Sample records for cardiac excitation-contraction coupling

  1. Integrative systems models of cardiac excitation-contraction coupling. (United States)

    Greenstein, Joseph L; Winslow, Raimond L


    Excitation-contraction coupling in the cardiac myocyte is mediated by a number of highly integrated mechanisms of intracellular Ca²(+) transport. The complexity and integrative nature of heart cell electrophysiology and Ca²(+) cycling has led to an evolution of computational models that have played a crucial role in shaping our understanding of heart function. An important emerging theme in systems biology is that the detailed nature of local signaling events, such as those that occur in the cardiac dyad, have important consequences at higher biological scales. Multiscale modeling techniques have revealed many mechanistic links between microscale events, such as Ca²(+) binding to a channel protein, and macroscale phenomena, such as excitation-contraction coupling gain. Here, we review experimentally based multiscale computational models of excitation-contraction coupling and the insights that have been gained through their application.

  2. Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling

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    Weckström Matti


    Full Text Available Abstract Background The cardiomyocyte is a prime example of inherently complex biological system with inter- and cross-connected feedback loops in signalling, forming the basic properties of intracellular homeostasis. Functional properties of cells and tissues have been studied e.g. with powerful tools of genetic engineering, combined with extensive experimentation. While this approach provides accurate information about the physiology at the endpoint, complementary methods, such as mathematical modelling, can provide more detailed information about the processes that have lead to the endpoint phenotype. Results In order to gain novel mechanistic information of the excitation-contraction coupling in normal myocytes and to analyze sophisticated genetically engineered heart models, we have built a mathematical model of a mouse ventricular myocyte. In addition to the fundamental components of membrane excitation, calcium signalling and contraction, our integrated model includes the calcium-calmodulin-dependent enzyme cascade and the regulation it imposes on the proteins involved in excitation-contraction coupling. With the model, we investigate the effects of three genetic modifications that interfere with calcium signalling: 1 ablation of phospholamban, 2 disruption of the regulation of L-type calcium channels by calcium-calmodulin-dependent kinase II (CaMK and 3 overexpression of CaMK. We show that the key features of the experimental phenotypes involve physiological compensatory and autoregulatory mechanisms that bring the system to a state closer to the original wild-type phenotype in all transgenic models. A drastic phenotype was found when the genetic modification disrupts the regulatory signalling system itself, i.e. the CaMK overexpression model. Conclusion The novel features of the presented cardiomyocyte model enable accurate description of excitation-contraction coupling. The model is thus an applicable tool for further studies of both

  3. Photoperiod-dependent modulation of cardiac excitation contraction coupling in the Siberian hamster. (United States)

    Dibb, K M; Hagarty, C L; Loudon, A S I; Trafford, A W


    In mammals, changes in photoperiod regulate a diverse array of physiological and behavioral processes, an example of which in the Siberian hamster (Phodopus sungorus) is the expression of bouts of daily torpor following prolonged exposure to a short photoperiod. During torpor, body temperature drops dramatically; however, unlike in nonhibernating or nontorpid species, the myocardium retains the ability to contract and is resistant to the development of arrhythmias. In the present study, we sought to determine whether exposure to a short photoperiod results in alterations to cardiac excitation-contraction coupling, thus potentially enabling the heart to survive periods of low temperature during torpor. Experiments were performed on single ventricular myocytes freshly isolated from the hearts of Siberian hamsters that had been exposed to either 12 wk of short-day lengths (SD) or 12 wk of long-day lengths (LD). In SD-acclimated animals, the amplitude of the systolic Ca(2+) transient was increased (e.g., from 142 +/- 17 nmol/l in LD to 229 +/- 31 nmol/l in SD at 4 Hz; P < 0.001). The increased Ca(2+) transient amplitude in the SD-acclimated animals was not associated with any change in the shape or duration of the action potential. However, sarcoplasmic reticulum Ca(2+) content measured after current-clamp stimulation was increased in the SD-acclimated animals (at 4 Hz, 110 +/- 5 vs. 141 +/- 15 mumol/l, P < 0.05). We propose that short photoperiods reprogram the function of the cardiac sarcoplasmic reticulum, resulting in an increased Ca(2+) content, and that this may be a necessary precursor for maintenance of cardiac function during winter torpor.

  4. Voltage dependence of cardiac excitation-contraction coupling: unitary Ca2+ current amplitude and open channel probability. (United States)

    Altamirano, Julio; Bers, Donald M


    Excitation-contraction coupling in cardiac myocytes occurs by Ca2+-induced Ca2+ release, where L-type Ca2+ current evokes a larger sarcoplasmic reticulum (SR) Ca2+ release. The Ca2+-induced Ca2+ release amplification factor or gain (SR Ca2+ release/I(Ca)) is usually assessed by the V(m) dependence of current and Ca2+ transients. Gain rises at negative V(m), as does single channel I(Ca) (i(Ca)), which has led to the suggestion that the increases of i(Ca) amplitude enhances gain at more negative V(m). However, I(Ca) = NP(o) x i(Ca) (where NP(o) is the number of open channels), and NP(o) and i(Ca) both depend on V(m). To assess how i(Ca) and NP(o) separately influence Ca2+-induced Ca2+ release, we measured I(Ca) and junctional SR Ca2+ release in voltage-clamped rat ventricular myocytes using "Ca2+ spikes" (confocal microscopy). To vary i(Ca) alone, we changed [Ca2+](o) rapidly at constant test V(m) (0 mV) or abruptly repolarized from +120 mV to different V(m) (at constant [Ca2+](o)). To vary NP(o) alone, we altered Ca2+ channel availability by varying holding V(m) (at constant test V(m)). Reducing either i(Ca) or NP(o) alone increased excitation-contraction coupling gain. Thus, increasing i(Ca) does not increase gain at progressively negative test V(m). Such enhanced gain depends on lower NP(o) and reduced redundant Ca2+ channel openings (per junction) and a consequently smaller denominator in the gain equation. Furthermore, modest i(Ca) (at V(m) = 0 mV) may still effectively trigger SR Ca2+ release, whereas at positive V(m) (and smaller i(Ca)), high and well-synchronized channel openings are required for efficient excitation-contraction coupling. At very positive V(m), reduced i(Ca) must explain reduced SR Ca2+ release.

  5. Effects of ryanodine on cardiac contraction, excitation-contraction coupling and "Treppe" in the conscious dog. (United States)

    Kalthof, B; Sato, N; Iwase, M; Shen, Y T; Mirsky, I; Patrick, T A; Vatner, S F


    The effects of ryanodine on left ventricular (LV) function and hemodynamics were studied in 16 conscious dogs, chronically instrumented for measurements of LV pressures and dimensions. Systemic infusion of ryanodine (0.5-4 micrograms/kg i.v.) resulted in a dose-dependent depression of cardiac contraction. For example, ryanodine, 4 micrograms/kg i.v., decreased LV fractional shortening by 30.5 +/- 4.1%, LV dP/dt by 41.5 +/- 4.0% and Vcfc by 37.8 +/- 4.1%, while increasing the isovolumic relaxation time constant, tau, from 23.1 +/- 1.4 to 34.1 +/- 3.6 ms without a major effect on preload or afterload. Ryanodine also depressed (P Treppe") was significantly enhanced (P Treppe" in the conscious dog under the condition of impaired SR calcium release caused by ryanodine, supports the concept that the classical Bowditch "Treppe" reflects either a state of myocardial depression due to alteration in SR calcium handling, or enhanced availability of trans-sarcolemmal Ca2+ influx. This finding may help to understand the discrepancy in the importance of the "Treppe" between conscious animals and more isolated preparations.

  6. Effect of Transmurally Heterogeneous Myocyte Excitation-Contraction Coupling on Left Ventricular Electromechanics



    The excitation-contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We embedded a cell-level excitation-contraction coupling model with region-dependent parameters within a simple finite element model of left ventricular geometry to study effects of electromechanical heterogeneity on local myocardial mechanics and global hemodynamics. This...

  7. Excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes

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    Christopher eKane


    Full Text Available Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs hold enormous potential in many fields of cardiovascular research. Overcoming many of the limitations of their embryonic counterparts, the application of iPSC-CMs ranges from facilitating investigation of familial cardiac disease and pharmacological toxicity screening to personalized medicine and autologous cardiac cell therapies. The main factor preventing the full realization of this potential is the limited maturity of iPSC-CMs, which display a number of substantial differences in comparison to adult cardiomyocytes. Excitation-contraction coupling, a fundamental property of cardiomyocytes, is often described in iPSC-CMs as being more analogous to neonatal than adult cardiomyocytes. With calcium handling linked, directly or indirectly, to almost all other properties of cardiomyocytes, a solid understanding of this process will be crucial to fully realizing the potential of this technology.Here we discuss the implications of differences in excitation-contraction coupling when considering the potential applications of iPSC-CMs in a number of areas as well as detailing the current understanding of this fundamental process in these cells.

  8. Fructose modulates cardiomyocyte excitation-contraction coupling and Ca²⁺ handling in vitro.

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    Kimberley M Mellor

    Full Text Available BACKGROUND: High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated. OBJECTIVE: The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting. METHODS AND RESULTS: The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca²⁺ handling were evaluated under physiological conditions (37°C, 2 mM Ca²⁺, HEPES buffer, 4 Hz stimulation using video edge detection and microfluorimetry (Fura2 methods. Compared with control glucose (11 mM superfusate, 2-deoxyglucose (2 DG, 11 mM substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05 and this effect was completely abrogated with fructose supplementation (11 mM. Similarly, fructose prevented the Ca²⁺ transient delay induced by exposure to 2 DG (time to peak Ca²⁺ transient: 2 DG: 29.0±2.1 ms vs. glucose: 23.6±1.1 ms vs. fructose +2 DG: 23.7±1.0 ms; p<0.05. The presence of the fructose transporter, GLUT5 (Slc2a5 was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT-PCR. CONCLUSION: This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function.

  9. Changes in the organization of excitation-contraction coupling structures in failing human heart.

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    David J Crossman

    Full Text Available BACKGROUND: The cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure. METHODS AND RESULTS: The organization of t-tubules, L-type calcium channels (DHPRs, ryanodine receptors (RyRs and contractile machinery were examined in fixed ventricular tissue samples from both normal and failing hearts (idiopathic (non-ischemic dilated cardiomyopathy using high resolution fluorescent imaging. Wheat germ agglutinin (WGA, Na-Ca exchanger, DHPR and caveolin-3 labels revealed a shift from a predominantly transverse orientation to oblique and axial directions in failing myocytes. In failure, dilation of peripheral t-tubules occurred and a change in the extent of protein glycosylation was evident. There was no change in the fractional area occupied by myofilaments (labeled with phalloidin but there was a small reduction in the number of RyR clusters per unit area. The general relationship between DHPRs and RyR was not changed and RyR labeling overlapped with 51±3% of DHPR labeling in normal hearts. In longitudinal (but not transverse sections there was an ∼30% reduction in the degree of colocalization between DHPRs and RyRs as measured by Pearson's correlation coefficient in failing hearts. CONCLUSIONS: The results show that extensive remodelling of the t-tubular network and associated excitation-contraction coupling proteins occurs in failing human heart. These changes may contribute to abnormal calcium handling in heart failure. The general organization of the t-system and changes observed in failure samples have subtle differences to some animal models although the general direction of changes are generally similar.

  10. Mechanical threshold as a factor in excitation-contraction coupling. (United States)

    Taylor, S R; Preiser, H; Sandow, A


    I(-), CH(3)SO(4) (-), and ClO(4) (-), like other previously studied type A twitch potentiators (Br(-), NO(3) (-), SCN(-), and caffeine), lower the mechanical threshold in K depolarization contractures of frog skeletal muscle. In potentiated twitches, I(-), Br(-), CH(3)SO(4) (-), ClO(4), and SCN, as already reported for NO(3) (-) and caffeine, slightly shorten the latent period (L) and considerably increase the rate of tension development (dP/dt) during the first few milliseconds of the contraction period. Divalent cations (8 mM Ca(2+), 0.5-1.0 mM Zn(2+) and Cd(2+)) raise the mechanical threshold of contractures, and correspondingly affect the twitch by depressing the tension output, increasing L, and decreasing the early dP/dt, thus acting oppositely to the type A potentiators. These various results form a broad, consistent pattern indicating that electromechanical coupling in the twitch is conditioned by a mechanical threshold as it is in the contracture, and suggesting that the lower the threshold, in reference to the raised threshold under the action of the divalent cations, the more effective is a given action potential in activating the twitch as regards especially both its early rate and peak magnitude of tension development. The results suggest that the direct action by which the various agents affect the level of the mechanical threshold involves effects on E-C coupling processes of the T tubular and/or the sarcoplasmic reticulum which control the release of Ca for activating contraction.

  11. Membrane Cholesterol in Skeletal Muscle: A Novel Player in Excitation-Contraction Coupling and Insulin Resistance (United States)

    Barrientos, G.; Sánchez-Aguilera, P.; Jaimovich, E.; Hidalgo, C.


    Membrane cholesterol is critical for signaling processes in a variety of tissues. We will address here current evidence supporting an emerging role of cholesterol on excitation-contraction coupling and glucose transport in skeletal muscle. We have centered our review on the transverse tubule system, a complex network of narrow plasma membrane invaginations that propagate membrane depolarization into the fiber interior and allow nutrient delivery into the fibers. We will discuss current evidence showing that transverse tubule membranes have remarkably high cholesterol levels and we will address how modifications of cholesterol content influence excitation-contraction coupling. In addition, we will discuss how membrane cholesterol levels affect glucose transport by modulating the insertion into the membrane of the main insulin-sensitive glucose transporter GLUT4. Finally, we will address how the increased membrane cholesterol levels displayed by obese animals, which also present insulin resistance, affect these two particular skeletal muscle functions. PMID:28367451

  12. The role of proteases in excitation-contraction coupling failure in muscular dystrophy. (United States)

    Mázala, Davi A G; Grange, Robert W; Chin, Eva R


    Duchenne muscular dystrophy (DMD) is one of the most frequent types of muscular dystrophy. Alterations in intracellular calcium (Ca(2+)) handling are thought to contribute to the disease severity in DMD, possibly due to the activation of Ca(2+)-activated proteases. The purpose of this study was twofold: 1) to determine whether prolonged excitation-contraction (E-C) coupling disruption following repeated contractions is greater in animals lacking both dystrophin and utrophin (mdx/Utr(-/-)) compared with mice lacking only dystrophin (mdx); and 2) to assess whether protease inhibition can prevent E-C coupling failure following repeated tetani in these dystrophic mouse models. Excitation-contraction coupling was assessed using Fura-2 ratio, as an index of intracellular free Ca(2+) concentration, in response to electrical stimulation of single muscle fibers from the flexor digitorum brevis muscle. Resting Fura-2 ratio was higher in dystrophic compared with control (Con) fibers, but peak Fura-2 ratios during stimulation were similar in dystrophic and Con fibers. One hour after a series of repeated tetani, peak Fura-2 ratios were reduced by 30 ± 5.6%, 23 ± 2%, and 36 ± 3.1% in mdx, mdx/Utr(+/-), and mdx/Utr(-/-), respectively, with the greatest reduction in mdx/Utr(-/-) fibers (P contractions is greatest in fibers lacking both dystrophin and utrophin and that prevention of protease activation can mitigate the prolonged E-C coupling impairment. These data further suggest that acute protease inhibition may be useful in reducing muscle weakness in DMD.

  13. Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

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    Fabio Francini


    Full Text Available Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury or disease. Thus, the etiology of atrophy can be different. Atrophy in denervated muscle is a consequence of two factors: 1 the complete lack of motoneuron activity inducing the deficiency of neurotransmitter release and 2 the muscles disuse. The balance of the muscular functions depends on extra- and intra-muscular signals. In the balance are involved the excitation-contraction coupling (ECC, local growth factors, Ca2+-dependent and independent intracellular signals, mechano-sensitivity and mechano-transduction that activate Ca2+-dependent signaling proteins and cytoskeleton- nucleus pathways to the nucleus, that regulate the gene expression. Moreover, retrograde signal from intracellular compartments and cytoskeleton to the sarcolemma are additional factors that regulate the muscle function. Proteolytic systems that operate in atrophic muscles progressively reduce the muscle protein content and so the sarcolemma, ECC and the force generation. In this review we will focus on the more relevant changes of the sarcolemma, excitation-contraction coupling, ECC and mechano-transduction evaluated by electrophysiological methods and observed from early- to long-term denervated skeletal muscles. This review put in particular evidence that long-term denervated muscle maintain a sub-population of fibers with ECC and contractile machinery able to be activated, albeit in lesser amounts, by electrical and mechanical stimulation. Accordingly, this provides a potential molecular explanation of the muscle recovery that occurs in response to rehabilitation strategy as transcutaneous electrical stimulation and passive stretching of denervated muscles, which wre developed as a result of empirical clinical observations.

  14. Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure (United States)

    Lou, Qing; Fedorov, Vadim V.; Glukhov, Alexey V.; Moazami, Nader; Fast, Vladimir G.; Efimov, Igor R.


    Background Excitation-contraction (EC) coupling is altered in the end-stage heart failure (HF). However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective is to study functional remodeling of EC coupling and calcium handling in failing and nonfailing human hearts. Methods and Results We simultaneously optically mapped action potentials (AP) and calcium transients (CaT) in coronary-perfused left ventricular wedge preparations from nonfailing (n = 6) and failing (n = 5) human hearts. Our major findings are: (1) CaT duration minus AP duration was longer at sub-endocardium in failing compared to nonfailing hearts during bradycardia (40 beats/min). (2) The transmural gradient of CaT duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 beats/min). (3) CaT in failing hearts had a flattened plateau at the midmyocardium; and exhibited a “two-component” slow rise at sub-endocardium in three failing hearts. (4) CaT relaxation was slower at sub-endocardium than that at sub-epicardium in both groups. Protein expression of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) was lower at sub-endocardium than that at sub-epicardium in both nonfailing and failing hearts. SERCA2a protein expression at sub-endocardium was lower in hearts with ischemic cardiomyopathy compared with nonischemic cardiomyopathy. Conclusions For the first time, we present direct experimental evidence of transmural heterogeneity of EC coupling and calcium handling in human hearts. End-stage HF is associated with the heterogeneous remodeling of EC coupling and calcium handling. PMID:21502574

  15. Electrical models of excitation-contraction coupling and charge movement in skeletal muscle. (United States)

    Mathias, R T; Levis, R A; Eisenberg, R S


    The consequences of ionic current flow from the T system to the sarcoplasmic reticulum (SR) of skeletal muscle are examined. The Appendix analyzes a simple model in which the conductance gx, linking T system and SR, is in series with a parallel resistor and capacitor having fixed values. The conductance gx is supposed to increase rapidly with depolarization and to decrease slowly with repolarization. Nonlinear transient currents computed from this model have some of the properties of gating currents produced by intramembrane charge movement. In particular, the integral of the transient current upon depolarization approximates that upon repolarization. Thus, equality of nonlinear charge movement can occur without intramembrane charge movement. A more complicated model is used in the text to fit the structure of skeletal muscle and other properties of its charge movement. Rectification is introduced into gx and the membrane conductance of the terminal cisternae to give asymmetry in the time-course of the transient currents and saturation in the curve relating charge movement to depolarization, respectively. The more complex model fits experimental data quite well if the longitudinal tubules of the sarcoplasmic reticulum are isolated from the terminal cisternae by a substantial resistance and if calcium release from the terminal cisternae is, for the most part, electrically silent. Specific experimental tests of the model are proposed, and the implications for excitation-contraction coupling are discussed.

  16. CaMKIId overexpression in hypertrophy and heart failure: cellular consequences for excitation-contraction coupling

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    Maier L.S.


    Full Text Available Ca/calmodulin-dependent protein kinase IIdelta (CaMKIIdelta is the predominant isoform in the heart. During excitation-contraction coupling (ECC CaMKII phosphorylates several Ca-handling proteins including ryanodine receptors (RyR, phospholamban, and L-type Ca channels. CaMKII expression and activity have been shown to correlate positively with impaired ejection fraction in the myocardium of patients with heart failure and CaMKII has been proposed to be a possible compensatory mechanism to keep hearts from complete failure. However, in addition to these acute effects on ECC, CaMKII was shown to be involved in hypertrophic signaling, termed excitation-transcription coupling (ETC. Thus, animal models have shown that overexpression of nuclear isoform CaMKIIdeltaB can induce myocyte hypertrophy. Recent study from our laboratory has suggested that transgenic overexpression of the cytosolic isoform CaMKIIdeltaC in mice causes severe heart failure with altered intracellular Ca handling and protein expression leading to reduced sarcoplasmic reticulum (SR Ca content. Interestingly, the frequency of diastolic spontaneous SR Ca release events (or opening of RyR was greatly enhanced, demonstrating increased diastolic SR Ca leak. This was attributed to increased CaMKII-dependent RyR phosphorylation, resulting in increased and prolonged openings of RyR since Ca spark frequency could be reduced back to normal levels by CaMKII inhibition. This review focuses on acute and chronic effects of CaMKII in ECC and ETC. In summary, CaMKII overexpression can lead to heart failure and CaMKII-dependent RyR hyperphosphorylation seems to be a novel and important mechanism in ECC due to SR Ca leak which may be important in the pathogenesis of heart failure.

