Fairman, Alexander S.; MacArthur, John W.; Goldstone, Andrew B.; Cohen, Jeffrey E.; Howard, Jessica L.; Zalewski, Christyna M.; Shudo, Yasuhiro; Woo, Y. Joseph

    2014-01-01

    Background Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair. Methods One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD. Results There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term. Conclusion Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant. PMID:24118109

  13. 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.

  14. Prevalence and Clinical Correlates of Ventricular Arrhythmias on 24 ...

    African Journals Online (AJOL)

    This study examined the prevalence and clinical correlates of ventricular arrhythmias in individuals without apparent heart disease. Method 24-Hour ambulatory electrocardiogram was recorded in 60 apparently healthy subjects with normal echocardiography findings. Premature ventricular complex was analyzed and

  15. Advanced quantitative echocardiography in arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Hastrup Svendsen, Jesper; Sogaard, Peter

    2007-01-01

    BACKGROUND: Arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) is a regional disease of the RV myocardium with variable degrees of left ventricular involvement. Three-dimensional echocardiography and Doppler tissue imaging (DTI) are new echocardiographic modalities for the evaluation of ...

  16. Reversal of left ventricular hypertrophy by propranolol in ...

    African Journals Online (AJOL)

    Background: Hypertension contributes significantly to the development of left ventricular hypertrophy. Left ventricular hypertrophy is associated with increased incidence of sudden cardiac death. Recognition and management of hypertension is, therefore, imperative. Objective: To establish whether propranolol can reverse ...

  17. Evaluation of right ventricular volumes measured by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Møgelvang, J; Stubgaard, M; Thomsen, C

    1988-01-01

    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...... 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...... 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...

  18. Ventricular tachycardia associated with radiation-induced cardiac sarcoma.

    Science.gov (United States)

    Beaty, Elijah H; Ballany, Wassim; Trohman, Richard G; Madias, Christopher

    2014-12-01

    Cardiac tumors can lead to distinct electrocardiographic changes and ventricular arrhythmias. Benign and malignant cardiac tumors have been associated with ventricular tachycardia. When possible, benign tumors should be resected when ventricular arrhythmias are intractable. Chemotherapy can shrink malignant tumors and eliminate arrhythmias. We report the case of a 52-year-old woman with breast sarcoma whom we diagnosed with myocardial metastasis after she presented with palpitations. The initial electrocardiogram revealed sinus rhythm with new right bundle branch block and ST-segment elevation in the anterior precordial leads. During telemetry, hemodynamically stable, sustained ventricular tachycardia with right ventricular localization was detected. Images showed a myocardial mass in the right ventricular free wall. Amiodarone suppressed the arrhythmia. To our knowledge, this is the first report of ventricular tachycardia associated with radiation-induced undifferentiated sarcoma. We discuss the distinct electrocardiographic changes and ventricular arrhythmias that can be associated with cardiac tumors, and we review the relevant medical literature.

  19. Failure in short-term prediction of ventricular tachycardia and ventricular fibrillation from continuous electrocardiogram in intensive care unit patients.

    Science.gov (United States)

    Sachdev, Molly; Fetics, Barry J; Lai, Shenghan; Dalal, Darshan; Insel, Jerald; Berger, Ronald D

    2010-01-01

    Patients in the intensive care unit (ICU) setting are prone to malignant ventricular arrhythmias. We sought to test whether electrocardiographic (ECG) markers of autonomic tone, ventricular irritability, and repolarization lability could be used in short-term prediction of ventricular arrhythmias in this patient population. We studied 38 patients with sustained (>30 seconds) monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, or ventricular fibrillation while monitored in the ICU and 30 patients without arrhythmia in the ICU who served as controls. All patients had at least 12 hours of continuously recorded multilead ECG before arrhythmic event. Mean heart rate and measures of heart rate variability, QT variability, and ventricular ectopy were quantified in 1-hour epochs for the 12 hours before the arrhythmic event and in 5-minute epochs for the last hour preevent (and using a random termination time point in controls). A modest downward trend in QT variability and a rise in heart rate were observed hours before polymorphic ventricular tachycardia and ventricular fibrillation events, although no significant changes heralded monomorphic ventricular tachycardia and no changes in any parameter predicted imminent ventricular arrhythmia of any type. There were no significant differences in ECG parameters between arrhythmia patients and controls. In ICU patients, sustained ventricular arrhythmias are not preceded by change in ECG measures of autonomic tone, repolarization variability, and ventricular ectopy. Short-term arrhythmia prediction may be difficult or impossible in this patient population based on ECG measures alone. Copyright 2010 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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.)