  17. Remodeling of excitation-contraction coupling in transgenic mice expressing ATP-insensitive sarcolemmal KATP channels. (United States)

    Flagg, Thomas P; Charpentier, Flavien; Manning-Fox, Jocelyn; Remedi, Maria Sara; Enkvetchakul, Decha; Lopatin, Anatoli; Koster, Joseph; Nichols, Colin


    Reducing the ATP sensitivity of the sarcolemmal ATP-sensitive K(+) (K(ATP)) channel is predicted to lead to active channels in normal metabolic conditions and hence cause shortened ventricular action potentials and reduced myocardial inotropy. We generated transgenic (TG) mice that express an ATP-insensitive K(ATP) channel mutant [Kir6.2(deltaN2-30,K185Q)] under transcriptional control of the alpha-myosin heavy chain promoter. Strikingly, myocyte contraction amplitude was increased in TG myocytes (15.68 +/- 1.15% vs. 10.96 +/- 1.49%), even though K(ATP) channels in TG myocytes are very insensitive to inhibitory ATP. Under normal metabolic conditions, steady-state outward K(+) currents measured under whole cell voltage clamp were elevated in TG myocytes, consistent with threshold K(ATP) activation, but neither the monophasic action potential measured in isolated hearts nor transmembrane action potential measured in right ventricular muscle preparations were shortened at physiological pacing cycles. Taken together, these results suggest that there is a compensatory remodeling of excitation-contraction coupling in TG myocytes. Whereas there were no obvious differences in other K(+) conductances, peak L-type Ca(2+) current (I(Ca)) density (-16.42 +/- 2.37 pA/pF) in the TG was increased compared with the wild type (-8.43 +/- 1.01 pA/pF). Isoproterenol approximately doubled both I(Ca) and contraction amplitude in wild-type myocytes but failed to induce a significant increase in TG myocytes. Baseline and isoproterenol-stimulated cAMP concentrations were not different in wild-type and TG hearts, suggesting that the enhancement of I(Ca) in the latter does not result from elevated cAMP. Collectively, the data demonstrate that a compensatory increase in I(Ca) counteracts a mild activation of ATP-insensitive K(ATP) channels to maintain the action potential duration and elevate the inotropic state of TG hearts.

  18. Effects of membrane cholesterol manipulation on excitation-contraction coupling in skeletal muscle of the toad. (United States)

    Launikonis, B S; Stephenson, D G


    1. Single mechanically skinned fibres and intact bundles of fibres from the twitch region of the iliofibularis muscle of cane toads were used to investigate the effects of membrane cholesterol manipulation on excitation-contraction (E-C) coupling. The cholesterol content of membranes was manipulated with methyl-beta-cyclodextrin (MbetaCD). 2. In mechanically skinned fibres, depletion of membrane cholesterol with MbetaCD caused a dose- and time-dependent decrease in transverse tubular (t)-system depolarization-induced force responses (TSDIFRs). TSDIFRs were completely abolished within 2 min in the presence of 10 mM MbetaCD but were not affected after 2 min in the presence of a 10 mM MbetaCD-1 mM cholesterol complex. There was a very steep dependence between the change in TSDIFRs and the MbetaCD : cholesterol ratio at 10 mM MbetaCD, indicating that the inhibitory effect of MbetaCD was due to membrane cholesterol depletion and not to a pharmacological effect of the agent. Tetanic responses in bundles of intact fibres were abolished after 3-4 h in the presence of 10 mM MbetaCD. 3. The duration of TSDIFRs increased markedly soon (< 2 min) after application of 10 mM MbetaCD and 10 mM MbetaCD-cholesterol complexes, but the Ca(2+) activation properties of the contractile apparatus were minimally affected by 10 mM MbetaCD. The Ca(2+) handling abilities of the sarcoplasmic reticulum appeared to be modified after 10 min exposure to 10 mM MbetaCD. 4. Confocal laser scanning microscopy revealed that the integrity of the t-system was not compromised by either intra- or extracellular application of 10 mM MbetaCD and that a large [Ca(2+)] gradient was maintained across the t-system. 5. Membrane cholesterol depletion caused rapid depolarization of the polarized t-system as shown independently by spontaneous TSDIFRs induced by MbetaCD and by changes in the fluorescence intensity of an anionic potentiometric dye (DiBAC(4)(3)) in the presence of MbetaCD. This rapid depolarization of

  19. Mitochondrial calcium uptake regulates rapid calcium transients in skeletal muscle during excitation-contraction (E-C) coupling. (United States)

    Yi, Jianxun; Ma, Changling; Li, Yan; Weisleder, Noah; Ríos, Eduardo; Ma, Jianjie; Zhou, Jingsong


    Defective coupling between sarcoplasmic reticulum and mitochondria during control of intracellular Ca(2+) signaling has been implicated in the progression of neuromuscular diseases. Our previous study showed that skeletal muscles derived from an amyotrophic lateral sclerosis (ALS) mouse model displayed segmental loss of mitochondrial function that was coupled with elevated and uncontrolled sarcoplasmic reticulum Ca(2+) release activity. The localized mitochondrial defect in the ALS muscle allows for examination of the mitochondrial contribution to Ca(2+) removal during excitation-contraction coupling by comparing Ca(2+) transients in regions with normal and defective mitochondria in the same muscle fiber. Here we show that Ca(2+) transients elicited by membrane depolarization in fiber segments with defective mitochondria display an ~10% increased amplitude. These regional differences in Ca(2+) transients were abolished by the application of 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, a fast Ca(2+) chelator that reduces mitochondrial Ca(2+) uptake. Using a mitochondria-targeted Ca(2+) biosensor (mt11-YC3.6) expressed in ALS muscle fibers, we monitored the dynamic change of mitochondrial Ca(2+) levels during voltage-induced Ca(2+) release and detected a reduced Ca(2+) uptake by mitochondria in the fiber segment with defective mitochondria, which mirrored the elevated Ca(2+) transients in the cytosol. Our study constitutes a direct demonstration of the importance of mitochondria in shaping the cytosolic Ca(2+) signaling in skeletal muscle during excitation-contraction coupling and establishes that malfunction of this mechanism may contribute to neuromuscular degeneration in ALS.

  20. Phosphoinositides in Ca(2+) signaling and excitation-contraction coupling in skeletal muscle: an old player and newcomers. (United States)

    Csernoch, Laszlo; Jacquemond, Vincent


    Since the postulate, 30 years ago, that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2) as the precursor of inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) would be critical for skeletal muscle excitation-contraction (EC) coupling, the issue of whether phosphoinositides (PtdInsPs) may have something to do with Ca(2+) signaling in muscle raised limited interest, if any. In recent years however, the PtdInsP world has expanded considerably with new functions for PtdIns(4,5)P 2 but also with functions for the other members of the PtdInsP family. In this context, the discovery that genetic deficiency in a PtdInsP phosphatase has dramatic consequences on Ca(2+) homeostasis in skeletal muscle came unanticipated and opened up new perspectives in regards to how PtdInsPs modulate muscle Ca(2+) signaling under normal and disease conditions. This review intends to make an update of the established, the questioned, and the unknown regarding the role of PtdInsPs in skeletal muscle Ca(2+) homeostasis and EC coupling, with very specific emphasis given to Ca(2+) signals in differentiated skeletal muscle fibers.

  1. Investigation of the effect of inositol trisphosphate in skinned skeletal muscle fibres with functional excitation-contraction coupling. (United States)

    Posterino, G S; Lamb, G D


    The effect of inositol trisphosphate (IP3) was investigated in mechanically skinned fibres which had the endogenous level of sarcoplasmic reticulum (SR) Ca2+ and in which the normal excitation-contraction (E-C) coupling mechanism was still functional. Application of 50 or 100 microM IP3 failed to induce a detectable force response in any such skinned fibre from either the extensor digitorum longus muscle of the rat or iliofibularis muscle of the toad, irrespective of whether the fibre was: (a) in its normally polarized, resting state; (b) chronically depolarized to inactivate the voltage sensors; (c) paralysed with D600; or (d) depolarized to threshold for force activation. Furthermore, the size of the response to subsequent depolarization or exposure to caffeine (2mM) or reduced myoplasmic [Mg2+] indicated that little if any Ca2+ had been lost from the SR during the period of IP3 exposure (> or = 1 min). Also, IP3 did not induce a detectable force response when SR Ca2+ uptake was potently inhibited with 20 microM TBQ. Exposure to IP3 (50 microM) slightly potentiated the peak force response to depolarization in toad fibres, and this was probably because of an accompanying small increase in Ca2+ sensitivity of the contractile apparatus. These results appear inconsistent with the proposal that IP3 acts as the second messenger in E-C coupling in skeletal muscle.

  2. Triclosan impairs swimming behavior and alters expression of excitation-contraction coupling proteins in fathead minnow (Pimephales promelas). (United States)

    Fritsch, Erika B; Connon, Richard E; Werner, Inge; Davies, Rebecca E; Beggel, Sebastian; Feng, Wei; Pessah, Isaac N


    Triclosan (TCS), a high volume chemical widely used in consumer products, is a known aquatic contaminant found in fish inhabiting polluted watersheds. Mammalian studies have recently demonstrated that TCS disrupts signaling between the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR), two proteins essential for excitation-contraction (EC) coupling in striated muscle. We investigated the swimming behavior and expression of EC coupling proteins in larval fathead minnows (Pimephales promelas) exposed to TCS for up to 7 days. Concentrations as low as 75 μg L(-1) significantly altered fish swimming activity after 1 day; which was consistent after 7 days of exposure. The mRNA transcription and protein levels of RyR and DHPR (subunit CaV1.1) isoforms changed in a dose and time dependent manner. Crude muscle homogenates from exposed larvae did not display any apparent changes in receptor affinity toward known radioligands. In nonexposed crude muscle homogenates, TCS decreased the binding of [(3)H]PN20-110 to the DHPR and decreased the binding of [(3)H]-ryanodine to the RyR, demonstrating a direct impact at the receptor level. These results support TCS's impact on muscle function in vertebrates further exemplifying the need to re-evaluate the risks this pollutant poses to aquatic environments.

  3. Defective excitation-contraction coupling is partially responsible for impaired contractility in hindlimb muscles of Stac3 knockout mice (United States)

    Cong, Xiaofei; Doering, Jonathan; Grange, Robert W.; Jiang, Honglin


    The Stac3 gene is exclusively expressed in skeletal muscle, and Stac3 knockout is perinatal lethal in mice. Previous data from Stac3-deleted diaphragms indicated that Stac3-deleted skeletal muscle could not contract because of defective excitation-contraction (EC) coupling. In this study, we determined the contractility of Stac3-deleted hindlimb muscle. In response to frequent electrostimulation, Stac3-deleted hindlimb muscle contracted but the maximal tension generated was only 20% of that in control (wild type or heterozygous) muscle (P < 0.05). In response to high [K+], caffeine, and 4-chloro-m-cresol (4-CMC), the maximal tensions generated in Stac3-deleted muscle were 29% (P < 0.05), 58% (P = 0.08), and 55% (P < 0.05) of those in control muscle, respectively. In response to 4-CMC or caffeine, over 90% of myotubes formed from control myoblasts contracted, but only 60% of myotubes formed from Stac3-deleted myoblasts contracted (P = 0.05). However, in response to 4-CMC or caffeine, similar increases in intracellular calcium concentration were observed in Stac3-deleted and control myotubes. Gene expression and histological analyses revealed that Stac3-deleted hindlimb muscle contained more slow type-like fibers than control muscle. These data together confirm a critical role of STAC3 in EC coupling but also suggest that STAC3 may have additional functions in skeletal muscle, at least in the hindlimb muscle. PMID:27184118

  4. Disruption of excitation-contraction coupling and titin by endogenous Ca2+-activated proteases in toad muscle fibres. (United States)

    Verburg, Esther; Murphy, Robyn M; Stephenson, D George; Lamb, Graham D


    This study investigated the effects of elevated, physiological levels of intracellular free [Ca(2+)] on depolarization-induced force responses, and on passive and active force production by the contractile apparatus in mechanically skinned fibres of toad iliofibularis muscle. Excitation-contraction (EC) coupling was retained after skinning and force responses could be elicited by depolarization of the transverse-tubular (T-) system. Raising the cytoplasmic [Ca(2+)] to approximately 1 microm or above for 3 min caused an irreversible reduction in the depolarization-induced force response by interrupting the coupling between the voltage sensors in the T-system and the Ca(2+) release channels in the sarcoplasmic reticulum. This uncoupling showed a steep [Ca(2+)] dependency, with 50% uncoupling at approximately 1.9 microm Ca(2+). The uncoupling occurring with 2 microm Ca(2+) was largely prevented by the calpain inhibitor leupeptin (1 mm). Raising the cytoplasmic [Ca(2+)] above 1 microm also caused an irreversible decline in passive force production in stretched skinned fibres in a manner graded by [Ca(2+)], though at a much slower relative rate than loss of coupling. The progressive loss of passive force could be rapidly stopped by lowering [Ca(2+)] to 10 nm, and was almost completely inhibited by 1 mm leupeptin but not by 10 microm calpastatin. Muscle homogenates preactivated by Ca(2+) exposure also evidently contained a diffusible factor that caused damage to passive force production in a Ca(2+)-dependent manner. Western blotting showed that: (a) calpain-3 was present in the skinned fibres and was activated by the Ca(2+)exposure, and (b) the Ca(2+) exposure in stretched skinned fibres resulted in proteolysis of titin. We conclude that the disruption of EC coupling occurring at elevated levels of [Ca(2+)] is likely to be caused at least in part by Ca(2+)-activated proteases, most likely by calpain-3, though a role of calpain-1 is not excluded.

  5. Ca(2+)-free, high-Ca2+ coronary perfusion suppresses contractility and excitation-contraction coupling energy. (United States)

    Araki, J; Takaki, M; Namba, T; Mori, M; Suga, H


    We studied the mechanoenergetic effects of a short-term Ca(2+)-free, high-Ca2+ Tyrode solution coronary perfusion in eight excised, cross-circulated canine hearts. The perfusion protocol consisted of coronary perfusion with Ca(2+)-free Tyrode solution for 10 min followed by high-Ca2+ (16 mM) Tyrode solution for 5 min. This new protocol successfully induced acute contractile failure in seven hearts, without myocardial ultrastructural changes. We studied the end-systolic pressure-volume relation (slope = Emax, a contractility index) and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA) in these failing hearts. These hearts had no increase in end-diastolic pressure at a given volume, a 40% decrease in Emax and a proportional decrease in the PVA-independent VO2 for 1-4 h, but no decrease in the oxygen cost of PVA, defined as the slope of the VO2-PVA relation. The oxygen cost of Emax for Ca2+ handling, defined as the slope of the relation between PVA-independent VO2 and Emax, was unchanged in the failing hearts. We conclude that the present protocol induced left ventricular contractile failure, primarily involving the suppression of Ca2+ handling energy for excitation-contraction coupling.

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

    Directory of Open Access Journals (Sweden)

    Heqing Zhan


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

  7. Cholesterol Removal from Adult Skeletal Muscle impairs Excitation-Contraction Coupling and Aging reduces Caveolin-3 and alters the Expression of other Triadic Proteins

    Directory of Open Access Journals (Sweden)

    Genaro eBarrientos


    Full Text Available Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not sarcoplasmic reticulum membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX activity and protein content of NOX2 subunits (p47phox and gp91phox, implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs excitation-contraction coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged

  8. Membrane proteins of the triad junction and excitation-contraction coupling in skeletal muscles%骨骼肌三联管膜蛋白与兴奋收缩偶联

    Institute of Scientific and Technical Information of China (English)

    马国震; 李文惠; 骆硕; 马彦芬


    BACKGROUND: The mechanism of excitation-contraction coupling (E-C coupling) in skeletal muscles and a fast and responsive E-C coupling mechanism directly determine the motor ability. The triad junction, which is the specific structure in skeletal muscles,is the infrastructures of E-C coupling. The membrane proteins in the triads play a key role in the development of the triads,maintaining the normal structural form of the triads and exerting the triadic full functions.OBJECTIVE: To review the research advances of triadic membrane proteins and to summarize the structure and functions of dihydropyridine receptor (DHPR), ryanodine receptor, MG29 protein, JP protein, Calumin and STIM1 protein, calsequestrin and TRIC.METHODS: Papers regarding skeletal muscle senescence and power-velocity were searched by computer in databases of CNKI,Duxiu, Elsevier SD and Springer Link from 1980 to 2010. The change laws of skeletal muscle power-velocity with aging and effect of this law on muscle was analyzed.RESULTS AND CONCLUSION: Totally 28 documents were included in this paper. Literature summary showed that, DHPR,ryanodine receptor, MG29 protein, JP protein, Calumin and STIM1 protein, calsequestrin and TRIC doing its own job in skeletal muscles, all of them play an indispensable role in maintaining normal function of skeletal muscles. However, the study of these proteins remains limited. which need further exDloration.%背景:骨骼肌的兴奋收缩偶联机制及快速、有效的兴奋收缩偶联直接决定了运动能力.三联管是骨骼肌中特有的结构,是兴奋收缩偶联的结构基础.位于三联管上的膜蛋白在三联管结构的发育、正常形态的维持和功能的发挥中均起着关键作用.目的:介绍三联管膜蛋白的研究进展,对双氢吡啶受体蛋白,兰诺定受体蛋白,MG29 蛋白,JP 蛋白,Calumin 与STIM1蛋白,隐钙素和TRIC 通道蛋白等的结构和功能进行了归纳总结.方法:电子检索中国学术期刊数据

  9. From Syncitium to Regulated Pump: A Cardiac Muscle Cellular Update (United States)

    Korzick, Donna H.


    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information…

  10. Cardiac Muscle Studies with Rat Ventricular Strips (United States)

    Whitten, Bert K.; Faleschini, Richard J.


    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  11. Coupling of cardiac and locomotor rhythms. (United States)

    Kirby, R L; Nugent, S T; Marlow, R W; MacLeod, D A; Marble, A E


    The pressure within exercising skeletal muscle rises and falls rhythmically during normal human locomotion, the peak pressure reaching levels that intermittently impede blood flow to the exercising muscle. Speculating that a reciprocal relationship between the timing of peak intramuscular and pulsatile arterial pressures should optimize blood flow through muscle and minimize cardiac load, we tested the hypothesis that heart rate becomes entrained with walking and running cadence at some locomotion speeds, by means of electrocardiography and an accelerometer to provide signals reflecting heart rate and cadence, respectively. In 18 of 25 subjects, 1:1 coupling of heart and step rates was present at one or more speeds on a motorized treadmill, generally at moderate to high exercise intensities. To determine how exercise specific this phenomenon is, and to refute the competing hypothesis that coupling is due to vertical accelerations of the heart during locomotion, we had 12 other subjects cycle on an electronically braked bicycle ergometer. Coupling was found between heart rate and pedaling frequency in 10 of them. Cardiac-locomotor coupling appears to be a normal physiological phenomenon, and its identification provides a fresh perspective from which to study endurance.

  12. Phosphatidylinositol-bisphosphate regulates intercellular coupling in cardiac myocytes

    DEFF Research Database (Denmark)

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


    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 hypothesi...

  13. Modelling Ca2+ bound Troponin in Excitation Contraction Coupling

    Directory of Open Access Journals (Sweden)

    Henry G. Zot


    Full Text Available To explain disparate decay rates of cytosolic Ca2+ and structural changes in the thin filaments during a twitch, we model the time course of Ca2+ bound troponin (Tn resulting from the free Ca2+ transient of fast skeletal muscle. In fibers stretched beyond overlap, the decay of Ca2+ as measured by a change in fluo 3 fluorescence is significantly slower than the intensity decay of the meridional 1/38.5 nm-1 reflection of Tn; this is not simply explained by considering only the Ca2+ binding properties of Tn alone (Matsuo, T., Iwamoto, H., and Yagi, N. (2010. Biophys. J. 99, 193-200. We apply a comprehensive model that includes the known Ca2+ binding properties of Tn in the context of the thin filament with and without cycling crossbridges. Calculations based on the model predict that the transient of Ca2+ bound Tn correlates with either the fluo 3 time course in muscle with overlapping thin and thick filaments or the intensity of the meridional 1/38.5 nm-1 reflection in overstretched muscle. Hence, cycling crossbridges delay the dissociation of Ca2+ from Tn. Correlation with the fluo 3 fluorescence change is not causal given that the transient of Ca2+ bound Tn depends on sarcomere length, whereas the fluo-3 fluorescence change does not. Transient positions of tropomyosin calculated from the time course of Ca2+ bound Tn are in reasonable agreement with the transient of measured perturbations of the Tn repeat in overlap and non-overlap muscle preparations.

  14. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T


    Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions...

  15. Cardiac contraction induces discordant alternans and localized block (United States)

    Radszuweit, M.; Alvarez-Lacalle, E.; Bär, M.; Echebarria, B.


    In this paper we use a simplified model of cardiac excitation-contraction coupling to study the effect of tissue deformation on the dynamics of alternans, i.e., alternations in the duration of the cardiac action potential, that occur at fast pacing rates and are known to be proarrhythmic. We show that small stretch-activated currents can produce large effects and cause a transition from in-phase to off-phase alternations (i.e., from concordant to discordant alternans) and to conduction blocks. We demonstrate numerically and analytically that this effect is the result of a generic change in the slope of the conduction velocity restitution curve due to electromechanical coupling. Thus, excitation-contraction coupling can potentially play a relevant role in the transition to reentry and fibrillation.

  16. Type 1 ryanodine receptor in cardiac mitochondria: transducer of excitation-metabolism coupling. (United States)

    Beutner, Gisela; Sharma, Virendra K; Lin, Lin; Ryu, Shin-Young; Dirksen, Robert T; Sheu, Shey-Shing


    Mitochondria in a variety of cell types respond to physiological Ca(2+) oscillations in the cytosol dynamically with Ca(2+) uptakes. In heart cells, mitochondrial Ca(2+) uptakes occur by a ruthenium red-sensitive Ca(2+) uniporter (CaUP), a rapid mode of Ca(2+) uptake (RaM) and a ryanodine receptor (RyR) localized in the inner mitochondrial membrane (IMM). Three subtypes of RyRs have been described and cloned, however, the subtype identity of the mitochondrial ryanodine receptor (mRyR) is unknown. Using subtype specific antibodies, we characterized the mRyR in the IMM from rat heart as RyR1. These results are substantiated by the absence of RyR protein in heart mitochondria from RyR1 knockout mice. The bell-shape Ca(2+)-dependent [(3)H]ryanodine binding curve and its modulation by caffeine and adenylylmethylenediphosphonate (AMPPCP) give further evidence that mRyR functions pharmacologically like RyR1. Ryanodine prevents mitochondrial Ca(2+) uptake induced by raising extramitochondrial Ca(2+) to 10 microM. Similarly, ryanodine inhibits oxidative phosphorylation stimulated by 10 microM extramitochondrial Ca(2+). In summary, our results show that the mRyR in cardiac muscle has similar biochemical and pharmacological properties to the RyR1 in the sarcoplasmic reticulum (SR) of skeletal muscle. These results could also suggest an efficient mechanism by which mitochondria sequesters Ca(2+) via mRyR during excitation-contraction coupling to stimulate oxidative phosphorylation for ATP production to meet metabolic demands. Thus, the mRyR functions as a transducer for excitation-metabolism coupling.

  17. Mechanisms of excitation-contraction uncoupling relevant to activity-induced muscle fatigue. (United States)

    Lamb, Graham D


    If the free [Ca2+] in the cytoplasm of a skeletal muscle fiber is raised substantially for a period of seconds to minutes or to high levels just briefly, it leads to disruption of the normal excitation-contraction (E-C) coupling process and a consequent long-lasting decrease in force production. It appears that the disruption to the coupling occurs at the triad junction, where the voltage-sensor molecules (dihydropyridine receptors) normally interact with and open the Ca2+ release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum (SR). This disruption results in inadequate release of SR Ca2+ upon stimulation. Such E-C uncoupling may underlie the long-duration low-frequency fatigue that can occur after various types of exercise, as well as possibly being a contributing factor to the muscle weakness in certain muscle diseases. The process or processes causing the disruption of the coupling between the voltage sensors and the release channels is not known with certainty, but might be associated with structural changes at the triad junction, possibly caused by activation of the Ca2+-dependent protease, micro-calpain.

  18. Great Expectations: Perceived Social Support in Couples Experiencing Cardiac Surgery. (United States)

    Rankin, Sally H.; Monahan, Patricia


    Compared patient and spousal perceived support during the cardiac surgery recovery period and explored effects of social support on patient/spouse subjective mood states for 117 couples. Social support buffered the impact of caregiving burden on mood disturbance for caregiving spouses but did not significantly impact physical or mental health…

  19. A continuum model for excitation-contraction of smooth muscle under finite deformations. (United States)

    Sharifimajd, Babak; Stålhand, Jonas


    The main focus in most of the continuum based muscle models is the mechanics of muscle contraction while other physiological processes governing muscle contraction, e.g., cell membrane excitation and activation, are ignored. These latter processes are essential to initiate contraction and to determine the amount of generated force, and by excluding them, the developed model cannot replicate the true behavior of the muscle in question. The aim of this study is to establish a thermodynamically and physiologically consistent framework which allows us to model smooth muscle contraction by including cell membrane excitability and kinetics of myosin phosphorylation, along with dynamics of smooth muscle contraction. The model accounts for these processes through a set of coupled dissipative constitutive equations derived by applying first principles. To show the performance of the derived model, it is evaluated for two different cases: a chemo-mechanical study of pig taenia coli cells where the excitation process is excluded, and an electro-chemo-mechanical study of rat myometrium. The results show that the model is able to replicate important aspects of the smooth muscle excitation-contraction process.

  20. The Molecular Basis for Calcium-dependent Regulation of Cardiac Structure and Function


    Shimizu, Hirohito


    Calcium homeostasis is essential for regulating a wide spectrum of biological processes. In the heart, Ca2+ plays a key role in excitation-contraction coupling, electrophysiological processes, activation of contractile proteins, energy metabolism, cell death, and transcriptional regulation. Alteration of Ca2+ homeostasis is often associated with cardiac pathology such as contractile dysfunction, arrhythmias and heart failure. In order to discover novel molecular mechanisms by which Ca2+ regul...

  1. Glycogen content and excitation-contraction coupling in mechanically skinned muscle fibres of the cane toad. (United States)

    Stephenson, D G; Nguyen, L T; Stephenson, G M


    1. Mechanically skinned skeletal muscle fibres from the twitch region of the iliofibularis muscle of cane toads were used to investigate the relationship between fibre glycogen content and fibre capacity to respond to transverse tubular (T-) system depolarization. 2. A large proportion of total fibre glycogen remained in mechanically skinned muscle fibres exposed to aqueous solutions. This glycogen pool (about 80% of total fibre glycogen) was very stable when the preparation was incubated in a rigor solution (pH 7.0) but decreased gradually at a rate of 0.59+/-0.20% min-1 in a relaxing solution (200 nM [Ca2+]). The rate was considerably higher (2.66+/-0.38% min(-1)) when the preparations were exposed to 30 microM [Ca2+]. An even greater rate of glycogen loss was found after T-system depolarization-induced contractions. The Ca2+-dependent loss of fibre glycogen was caused by endogenous glycogenolytic processes. 3. Silver stained SDS gels of components eluted into relaxing solution from single skinned fibres revealed a rapid (2 min) loss of parvalbumin and at least 10 other proteins varying in molecular mass between 10 and 80 kDa but there was essentially no loss of myosin heavy and light chains and actin. Subsequent elution for a further 30 min in either relaxing or maximally Ca2+-activating solution did not result in additional, appreciable detectable loss of fibre protein. 4. Depletion of fibre glycogen was associated with loss of fibre ability to respond to T-system depolarization even though the bathing solutions contained high levels of ATP (8 mM) and creatine phosphate (10 mM). 5. The capacity of mechanically skinned fibres to respond to T-system depolarization was highly positively correlated (Pmuscle to respond to T-system depolarization is related directly or indirectly to the non-washable glycogen pool in fibres, (ii) this relationship holds for conditions where glycogen is not required as a source of energy and (iii) the mechanically skinned fibre preparation is well suited to study the regulation of endogenous glycogenolytic enzymes.

  2. Thermal sensitivity of excitation-contraction-coupling in a chill susceptible insect, Locusta migratoria

    DEFF Research Database (Denmark)

    Findsen, Anders; Pedersen, Thomas Holm; Overgaard, Johannes

    Many insect species enter a state of neuromuscular paralysis when their body temperature is lowered to a critical limit but the physiological and cellular processes underlying this chill coma are largely unknown. Previous studies on locusts show that muscle force production is highly depressed at...

  3. β-Adrenergic modulation of skeletal muscle contraction: key role of excitation-contraction coupling. (United States)

    Cairns, Simeon P; Borrani, Fabio


    Our aim is to describe the acute effects of catecholamines/β-adrenergic agonists on contraction of non-fatigued skeletal muscle in animals and humans, and explain the mechanisms involved. Adrenaline/β-agonists (0.1-30 μm) generally augment peak force across animal species (positive inotropic effect) and abbreviate relaxation of slow-twitch muscles (positive lusitropic effect). A peak force reduction also occurs in slow-twitch muscles in some conditions. β2 -Adrenoceptor stimulation activates distinct cyclic AMP-dependent protein kinases to phosphorylate multiple target proteins. β-Agonists modulate sarcolemmal processes (increased resting membrane potential and action potential amplitude) via enhanced Na(+) -K(+) pump and Na(+) -K(+) -2Cl(-) cotransporter function, but this does not increase force. Myofibrillar Ca(2+) sensitivity and maximum Ca(2+) -activated force are unchanged. All force potentiation involves amplified myoplasmic Ca(2+) transients consequent to increased Ca(2+) release from sarcoplasmic reticulum (SR). This unequivocally requires phosphorylation of SR Ca(2+) release channels/ryanodine receptors (RyR1) which sensitize the Ca(2+) -induced Ca(2+) release mechanism. Enhanced trans-sarcolemmal Ca(2+) influx through phosphorylated voltage-activated Ca(2+) channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca(2+) pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca(2+) loading of SR may assist force potentiation in fast-twitch muscle. Some human studies show no significant force potentiation which appears to be related to the β-agonist concentration used. Indeed high-dose β-agonists (∼0.1 μm) enhance SR Ca(2+) -release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline/β-agonists influence muscle performance during exercise/stress in humans.

  4. Excitation-contraction coupling in rested-state contractions of guinea-pig ventricular myocardium. (United States)

    Reiter, M; Vierling, W; Seibel, K


    Different types of rested-state contractions were examined under the influence of various inotropic agents. In magnesium-free solution, in low sodium (40 mmol/l) solution or in the presence of dihydroouabain, an "early" rested-state contraction developed without delay after stimulation. A distinctive "late" rested-state contraction was observed under the influence of noradrenaline. It is characterized by a latent period of about 100 ms between stimulation and onset of contraction. This latency was not reduced by increasing the catecholamine concentration, despite a concentration-dependent increase in the height of the "late" rested-state contraction. The late rested-state contraction under the influence of noradrenaline was suppressed by the slow inward current inhibitor nifedipine whether or not the nifedipine-dependent shortening of the action potential duration was prevented by caesium. When the slow inward current was not inhibited, the prolongation of the action potential duration by caesium resulted in an increase of the late rested-state contraction because of a prolongation of the time to peak force. High concentrations of dihydroouabain led to the appearance of an early contraction component without appreciably influencing the noradrenaline-dependent late component. From this it was deduced that the activator calcium for the late rested-state contraction was not stored intracellularly during rest prior to stimulation and, consequently, could not have been released by inflowing calcium. Instead, it is proposed that the activator calcium for the late rested-state contraction entered the sites of the sarcoplasmic reticulum and subsequently released from its release sites as long as the cell was depolarized. The "early" rested-state contractions in Mg2+-free solution, in low sodium solution or in the presence of dihydroouabain were not influenced in their contraction velocity by high concentrations of nifedipine which fully inhibited the late rested-state contractions. Nifedipine caused only a slight reduction in peak force due to a shortening of the time to peak force as a result of a shortening in action potential duration. This indicates that the activator calcium for the "early" rested-state contractions had accumulated in the sarcoplasmic reticulum during rest prior to stimulation and that it was released immediately by depolarization without a participation of the slow inward current.

  5. Landmark detection and coupled patch registration for cardiac motion tracking (United States)

    Wang, Haiyan; Shi, Wenzhe; Zhuang, Xiahai; Wu, Xianliang; Tung, Kai-Pin; Ourselin, Sebastien; Edwards, Philip; Rueckert, Daniel


    Increasing attention has been focused on the estimation of the deformation of the endocardium to aid the diagnosis of cardiac malfunction. Landmark tracking can provide sparse, anatomically relevant constraints to help establish correspondences between images being tracked or registered. However, landmarks on the endocardium are often characterized by ambiguous appearance in cardiac MR images which makes the extraction and tracking of these landmarks problematic. In this paper we propose an automatic framework to select and track a sparse set of distinctive landmarks in the presence of relatively large deformations in order to capture the endocardial motion in cardiac MR sequences. To achieve this a sparse set of the landmarks is identified using an entropy-based approach. In particular we use singular value decomposition (SVD) to reduce the search space and localize the landmarks with relatively large deformation across the cardiac cycle. The tracking of the sparse set of landmarks is performed simultaneously by optimizing a two-stage Markov Random Field (MRF) model. The tracking result is further used to initialize registration based dense motion tracking. We have applied this framework to extract a set of landmarks at the endocardial border of the left ventricle in MR image sequences from 51 subjects. Although the left ventricle undergoes a number of different deformations, we show how the radial, longitudinal motion and twisting of the endocardial surface can be captured by the proposed approach. Our experiments demonstrate that motion tracking using sparse landmarks can outperform conventional motion tracking by a substantial amount, with improvements in terms of tracking accuracy of 20:8% and 19:4% respectively.

  6. Phospholemman: a novel cardiac stress protein. (United States)

    Cheung, Joseph Y; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Rabinowitz, Joseph E; Chan, Tung O; Wang, Jufang


    Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. Functionally, when phosphorylated at serine(68), PLM stimulates Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca(2+) channel. Therefore, PLM occupies a key modulatory role in intracellular Na(+) and Ca(2+) homeostasis and is intimately involved in regulation of excitation-contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na(+) overload and simultaneously preserves inotropy by inhibiting Na(+)/Ca(2+) exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and potentially L-type Ca(2+) channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189-196.

  7. Cardiac energetics: sense and nonsense. (United States)

    Gibbs, Colin L


    1. The background to current ideas in cardiac energetics is outlined and, in the genomic era, the need is stressed for detailed knowledge of mouse heart mechanics and energetics. 2. The mouse heart is clearly different to the rat in terms of its excitation-contraction (EC) coupling and the common assumption that heart rate difference between mice and humans will account for the eightfold difference in myocardial oxygen consumption is wrong, because the energy per beat of the mouse heart is approximately one-third that of the human heart. 3. In vivo evidence suggests that there may well be an eightfold species difference in the non-beating metabolism of mice and human hearts. It is speculated that the magnitude of basal metabolism in the heart is regulatable and that, in the absence of perfusion, it falls to approximately one-quarter of its in vivo rate and that in clinical conditions, such as hibernation, it probably decreases; its magnitude may be controlled by the endothelium. 4. The active energy balance sheet is briefly discussed and it is suggested that the activation heat accounts for 20-25% of the active energy per beat and cross-bridge turnover accounts for the balance. It is argued that force, not shortening, is the major determinant of cardiac energy usage. 5. The outcome of recent cardiac modelling with variants of the Huxley and Hill/Eisenberg models is described. It has been necessary to invoke 'loose coupling' to replicate the low cardiac energy flux measured at low afterloads (medium to high velocities of shortening). 6. Lastly, some of the unexplained or 'nonsense' energetic data are outlined and eight unsolved problems in cardiac energetics are discussed.

  8. Calcium binding to cardiac myocytes protected from proteolytic enzyme activity. (United States)

    Bailey, L E; Fawzi, A B


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

  9. p53 regulates the cardiac transcriptome (United States)

    Mak, Tak W.; Hauck, Ludger; Grothe, Daniela; Billia, Filio


    The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP–mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed. Genome-wide annotation and pathway analyses of >5,000 differentially expressed transcripts identified many p53-regulated gene clusters. Correlative analyses identified >20 gene sets containing more than 1,000 genes relevant to cardiac architecture and function. These transcriptomic changes orchestrate cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation capacity. Interestingly, the gene expression signature in p53-deficient hearts confers resistance to acute biomechanical stress. The data presented here demonstrate a role for p53, a previously unrecognized master regulator of the cardiac transcriptome. The complex contributions of p53 define a biological paradigm for the p53 regulator network in the heart under physiological conditions. PMID:28193895

  10. The other side of cardiac Ca2+ signaling: transcriptional control

    Directory of Open Access Journals (Sweden)

    Alejandro eDomínguez-Rodríquez


    Full Text Available Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling, but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling. ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII and phosphatase calcineurin, both of which are activated by the complex Ca2+/ /Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n or cytoplasmic ([Ca2+]c, and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs in [Ca2+]c, needed to activate calcineurin.

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

    Directory of Open Access Journals (Sweden)

    Fuyu Kobirumaki-Shimozawa


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

  12. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis

    Directory of Open Access Journals (Sweden)

    Ying Li


    Full Text Available Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe burns, trauma, and inflammatory diseases causes cardiac dysfunction, which is one of the leading causes of mortality in these patients. Acute sepsis decreases cardiac contractility and impairs myocardial compliance. Chronic inflammation such as that occurring in Duchenne muscular dystropshy and myocarditis may cause adverse cardiac remodeling including myocyte hypertrophy and death, fibrosis, and altered myocyte function. However, the underlying cellular and molecular mechanisms for inflammatory cardiomyopathy are still controversial probably due to multiple factors involved. Potential mechanisms include the change in circulating blood volume; a direct inhibition of myocyte contractility by cytokines (tumor necrosis factor (TNF-a, interleukin (IL-1b; abnormal nitric oxide and reactive oxygen species (ROS signaling; mitochondrial dysfunction; abnormal excitation-contraction coupling; and reduced calcium sensitivity at the myofibrillar level and blunted b-adrenergic signaling. This review will summarize recent advances in diagnostic technology, mechanisms, and potential therapeutic strategies for inflammation-induced cardiac dysfunction.

  13. Crude oil exposures reveal roles for intracellular calcium cycling in haddock craniofacial and cardiac development (United States)

    Sørhus, Elin; Incardona, John P.; Karlsen, Ørjan; Linbo, Tiffany; Sørensen, Lisbet; Nordtug, Trond; van der Meeren, Terje; Thorsen, Anders; Thorbjørnsen, Maja; Jentoft, Sissel; Edvardsen, Rolf B.; Meier, Sonnich


    Recent studies have shown that crude oil exposure affects cardiac development in fish by disrupting excitation-contraction (EC) coupling. We previously found that eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets, potentially leading to more profound toxic effects from uptake of polycyclic aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil (0.7-7 μg/L ∑PAH), here we exposed a broader range of developmental stages over both short and prolonged durations. We quantified effects on cardiac function and morphogenesis, characterized novel craniofacial defects, and examined the expression of genes encoding potential targets underlying cardiac and craniofacial defects. Because of oil droplet binding, a 24-hr exposure was sufficient to create severe cardiac and craniofacial abnormalities. The specific nature of the craniofacial abnormalities suggests that crude oil may target common craniofacial and cardiac precursor cells either directly or indirectly by affecting ion channels and intracellular calcium in particular. Furthermore, down-regulation of genes encoding specific components of the EC coupling machinery suggests that crude oil disrupts excitation-transcription coupling or normal feedback regulation of ion channels blocked by PAHs. These data support a unifying hypothesis whereby depletion of intracellular calcium pools by crude oil-derived PAHs disrupts several pathways critical for organogenesis in fish.

  14. From syncitium to regulated pump: a cardiac muscle cellular update. (United States)

    Korzick, Donna H


    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca(2+) microdomains and local control theory, with particular emphasis on the role of Ca(2+) sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca(2+) cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca(2+) from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca(2+) homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca(2+)-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle.

  15. Mechanism for Muscarinic Inhibitory Regulation of the L-type Ca2 + Current in Cardiac Ventricular Myocytes

    Institute of Scientific and Technical Information of China (English)

    蒋彬; 杨向军; 惠杰; 蒋廷波; 宋建平; 刘志华


    @@ Objective The autonomic nervous system plays a key role in regulating cardiac function by modifying heart rate, contractility and impulse. The parasympathetic neurotransmitter acetyl-choline and muscarinic agonist carbachol (Cch) inhibit excitation-contraction coupling in cardiac ventricular myocytes. Muscarinic agonists suppress adenylyl cyclase (AC) acitivity and,by reducing activation of the cAMP/protein kinase A (PKA)cascade, inhibit the L-type Ca2+ current (ICa(L) ). They also increase the content of cGMP by stimulating guanylyl cyclase (GC) activity. The role of nitric oxide (NO)/cGMP in muscarinic inhibition has undergone considerable scrutiny. The role of the NO/cGMP pathway in the inhibition of ICa(L) by Cch was examined in guinea-pig ventricular myocytes.

  16. Deletion of Pr130 Interrupts Cardiac Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Jie Yang


    Full Text Available Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A, a regulatory subunit of protein phosphatase 2A (PP2A, is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR, plays an important role in the excitation-contraction (EC coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated proteins (Cas system. Pr130-knockout zebrafish exhibited cardiac looping defects and decreased cardiac function (decreased fractional area and fractional shortening. Hematoxylin and eosin (H&E staining demonstrated reduced cardiomyocytes. Subsequent transmission electron microscopy revealed that the bright and dark bands were narrowed and blurred, the Z- and M-lines were fogged, and the gaps between longitudinal myocardial fibers were increased. Additionally, increased apoptosis was observed in cardiomyocyte in pr130-knockout zebrafish compared to wild-type (WT. Taken together, our results suggest that pr130 is required for normal myocardium formation and efficient cardiac contractile function.

  17. Deletion of Pr130 Interrupts Cardiac Development in Zebrafish (United States)

    Yang, Jie; Li, Zuhua; Gan, Xuedong; Zhai, Gang; Gao, Jiajia; Xiong, Chenling; Qiu, Xueping; Wang, Xuebin; Yin, Zhan; Zheng, Fang


    Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A), a regulatory subunit of protein phosphatase 2A (PP2A), is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR), plays an important role in the excitation-contraction (EC) coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system. Pr130-knockout zebrafish exhibited cardiac looping defects and decreased cardiac function (decreased fractional area and fractional shortening). Hematoxylin and eosin (H&E) staining demonstrated reduced cardiomyocytes. Subsequent transmission electron microscopy revealed that the bright and dark bands were narrowed and blurred, the Z- and M-lines were fogged, and the gaps between longitudinal myocardial fibers were increased. Additionally, increased apoptosis was observed in cardiomyocyte in pr130-knockout zebrafish compared to wild-type (WT). Taken together, our results suggest that pr130 is required for normal myocardium formation and efficient cardiac contractile function. PMID:27845735

  18. Comparison of myoplasmic calcium movements during excitation-contraction coupling in frog twitch and mouse fast-twitch muscle fibers. (United States)

    Hollingworth, Stephen; Baylor, Stephen M


    Single twitch fibers from frog leg muscles were isolated by dissection and micro-injected with furaptra, a rapidly responding fluorescent Ca(2+) indicator. Indicator resting fluorescence (FR) and the change evoked by an action potential (ΔF) were measured at long sarcomere length (16°C); ΔF/FR was scaled to units of ΔfCaD, the change in fraction of the indicator in the Ca(2+)-bound form. ΔfCaD was simulated with a multicompartment model of the underlying myoplasmic Ca(2+) movements, and the results were compared with previous measurements and analyses in mouse fast-twitch fibers. In frog fibers, sarcoplasmic reticulum (SR) Ca(2+) release evoked by an action potential appears to be the sum of two components. The time course of the first component is similar to that of the entire Ca(2+) release waveform in mouse fibers, whereas that of the second component is severalfold slower; the fractional release amounts are ~0.8 (first component) and ~0.2 (second component). Similar results were obtained in frog simulations with a modified model that permitted competition between Mg(2+) and Ca(2+) for occupancy of the regulatory sites on troponin. An anatomical basis for two release components in frog fibers is the presence of both junctional and parajunctional SR Ca(2+) release channels (ryanodine receptors [RyRs]), whereas mouse fibers (usually) have only junctional RyRs. Also, frog fibers have two RyR isoforms, RyRα and RyRβ, whereas the mouse fibers (usually) have only one, RyR1. Our simulations suggest that the second release component in frog fibers functions to supply extra Ca(2+) to activate troponin, which, in mouse fibers, is not needed because of the more favorable location of their triadic junctions (near the middle of the thin filament). We speculate that, in general, parajunctional RyRs permit increased myofilament activation in fibers whose triadic junctions are located at the z-line.