  2. Aneurysmal aorto-right ventricular tunnel.

    Science.gov (United States)

    Singh, Sushil Kumar; Dwivedi, Sudhanshu Kumar; Kumar, Ambrish; Vijay, Sudarshan Kumar; Rajput, Nitin; Devenraj, Vijyant; Lal Sahni, Jeevan

    2012-02-01

    A successful closure of an aneurysmal aorto-right ventricular tunnel (ARVT) in a 16-year-old male patient is reported here. An attempt at device closure had failed in this patient. Diagnosis was confirmed by Doppler echocardiography, 3-dimensional computed tomography, and cardiac catheterization. Surgical closure with a Dacron patch (W.L. Gore & Associates, Flagstaff, AZ) at the aortic end and direct closure at the ventricular end was done successfully with the patient under mild hypothermia. The postoperative echocardiogram showed a competent aortic valve with a closed ARVT. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  3. 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.

  4. Double sequential defibrillation for refractory ventricular fibrillation.

    Science.gov (United States)

    El Tawil, Chady; Mrad, Sandra; Khishfe, Basem F

    2017-12-01

    A 54-year-old suffered from an out-of-hospital cardiac arrest. Compressions were started within minutes and the patient was in refractory ventricular fibrillation despite multiple asynchronized shocks and maximal doses of antiarrhythmic agents. Double sequential defibrillation was attempted with successful Return Of Spontaneous Circulation (ROSC) after a total of 61min of cardiac arrest. The patient was discharged home neurologically intact. Double sequential defibrillation could be a simple effective approach to patients with refractory ventricular fibrillation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. 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

  6. Cardiac sarcoidosis mimicking arrhythmogenic right ventricular dysplasia

    Science.gov (United States)

    Steger, Christina Maria; Hager, Thomas; Antretter, Herwig; Hoyer, Hans Xaver; Altenberger, Johann; Pölzl, Gerhard; Müller, Ludwig; Höfer, Daniel

    2009-01-01

    Isolated manifestation of sarcoidosis in the heart is very rare. The present work describes the case of a 41-year-old woman with ventricular tachycardia and severe symptoms of heart failure in June 2006. Clinical, MRI and echocardiographic findings revealed the diagnosis of an arrhythmogenic right ventricular dysplasia. Due to the severe progression of the disease, cardiac transplantation was performed in August 2007. Histopathological examination of the explanted heart, however, revealed numerous non-necrotising granulomas with giant cells, lymphocytic infiltration and interstitial fibrosis, finally confirming the diagnosis of a myocardial sarcoidosis. PMID:22096465

  7. Right ventricular cardiomyopathy meeting the arrhythmogenic right ventricular dysplasia revised criteria? Do not forget sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Vasaturo, Sabina; Ploeg, David E.; Zeppenfeld, Katja; Veselic-Charvat, Maud [Leiden University Medical Center, Leiden (Netherlands); Buitrago, Guadalupe [Dept. of Radiology, Hospital General Universitario Gregorio Maranon, Madrid (Spain)

    2015-06-15

    A 53-year-old woman was referred for ventricular fibrillation with resuscitation. A CT-angiography showed signs of a right ventricular enlargement without obvious cause. A cardiac MRI demonstrated a dilated and hypokinetic right ventricle with extensive late gadolinium enhancement. Arrhythmogenic right ventricular dysplasia (ARVD) was suspected according to the {sup r}evised ARVD task force criteria{sup .} An endomyocardial biopsy was inconclusive. The patient developed purulent pericarditis after epicardial ablation therapy and died of toxic shock syndrome. The post-mortem pathologic examination demonstrated sarcoidosis involving the heart, lungs, and thyroid gland.