  19. From action potential to contraction: neural control and excitation-contraction coupling in larval muscles of Drosophila. (United States)

    Peron, Samantha; Zordan, Mauro A; Magnabosco, Anna; Reggiani, Carlo; Megighian, Aram


    The neuromuscular system of Drosophila melanogaster has been studied for many years for its relative simplicity and because of the genetic and molecular versatilities. Three main types of striated muscles are present in this dipteran: fibrillar muscles, tubular muscles and supercontractile muscles. The visceral muscles in adult flies and the body wall segmental muscles in embryos and larvae belong to the group of supercontractile muscles. Larval body wall muscles have been the object of detailed studies as a model for neuromuscular junction function but have received much less attention with respect to their mechanical properties and to the control of contraction. In this review we wish to assess available information on the physiology of the Drosophila larval muscular system. Our aim is to establish whether this system has the requisites to be considered a good model in which to perform a functional characterization of Drosophila genes, with a known muscular expression, as well as Drosophila homologs of human genes, the dysfunction of which, is known to be associated with human hereditary muscle pathologies.

  20. Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death. (United States)

    Nomikos, Michail; Thanassoulas, Angelos; Beck, Konrad; Vassilakopoulou, Vyronia; Hu, Handan; Calver, Brian L; Theodoridou, Maria; Kashir, Junaid; Blayney, Lynda; Livaniou, Evangelia; Rizkallah, Pierre; Nounesis, George; Lai, F Anthony


    Calmodulin (CaM) association with the cardiac muscle ryanodine receptor (RyR2) regulates excitation-contraction coupling. Defective CaM-RyR2 interaction is associated with heart failure. A novel CaM mutation (CaM(F90L)) was recently identified in a family with idiopathic ventricular fibrillation (IVF) and early onset sudden cardiac death. We report the first biochemical characterization of CaM(F90L). F90L confers a deleterious effect on protein stability. Ca(2+)-binding studies reveal reduced Ca(2+)-binding affinity and a loss of co-operativity. Moreover, CaM(F90L) displays reduced RyR2 interaction and defective modulation of [(3)H]ryanodine binding. Hence, dysregulation of RyR2-mediated Ca(2+) release via aberrant CaM(F90L)-RyR2 interaction is a potential mechanism that underlies familial IVF.

  1. Exercise capacity in the Bidirectional Glenn physiology: Coupling cardiac index, ventricular function and oxygen extraction ratio. (United States)

    Vallecilla, Carolina; Khiabani, Reza H; Trusty, Phillip; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P


    In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data.

  2. Role of TGF-β on cardiac structural and electrical remodeling

    Directory of Open Access Journals (Sweden)

    Roberto Ramos-Mondragón


    Full Text Available Roberto Ramos-Mondragón, Carlos A Galindo, Guillermo AvilaDepartamento de Bioquímica, Cinvestav-IPN, MéxicoAbstract: The type β transforming growth factors (TGF-βs are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-β affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-β signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-β affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-β on cardiac excitation-contraction (EC coupling, action potentials, and ion channels. We also discuss the effects of TGF-β on cardiac development and disease from structural and electrophysiological points of view.Keywords: transforming growth factor, ion channel, cardiac electrophysiology

  3. Microfluidic systems to examine intercellular coupling of pairs of cardiac myocytes. (United States)

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


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

  4. Cardiac system bioenergetics: metabolic basis of the Frank-Starling law. (United States)

    Saks, Valdur; Dzeja, Petras; Schlattner, Uwe; Vendelin, Marko; Terzic, Andre; Wallimann, Theo


    The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation-contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for 'metabolic pacing', synchronizing the cellular electrical and mechanical activities with energy supply processes.

  5. Modeling calcium wave based on anomalous subdiffusion of calcium sparks in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Xi Chen

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

  6. Preserved metabolic coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest.

    NARCIS (Netherlands)

    Bisschops, L.L.A.; Hoedemaekers, C.W.E.; Simons, K.S.; Hoeven, J.G. van der


    OBJECTIVE: Although mild hypothermia improves outcome in patients after out-of-hospital cardiac arrest, the cardiodepressive effects of hypothermia may lead to secondary brain damage. This study was performed to assess the cerebral blood flow, cerebral oxygen extraction, and cerebrovascular reactivi

  7. A coupled 3D-1D numerical monodomain solver for cardiac electrical activation in the myocardium with detailed Purkinje network (United States)

    Vergara, Christian; Lange, Matthias; Palamara, Simone; Lassila, Toni; Frangi, Alejandro F.; Quarteroni, Alfio


    We present a model for the electrophysiology in the heart to handle the electrical propagation through the Purkinje system and in the myocardium, with two-way coupling at the Purkinje-muscle junctions. In both the subproblems the monodomain model is considered, whereas at the junctions a resistor element is included that induces an orthodromic propagation delay from the Purkinje network towards the heart muscle. We prove a sufficient condition for convergence of a fixed-point iterative algorithm to the numerical solution of the coupled problem. Numerical comparison of activation patterns is made with two different combinations of models for the coupled Purkinje network/myocardium system, the eikonal/eikonal and the monodomain/monodomain models. Test cases are investigated for both physiological and pathological activation of a model left ventricle. Finally, we prove the reliability of the monodomain/monodomain coupling on a realistic scenario. Our results underlie the importance of using physiologically realistic Purkinje-trees with propagation solved using the monodomain model for simulating cardiac activation.

  8. Immobilization Stress With α2-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats. (United States)

    Kuroda, Ryohei; Shintani-Ishida, Kaori; Unuma, Kana; Yoshida, Ken-ichi


    Stress cardiomyopathy is characterized by transient apical hypokinesia related to catecholamine overflow. Recently, excessive epinephrine administration was shown to recapitulate stress cardiomyopathy through β2-adrenoceptor (AR)-inhibitory G protein (Gi) coupling in rats. We aimed to study whether α2-AR and Gi affect cardiac contraction in rats in which emotional stress was evoked using immobilization (IMO). Echocardiography results showed that when male rats were exposed to IMO for 30 minutes and then injected with the α2-AR agonist xylazine (Xy), ejection fraction and the movement of the anterior wall (AW) were suppressed, maximally at 5 minutes post-injection, whereas posterior wall (PW) movement was preserved. At the same time points, the phosphorylation of Ser282 in myosin-binding protein-C (MyBP-C-Ser282) was higher in the PW than in the AW. Pretreatment with the Gi inhibitor pertussis toxin (PTX) reversed the low contractility and MyBP-C-Ser282 phosphorylation in the AW, but induced lethal heart failure in 3 out of 11 rats. Moreover, at 5 minutes after Xy injection following 30 minutes of IMO, serum epinephrine levels were increased. Thus, in rats exposed to psychological stress, α2-AR stimulation triggered transient hypo-contractility and MyBP-C-Ser282 hypo-phosphorylation in the AW, in association with an epinephrine surge. PTX treatment reversed the AW hypo-contractility and MyBP-C hypo-phosphorylation, but induced acute heart failure. These findings suggest α2AR/Gi-dependent signaling attenuates MyBP-C phosphorylation and contractility in the AW through an epinephrine surge in rats subjected to IMO and α2-AR stimulation. This model can recapitulate stress cardiomyopathy and thereby deepen our understanding of regional cardiac hypo-contractility and prosurvival mechanisms.

  9. Effect of Verapamil on Excitation-Contraction Coupling in Frog Single Twitch Muscle Fiber. I. Effect of Verapamil in Low Concentration


    小原, 一男; 鈴木, 稔子; 永井, 寅男


    The effects of verapamil in low concentration (0.1 mM) on electrical and mechanical responses in single twitch muscle fiber of the frog were examined and the following results were obtained. 1) Twitch tension was potentiated by verapamil during the first 2 min after application and then declined little by little. 2) Resting and action potentials were not changed by verapamil except for an enhancement of a negative afterpotential. 3) The duration of the active state was prolonged by 1.5 times ...

  10. Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation

    DEFF Research Database (Denmark)

    William, M.; Hamilton, E.J.; Garcia, A.;


    ) regulates the pump. We voltage clamped rabbit ventricular myocytes and identified electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange and normalized for membrane capacitance) as the shift in membrane current induced by 100 micromol/l ouabain. Ten nanomoles per liter ANP stimulated......Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal Na(+)-K(+) pump, we examined whether atrial natriuretic peptide (ANP...... the Na(+)-K(+) pump when the intracellular compartment was perfused with pipette solutions containing 10 mmol/l Na(+) but had no effect when the pump was at near maximal activation with 80 mmol/l Na(+) in the pipette solution. Stimulation was abolished by inhibition of cGMP-activated protein kinase...

  11. BIN1 localizes the L-type calcium channel to cardiac T-tubules.

    Directory of Open Access Journals (Sweden)

    Ting-Ting Hong


    Full Text Available The BAR domain protein superfamily is involved in membrane invagination and endocytosis, but its role in organizing membrane proteins has not been explored. In particular, the membrane scaffolding protein BIN1 functions to initiate T-tubule genesis in skeletal muscle cells. Constitutive knockdown of BIN1 in mice is perinatal lethal, which is associated with an induced dilated hypertrophic cardiomyopathy. However, the functional role of BIN1 in cardiomyocytes is not known. An important function of cardiac T-tubules is to allow L-type calcium channels (Cav1.2 to be in close proximity to sarcoplasmic reticulum-based ryanodine receptors to initiate the intracellular calcium transient. Efficient excitation-contraction (EC coupling and normal cardiac contractility depend upon Cav1.2 localization to T-tubules. We hypothesized that BIN1 not only exists at cardiac T-tubules, but it also localizes Cav1.2 to these membrane structures. We report that BIN1 localizes to cardiac T-tubules and clusters there with Cav1.2. Studies involve freshly acquired human and mouse adult cardiomyocytes using complementary immunocytochemistry, electron microscopy with dual immunogold labeling, and co-immunoprecipitation. Furthermore, we use surface biotinylation and live cell confocal and total internal fluorescence microscopy imaging in cardiomyocytes and cell lines to explore delivery of Cav1.2 to BIN1 structures. We find visually and quantitatively that dynamic microtubules are tethered to membrane scaffolded by BIN1, allowing targeted delivery of Cav1.2 from the microtubules to the associated membrane. Since Cav1.2 delivery to BIN1 occurs in reductionist non-myocyte cell lines, we find that other myocyte-specific structures are not essential and there is an intrinsic relationship between microtubule-based Cav1.2 delivery and its BIN1 scaffold. In differentiated mouse cardiomyocytes, knockdown of BIN1 reduces surface Cav1.2 and delays development of the calcium transient

  12. Phospholamban Modulates the Functional Coupling between Nucleotide Domains in Ca-ATPase Oligomeric Complexes in Cardiac Sarcoplasmic Reticulum

    Energy Technology Data Exchange (ETDEWEB)

    Chen, L.; Yao, Qing; Soares, Thereza A.; Squier, Thomas C.; Bigelow, Diana J.


    Oligomeric interactions between Ca-ATPase polypeptide chains and their modulation by phospholamban (PLB) were measured in native cardiac sarcoplasmic reticulum (SR) microsomes. Progressive modification of Lys514 with fluorescein-5-isothiocyanate (FITC), which physically blocks access to the nucleotide binding site by ATP, demonstrates that Ca-ATPase active sites function independently of one another prior to the phosphorylation of PLB. However, upon PKA-dependent phosphorylation of PLB, a second-order dependence between enzyme activity and the fraction of active sites is observed, consistent with a dimeric functional complex. Complementary distance measurements were made using FITC or 5-iodoacetamido-fluorescein (IAF) bound to Cys674 within the N- or P-domains respectively, to detect structural coupling within oligomeric complexes. Accompanying the phosphorylation of PLB, neighboring Ca-ATPase polypeptide chains exhibit a 4 ± 2 Å decrease in the proximity between FITC sites within the N-domain and a 9 ± 3 Å increase in the proximity between IAF sites within P-domains. Thus, the phosphorylation of PLB induces spatial rearrangements between the N- and P-domain elements of proximal Ca-ATPase polypeptide chains which restore functional interactions between neighboring polypeptide chains and, in turn, result in increased rates of catalytic turnover. These results are interpreted in terms of a structural model, calculated through optimization of shape complementarity, desolvation, and electrostatic energies, which suggests a dimeric arrangement of Ca-ATPase polypeptide chains through the proximal association of N-domains. We suggest that the phosphorylation of PLB acts to release constraints involving interdomain subunit interactions that enhance catalytically important N-domain motions.

  13. In Silico Investigation into Cellular Mechanisms of Cardiac Alternans in Myocardial Ischemia

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    Jiaqi Liu


    Full Text Available Myocardial ischemia is associated with pathophysiological conditions such as hyperkalemia, acidosis, and hypoxia. These physiological disorders may lead to changes on the functions of ionic channels, which in turn form the basis for cardiac alternans. In this paper, we investigated the roles of hyperkalemia and calcium handling components played in the genesis of alternans in ischemia at the cellular level by using computational simulations. The results show that hyperkalemic reduced cell excitability and delayed recovery from inactivation of depolarization currents. The inactivation time constant τf of L-type calcium current (ICaL increased obviously in hyperkalemia. One cycle length was not enough for ICaL to recover completely. Alternans developed as a result of ICaL responding to stimulation every other beat. Sarcoplasmic reticulum calcium-ATPase (SERCA2a function decreased in ischemia. This change resulted in intracellular Ca (Cai alternans of small magnitude. A strong Na+-Ca2+ exchange current (INCX increased the magnitude of Cai alternans, leading to APD alternans through excitation-contraction coupling. Some alternated repolarization currents contributed to this repolarization alternans.

  14. In Silico Investigation into Cellular Mechanisms of Cardiac Alternans in Myocardial Ischemia (United States)

    Liu, Jiaqi; Zhao, Xiaopeng


    Myocardial ischemia is associated with pathophysiological conditions such as hyperkalemia, acidosis, and hypoxia. These physiological disorders may lead to changes on the functions of ionic channels, which in turn form the basis for cardiac alternans. In this paper, we investigated the roles of hyperkalemia and calcium handling components played in the genesis of alternans in ischemia at the cellular level by using computational simulations. The results show that hyperkalemic reduced cell excitability and delayed recovery from inactivation of depolarization currents. The inactivation time constant τf of L-type calcium current (ICaL) increased obviously in hyperkalemia. One cycle length was not enough for ICaL to recover completely. Alternans developed as a result of ICaL responding to stimulation every other beat. Sarcoplasmic reticulum calcium-ATPase (SERCA2a) function decreased in ischemia. This change resulted in intracellular Ca (Cai) alternans of small magnitude. A strong Na+-Ca2+ exchange current (INCX) increased the magnitude of Cai alternans, leading to APD alternans through excitation-contraction coupling. Some alternated repolarization currents contributed to this repolarization alternans. PMID:28070211

  15. Rhythmic beating of stem cell-derived cardiac cells requires dynamic coupling of electrophysiology and Ca cycling. (United States)

    Zahanich, Ihor; Sirenko, Syevda G; Maltseva, Larissa A; Tarasova, Yelena S; Spurgeon, Harold A; Boheler, Kenneth R; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A


    There is an intense interest in differentiating embryonic stem cells to engineer biological pacemakers as an alternative to electronic pacemakers for patients with cardiac pacemaker function deficiency. Embryonic stem cell-derived cardiocytes (ESCs), however, often exhibit dysrhythmic excitations. Using Ca(2+) imaging and patch-clamp techniques, we studied requirements for generation of spontaneous rhythmic action potentials (APs) in late-stage mouse ESCs. Sarcoplasmic reticulum (SR) of ESCs generates spontaneous, rhythmic, wavelet-like Local Ca(2+)Releases (LCRs) (inhibited by ryanodine, tetracaine, or thapsigargin). L-type Ca(2+)current (I(CaL)) induces a global Ca(2+) release (CICR), depleting the Ca(2+) content SR which resets the phases of LCR oscillators. Following a delay, SR then generates a highly synchronized spontaneous Ca(2+)release of multiple LCRs throughout the cell. The LCRs generate an inward Na(+)/Ca(2+)exchanger (NCX) current (absent in Na(+)-free solution) that ignites the next AP. Interfering with SR Ca(2+) cycling (ryanodine, caffeine, thapsigargin, cyclopiazonic acid, BAPTA-AM), NCX (Na(+)-free solution), or I(CaL) (nifedipine) results in dysrhythmic excitations or cessation of automaticity. Inhibition of cAMP/PKA signaling by a specific PKA inhibitor, PKI, decreases SR Ca(2+) loading, substantially reducing both spontaneous LCRs (number, size, and amplitude) and rhythmic AP firing. In contrast, enhancing PKA signaling by cAMP increases the LCRs (number, size, duration) and converts irregularly beating ESCs to rhythmic "pacemaker-like" cells. SR Ca(2+) loading and LCR activity could be also increased with a selective activation of SR Ca(2+) pumping by a phospholamban antibody. We conclude that SR Ca(2+) loading and spontaneous rhythmic LCRs are driven by inherent cAMP/PKA activity. I(CaL) synchronizes multiple LCR oscillators resulting in strong, partially synchronized diastolic Ca(2+) release and NCX current. Rhythmic ESC automaticity can be

  16. Genetically engineered excitable cardiac myofibroblasts coupled to cardiomyocytes rescue normal propagation and reduce arrhythmia complexity in heterocellular monolayers.

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    Luqia Hou

    Full Text Available RATIONALE AND OBJECTIVE: The use of genetic engineering of unexcitable cells to enable expression of gap junctions and inward rectifier potassium channels has suggested that cell therapies aimed at establishing electrical coupling of unexcitable donor cells to host cardiomyocytes may be arrhythmogenic. Whether similar considerations apply when the donor cells are electrically excitable has not been investigated. Here we tested the hypothesis that adenoviral transfer of genes coding Kir2.1 (I(K1, Na(V1.5 (I(Na and connexin-43 (Cx43 proteins into neonatal rat ventricular myofibroblasts (NRVF will convert them into fully excitable cells, rescue rapid conduction velocity (CV and reduce the incidence of complex reentry arrhythmias in an in vitro model. METHODS AND RESULTS: We used adenoviral (Ad- constructs encoding Kir2.1, Na(V1.5 and Cx43 in NRVF. In single NRVF, Ad-Kir2.1 or Ad-Na(V1.5 infection enabled us to regulate the densities of I(K1 and I(Na, respectively. At varying MOI ratios of 10/10, 5/10 and 5/20, NRVF co-infected with Ad-Kir2.1+ Na(V1.5 were hyperpolarized and generated action potentials (APs with upstroke velocities >100 V/s. However, when forming monolayers only the addition of Ad-Cx43 made the excitable NRVF capable of conducting electrical impulses (CV = 20.71±0.79 cm/s. When genetically engineered excitable NRVF overexpressing Kir2.1, Na(V1.5 and Cx43 were used to replace normal NRVF in heterocellular monolayers that included neonatal rat ventricular myocytes (NRVM, CV was significantly increased (27.59±0.76 cm/s vs. 21.18±0.65 cm/s, p<0.05, reaching values similar to those of pure myocytes monolayers (27.27±0.72 cm/s. Moreover, during reentry, propagation was faster and more organized, with a significantly lower number of wavebreaks in heterocellular monolayers formed by excitable compared with unexcitable NRVF. CONCLUSION: Viral transfer of genes coding Kir2.1, Na(V1.5 and Cx43 to cardiac myofibroblasts endows them with

  17. Calpains and proteasomes mediate degradation of ryanodine receptors in a model of cardiac ischemic reperfusion. (United States)

    Pedrozo, Zully; Sánchez, Gina; Torrealba, Natalia; Valenzuela, Rodrigo; Fernández, Carolina; Hidalgo, Cecilia; Lavandero, Sergio; Donoso, Paulina


    Type-2 ryanodine receptors (RyR2)--the calcium release channels of cardiac sarcoplasmic reticulum--have a central role in cardiac excitation-contraction coupling. In the heart, ischemia/reperfusion causes a rapid and significant decrease in RyR2 content but the mechanisms responsible for this effect are not fully understood. We have studied the involvement of three proteolytic systems--calpains, the proteasome and autophagy--on the degradation of RyR2 in rat neonatal cardiomyocyte cultures subjected to simulated ischemia/reperfusion (sI/R). We found that 8h of ischemia followed by 16h of reperfusion decreased RyR2 content by 50% without any changes in RyR2 mRNA. Specific inhibitors of calpains and the proteasome prevented the decrease of RyR2 caused by sI/R, implicating both pathways in its degradation. Proteasome inhibitors also prevented the degradation of calpastatin, the endogenous calpain inhibitor, hindering the activation of calpain induced by calpastatin degradation. Autophagy was activated during sI/R as evidenced by the increase in LC3-II and beclin-1, two proteins involved in autophagosome generation, and in the emergence of GFP-LC3 containing vacuoles in adenovirus GFP-LC3 transduced cardiomyocytes. Selective autophagy inhibition, however, induced even further RyR2 degradation, making unlikely the participation of autophagy in sI/R-induced RyR2 degradation. Our results suggest that calpain activation as a result of proteasome-induced degradation of calpastatin initiates RyR2 proteolysis, which is followed by proteasome-dependent degradation of the resulting RyR2 fragments. The decrease in RyR2 content during ischemia/reperfusion may be relevant to the decrease of heart contractility after ischemia.

  18. MDIMP, a novel cardiac Ca(2+) channel blocker with atrial selectivity. (United States)

    Santamaria-Herrera, Mireille Aline; Ríos-Pérez, Erick Benjamín; de la Rosa, Juan Antonio Manuel; García-Castañeda, Maricela; Osornio-Garduño, Diana Stephanie; Ramos-Mondragón, Roberto; Mancilla-Percino, Teresa; Avila, Guillermo


    In cardiac muscle cells both T-and L-type Ca(2+) channels (TTCCs and LTCCs, respectively) are expressed, and the latter are relevant to a process known as excitation-contraction coupling (ECC). Evidence obtained from docking studies suggests that isoindolines derived from α-amino acids bind to the LTCC CaV1.2. In the present study, we investigated whether methyl (S)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate (MDIMP), which is derived from L-leucine, modulates both Ca(2+) channels and ECC. To this end, mechanical properties, as well as Ca(2+) transients and currents, were all investigated in isolated cardiac myocytes. The effects of MDIMP on CaV1.2 (transiently expressed in 293T/17 cells) were also studied. In this system, evidence was found for an inhibitory action that develops and recovers in min, with an IC50 of 450µM. With respect to myocytes: atrial-TTCCs, atrial-LTCCs, and ventricular-LTCCs were also inhibited, in that order of potency. Accordingly, Ca(2+) transients, contractions, and window currents of LTCCs were all reduced more strongly in atrial cells. Interestingly, while the modulation of LTCCs was state-independent in these cells, it was state-dependent, and dual, on the ventricular ones. Furthermore, practically all of the ventricular LTCCs were closed at resting membrane potentials. This could explain their resistance to MDIMP, as they were affected in only open or inactivated states. All these features in turn explain the preferential down-regulation of the atrial ECC. Thus, our results support the view that isoindolines bind to Ca(2+) channels, improve our knowledge of the corresponding structure-function relationship, and may be relevant for conditions where decreased atrial activity is desired.

  19. Cardiac Resynchronization Therapy and phase resetting of the sinoatrial node: A conjecture (United States)

    Cantini, Federico; Varanini, Maurizio; Macerata, Alberto; Piacenti, Marcello; Morales, Maria-Aurora; Balocchi, Rita


    Congestive heart failure is a severe chronic disease often associated with disorders that alter the mechanisms of excitation-contraction coupling that may result in an asynchronous left ventricular motion which may further impair the ability of the failing heart to eject blood. In recent years a therapeutic approach to resynchronize the ventricles (cardiac resynchronization therapy, CRT) has been performed through the use of a pacemaker device able to provide atrial-based biventricular stimulation. Atrial lead senses the spontaneous occurrence of cells depolarization and sends the information to the generator which, in turn, after a settled delay [atrioventricular (AV) delay], sends electrical impulses to both ventricles to stimulate their synchronous contraction. Recent studies performed on heart rate behavior of chronically implanted patients at different epochs after implantation have shown that CRT can lead to sustained overall improvement of heart function with a reduction in morbidity and mortality. At this moment, however, there are no studies about CRT effects on spontaneous heart activity of chronically implanted patients. We performed an experimental study in which the electrocardiographic signal of five subjects under chronic CRT was recorded during the activity of the pacemaker programmed at different AV delays and under spontaneous cardiac activity after pacemaker deactivation. The different behavior of heart rate variability during pacemaker activity and after pacemaker deactivation suggested the hypothesis of a phase resetting mechanism induced by the pacemaker stimulus on the sinoatrial (SA) node, a phenomenon already known in literature for aggregate of cardiac cells, but still unexplored in vivo. The constraints imposed by the nature of our study (in vivo tests) made it impossible to plan an experiment to prove our hypothesis directly. We therefore considered the best attainable result would be to prove the accordance of our data to the conjecture

  20. Cardiac resynchronization therapy and phase resetting of the sinoatrial node: a conjecture. (United States)

    Cantini, Federico; Varanini, Maurizio; Macerata, Alberto; Piacenti, Marcello; Morales, Maria-Aurora; Balocchi, Rita


    Congestive heart failure is a severe chronic disease often associated with disorders that alter the mechanisms of excitation-contraction coupling that may result in an asynchronous left ventricular motion which may further impair the ability of the failing heart to eject blood. In recent years a therapeutic approach to resynchronize the ventricles (cardiac resynchronization therapy, CRT) has been performed through the use of a pacemaker device able to provide atrial-based biventricular stimulation. Atrial lead senses the spontaneous occurrence of cells depolarization and sends the information to the generator which, in turn, after a settled delay [atrioventricular (AV) delay], sends electrical impulses to both ventricles to stimulate their synchronous contraction. Recent studies performed on heart rate behavior of chronically implanted patients at different epochs after implantation have shown that CRT can lead to sustained overall improvement of heart function with a reduction in morbidity and mortality. At this moment, however, there are no studies about CRT effects on spontaneous heart activity of chronically implanted patients. We performed an experimental study in which the electrocardiographic signal of five subjects under chronic CRT was recorded during the activity of the pacemaker programmed at different AV delays and under spontaneous cardiac activity after pacemaker deactivation. The different behavior of heart rate variability during pacemaker activity and after pacemaker deactivation suggested the hypothesis of a phase resetting mechanism induced by the pacemaker stimulus on the sinoatrial (SA) node, a phenomenon already known in literature for aggregate of cardiac cells, but still unexplored in vivo. The constraints imposed by the nature of our study (in vivo tests) made it impossible to plan an experiment to prove our hypothesis directly. We therefore considered the best attainable result would be to prove the accordance of our data to the conjecture

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

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


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

  2. Structure and Regulation of Cardiac L-type Ca2+ Channel and Its Re-lationship with Heart Diseases%心肌L型钙通道结构、调节及与心脏疾病关系

    Institute of Scientific and Technical Information of China (English)

    杨晓敏; 赵俊云; 屠蘅菁; 汤轶波; 王勇


    心肌L型钙通道CaV1. 2是维持心肌细胞兴奋和兴奋-收缩偶联的多亚基跨膜蛋白. 多种信号通路参与CaV1. 2的调节, 其中主要包括蛋白激酶A、 蛋白激酶G和蛋白激酶C途径. CaV1. 2基因突变或调节异常导致心律失常、 心肌肥大和心衰等心脏疾病的发生.%Cardiac L-type calcium channel CaV1. 2 is a transmembrane protein, which is cruci-al for excitement and excitement-contraction coupling in cardiac cells. It is regulated by a variety of second messengers and different kinases such as protein kinase A, protein kinase G, and protein kinase C. The genetic defects or the abnormal regulation of CaV1. 2 can cause a variety of heart dis-eases including arrhythmia, myocardial hypertrophy and heart failure.

  3. CaMKII Regulation of Cardiac Ryanodine Receptors and Inositol Triphosphate Receptors

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    Emmanuel eCamors


    Full Text Available Ryanodine receptors (RyRs and inositol triphosphate receptors (InsP3Rs are structurally related intracellular calcium release channels that participate in multiple primary or secondary amplified Ca2+ signals, triggering muscle contraction and oscillatory Ca2+ waves, or activating transcription factors. In the heart, RyRs play an indisputable role in the process of excitation-contraction coupling as the main pathway for Ca2+ release from sarcoplasmic reticulum (SR, and a less prominent role in the process of excitation-transcription coupling. Conversely, InsP3Rs are believed to contribute in subtle ways, only, to contraction of the heart, and in more important ways to regulation of transcription factors. Because uncontrolled activity of either RyRs or InsP3Rs may elicit life-threatening arrhythmogenic and/or remodeling Ca2+ signals, regulation of their activity is of paramount importance for normal cardiac function. Due to their structural similarity, many regulatory factors, accessory proteins, and posttranslational processes are equivalent for RyRs and InsP3Rs. Here we discuss regulation of RyRs and InsP3Rs by CaMKII phosphorylation, but touch on other kinases whenever appropriate. CaMKII is emerging as a powerful modulator of RyR and InsP3R activity but interestingly, some of the complexities and controversies surrounding phosphorylation of RyRs also apply to InsP3Rs, and a clear-cut effect of CaMKII on either channel eludes investigators for now. Nevertheless, some effects of CaMKII on global cellular activity, such as SR Ca2+ leak or force-frequency potentiation, appear clear now, and this constrains the limits of the controversies and permits a more tractable approach to elucidate the effects of phosphorylation at the single channel level.

  4. Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure. (United States)

    Zhang, Yunhe; Chen, Ao; Song, Lei; Li, Min; Luo, Zhangyuan; Zhang, Wenzan; Chen, Yingmin; He, Ben


    Vagus nerve stimulation (VNS), targeting the imbalanced autonomic nervous system, is a promising therapeutic approach for chronic heart failure (HF). Moreover, calcium cycling is an important part of cardiac excitation-contraction coupling (ECC), which also participates in the antiarrhythmic effects of VNS. We hypothesized that low-level VNS (LL-VNS) could improve cardiac function by regulation of intracellular calcium handling properties. The experimental HF model was established by ligation of the left anterior descending coronary artery (LAD). Thirty-two male Sprague-Dawley rats were divided into 3 groups as follows; control group (sham operated without coronary ligation, n = 10), HF-VNS group (HF rats with VNS, n = 12), and HF-SS group (HF rats with sham nerve stimulation, n = 10). After 8 weeks of treatment, LL-VNS significantly improved left ventricular ejection fraction (LVEF) and attenuated myocardial interstitial fibrosis in the HF-VNS group compared with the HF-SS group. Elevated plasma norepinephrine and dopamine, but not epinephrine, were partially reduced by LL-VNS. Additionally, LL-VNS restored the protein and mRNA levels of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), Na(+)-Ca(2+) exchanger 1 (NCX1), and phospholamban (PLB) whereas the expression of ryanodine receptor 2 (RyR2) as well as mRNA level was unaffected. Thus, our study results suggest that the improvement of cardiac performance by LL-VNS is accompanied by the reversal of dysfunctional calcium handling properties including SERCA2a, NCX1, and PLB which may be a potential molecular mechanism of VNS for HF.

  5. Calcium response of KCl-excited populations of ventricular myocytes from the European sea bass (Dicentrarchus labrax): a promising approach to integrate cell-to-cell heterogeneity in studying the cellular basis of fish cardiac performance. (United States)

    Ollivier, Hélène; Marchant, James; Le Bayon, Nicolas; Servili, Arianna; Claireaux, Guy


    Climate change challenges the capacity of fishes to thrive in their habitat. However, through phenotypic diversity, they demonstrate remarkable resilience to deteriorating conditions. In fish populations, inter-individual variation in a number of fitness-determining physiological traits, including cardiac performance, is classically observed. Information about the cellular bases of inter-individual variability in cardiac performance is scarce including the possible contribution of excitation-contraction (EC) coupling. This study aimed at providing insight into EC coupling-related Ca(2+) response and thermal plasticity in the European sea bass (Dicentrarchus labrax). A cell population approach was used to lay the methodological basis for identifying the cellular determinants of cardiac performance. Fish were acclimated at 12 and 22 °C and changes in intracellular calcium concentration ([Ca(2+)]i) following KCl stimulation were measured using Fura-2, at 12 or 22 °C-test. The increase in [Ca(2+)]i resulted primarily from extracellular Ca(2+) entry but sarcoplasmic reticulum stores were also shown to be involved. As previously reported in sea bass, a modest effect of adrenaline was observed. Moreover, although the response appeared relatively insensitive to an acute temperature change, a difference in Ca(2+) response was observed between 12- and 22 °C-acclimated fish. In particular, a greater increase in [Ca(2+)]i at a high level of adrenaline was observed in 22 °C-acclimated fish that may be related to an improved efficiency of adrenaline under these conditions. In conclusion, this method allows a rapid screening of cellular characteristics. It represents a promising tool to identify the cellular determinants of inter-individual variability in fishes' capacity for environmental adaptation.

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

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    Laura Doyle Gauthier


    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. Effect of intracellular Ca2+ and action potential duration on L-type Ca2+ channel inactivation and recovery from inactivation in rabbit cardiac myocytes. (United States)

    Altamirano, Julio; Bers, Donald M


    Ca(2+) current (I(Ca)) recovery from inactivation is necessary for normal cardiac excitation-contraction coupling. In normal hearts, increased stimulation frequency increases force, but in heart failure (HF) this force-frequency relationship (FFR) is often flattened or reversed. Although reduced sarcoplasmic reticulum Ca(2+)-ATPase function may be involved, decreased I(Ca) availability may also contribute. Longer action potential duration (APD), slower intracellular Ca(2+) concentration ([Ca(2+)](i)) decline, and higher diastolic [Ca(2+)](i) in HF could all slow I(Ca) recovery from inactivation, thereby decreasing I(Ca) availability. We measured the effect of different diastolic [Ca(2+)](i) on I(Ca) inactivation and recovery from inactivation in rabbit cardiac myocytes. Both I(Ca) and Ba(2+) current (I(Ba)) were measured. I(Ca) decay was accelerated only at high diastolic [Ca(2+)](i) (600 nM). I(Ba) inactivation was slower but insensitive to [Ca(2+)](i). Membrane potential dependence of I(Ca) or I(Ba) availability was not affected by [Ca(2+)](i) <600 nM. Recovery from inactivation was slowed by both depolarization and high [Ca(2+)](i). We also used perforated patch with action potential (AP)-clamp and normal Ca(2+) transients, using various APDs as conditioning pulses for different frequencies (and to simulate HF APD). Recovery of I(Ca) following longer APD was increasingly incomplete, decreasing I(Ca) availability. Trains of long APs caused a larger I(Ca) decrease than short APD at the same frequency. This effect on I(Ca) availability was exacerbated by slowing twitch [Ca(2+)](i) decline by approximately 50%. We conclude that long APD and slower [Ca(2+)](i) decline lead to cumulative inactivation limiting I(Ca) at high heart rates and might contribute to the negative FFR in HF, independent of altered Ca(2+) channel properties.

  8. Cardiac arrest (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  9. Cardiac applications of optogenetics. (United States)

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia


    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  10. 骨骼肌兴奋-收缩偶联超微结构瞬时变化研究%Study on the instant changes of ultrastructural morphological during excitation-contraction coupling in skeletal muscles

    Institute of Scientific and Technical Information of China (English)

    杨勇骥; 雷长海; 吴越; 沙继宏; 叶煦亭; 余宏宇; 夏金辉



  11. 骨骼肌兴奋收缩偶联时肌浆网膜Ca2+通道的研究%Research on Ca2+ channels of SR at skeletal muscular excitation-contraction coupling

    Institute of Scientific and Technical Information of China (English)

    王慧娥; 李霆; 杨勇骥; 宋田斌; 汤莹


    目的:从毫秒级功能变化水平实时观察骨骼肌肌浆网、T-管在收缩潜伏期内超微结构的时相-形态变化.方法:采用双红外线探测器-计算机控制的电刺激-超低温快速冷冻固定同步技术,对电刺激后的蟾蜍骨骼肌组织作快速冷冻固定,采用透射电镜对骨骼肌在电刺激后0.8 ms,2 ms,4.6 ms,10.8 ms和18.4 ms的超微结构变化进行观察.结果:刺激0 8 ms后,肌浆网和T-管未见明显改变.刺激2 ms后,SR内出现电子密度较大的物质.刺激4.6 ms后,肌浆网膜内外侧可见一一对应的电子密度大的物质.刺激10.8 ms后,SR与T-管形态又恢复原状,SR内电子密度大的物质消失.结论:骨骼肌兴奋-收缩偶联发生时,肌浆网的形态发生改变,肌浆网内出现电子密度较大的物质且逐渐向靠近T-管的方向移动.

  12. Ultrastructural change of subsarcolemic vesicles of the muscle cell during skeletal muscular excitation-contraction coupling%骨骼肌兴奋收缩偶联时肌膜下小泡的超微结构变化

    Institute of Scientific and Technical Information of China (English)

    李霆; 王慧娥; 杨勇骥; 宋田斌; 汤莹; 江键


    目的:从毫秒级功能变化水平实时观察骨骼肌肌膜下小泡在收缩潜伏期内的时相-形态变化.方法:采用双红外线探测器-计算机控制的电刺激-超低温快速冷冻固定同步技术,对电刺激后的蟾蜍骨骼肌组织作快速冷冻固定,冷冻置换,微波浸透包埋和超薄切片,在透射电镜下观察该骨骼肌细胞在电刺激后0.0ms,4.6 ms,24ms的超微结构变化.结果:未加刺激的骨骼肌细胞的肌膜下仅见少量小泡分布;施加刺激4.6ms后肌膜下出现大量小泡,并由3~8个小泡融合成聚合体;24ms后小泡急剧减少,仅残留少量小泡紧靠肌膜下.结论:骨骼肌兴奋-收缩偶联发生时,肌膜下出现大量小泡.

  13. Cardiac Sarcoidosis. (United States)

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


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

  14. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  15. Cardiac cameras. (United States)

    Travin, Mark I


    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  16. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.


    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  17. Cardiac Rehabilitation (United States)

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  18. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian


    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  19. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)



    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  20. Differential coupling of Arg- and Gly389 polymorphic forms of the β1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs



    The β1-adrenergic receptor (β1AR; ADRB1) polymorphism Arg389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that β1-Arg389 and β1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wild-type and transgenic mice that expressed either human β1-Arg389 or β1-Gly389 rece...

  1. Cardiac activation mapping using ultrasound current source density imaging (UCSDI). (United States)

    Olafsson, Ragnar; Witte, Russell S; Jia, Congxian; Huang, Sheng-Wen; Kim, Kang; O'Donnell, Matthew


    We describe the first mapping of biological current in a live heart using ultrasound current source density imaging (UCSDI). Ablation procedures that treat severe heart arrhythmias require detailed maps of the cardiac activation wave. The conventional procedure is time-consuming and limited by its poor spatial resolution (5-10 mm). UCSDI can potentially improve on existing mapping procedures. It is based on a pressure-induced change in resistivity known as the acousto-electric (AE) effect, which is spatially confined to the ultrasound focus. Data from 2 experiments are presented. A 540 kHz ultrasonic transducer (f/# = 1, focal length = 90 mm, pulse repetition frequency = 1600 Hz) was scanned over an isolated rabbit heart perfused with an excitation-contraction decoupler to reduce motion significantly while retaining electric function. Tungsten electrodes inserted in the left ventricle recorded simultaneously the AE signal and the low-frequency electrocardiogram (ECG). UCSDI displayed spatial and temporal patterns consistent with the spreading activation wave. The propagation velocity estimated from UCSDI was 0.25 +/- 0.05 mm/ms, comparable to the values obtained with the ECG signals. The maximum AE signal-to-noise ratio after filtering was 18 dB, with an equivalent detection threshold of 0.1 mA/ cm(2). This study demonstrates that UCSDI is a potentially powerful technique for mapping current flow and biopotentials in the heart.

  2. Cardiac Arrest: Obstetric CPR/ACLS. (United States)

    Cobb, Benjamin; Lipman, Steven


    In contrast with other high-resource countries, maternal mortality has seen an increase in the United States. Caring for pregnant women in cardiac arrest may prove uniquely challenging given the rarity of the event coupled by the physiological changes of pregnancy. Optimization of resuscitative efforts warrants special attention as described in the 2015 American Heart Association's "Scientific Statement on Maternal Cardiac Arrest." Current recommendations address a variety of topics ranging from the basic components of chest compressions and airway management to some of the logistical complexities and operational challenges involved in maternal cardiac arrest.

  3. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.


    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  4. Cardiac tamponade (image) (United States)

    Cardiac tamponade is a condition involving compression of the heart caused by blood or fluid accumulation in the space ... they cannot adequately fill or pump blood. Cardiac tamponade is an emergency condition that requires hospitalization.

  5. What Is Cardiac Rehabilitation? (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  6. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    Amin, A.S.; Asghari-Roodsari, A.; Tan, H.L.


    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  7. Mechanisms of cardiac pain. (United States)

    Foreman, Robert D; Garrett, Kennon M; Blair, Robert W


    Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF-kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1-C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain.

  8. Stem cells for cardiac repair: an introduction

    Institute of Scientific and Technical Information of China (English)

    Bastiaan C du Pr(e); Pieter A Doevendans; Linda W van Laake


    Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair.

  9. Cardiac mitochondria exhibit dynamic functional clustering

    Directory of Open Access Journals (Sweden)

    Felix Tobias Kurz


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

  10. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan


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

  11. Marketing cardiac CT programs. (United States)

    Scott, Jason


    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  12. Interaction among cardiac, respiratory, and locomotor rhythms during cardiolocomotor synchronization. (United States)

    Niizeki, K; Kawahara, K; Miyamoto, Y


    The nature of entrainment between cardiac and locomotor rhythms was investigated while normal human subjects walked or ran on a treadmill. To detect the incidence of entrainment occurrence, the phase relationships among cardiac, respiratory, and locomotor rhythms were analyzed. The phase relationship between heartbeats and gait signals showed that entrainment of cardiac rhythm to locomotor rhythm occurred in all subjects at one or more treadmill speeds. To elucidate interactions among cardiac, respiratory, and locomotor rhythms during the cardiolocomotor synchronization, spectral and coherence analyses were done for these three rhythms. Spectral and coherence analyses on fluctuations in the heart period and respiratory rhythms revealed that the strength of coupling between cardiac and respiratory rhythms decreased in the presence of cardiolocomotor synchronization. In addition, the coupling of cardiac and locomotor rhythms appeared to induce dissociation of coupling between respiratory and locomotor rhythms. These results were similar to those observed when stepping was voluntarily synchronized with cardiac rhythm. Possible mechanisms to explain coordination and interaction among the neural oscillators innervating these three rhythms are discussed.