  8. Symbolic representation and visual querying of left ventricular image sequences.

    Science.gov (United States)

    Baroni, M; Del Bimbo, A; Evangelist, A; Vicario, E

    1999-01-01

    In the evaluation of regional left ventricular function, relevant cardiac disorders manifest themselves not only in static features, such as shape descriptors and motion excursion in end-diastolic and end-systolic frames, but also in their temporal evolution. In common diagnostic practice, such dynamic patterns are analysed by direct inspection of frame sequences through the use of a moviola. This permits only a subjective and poorly defined evaluation of functional parameters, and definitely prevents a systematic and reproducible analysis of large sets of reports. Retrieval by contents techniques may overcome this limitation by permitting the automatic comparison of the reports in a database against queries expressing descriptive properties related to significant pathological conditions. A system is presented which is aimed at investigating the potential of this approach by supporting retrieval by contents from a database of cineangiographic or echocardiographic images. The system relies on a symbolic description of both geometrical and temporal properties of left ventricular contours. This is derived automatically by an image processing and interpretation module and associated with the report at its storage time. In the retrieval stage, queries are expressed by means of an iconic visual language which describes searched content properties over a computer screen. The system automatically interprets iconic statements and compares them against concrete descriptions in the database. This enables medical users to interact with the system to search for motion and shape abnormalities on a regional basis, in single or homogeneous groups of reports, so as to enable both prospective and retrospective diagnosis.

  9. 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.

  10. Right Ventricular Assist Device Configuration for Remote Decannulation.

    Science.gov (United States)

    Tchantchaleishvili, Vakhtang; Sagebin, Fabio; Massey, Howard Todd

    2016-01-01

    Preoperative risk factors, intraoperative fluid shifts, and transfusions place patients at increased risk for right ventricular failure during left ventricular assist device implantation. Despite aggressive use of inotropes and pulmonary vasodilators, in severe cases of RV failure, a right ventricular assist device may be required. For the past several years, we have been implanting right ventricular assist devices in the presented configuration, allowing less invasive removal without sternotomy. The method is presented herein.

  11. Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy

    NARCIS (Netherlands)

    Schroen, Blanche; Leenders, Joost J.; van Erk, Arie; Bertrand, Anne T.; van Loon, Mirjam; van Leeuwen, Rick E.; Kubben, Nard; Duisters, Rudy F.; Schellings, Mark W.; Janssen, Ben J.; Debets, Jacques J.; Schwake, Michael; Høydal, Morten A.; Heymans, Stephane; Saftig, Paul; Pinto, Yigal M.

    2007-01-01

    The intercalated disc (ID) of cardiac myocytes is emerging as a crucial structure in the heart. Loss of ID proteins like N-cadherin causes lethal cardiac abnormalities, and mutations in ID proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated

  12. Effects of insulin-like growth factor-I, insulin, and leucine on protein turnover and pathways that regulate ubiquitin ligase expression in rainbow trout primary myocytes

    Science.gov (United States)

    The effects of insulin-like growth factor-I (IGF-I), insulin, and leucine on protein turnover and pathways that regulate proteolytic gene expression and protein polyubiquitination were investigated in primary cultures of four day old rainbow trout myocytes. Supplementing media with 100 nM IGF-I inc...

  13. 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.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    that phosphorylates p90 Ribosomal S6 Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction. Moreover, the beta-arrestin2-dependent ERK1/2 signal supports intact proliferation of cardiac myocytes. In contrast to G(q)-activated ERK1/2, and in keeping with its failure to translocate to the nucleus...

  15. 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.

  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. 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.

  18. 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.

  19. Prevalence of left ventricular diastolic dysfunction in newly ...

    African Journals Online (AJOL)

    They were divided into hypertensives without left ventricular hypertrophy and those with left ventricular hypertrophy based on echocardiographically determined left ventricular mass index. Pulsed Doppler transmitral inflow and the pulmonary venous flow waves were used to categorise the patterns of diastolic dysfunction.

  20. Patterns of left ventricular geometry in hypertensive patients in ...

    African Journals Online (AJOL)

    Systemic hypertension is associated with different left ventricular geometric adaptations, which are matched to systemic hemodynamics and ventricular load. Four geometric patterns have been described. The prevalence of these left ventricular geometric patterns in hypertension has been reported in other places but, the ...

  1. 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 ...

  2. Left Ventricular Pseudoaneurysm Perceived as a Left Lung Mass

    Directory of Open Access Journals (Sweden)

    Ugur Gocen

    2013-02-01

    Full Text Available Left ventricular pseudo-aneurysm is a rare complication of aneurysmectomy. We present a case of surgically-treated left ventricular pseudo-aneurysm which was diagnosed three years after coronary artery bypass grafting and left ventricular aneurysmectomy. The presenting symptoms, diagnostic evaluation and surgical repair are described. [Cukurova Med J 2013; 38(1.000: 123-125

  3. 21 CFR 870.3545 - Ventricular bypass (assist) device.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ventricular bypass (assist) device. 870.3545... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3545 Ventricular bypass (assist) device. (a) Identification. A ventricular bypass (assist) device is a device that assists...