  13. Cardiac Procedures and Surgeries (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cardiac Procedures and Surgeries Updated:Sep 16,2016 If you've had ... degree of coronary artery disease (CAD) you have. Cardiac Procedures and Surgeries Angioplasty Also known as Percutaneous Coronary Interventions [PCI], ...

  14. [Advances in cardiac pacing]. (United States)

    de Carranza, María-José Sancho-Tello; Fidalgo-Andrés, María Luisa; Ferrer, José Martínez; Mateas, Francisco Ruiz


    This article contains a review of the current status of remote monitoring and follow-up involving cardiac pacing devices and of the latest developments in cardiac resynchronization therapy. In addition, the most important articles published in the last year are discussed.

  15. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc


    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  16. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone


    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  17. Cardiac, respiratory, and locomotor coordination during walking in humans. (United States)

    Niizeki, K; Kawahara, K; Miyamoto, Y


    Interactions between locomotor, respiratory, and cardiac rhythms were investigated in human subjects (n = 11) walking on a treadmill. Investigation of the phase relationship between heart rate and gait signals revealed that cardiac rhythms were entrained to locomotor rhythms when both frequencies were close to an integer ratio. Coherence spectra were estimated between heartbeat fluctuation, respiratory, and gait signals, and their magnitudes were evaluated. The results suggest that the respiratory-induced fluctuation in heartbeat would vary depending on the strength of the cardiolocomotor coupling. The synchronization tends to occur for one or two specific phases in an individual subject, but there was some variation among subjects. When the subjects voluntarily synchronized their cadence with the cardiac rhythm, the heart rate and blood pressure varied depending on the phase lag within a cardiac cycle. The coordination of locomotor and cardiac rhythms is discussed.

  18. Cardiac tumors: echo assessment. (United States)

    Mankad, Rekha; Herrmann, Joerg


    Cardiac tumors are exceedingly rare (0.001-0.03% in most autopsy series). They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1) thrombus or vegetations are the most likely etiology, (2) cardiac tumors are mostly secondary and (3) primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses.

  19. Molecular Basis of Cardiac Myxomas

    Directory of Open Access Journals (Sweden)

    Pooja Singhal


    Full Text Available Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer. Metastatic cardiac tumors are about 100 times more common than the primary tumors. About 90% of primary cardiac tumors are benign, and of these the most common are cardiac myxomas. Approximately 12% of primary cardiac tumors are completely asymptomatic while others present with one or more signs and symptoms of the classical triad of hemodynamic changes due to intracardiac obstruction, embolism and nonspecific constitutional symptoms. Echocardiography is highly sensitive and specific in detecting cardiac tumors. Other helpful investigations are chest X-rays, magnetic resonance imaging and computerized tomography scan. Surgical excision is the treatment of choice for primary cardiac tumors and is usually associated with a good prognosis. This review article will focus on the general features of benign cardiac tumors with an emphasis on cardiac myxomas and their molecular basis.


    Institute of Scientific and Technical Information of China (English)

    蒋彬; 周希平; Achilles J.Pappano


    目的:比较和探讨L型钙流[ICa(L)]和反向钠-钙交换(NCX)在触发豚鼠心室肌细胞兴奋-收缩偶联中的作用.方法:以分离的豚鼠单个心室肌细胞为对象,采用膜片钳和单细胞收缩测量技术,给予35℃的各种含药物细胞外液快速灌流,同时记录ICa(L)和细胞收缩.结果:①在+10 mV的钳制电压,使用硝苯地平(Nif)10~100μmol/L和Nif 30μmol/L+Cd2+30μmol/L,阻滞ICa(L)越多,细胞收缩被阻滞得越多,呈线性相关.②在+50 mV的钳制电压,Nif 100μmol/L以及Nif 30 μmol/L+Cd2+30 pmol/L仅能抑制部分细胞收缩,但剩余的细胞收缩起始时间明显延迟,且能被5 mmol/L Ni2+所阻滞.③在+100mV的钳制电压,细胞收缩起始时间较+50 mV明显延迟,且不能被Nif 100μmol/L和Nif 30μmol/L+Cd2+30μmol/L所阻滞.结论:在生理条件下,Ica(L)是触发心室肌细胞兴奋-收缩偶联的主要途径,但在膜电位>+50 mV时,反向NCX也参与兴奋-收缩偶联.

  1. Cardiac Tumors; Tumeurs cardiaques

    Energy Technology Data Exchange (ETDEWEB)

    Laissy, J.P.; Fernandez, P. [Centre Hospitalier Universitaire Bichat Claude Bernard, Service d' Imagerie, 76 - Rouen (France); Mousseaux, E. [Hopital Europeen Georges Pompidou (HEGP), Service de Radiologie Cardio Vasculaire et Interventionnelle, 75 - Paris (France); Dacher, J.N. [Centre Hospitalier Universitaire Charles Nicolle, 75 - Rouen (France); Crochet, D. [Centre Hospitalier Universitaire, Hopital Laennec, Centre Hemodynamique, Radiologie Thoracique et Vasculaire, 44 - Nantes (France)


    Metastases are the most frequent tumors of the heart even though they seldom are recognized. Most primary cardiac tumors are benign. The main role of imaging is to differentiate a cardiac tumor from thrombus and rare pseudo-tumors: tuberculoma, hydatid cyst. Echocardiography is the fist line imaging technique to detect cardiac tumors, but CT and MRl arc useful for further characterization and differential diagnosis. Myxoma of the left atrium is the most frequent benign cardiac tumor. It usually is pedunculated and sometimes calcified. Sarcoma is the most frequent primary malignant tumor and usually presents as a sessile infiltrative tumor. Lymphoma and metastases are usually recognized by the presence of known tumor elsewhere of by characteristic direct contiguous involvement. Diagnosing primary and secondary pericardial tumors often is difficult. Imaging is valuable for diagnosis, characterization, pre-surgical evaluation and follow-up. (author)

  2. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;


    to a standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social......Aim: The comprehensive cardiac rehabilitation (CR) programme after myocardial infarction (MI) improves quality of life and results in reduced cardiac mortality and recurrence of MI. Hospitals worldwide face problems with low participation rates in rehabilitation programmes. Inequality...

  3. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi


    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  4. Cardiac imaging in adults

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, C.C.


    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  5. Port Access Cardiac Surgery. (United States)

    Viganó, Mario; Minzioni, Gaetano; Spreafico, Patrizio; Rinaldi, Mauro; Pasquino, Stefano; Ceriana, Piero; Locatelli, Alessandro


    The port-access technique for cardiac surgery was recently developed at Stanford University in California as a less invasive method to perform some cardiac operations. The port-access system has been described in detail elsewhere. It is based on femoral arterial and venous access for cardiopulmonary bypass (CPB) and on the adoption of a specially designed triple-lumen catheter described originally by Peters, and subsequently modified and developed in the definitive configuration called the endoaortic clamp.

  6. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon


    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  7. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E


    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  8. Autonomic cardiac innervation


    Hasan, Wohaib


    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targe...

  9. Infected cardiac hydatid cyst


    Ceviz, M; Becit, N; Kocak, H.


    A 24 year old woman presented with chest pain and palpitation. The presence of a semisolid mass—an echinococcal cyst or tumour—in the left ventricular apex was diagnosed by echocardiography, computed tomography, and magnetic resonance imaging. The infected cyst was seen at surgery. The cyst was removed successfully by using cardiopulmonary bypass with cross clamp.

Keywords: cardiac hydatid cyst; infected cardiac hydatid cyst

  10. Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4. (United States)

    Ounzain, Samir; Kobayashi, Satoru; Peterson, Richard E; He, Aibin; Motterle, Anna; Samani, Nilesh J; Menick, Donald R; Pu, William T; Liang, Qiangrong; Chong, Nelson W


    Ms1/STARS is a novel muscle-specific actin-binding protein that specifically modulates the myocardin-related transcription factor (MRTF)-serum response factor (SRF) regulatory axis within striated muscle. This ms1/STARS-dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and postnatal cardiac function/homeostasis. The dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter, gain-of-function, and loss-of-function approaches. Through this integrated analysis, we have identified three evolutionarily conserved regions (ECRs), α, SINA, and DINA, that act as cis-regulatory modules and confer differential cardiac cell-specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall, our results demonstrate that within embryonic, neonatal, and adult hearts, GATA4 represses ms1/STARS expression with the pathologically associated depletion of GATA4 (type 1/type 2 diabetic models), resulting in ms1/STARS upregulation. This GATA4-dependent repression of ms1/STARS expression has major implications for MRTF-SRF signaling in the context of cardiac development and disease.

  11. Gold nanoparticle-decellularized matrix hybrids for cardiac tissue engineering. (United States)

    Shevach, Michal; Fleischer, Sharon; Shapira, Assaf; Dvir, Tal


    Decellularized matrices are valuable scaffolds for engineering functional cardiac patches for treating myocardial infarction. However, the lack of quick and efficient electrical coupling between adjacent cells may jeopardize the success of the treatment. To address this issue, we have deposited gold nanoparticles on fibrous decellularized omental matrices and investigated their morphology, conductivity, and degradation. We have shown that cardiac cells engineered within the hybrid scaffolds exhibited elongated and aligned morphology, massive striation, and organized connexin 43 electrical coupling proteins. Finally, we have shown that the hybrid patches demonstrated superior function as compared to pristine patches, including a stronger contraction force, lower excitation threshold, and faster calcium transients.

  12. [Psychosomatic aspects of cardiac arrhythmias]. (United States)

    Siepmann, Martin; Kirch, Wilhelm


    Emotional stress facilitates the occurrence of cardiac arrhythmias including sudden cardiac death. The prevalence of anxiety and depression is increased in cardiac patients as compared to the normal population. The risk of cardiovascular mortality is enhanced in patients suffering from depression. Comorbid anxiety disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac regulation with predominance of the sympathetic tone is hypothesized to be causative for this. The emotional reaction to cardiac arrhythmias is differing to a large extent between individuals. Emotional stress may result from coping with treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may influence each other in the sense of a vicious circle. Somatoform cardiac arrhythmias are predominantly of psychogenic origin. Instrumental measures and frequent contacts between physicians and patients may facilitate disease chronification. The present review is dealing with the multifaceted relationships between cardiac arrhythmias and emotional stress. The underlying mechanisms and corresponding treatment modalities are discussed.

  13. Cardiac radiology: centenary review. (United States)

    de Roos, Albert; Higgins, Charles B


    During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

  14. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa


    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  15. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O;


    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... for the situation at hand. Due to challenging circumstances, the cost assessment turned out to be ex-post and top-down. RESULTS: Cost per treatment sequence is estimated to be approximately euro 976, whereas the incremental cost (compared with usual care) is approximately euro 682. The cost estimate is uncertain...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  16. Toothache of cardiac origin. (United States)

    Kreiner, M; Okeson, J P


    Pain referred to the orofacial structures can sometimes be a diagnostic challenge for the clinician. In some instances, a patient may complain of tooth pain that is completely unrelated to any dental source. This poses a diagnostic and therapeutic problem for the dentist. Cardiac pain most commonly radiates to the left arm, shoulder, neck, and face. In rare instances, angina pectoris may present as dental pain. When this occurs, an improper diagnosis frequently leads to unnecessary dental treatment or, more significantly, a delay of proper treatment. This delay may result in the patient experiencing an acute myocardial infarction. It is the dentist's responsibility to establish a proper diagnosis so that the treatment will be directed toward the source of pain and not to the site of pain. This article reviews the literature concerning referred pain of cardiac origin and presents a case report of toothache of cardiac origin.

  17. The cardiac anxiety questionnaire: cross-validation among cardiac inpatients

    NARCIS (Netherlands)

    Beek, M.H. van; Oude Voshaar, R.C.; Deelen, F.M. van; Balkom, A.J. van; Pop, G.A.; Speckens, A.E.


    OBJECTIVE: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D


    NARCIS (Netherlands)

    van Beek, M. H. C. T.; Voshaar, R. C. Oude; van Deelen, F. M.; van Balkom, A. J. L. M.; Pop, G.; Speckens, A. E. M.


    Objective: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  19. Perioperative management of cardiac disease. (United States)

    Aresti, N A; Malik, A A; Ihsan, K M; Aftab, S M E; Khan, W S


    Pre-existing cardiac disease contributes significantly to morbidity and mortality amongst patients undergoing non cardiac surgery. Patients with pre-existing cardiac disease or with risk factors for it, have as much as a 3.9% risk of suffering a major perioperative cardiac event (Lee et al 1999, Devereaux 2005). Furthermore, the incidence of perioperative myocardial infarction (MI) is increased 10 to 50 fold in patients with previous coronary events (Jassal 2008).

  20. Data analysis in cardiac arrhythmias. (United States)

    Rodrigo, Miguel; Pedrón-Torecilla, Jorge; Hernández, Ismael; Liberos, Alejandro; Climent, Andreu M; Guillem, María S


    Cardiac arrhythmias are an increasingly present in developed countries and represent a major health and economic burden. The occurrence of cardiac arrhythmias is closely linked to the electrical function of the heart. Consequently, the analysis of the electrical signal generated by the heart tissue, either recorded invasively or noninvasively, provides valuable information for the study of cardiac arrhythmias. In this chapter, novel cardiac signal analysis techniques that allow the study and diagnosis of cardiac arrhythmias are described, with emphasis on cardiac mapping which allows for spatiotemporal analysis of cardiac signals.Cardiac mapping can serve as a diagnostic tool by recording cardiac signals either in close contact to the heart tissue or noninvasively from the body surface, and allows the identification of cardiac sites responsible of the development or maintenance of arrhythmias. Cardiac mapping can also be used for research in cardiac arrhythmias in order to understand their mechanisms. For this purpose, both synthetic signals generated by computer simulations and animal experimental models allow for more controlled physiological conditions and complete access to the organ.

  1. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter


    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...

  2. Cardiac troponins and high-sensitivity cardiac troponin assays. (United States)

    Conrad, Michael J; Jarolim, Petr


    Measurement of circulating cardiac troponins I and T has become integral to the diagnosis of myocardial infarction. This article discusses the structure and function of the troponin complex and the release of cardiac troponin molecules from the injured cardiomyocyte into the circulation. An overview of current cardiac troponin assays and their classification according to sensitivity is presented. The diagnostic criteria, role, and usefulness of cardiac troponin for myocardial infarction are discussed. In addition, several examples are given of the usefulness of high-sensitivity cardiac troponin assays for short-term and long-term prediction of adverse events.

  3. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter


    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...

  4. Cardiac Risk Assessment (United States)

    ... Risk Assessment Related tests: Lipid Profile , VLDL Cholesterol , hs-CRP , Lp(a) Overview | Common Questions | Related Pages What ... cardiac risk include: High-sensitivity C-reactive protein (hs-CRP) : Studies have shown that measuring CRP with a ...

  5. The cardiac malpositions. (United States)

    Perloff, Joseph K


    Dextrocardia was known in the 17th century and was 1 of the first congenital malformations of the heart to be recognized. Fifty years elapsed before Matthew Baillie published his account of complete transposition in a human of the thoracic and abdominal viscera to the opposite side from what is natural. In 1858, Thomas Peacock stated that "the heart may be congenitally misplaced in various ways, occupying either an unusual position within the thorax, or being situated external to that cavity." In 1915, Maude Abbott described ectopia cordis, and Richard Paltauf's remarkable illustrations distinguished the various types of dextrocardia. In 1928, the first useful classification of the cardiac malpositions was proposed, and in 1966, Elliott et al's radiologic classification set the stage for clinical recognition. The first section of this review deals with the 3 basic cardiac malpositions in the presence of bilateral asymmetry. The second section deals with cardiac malpositions in the presence of bilateral left-sidedness or right-sidedness. Previous publications on cardiac malpositions are replete with an arcane vocabulary that confounds rather than clarifies. Even if the terms themselves are understood, inherent complexity weighs against clarity. This review was designed as a guided tour of an unfamiliar subject.

  6. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia


    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  7. Coupled transfers; Transferts couples

    Energy Technology Data Exchange (ETDEWEB)

    Nicolas, X.; Lauriat, G.; Jimenez-Rondan, J. [Universite de Marne-la-Vallee, Lab. d' Etudes des Transferts d' Energie et de Matiere (LETEM), 77 (France); Bouali, H.; Mezrhab, A. [Faculte des Sciences, Dept. de Physique, Lab. de Mecanique et Energetique, Oujda (Morocco); Abid, C. [Ecole Polytechnique Universitaire de Marseille, IUSTI UMR 6595, 13 Marseille (France); Stoian, M.; Rebay, M.; Lachi, M.; Padet, J. [Faculte des Sciences, Lab. de Thermomecanique, UTAP, 51 - Reims (France); Mladin, E.C. [Universitaire Polytechnique Bucarest, Faculte de Genie Mecanique, Bucarest (Romania); Mezrhab, A. [Faculte des Sciences, Lab. de Mecanique et Energetique, Dept. de Physique, Oujda (Morocco); Abid, C.; Papini, F. [Ecole Polytechnique, IUSTI, 13 - Marseille (France); Lorrette, C.; Goyheneche, J.M.; Boechat, C.; Pailler, R. [Laboratoire des Composites ThermoStructuraux, UMR 5801, 33 - Pessac (France); Ben Salah, M.; Askri, F.; Jemni, A.; Ben Nasrallah, S. [Ecole Nationale d' Ingenieurs de Monastir, Lab. d' Etudes des Systemes Thermiques et Energetiques (Tunisia); Grine, A.; Desmons, J.Y.; Harmand, S. [Laboratoire de Mecanique et d' Energetique, 59 - Valenciennes (France); Radenac, E.; Gressier, J.; Millan, P. [ONERA, 31 - Toulouse (France); Giovannini, A. [Institut de Mecanique des Fluides de Toulouse, 31 (France)


    This session about coupled transfers gathers 30 articles dealing with: numerical study of coupled heat transfers inside an alveolar wall; natural convection/radiant heat transfer coupling inside a plugged and ventilated chimney; finite-volume modeling of the convection-conduction coupling in non-stationary regime; numerical study of the natural convection/radiant heat transfer coupling inside a partitioned cavity; modeling of the thermal conductivity of textile reinforced composites: finite element homogenization on a full periodical pattern; application of the control volume method based on non-structured finite elements to the problems of axisymmetrical radiant heat transfers in any geometries; modeling of convective transfers in transient regime on a flat plate; a conservative method for the non-stationary coupling of aero-thermal engineering codes; measurement of coupled heat transfers (forced convection/radiant transfer) inside an horizontal duct; numerical simulation of the combustion of a water-oil emulsion droplet; numerical simulation study of heat and mass transfers inside a reactor for nano-powders synthesis; reduction of a combustion and heat transfer model of a direct injection diesel engine; modeling of heat transfers inside a knocking operated spark ignition engine; heat loss inside an internal combustion engine, thermodynamical and flamelet model, composition effects of CH{sub 4}H{sub 2} mixtures; experimental study and modeling of the evolution of a flame on a solid fuel; heat transfer for laminar subsonic jet of oxygen plasma impacting an obstacle; hydrogen transport through a A-Si:H layer submitted to an hydrogen plasma: temperature effects; thermal modeling of the CO{sub 2} laser welding of a magnesium alloy; radiant heat transfer inside a 3-D environment: application of the finite volume method in association with the CK model; optimization of the infrared baking of two types of powder paints; optimization of the emission power of an infrared

  8. Where is the origin of the activator calcium in cardiac ventricular contraction? (United States)

    Reiter, M; Vierling, W; Seibel, K


    Under normal experimental conditions, the force of rested-state contractions (i.e., contractions after a rest period of 15 min or longer) of mammalian ventricular myocardium is insignificant. In Mg2+-free solution, in low sodium solution or in the presence of a cardioactive steroid, a strong "early" rested-state contraction develops without delay after stimulation, indicating the accumulation during rest of intracellularly stored activator calcium. By contrast, catecholamines cause a "late" rested-state contraction with a characteristic latent period of about 100 ms between stimulation and onset of contraction. Inhibition of the slow inward current by nifedipine has no influence on the contraction velocity of the "early" rested-state contraction, indicating that Ca2+ of the slow inward current is not involved in the calcium release mechanism of prefilled stores during excitation-contraction coupling. Nifedipine suppresses the "late" rested-state contraction in the presence of noradrenaline. In view of the constancy of the latent period, it is proposed that the activator calcium for the "late" rested-state contraction enters the cell with the slow inward current, is sequestered at first by uptake sites of the sarcoplasmic reticulum and subsequently released from its release sites as long as the cell is depolarized. The model of the different origin of activator calcium is discussed in its implication for high-frequency contractions.