  4. Detrusor myocyte autophagy protects the bladder function via inhibiting the inflammation in cyclophosphamide-induced cystitis in rats.

    Directory of Open Access Journals (Sweden)

    Jiang Zhao

    Full Text Available Autophagy, a highly conserved homeostatic cellular process that removes and recycles damaged proteins and organelles in response to cellular stress, is believed to play a crucial role in the immune response and inflammation. The role of autophagy in bladder cystitis, however, has not well been clarified. Here we investigate the role of detrusor myocytes autophagy (DMA in cyclophosphamide-induced cystitis animal model. 164 female Sprague-Dawley rats were randomized into three experimental groups and compared to three control groups, respectively. The expressions of microtubule-associated protein 1 light chain 3 (LC3, p-p70s6k (the phosphorylated form of ribosomal protein S6, SOD2 (superoxide dismutase 2 in the bladder muscular layer were measured using western blot. The co-location of LC3, alpha-smooth muscle actin (α-SMA, and autophagic vacuoles were investigated with double-labeled immunofluorescence and transmission electron microscopy (TEM. The expression of lL-1β, IL-6, IL-8, malondialdehyde (MDA, and glutathione (GSH in the detrusor layer were analyzed using ELISA. The bladder inflammation and the number of mast cells in the muscular layer were analyzed by histology. The bladder function was evaluated using cystometry. In cyclophosphamide-induced cystitis, autophagy was detected in detrusor myocytes by increased LC3, p-p70s6k expression, and autophagosomes. However, the presence of enhanced inflammation and oxidative stress in the cyclophosphamide-treated group suggest autophagy of detrusor myocytes may not be sufficiently activated. Inflammation and oxidative stress were significantly decreased and the bladder histology and micturition function were significantly improved with rapamycin (RAPA, autophagy agonist pre-treatment. In contrast, inflammation and oxidative stress were dramatically increased and the bladder histology and function were negatively affected with chloroquine (CQ, autophagy blocker pre-treated. These findings

  5. 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.

  6. left ventricular hypertrophy in renal failure a review

    African Journals Online (AJOL)

    Myocyte Lengthening lntermyocardial. fibrosis. However, it appears that factors other than hypertension are also important in the pathogenesis of LVH, since they observed substantial regression of. LVH in 8 of 12 patients following renal transplantation despite no change in blood pressure levels.24. Many authors found a ...

  7. 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

  8. Left ventricular non-compaction cardiomyopathy and left ventricular assist device: a word of caution.

    Science.gov (United States)

    Kornberger, A; Stock, U A; Risteski, P; Beiras Fernandez, A

    2016-07-15

    In patients with left ventricular non-compaction (LVNC), implantation of a left ventricular assist device (LVAD) may be performed as a bridge to transplantation. In this respect, the particular characteristics of the left ventricular myocardium may represent a challenge. We report a patient with LVNC who required urgent heart transplantation for inflow cannula obstruction nine months after receiving a LVAD. LVAD parameters, echocardiography and examination of the explanted heart suggested changes of left ventricular configuration brought about by LVAD support as the most likely cause of inflow cannula obstruction. We conclude that changes experienced by non-compacted myocardium during LVAD support may give rise to inflow cannula obstruction and flow reduction. Presence of LVNC mandates tight surveillance for changes in LV configuration and LVAD flow characteristics and may justify urgent transplantation listing status.

  9. 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

    2013-01-01

    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. PMID:24287918

  10. 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.

  11. Left ventricular mass: Myxoma or thrombus?

    Directory of Open Access Journals (Sweden)

    Monish S Raut

    2015-01-01

    Full Text Available Patient with embolic episode should always be evaluated for cardiac mass. Mass in left ventricular can be a myxoma or thrombus even in a normal functioning heart . In either case, mobile mass with embolic potential should be surgically resected.

  12. 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 ...

  13. CASE REPORT Arrythmogenic right ventricular dysplasia ...

    African Journals Online (AJOL)

    A 60-year-old woman with metabolic syndrome was referred to us with a history of chest pain, syncopy and ... a dedicated cardiac phased array coil. Bright blood cine imaging in the short axis, right ventricular outflow tract (RVOT) and 4 chamber planes were obtained. Black blood images were acquired in short axis and 4.

  14. Echocardiography in the diagnosis left ventricular noncompaction

    Directory of Open Access Journals (Sweden)

    Song Ze-Zhou

    2008-12-01

    Full Text Available Abstract Echocardiography is the method of choice to establish a diagnosis and determine a treatment plan for patients with noncompaction of ventricular myocardium (NVM. The 2-dimentional echocardiography, 3-dimentional echocardiography, color Doppler echocardiography and contrast-enhanced echocardiography are of critical importance for diagnosis and family screening of NVM.

  15. Left Ventricular Thrombus among patients undergoing Transthoracic ...

    African Journals Online (AJOL)

    Objective: Left Ventricular Thrombus (LVT) is a well recognized complication of various cardiac conditions, particularly following an acute anterior myocardial infarction and in those with systolic congestive heart failure. Transthoracic echocardiography (TTE) remains the most common imaging modality to make the diagnosis ...

  16. 3-Dimensional Right Ventricular Volume Assessment

    NARCIS (Netherlands)

    Jainandunsing, Jayant S.; Matyal, Robina; Shahul, Sajid S.; Wang, Angela; Woltersom, Bozena; Mahmood, Feroze

    Purpose: The purpose of this review was to evaluate new computer software available for 3-dimensional right ventricular (RV) volume estimation. Description: Based on 2-dimensional echocardiography, various algorithms have been used for RV volume estimation. These are complex, time-consuming

  17. 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.

    2015-01-01

    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. PMID:26002969

  18. 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.

  19. Local control of nuclear calcium signaling in cardiac myocytes by perinuclear microdomains of sarcolemmal insulin-like growth factor 1 receptors.

    Science.gov (United States)

    Ibarra, Cristian; Vicencio, Jose M; Estrada, Manuel; Lin, Yingbo; Rocco, Paola; Rebellato, Paola; Munoz, Juan P; Garcia-Prieto, Jaime; Quest, Andrew F G; Chiong, Mario; Davidson, Sean M; Bulatovic, Ivana; Grinnemo, Karl-Henrik; Larsson, Olle; Szabadkai, Gyorgy; Uhlén, Per; Jaimovich, Enrique; Lavandero, Sergio

    2013-01-18

    The ability of a cell to independently regulate nuclear and cytosolic Ca(2+) signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca(2+) signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca(2+) signals locally has not been explored. To study the role of perinuclear sarcolemma in selective nuclear Ca(2+) signaling. We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca(2+) signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca(2+) signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca(2+) release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca(2+) buffers--parvalbumin--with cytosolic or nuclear localization demonstrated that the nuclear Ca(2+) handling system is physically and functionally segregated from the cytosolic Ca(2+) signaling machinery. These data reveal the existence of an inositol 1,4,5-trisphosphate-dependent nuclear Ca(2+) toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca(2+) signaling in response to an extracellular ligand.

  20. Role of Ca2+ in the control of H2O2-modulated phosphorylation pathways leading to eNOS activation in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Juliano L Sartoretto

    Full Text Available Nitric oxide (NO and hydrogen peroxide (H(2O(2 play key roles in physiological and pathological responses in cardiac myocytes. The mechanisms whereby H(2O(2-modulated phosphorylation pathways regulate the endothelial isoform of nitric oxide synthase (eNOS in these cells are incompletely understood. We show here that H(2O(2 treatment of adult mouse cardiac myocytes leads to increases in intracellular Ca(2+ ([Ca(2+](i, and document that activity of the L-type Ca(2+ channel is necessary for the H(2O(2-promoted increase in sarcomere shortening and of [Ca(2+](i. Using the chemical NO sensor Cu(2(FL2E, we discovered that the H(2O(2-promoted increase in cardiac myocyte NO synthesis requires activation of the L-type Ca(2+ channel, as well as phosphorylation of the AMP-activated protein kinase (AMPK, and mitogen-activated protein kinase kinase 1/2 (MEK1/2. Moreover, H(2O(2-stimulated phosphorylations of eNOS, AMPK, MEK1/2, and ERK1/2 all depend on both an increase in [Ca(2+](i as well as the activation of protein kinase C (PKC. We also found that H(2O(2-promoted cardiac myocyte eNOS translocation from peripheral membranes to internal sites is abrogated by the L-type Ca(2+ channel blocker nifedipine. We have previously shown that kinase Akt is also involved in H(2O(2-promoted eNOS phosphorylation. Here we present evidence documenting that H(2O(2-promoted Akt phosphorylation is dependent on activation of the L-type Ca(2+ channel, but is independent of PKC. These studies establish key roles for Ca(2+- and PKC-dependent signaling pathways in the modulation of cardiac myocyte eNOS activation by H(2O(2.