  9. Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)


    Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

  10. Interest of {sup 123}I-mibg cardiac tomo-scintigraphy coupled with myocardial perfusion in diagnosis of multiple system atrophy;Interet de la tomoscintigraphie cardiaque a la {sup 123}I-mIBG couplee a la perfusion myocardique dans le diagnostic de l'atrophie multisystematisee

    Energy Technology Data Exchange (ETDEWEB)

    Andriamisandratsoa, N.; Grucker, D.; Namer, I.J. [Hopitaux universitaires de Strasbourg, hopital de Hautepierre, Service de biophysique et medecine nucleaire, 67 - Strasbourg (France); Anheim, M.; Tranchant, C. [Hopitaux universitaires de Strasbourg, Departement de neurologie, 67 - Strasbourg (France)


    Objective: The aim of this prospective study is to assess the pertinence of using {sup 123}I-mibg myocardial tomo-scintigraphy coupled with perfusion scintigraphy as a diagnostic tool, to discriminate between multiple system atrophy (M.S.A.) and idiopathic Parkinson's disease (P.D.) at first guided by clinical data and L-DOPA tests. Material and methods: Forty patients, aged from 43 to 78 years (median 62 years) with Parkinson's syndrome were studied. Nineteen had a diagnosis of P.D. (criteria of brain bank) and 21 A.M.S. (Gibbs criteria). All were given test to acute L-DOPA. Chest-centered planar imaging (128 x 128 matrix, 5 minutes of duration) is performed at 1 hour and 4 hours after injection of 220 MBq of {sup 123}I-mibg, in addition a non-synchronized tomo-scintigraphy (64 x 64 matrix, 32 images of 50 seconds, zoom 1.45) was performed after the 4. hour and 15 minutes after injection of 200 to 400 MBq of {sup 99m}Tc-tetrofosmin. Besides neurological data, the parameters retained for comparison purposes with {sup 123}I-mibg cardiac tomo-scintigraphy were patients age, duration of disease and L-DOPA test results. Two regions of interest (R.O.I.) identical in size and in shape are used for {sup 123}I-mibg uptake quantifications (H/M and washout [W.o.]). The first one was placed in projection of mediastinum (M) and the other one in projection of heart (H). Results: We found an overall decreased uptake of the myocardial {sup 123}I-mibg without perfusion abnormality in 15 of 19 patients with P.D. and 11 among them were L-DOPA sensitive (L-DOPA test greater than 30%). Normal tracer uptake with {sup 123}I-mibg associated with an almost quite normal perfusion was seen in 15 of 21 patients with M.S.A. and they were little or not L-DOPA sensitive (L-DOPA test less than 30%). Therefore, 10 discordant cases (25%) between cardiac scintigraphy and clinical evolution of disease with also discordant L-DOPA tests were observed. In the P.D. group, quantification of

  11. G-protein-coupled inward rectifier potassium current contributes to ventricular repolarization

    DEFF Research Database (Denmark)

    Liang, Bo; Nissen, Jakob D; Laursen, Morten;


    The purpose of this study was to investigate the functional role of G-protein-coupled inward rectifier potassium (GIRK) channels in the cardiac ventricle.......The purpose of this study was to investigate the functional role of G-protein-coupled inward rectifier potassium (GIRK) channels in the cardiac ventricle....

  12. Cardiac nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Gerson, M.C.


    The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma.

  13. Sudden Cardiac Death

    Directory of Open Access Journals (Sweden)

    Yipsy María Gutiérrez Báez


    Full Text Available Since the second half of the twentieth century, dying suddenly due to heart-related problems has become the main health issue in all countries where infectious diseases are not prevalent. Sudden death from cardiac causes is an important global health problem. Major databases were searched for the leading causes of sudden cardiac death. It has been demonstrated that there is a group of hereditary diseases with structural alterations or without apparent organic cause that explains many cases of sudden death in young people, whether related or not to physical exertion. Certain population groups are at higher risk for this disease. They are relatively easy to identify and can be the target of primary prevention measures.

  14. Cardiac arrhythmias in pregnancy. (United States)

    Knotts, Robert J; Garan, Hasan


    As more women with repaired congenital heart disease survive to their reproductive years and many other women are delaying pregnancy until later in life, a rising concern is the risk of cardiac arrhythmias during pregnancy. Naturally occurring cardiovascular changes during pregnancy increase the likelihood that a recurrence of a previously experienced cardiac arrhythmia or a de novo arrhythmia will occur. Arrhythmias should be thoroughly investigated to determine if there is a reversible etiology, and risks/benefits of treatment options should be fully explored. We discuss the approach to working up and treating various arrhythmias during pregnancy with attention to fetal and maternal risks as well as treatment of fetal arrhythmias. Acute management in stable patients includes close monitoring and intravenous pharmacologic therapy, while DC cardioversion should be used to terminate arrhythmias in hemodynamically unstable patients. Long-term management may require continued oral antiarrhythmic therapy, with particular attention to fetal safety, to prevent complications associated with arrhythmias.

  15. Cardiac surgery 2015 reviewed. (United States)

    Doenst, Torsten; Strüning, Constanze; Moschovas, Alexandros; Gonzalez-Lopez, David; Essa, Yasin; Kirov, Hristo; Diab, Mahmoud; Faerber, Gloria


    For the year 2015, almost 19,000 published references can be found in PubMed when entering the search term "cardiac surgery". The last year has been again characterized by lively discussions in the fields where classic cardiac surgery and modern interventional techniques overlap. Lacking evidence in the field of coronary revascularization with either percutaneous coronary intervention or bypass surgery has been added. As in the years before, CABG remains the gold standard for the revascularization of complex stable triple-vessel disease. Plenty of new information has been presented comparing the conventional to transcatheter aortic valve implantation (TAVI) demonstrating similar short- and mid-term outcomes at high and low risk, but even a survival advantage with transfemoral TAVI at intermediate risk. In addition, there were many relevant and interesting other contributions from the purely operative arena. This review article will summarize the most pertinent publications in the fields of coronary revascularization, surgical treatment of valve disease, heart failure (i.e., transplantation and ventricular assist devices), and aortic surgery. While the article does not have the expectation of being complete and cannot be free of individual interpretation, it provides a condensed summary that is intended to give the reader "solid ground" for up-to-date decision-making in cardiac surgery.

  16. Cardiac hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)


    Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

  17. Cardiac MRI for myocardial ischemia.

    LENUS (Irish Health Repository)

    Daly, Caroline


    Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging.

  18. Excitation-transcription coupling in sympathetic neurons and the molecular mechanism of its initiation. (United States)

    Ma, Huan; Groth, Rachel D; Wheeler, Damian G; Barrett, Curtis F; Tsien, Richard W


    In excitable cells, membrane depolarization and activation of voltage-gated Ca²+ (Ca(V)) channels trigger numerous cellular responses, including muscle contraction, secretion, and gene expression. Yet, while the mechanisms underlying excitation-contraction and excitation-secretion coupling have been extensively characterized, how neuronal activity is coupled to gene expression has remained more elusive. In this article, we will discuss recent progress toward understanding the relationship between patterns of channel activity driven by membrane depolarization and activation of the nuclear transcription factor CREB. We show that signaling strength is steeply dependent on membrane depolarization and is more sensitive to the open probability of Ca(V) channels than the Ca²+ entry itself. Furthermore, our data indicate that by decoding Ca(V) channel activity, CaMKII (a Ca²+/calmodulin-dependent protein kinase) links membrane excitation to activation of CREB in the nucleus. Together, these results revealed some interesting and unexpected similarities between excitation-transcription coupling and other forms of excitation-response coupling.

  19. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng


    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  20. Signaling Pathways Involved in Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Tao Zewei; Li Longgui


    Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress.Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy (normal growth) and physiological hypertrophy (growth induced by physical conditioning), and maladaptive hypertrophy, including pathologic or reactive hypertrophy (growth induced by pathologic stimuli) and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response,including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt (PI3Ks/Akt),G protein-coupled receptors, small G proteins,MAPK, PKCs, Gp130/STAT'3, Na+/H+ exchanger,peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

  1. Case Report: Penetrating Cardiac Injury

    Directory of Open Access Journals (Sweden)

    Adem Grbolar


    Full Text Available Summary: Penetrating cardiac injurys caused by gunshots and penetrating tools have high mortality rates. The way of injury, how the cardiac area is effected and the presence of cardiac tamponadecauses mortality in different rates. However the better treatment quality of hospitals, increasingoperative techniques, and internel care unit quality has not been change during the years. Searching the literature, we want to present a 42 years old male patient whowas injured by knife and had a 1 cm skin wound on chest with cardiac tamponade. After sternotomy a 7 cm laseration was observed in heart. Cardioraphy was performed.

  2. Cardiac surgery for Kartagener syndrome. (United States)

    Tkebuchava, T; von Segesser, L K; Niederhäuser, U; Bauersfeld, U; Turina, M


    Two patients (one girl, one boy) with Kartagener syndrome (situs inversus, bronchiectasis, sinusitis), despite pulmonary problems and associated congenital cardiac anomalies, were operated on at the ages of 4 years and 7 years, respectively. They had had previous palliative treatment at the age of 3 months and 1.3 years, respectively. Both postoperative periods after total correction were without significant complications. Long-term follow-up was available for 9 and 19 years, respectively, with no manifestations of heart insufficiency. Both patients are physically active, and neither requires cardiac medication. Patients with Kartagener syndrome and associated congenital cardiac anomalies can successfully undergo multiple cardiac operations with good long-term outcome.

  3. Human cardiac systems electrophysiology and arrhythmogenesis: iteration of experiment and computation. (United States)

    Holzem, Katherine M; Madden, Eli J; Efimov, Igor R


    Human cardiac electrophysiology (EP) is a unique system for computational modelling at multiple scales. Due to the complexity of the cardiac excitation sequence, coordinated activity must occur from the single channel to the entire myocardial syncytium. Thus, sophisticated computational algorithms have been developed to investigate cardiac EP at the level of ion channels, cardiomyocytes, multicellular tissues, and the whole heart. Although understanding of each functional level will ultimately be important to thoroughly understand mechanisms of physiology and disease, cardiac arrhythmias are expressly the product of cardiac tissue-containing enough cardiomyocytes to sustain a reentrant loop of activation. In addition, several properties of cardiac cellular EP, that are critical for arrhythmogenesis, are significantly altered by cell-to-cell coupling. However, relevant human cardiac EP data, upon which to develop or validate models at all scales, has been lacking. Thus, over several years, we have developed a paradigm for multiscale human heart physiology investigation and have recovered and studied over 300 human hearts. We have generated a rich experimental dataset, from which we better understand mechanisms of arrhythmia in human and can improve models of human cardiac EP. In addition, in collaboration with computational physiologists, we are developing a database for the deposition of human heart experimental data, including thorough experimental documentation. We anticipate that accessibility to this human heart dataset will further human EP computational investigations, as well as encourage greater data transparency within the field of cardiac EP.

  4. Hypokalemia and sudden cardiac death

    DEFF Research Database (Denmark)

    Kjeldsen, Keld


    Worldwide, approximately three million people suffer sudden cardiac death annually. These deaths often emerge from a complex interplay of substrates and triggers. Disturbed potassium homeostasis among heart cells is an example of such a trigger. Thus, hypokalemia and, also, more transient...... of fatal arrhythmia and sudden cardiac death a patient is, the more attention should be given to the potassium homeostasis....

  5. The Danish Cardiac Rehabilitation Database

    DEFF Research Database (Denmark)

    Zwisler, Ann-Dorthe; Rossau, Henriette Knold; Nakano, Anne


    AIM OF DATABASE: The Danish Cardiac Rehabilitation Database (DHRD) aims to improve the quality of cardiac rehabilitation (CR) to the benefit of patients with coronary heart disease (CHD). STUDY POPULATION: Hospitalized patients with CHD with stenosis on coronary angiography treated with percutane...

  6. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter


    . An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  7. [Cardiac myxoma with cerebral metastases]. (United States)

    Bazin, A; Peruzzi, P; Baudrillard, J C; Pluot, M; Rousseaux, P


    A 56 year old woman developed multiple metastases in the cerebrum and cerebellum, four years after cardiac intervention on a left atrial myxoma. The absence of stroke is noteworthy. Multiple high density lesions with contrast enhancement were seen by CT scan, suggesting metastatic neoplasms. Histological examination confirmed the diagnosis of metastases of cardiac myxoma. Only four cases were recorded in the literature.

  8. Health Instruction Packages: Cardiac Anatomy. (United States)

    Phillips, Gwen; And Others

    Text, illustrations, and exercises are utilized in these five learning modules to instruct nurses, students, and other health care professionals in cardiac anatomy and functions and in fundamental electrocardiographic techniques. The first module, "Cardiac Anatomy and Physiology: A Review" by Gwen Phillips, teaches the learner to draw…

  9. Pneumothorax in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;


    AIM: To identify risk factors for pneumothorax treated with a chest tube after cardiac pacing device implantation in a population-based cohort.METHODS AND RESULTS: A nationwide cohort study was performed based on data on 28 860 patients from the Danish Pacemaker Register, which included all Danish...... patients who received their first pacemaker (PM) or cardiac resynchronization device from 1997 to 2008. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the association between risk factors and pneumothorax treated with a chest tube. The median...... age was 77 years (25th and 75th percentile: 69-84) and 55% were male (n = 15 785). A total of 190 patients (0.66%) were treated for pneumothorax, which was more often in women [aOR 1.9 (1.4-2.6)], and in patients with age >80 years [aOR 1.4 (1.0-1.9)], a prior history of chronic obstructive pulmonary...

  10. Leadership in cardiac surgery. (United States)

    Rao, Christopher; Patel, Vanash; Ibrahim, Michael; Ahmed, Kamran; Wong, Kathie A; Darzi, Ara; von Segesser, Ludwig K; Athanasiou, Thanos


    Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importance.

  11. Entrepreneurial Couples

    DEFF Research Database (Denmark)

    Dahl, Michael S.; Van Praag, Mirjam; Thompson, Peter


    We study motivations for and outcomes of couples starting up a joint firm, using a sample of 1,069 Danish couples that established a joint enterprise between 2001 and 2010, while comparing them to a set of comparable firms and couples. The main motivation for joint entrepreneurship is to create...

  12. Acetaminophen protects against iron-induced cardiac damage in gerbils. (United States)

    Walker, Ernest M; Epling, Christopher P; Parris, Cordel; Cansino, Silvestre; Ghosh, Protip; Desai, Devashish H; Morrison, Ryan G; Wright, Gary L; Wehner, Paulette; Mangiarua, Elsa I; Walker, Sandra M; Blough, Eric R


    There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology.

  13. Modern perspectives on numerical modeling of cardiac pacemaker cell. (United States)

    Maltsev, Victor A; Yaniv, Yael; Maltsev, Anna V; Stern, Michael D; Lakatta, Edward G


    Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent "coupled-clock" theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age.

  14. Respiratory and cardiac motion correction in dual gated PET/MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fayad, Hadi; Monnier, Florian [LaTIM, INSERM, UMR 1101, Brest (France); Odille, Freedy; Felblinger, Jacques [INSERM U947, University of Nancy, Nancy (France); Lamare, Frederic [INCIA, UMR5287, CNRS, CHU Bordeaux, Bordeaux (France); Visvikis, Dimitris [LaTIM, INSERM, UMR 1101, Brest (France)


    Respiratory and cardiac motion in PET/MR imaging leads to reduced quantitative and qualitative image accuracy. Correction methodologies involve the use of double gated acquisitions which lead to low signal-to-noise ratio (SNR) and to issues concerning the combination of cardiac and respiratory frames. The objective of this work is to use a generalized reconstruction by inversion of coupled systems (GRICS) approach, previously used for PET/MR respiratory motion correction, combined with a cardiac phase signal and a reconstruction incorporated PET motion correction approach in order to reconstruct motion free images from dual gated PET acquisitions. The GRICS method consists of formulating parallel MRI in the presence of patient motion as a coupled inverse problem. Its resolution, using a fixed-point method, allows the reconstructed image to be improved using a motion model constructed from the raw MR data and two respiratory belts. GRICS obtained respiratory displacements are interpolated using the cardiac phase derived from an ECG to model simultaneous cardiac and respiratory motion. Three different volunteer datasets (4DMR acquisitions) were used for evaluation. GATE was used to simulate 4DPET datasets corresponding to the acquired 4DMR images. Simulated data were subsequently binned using 16 cardiac phases (M1) vs diastole only (M2), in combination with 8 respiratory amplitude gates. Respiratory and cardiac motion corrected PET images using either M1 or M2 were compared to respiratory only corrected images and evaluated in terms of SNR and contrast improvement. Significant visual improvements were obtained when correcting simultaneously for respiratory and cardiac motion (using 16 cardiac phase or diastole only) compared to respiratory motion only compensation. Results were confirmed by an associated increased SNR and contrast. Results indicate that using GRICS is an efficient tool for respiratory and cardiac motion correction in dual gated PET/MR imaging.

  15. Physics of Cardiac Arrhythmogenesis (United States)

    Karma, Alain


    A normal heartbeat is orchestrated by the stable propagation of an excitation wave that produces an orderly contraction. In contrast, wave turbulence in the ventricles, clinically known as ventricular fibrillation (VF), stops the heart from pumping and is lethal without prompt defibrillation. I review experimental, computational, and theoretical studies that have shed light on complex dynamical phenomena linked to the initiation, maintenance, and control of wave turbulence. I first discuss advances made to understand the precursor state to a reentrant arrhythmia where the refractory period of cardiac tissue becomes spatiotemporally disordered; this is known as an arrhythmogenic tissue substrate. I describe observed patterns of transmembrane voltage and intracellular calcium signaling that can contribute to this substrate, and symmetry breaking instabilities to explain their formation. I then survey mechanisms of wave turbulence and discuss novel methods that exploit electrical pacing stimuli to control precursor patterns and low-energy pulsed electric fields to control turbulence.

  16. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong


    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  17. Mediastinitis after cardiac transplantation

    Directory of Open Access Journals (Sweden)

    Noedir A. G. Stolf


    Full Text Available OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were performed, 12 (5.6% of the transplanted patients developed confirmed mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3±10.0 years and 10 (83.3% patients were males. Seven (58.3% patients showed sternal stability on palpation, 4 (33.3% patients had pleural empyema, and 2 (16.7% patients did not show purulent secretion draining through the wound. RESULTS: Staphylococcus aureus was the infectious agent identified in the wound secretion or in the mediastinum, or both, in 8 (66.7% patients. Staphylococcus epidermidis was identified in 2 (16.7% patients, Enterococcus faecalis in 1 (8.3% patient, and the cause of mediastinitis could not be determined in 1 (8.3% patient. Surgical treatment was performed on an emergency basis, and the extension of the débridement varied with local conditions. In 2 (16.7% patients, we chose to leave the surgical wound open and performed daily dressings with granulated sugar. Total sternal resection was performed in only 1 (8.3% patient. Out of this series, 5 (41.7% patients died, and the causes of death were related to the infection. Autopsy revealed persistence of mediastinitis in 1 (8.3% patient. CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical drainage have changed the natural evolution of this disease. Nevertheless, observance of the basic precepts of prophylaxis of infection is still the best way to treat mediastinitis.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  19. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore


    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  20. Fetal cardiac rhabdomyoma: case report

    Directory of Open Access Journals (Sweden)

    Seyed Mostafa Ghavami


    Full Text Available Background: The primary manifestation of cardiac tumors in embryonic period is a very rare condition. Cardiac rhabdomyomas most frequently arise in the ventricular myocardium, they may also occur in the atria and the epicardial surface. In spite of its benign nature, the critical location of the tumor inside the heart can lead to lethal arrhythmias and chamber obstruction. Multiple rhabdomyomas are strongly associated with tuberous sclerosis which is associated with mental retardation and epilepsy of variable severity. Ultrasonography as a part of routine prenatal screening, is the best method for the diagnosis of cardiac rhabdomyomas. In the review of articles published in Iran, fetal cardiac rhabdomyoma was not reported. Case presentation: We report a case of cardiac rhabdomyoma on a 24-year-old gravid 1, referred to Day Medical Imaging Center for routine evaluation of fetal abnormalities at 31 weeks of her gestational age. Ultrasonographic examination displayed a homogenous echogenic mass (13×9mm, originating from the left ventricle of the fetal heart. It was a normal pregnancy without any specific complications. Other organs of the fetus were found normal and no cardiac abnormalities were appeared. No Pericardial fluid effusion was found. The parents did not have consanguineous marriage. They did not also have any specific disease such as tuberous sclerosis. Conclusion: The clinical features of cardiac rhabdomyomas vary widely, depending on the location, size, and number of tumors in the heart. Although cardiac rhabdomyoma is a benign tumor in many affected fetuses, an early prenatal diagnosis of the tumor is of great significance in making efficient planning and providing adequate follow up visits of the patients and the complications such as, heart failure and outlet obstruction of cardiac chambers.

  1. Application of HTS technology to cardiac dysrhythmia detection

    Energy Technology Data Exchange (ETDEWEB)

    Sobel, A.L. [Sandia National Labs., Albuquerque, NM (United States); Avrin, W.F. [Quantum Magnetics, Inc., San Diego, CA (United States)


    This paper discusses the conceptual design considerations and challenges for development of a contactless, mobile, single channel biomagnetic sensor system based on High-Temperature Superconductor (HTS) Superconducting Quantum Interference Devices (SQUIDs) and employing the Three-SQUID Gradiometer (TSG) concept. Operating in magnetically unshielded environments, as are encountered in many medical scenarios, this instrument class would monitor cardiac electrical activity with minimal patient preparation and intrusiveness, and would notionally be coupled with a clinically adaptive human-system interface (HSI).