  1. RIGHT VENTRICULAR MYXOMA INFILTRATING THE TRICUSPID VALVE AND OBSTRUCTING THE RIGHT VENTRICULAR INFLOW AND OUTFLOW TRACTS

    OpenAIRE

    Tezcan, Hakan; Caymaz, Oğuz; Toprak, Ahmet; Fak, Ali Serdar; Yakut, Cevat; Oktay, Ahmet

    2016-01-01

    Myxomas originating in the right ventricle are extremely rare tumors. Herein, a case of right ventricular myxoma, infiltrating the tricuspid valve and causing right ventricular inflow and outflow tract obstruction, is described. Two-dimentional echocardiography diagnosed the mass easily and cardiac Doppler with color-flow examinations defined precisely its hemodynamic consequences to the heart. Magnetic resonance imaging study helped In preoperatively defining its intracardiac extension and t...

  2. Implantation of left ventricular assist device in a patient with left ventricular non-compaction.

    Science.gov (United States)

    Balsara, Keki R; Bierhals, Andrew; Vader, Justin; Pasque, Michael K; Itoh, Aki

    2017-02-01

    Left ventricular noncompaction (LVNC) may result in systolic left ventricular (LV) failure resulting in the need for heart transplantation. LV assist devices (LVAD) have been used to bridge these patients to transplantation; however, the extensive trabeculations found in these patients predispose them to thromboembolic events and pump thrombosis. We describe a patient with LVNC in whom an aggressive surgical approach was used to debride the LV cavity of trabeculations to successfully implant an LVAD. © 2017 Wiley Periodicals, Inc.

  3. 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

  4. A miR-208-Mef2 axis drives the decompensation of right ventricular function in pulmonary hypertension.

    Science.gov (United States)

    Paulin, Roxane; Sutendra, Gopinath; Gurtu, Vikram; Dromparis, Peter; Haromy, Alois; Provencher, Steeve; Bonnet, Sebastien; Michelakis, Evangelos D

    2015-01-02

    Right ventricular (RV) failure is a major cause of morbidity and mortality in pulmonary hypertension, but its mechanism remains unknown. Myocyte enhancer factor 2 (Mef2) has been implicated in RV development, regulating metabolic, contractile, and angiogenic genes. Moreover, Mef2 regulates microRNAs that have emerged as important determinants of cardiac development and disease, but for which the role in RV is still unclear. We hypothesized a critical role of a Mef2-microRNAs axis in RV failure. In a rat pulmonary hypertension model (monocrotaline), we studied RV free wall tissues from rats with normal, compensated, and decompensated RV hypertrophy, carefully defined based on clinically relevant parameters, including RV systolic and end-diastolic pressures, cardiac output, RV size, and morbidity. Mef2c expression was sharply increased in compensating phase of RVH tissues but was lost in decompensation phase of RVH. An unbiased screening of microRNAs in our model resulted to a short microRNA signature of decompensated RV failure, which included the myocardium-specific miR-208, which was progressively downregulated as RV failure progressed, in contrast to what is described in left ventricular failure. With mechanistic in vitro experiments using neonatal and adult RV cardiomyocytes, we showed that miR-208 inhibition, as well as tumor necrosis factor-α, activates the complex mediator of transcription 13/nuclear receptor corepressor 1 axis, which in turn promotes Mef2 inhibition, closing a self-limiting feedback loop, driving the transition from compensating phase of RVH toward decompensation phase of RVH. In our model, serum tumor necrosis factor-α levels progressively increased with time while serum miR-208 levels decreased, mirroring its levels in RV myocardium. We describe an RV-specific mechanism for heart failure, which could potentially lead to new biomarkers and therapeutic targets. © 2014 American Heart Association, Inc.

  5. Ventricular Energetics in Pediatric Left Ventricular