  2. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu


    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  3. Cardiac Involvement in Ankylosing Spondylitis (United States)

    Ozkan, Yasemin


    Ankylosing spondylitis is one of the subgroup of diseases called “seronegative spondyloarthropathy”. Frequently, it affects the vertebral colon and sacroiliac joint primarily and affects the peripheral joints less often. This chronic, inflammatory and rheumatic disease can also affect the extraarticular regions of the body. The extraarticular affections can be ophthalmologic, cardiac, pulmonary or neurologic. The cardiac affection can be 2-10% in all patients. Cardiac complications such as left ventricular dysfunction, aortitis, aortic regurgitation, pericarditis and cardiomegaly are reviewed. PMID:27222669

  4. Acupuncture therapy related cardiac injury. (United States)

    Li, Xue-feng; Wang, Xian


    Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

  5. Normal cardiac function in mice with supraphysiological cardiac creatine levels. (United States)

    Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O


    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

  6. Entrepreneurial Couples

    DEFF Research Database (Denmark)

    Dahl, Michael S.; Van Praag, Mirjam; Thompson, Peter

    We study possible motivations for co-entrepenurial couples to start up a joint firm, using a sample of 1,069 Danish couples that established a joint enterprise between 2001 and 2010. We compare their pre-entry characteristics, firm performance and postdissolution private and financial outcomes...... with a selected set of comparable firms and couples. We find evidence that couples often establish a business together because one spouse – most commonly the female – has limited outside opportunities in the labor market. However, the financial benefits for each of the spouses, and especially the female...

  7. Entrepreneurial Couples

    DEFF Research Database (Denmark)

    Dahl, Michael S.; Van Praag, Mirjam; Thompson, Peter

    We study possible motivations for co-entrepenurial couples to start up a joint firm, us-ing a sample of 1,069 Danish couples that established a joint enterprise between 2001 and 2010. We compare their pre-entry characteristics, firm performance and post-dissolution private and financial outcomes...... with a selected set of comparable firms and couples. We find evidence that couples often establish a business together because one spouse - most commonly the female - has limited outside opportunities in the labor market. However, the financial benefits for each of the spouses, and especially the female...

  8. Entrepreneurial Couples

    DEFF Research Database (Denmark)

    Dahl, Michael S.; Van Praag, Mirjam; Thompson, Peter


    We study possible motivations for co-entreprenurial couples to start up a joint firm, using a sample of 1,069 Danish couples that established a joint enterprise between 2001 and 2010. We compare their pre-entry characteristics, firm performance and post-dissolution private and financial outcomes...... with a selected set of comparable firms and couples. We find evidence that couples often establish a business together because one spouse – most commonly the female – has limited outside opportunities in the labor market. However, the financial benefits for each of the spouses, and especially the female...

  9. Use of cardiac biomarkers in neonatology. (United States)

    Vijlbrief, Daniel C; Benders, Manon J N L; Kemperman, Hans; van Bel, Frank; de Vries, Willem B


    Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

  10. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  11. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering (United States)

    Rogozhnikov, Dmitry; O’Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.


    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

  12. Mechanical communication in cardiac cell synchronized beating (United States)

    Nitsan, Ido; Drori, Stavit; Lewis, Yair E.; Cohen, Shlomi; Tzlil, Shelly


    Cell-cell communication, which enables cells to coordinate their activity and is essential for growth, development and function, is usually ascribed a chemical or electrical origin. However, cells can exert forces and respond to environment elasticity and to mechanical deformations created by their neighbours. The extent to which this mechanosensing ability facilitates intercellular communication remains unclear. Here we demonstrate mechanical communication between cells directly for the first time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations are induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighbouring cardiac cell. Unlike electrical field stimulation, the probe-induced beating rate is maintained by the cell for an hour after the stimulation stops, implying that long-term modifications occur within the cell. These long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication.

  13. Recent developments in cardiac pacing. (United States)

    Rodak, D J


    Indications for cardiac pacing continue to expand. Pacing to improve functional capacity, which is now common, relies on careful patient selection and technical improvements, such as complex software algorithms and diagnostic capabilities.

  14. Robotic Applications in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alan P. Kypson


    Full Text Available Traditionally, cardiac surgery has been performed through a median sternotomy, which allows the surgeon generous access to the heart and surrounding great vessels. As a paradigm shift in the size and location of incisions occurs in cardiac surgery, new methods have been developed to allow the surgeon the same amount of dexterity and accessibility to the heart in confined spaces and in a less invasive manner. Initially, long instruments without pivot points were used, however, more recent robotic telemanipulation systems have been applied that allow for improved dexterity, enabling the surgeon to perform cardiac surgery from a distance not previously possible. In this rapidly evolving field, we review the recent history and clinical results of using robotics in cardiac surgery.

  15. Cardiac manifestations in systemic sclerosis

    Institute of Scientific and Technical Information of China (English)

    Sevdalina; Lambova


    Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.

  16. Cardiac transplantation in Friedreich ataxia. (United States)

    Yoon, Grace; Soman, Teesta; Wilson, Judith; George, Kristen; Mital, Seema; Dipchand, Anne I; McCabe, Jane; Logan, William; Kantor, Paul


    In this article, we describe a 14-year-old boy with a confirmed diagnosis of Friedreich ataxia who underwent cardiac transplantation for left ventricular failure secondary to dilated cardiomyopathy with restrictive physiology. His neurological status prior to transplantation reflected early signs of neurological disease, with evidence of dysarthria, weakness, mild gait impairment, and limb ataxia. We review the ethical issues considered during the process leading to the decision to offer cardiac transplantation.

  17. Cardiac Transplantation in Friedreich Ataxia


    Yoon, Grace; Soman, Teesta; Wilson, Judith; George, Kristen; Mital, Seema; Dipchand, Anne I; McCabe, Jane; Logan, William; Kantor, Paul


    In this paper, we describe a 14-year-old boy with a confirmed diagnosis of Friedreich ataxia who underwent cardiac transplantation for left ventricular failure secondary to dilated cardiomyopathy with restrictive physiology. His neurological status prior to transplantation reflected early signs of neurologic disease, with evidence of dysarthria, weakness, mild gait impairment, and limb ataxia. We review the ethical issues considered during the process leading to the decision to offer cardiac ...

  18. [Stem cells and cardiac regeneration]. (United States)

    Perez Millan, Maria Ines; Lorenti, Alicia


    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  19. Cardiac Regeneration and Stem Cells. (United States)

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


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

  20. Cardiac imaging. A multimodality approach

    Energy Technology Data Exchange (ETDEWEB)

    Thelen, Manfred [Johannes Gutenberg University Hospital, Mainz (Germany); Erbel, Raimund [University Hospital Essen (Germany). Dept. of Cardiology; Kreitner, Karl-Friedrich [Johannes Gutenberg University Hospital, Mainz (Germany). Clinic and Polyclinic for Diagnostic and Interventional Radiology; Barkhausen, Joerg (eds.) [University Hospital Schleswig-Holstein, Luebeck (Germany). Dept. of Radiology and Nuclear Medicine


    An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

  1. Recurrent late cardiac tamponade following cardiac surgery : a deceiving and potentially lethal complication

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Meuzelaar, Jacobus J.


    Background - Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. Case report - We present a case of recurrent cardiac tamponade following valve surgery. At first presentation, diagno

  2. Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT

    DEFF Research Database (Denmark)

    Perkiomaki, Juha S; Ruwald, Anne-Christine; Kutyifa, Valentina;


    causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P ...AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify...... the action and limitations of cardiac resynchronization therapy (CRT) in relieving myocardial dysfunction. METHODS AND RESULTS: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), during 4 years of follow-up, 169 (9.3%) of 1820 patients died of known...

  3. Cardiac output during exercise

    DEFF Research Database (Denmark)

    Siebenmann, C; Rasmussen, P.; Sørensen, H.


    Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from...... the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2  = 12%). While all four methods reported...... a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0...

  4. [Calpains and cardiac diseases]. (United States)

    Perrin, C; Vergely, C; Rochette, L


    Calpains are a large family of cytosolic cysteine proteases composed of at least fourteen distinct isoforms. The family can be divided into two groups on the basis of distribution: ubiquitous and tissue-specific. Our current knowledge about calpains properties apply mainly to the ubiquitous isozymes, micro- and milli-calpain (classic calpains). These forms are activated after autolysis. Translocation and subsequent interactions with phospholipids of these enzymes increase their activity. Calpains are able to cleave a subset of substrates, as enzymes, structural and signalling proteins. Cardiac pathologies, such as heart failure, atrial fibrillation or clinical states particularly ischemia reperfusion, are associated with an increase of cytosolic calcium and in this regards, calpain activation has been evoked as one of the mediators leading to myocardial damage. Calpain activities have been shown to be increased in hearts experimentally subjected to ischemia reperfusion or during hypertrophy, but also in atrial tissue harvested from patients suffering from atrial fibrillations. These activities have been related to an increase of the proteolysis of different myocardial components, particularly, troponins, which are major regulators of the contraction of cardiomyocytes. Moreover, recent works have demonstrated that calpains are involved in the development of myocardial cell death by necrosis or apoptosis.

  5. Cardiac Imaging System (United States)


    Although not available to all patients with narrowed arteries, balloon angioplasty has expanded dramatically since its introduction with an estimated further growth to 562,000 procedures in the U.S. alone by 1992. Growth has fueled demand for higher quality imaging systems that allow the cardiologist to be more accurate and increase the chances of a successful procedure. A major advance is the Digital Cardiac Imaging (DCI) System designed by Philips Medical Systems International, Best, The Netherlands and marketed in the U.S. by Philips Medical Systems North America Company. The key benefit is significantly improved real-time imaging and the ability to employ image enhancement techniques to bring out added details. Using a cordless control unit, the cardiologist can manipulate images to make immediate assessment, compare live x-ray and roadmap images by placing them side-by-side on monitor screens, or compare pre-procedure and post procedure conditions. The Philips DCI improves the cardiologist's precision by expanding the information available to him.

  6. Dying from cardiac tamponade

    Directory of Open Access Journals (Sweden)

    Powari Manish


    Full Text Available Abstract Background To determine the causes of cardiac tamponade (CT, focussing especially on haemopericardium (HP, as a terminal mode of death, within a 430,000 rural English population. Methods Our hospital mortuary register and, all postmortem reports between 1995 and 2004 inclusive, were interrogated for patients dying of CT or HP. The causes of CT/HP and selected morphological characteristics were then determined. Results 14,368 postmortems were performed in this period: of these, 461 patients died of CT. Three cases were due to non-haemorrhagic pericardial effusion. HP accounted for the remaining 458 cases of which, five were post-traumatic, 311 followed rupture of an acute myocardial infarction (RAMI, 138 after intra-pericardial rupture of dissecting ascending aortic aneurysms (RD3A and four were due to miscellaneous causes. HP was more commonly due to RAMI. Men tended to die from RAMI or RD3A earlier than women. RAMI or RD3A were commoner in men Two thirds of RAMI were associated with coronary artery thrombosis. Anterior free wall rupture was commonest overall, and in women, but posterior free wall rupture was commoner in men. The volume of intrapericardial blood in RAMI (mean = 440 ml and RD3A (mean = 498 ml varied between 150 and 1000 ml: intrapericardial blood volume was greater in men than in women dying from either RAMI or RD3A. Conclusion At postmortem, CT is most often related to HP, attributable to either RAMI or intrapericardial RD3A. Post-traumatic and other causes of CT are infrequent.

  7. Cardiac output monitoring

    Directory of Open Access Journals (Sweden)

    Mathews Lailu


    Full Text Available Minimally invasive and non-invasive methods of estimation of cardiac output (CO were developed to overcome the limitations of invasive nature of pulmonary artery catheterization (PAC and direct Fick method used for the measurement of stroke volume (SV. The important minimally invasive techniques available are: oesophageal Doppler monitoring (ODM, the derivative Fick method (using partial carbon dioxide (CO 2 breathing, transpulmonary thermodilution, lithium indicator dilution, pulse contour and pulse power analysis. Impedance cardiography is probably the only non-invasive technique in true sense. It provides information about haemodynamic status without the risk, cost and skill associated with the other invasive or minimally invasive techniques. It is important to understand what is really being measured and what assumptions and calculations have been incorporated with respect to a monitoring device. Understanding the basic principles of the above techniques as well as their advantages and limitations may be useful. In addition, the clinical validation of new techniques is necessary to convince that these new tools provide reliable measurements. In this review the physics behind the working of ODM, partial CO 2 breathing, transpulmonary thermodilution and lithium dilution techniques are dealt with. The physical and the physiological aspects underlying the pulse contour and pulse power analyses, various pulse contour techniques, their development, advantages and limitations are also covered. The principle of thoracic bioimpedance along with computation of CO from changes in thoracic impedance is explained. The purpose of the review is to help us minimize the dogmatic nature of practice favouring one technique or the other.

  8. Patch in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alireza Alizadeh Ghavidel


    Full Text Available Introduction: Excessive bleeding presents a risk for the patient in cardiovascular surgery. Local haemostatic agents are of great value to reduce bleeding and related complications. TachoSil (Nycomed, Linz, Austria is a sterile, haemostatic agent that consists of an equine collagen patchcoated with human fibrinogen and thrombin. This study evaluated the safety and efficacy of TachoSil compared to conventional technique.Methods: Forty-two patients scheduled for open heart surgeries, were entered to this study from August 2010 to May 2011. After primary haemostatic measures, patients divided in two groups based on surgeon’s judgment. Group A: 20 patients for whom TachoSil was applied and group B: 22 patients that conventional method using Surgicel (13 patients or wait and see method (9 cases, were performed in order to control the bleeding. In group A, 10 patients were male with mean age of 56.95±15.67 years and in group B, 9 cases were male with mean age of 49.95±14.41 years. In case group 70% (14/20 of the surgeries were redo surgeries versus 100% (22/22 in control group.Results: Baseline characteristics were similar in both groups. In TachoSil group 75% of patients required transfusion versus 90.90% in group B (P=0.03.Most transfusions consisted of packed red blood cell; 2±1.13 units in group A versus 3.11±1.44 in group B (P=0.01, however there were no significant differences between two groups regarding the mean total volume of intra and post-operative bleeding. Re-exploration was required in 10% in group A versus 13.63% in group B (P=0.67.Conclusion: TachoSil may act as a superior alternative in different types of cardiac surgery in order to control the bleeding and therefore reducing transfusion requirement.

  9. Isolation, Characterization, and Transplantation of Cardiac Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Busadee Pratumvinit


    due to difficulties in isolation, cell heterogeneity, lack of specific markers to identify myocardial endothelial cells, and inadequate conditions to maintain long-term cultures. Herein, we developed a method for isolation, characterization, and expansion of cardiac endothelial cells applicable to study endothelial cell biology and clinical applications such as neoangiogenesis. First, we dissociated the cells from murine heart by mechanical disaggregation and enzymatic digestion. Then, we used flow cytometry coupled with specific markers to isolate endothelial cells from murine hearts. CD45+ cells were gated out to eliminate the hematopoietic cells. CD31+/Sca-1+ cells were isolated as endothelial cells. Cells isolated from atrium grew faster than those from ventricle. Cardiac endothelial cells maintain endothelial cell function such as vascular tube formation and acetylated-LDL uptake in vitro. Finally, cardiac endothelial cells formed microvessels in dorsal matrigel plug and engrafted in cardiac microvessels following intravenous and intra-arterial injections. In conclusion, our multicolor flow cytometry method is an effective method to analyze and purify endothelial cells from murine heart, which in turn can be ex vivo expanded to study the biology of endothelial cells or for clinical applications such as therapeutic angiogenesis.

  10. Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias. (United States)

    Shi, Dan; Xie, Duanyang; Zhang, Hong; Zhao, Hong; Huang, Jian; Li, Changming; Liu, Yi; Lv, Fei; The, Erlinda; Liu, Yuan; Yuan, Tianyou; Wang, Shiyi; Chen, Jinjin; Pan, Lei; Yu, Zuoren; Liang, Dandan; Zhu, Weidong; Zhang, Yuzhen; Li, Li; Peng, Luying; Li, Jun; Chen, Yi-Han


    Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies.

  11. Nonadiabatic Coupling (United States)

    Kryachko, Eugene S.

    The general features of the nonadiabatic coupling and its relation to molecular properties are surveyed. Some consequences of the [`]equation of motion', formally expressing a [`]smoothness' of a given molecular property within the diabatic basis, are demonstrated. A particular emphasis is made on the relation between a [`]smoothness' of the electronic dipole moment and the generalized Mulliken-Hush formula for the diabatic electronic coupling.

  12. Nuclear imaging in cardiac amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Glaudemans, A.W.J.M.; Slart, R.H.J.A.; Veltman, N.C.; Dierckx, R.A.J.O. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, P.O. Box 30001, Groningen (Netherlands); Zeebregts, C.J. [University Medical Center Groningen, Department of Surgery (Division of Vascular Surgery), Groningen (Netherlands); Tio, R.A. [University Medical Center Groningen, Department of Cardiology, Groningen (Netherlands); Hazenberg, B.P.C. [University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen (Netherlands)


    Amyloidosis is a disease characterized by depositions of amyloid in organs and tissues. It can be localized (in just one organ) or systemic. Cardiac amyloidosis is a debilitating disease and can lead to arrhythmias, deterioration of heart function and even sudden death. We reviewed PubMed/Medline, without time constraints, on the different nuclear imaging modalities that are used to visualize myocardial amyloid involvement. Several SPECT tracers have been used for this purpose. The results with these tracers in the evaluation of myocardial amyloidosis and their mechanisms of action are described. Most clinical evidence was found for the use of {sup 123}I-MIBG. Myocardial defects in MIBG activity seem to correlate well with impaired cardiac sympathetic nerve endings due to amyloid deposits. {sup 123}I-MIBG is an attractive option for objective evaluation of cardiac sympathetic level and may play an important role in the indirect measurement of the effect of amyloid myocardial infiltration. Other, less sensitive, options are {sup 99m}Tc-aprotinin for imaging amyloid deposits and perhaps {sup 99m}Tc-labelled phosphate derivatives, especially in the differential diagnosis of the aetiology of cardiac amyloidosis. PET tracers, despite the advantage of absolute quantification and higher resolution, are not yet well evaluated for the study of cardiac amyloidosis. Because of these advantages, there is still the need for further research in this field. (orig.)

  13. Cardiac Penetrating Injuries and Pseudoaneurysm

    Institute of Scientific and Technical Information of China (English)

    CHEN Shifeng


    Objective To discuss the early diagnosis and treatment of cardiac penetrating injuries and pseudoaneurysm. Methods 18 cases of cardiac penetrating injuries, in which 2 cases were complicated with pseudoaneurysm, were diagnosed by emergency operation and color Doppler echocardiography between May 1973 and Dec. 2001 in our hospital. The basis for emergency operation is the injured path locating in cardiac dangerous zone, severe shock or pericardial tamponade. ResultsAmong 18 cases of this study, 17 cases underwent emergency operation. During the operation, 11 cases were found injured in right ventricle, 2 cases were found injured in right atrium, 1 case was found injured in pulmonary artery,4 cases were found injured in left ventricle, 2 cases were found complicated with pseudoaneurysm. 17cases underwent cardiac repair including 1 case of rupture of aneurysm. 1 case underwent elective aneurysm resection. In whole group, 15 cases survived(83.33% ), 3 cases died( 16.67%). The cause of death is mainly hemorrhagic shock. Conclusion Highly suspicious cardiac penetrating injuries or hemopericaridium should undergo direct operative exploration. Pseudoaneurysm should be resected early,which can prevent severe complications.

  14. Interactions between cardiac, respiratory, and brain activity in humans (United States)

    Musizza, Bojan; Stefanovska, Aneta


    The electrical activity of the heart (ECG), respiratory function and electric activity of the brain (EEG) were simultaneously recorded in conscious, healthy humans. Instantaneous frequencies of the heart beat, respiration and α-waves were then determined from 30-minutes recordings. The instantaneous cardiac frequency was defined as the inverse value of the time interval between two consecutive R-peaks. The instantaneous respiratory frequency was obtained from recordings of the excursions of thorax by application of the Hilbert transform. To obtain the instantaneous frequency of α-waves, the EEG signal recorded from the forehead was first analysed using the wavelet transform. Then the frequency band corresponding to α-waves was extracted and the Hilbert transform applied. Synchronization analysis was performed and the direction of coupling was ascertained, using pairs of instantaneous frequencies in each case. It is shown that the systems are weakly bidirectionally coupled. It was confirmed that, in conscious healthy humans, respiration drives cardiac activity. We also demonstrate from these analyses that α-activity drives both respiration and cardiac activity.

  15. Exercise-induced cardiac remodeling. (United States)

    Weiner, Rory B; Baggish, Aaron L


    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

  16. [Ectopia cordis and cardiac anomalies]. (United States)

    Cabrera, Alberto; Rodrigo, David; Luis, María Teresa; Pastor, Esteban; Galdeano, José Miguel; Esteban, Susana


    Ectopia cordis is a rare disease that occurs in 5.5 to 7.9 per million live births. Only 267 cases had been reported as of 2001, most (95%) associated with other cardiac anomalies. We studied the cardiac malformations associated in 6 patients with ectopia cordis. Depending on where the defect was located, the cases of ectopia were classified into four groups: cervical, thoracic, thoraco-abdominal, and abdominal. All 6 patients died before the third day of life, 4 during delivery. Three of the patients were included in the thoracic group, whereas the other 3 belonged to the thoraco-abdominal group. All the patients had associated ventricular septal defects, 3 double-outlet right ventricle (50%) and the rest (50%) tetralogy of Fallot-pulmonary atresia. Two patients with double-outlet right ventricle presented mitral-valve pathology, a parachute valve and an atresic mitral valve. None of these cardiac anomalies have been reported to date.

  17. Electrophysiological Cardiac Modeling: A Review. (United States)

    Beheshti, Mohammadali; Umapathy, Karthikeyan; Krishnan, Sridhar


    Cardiac electrophysiological modeling in conjunction with experimental and clinical findings has contributed to better understanding of electrophysiological phenomena in various species. As our knowledge on underlying electrical, mechanical, and chemical processes has improved over time, mathematical models of the cardiac electrophysiology have become more realistic and detailed. These models have provided a testbed for various hypotheses and conditions that may not be easy to implement experimentally. In addition to the limitations in experimentally validating various scenarios implemented by the models, one of the major obstacles for these models is computational complexity. However, the ever-increasing computational power of supercomputers facilitates the clinical application of cardiac electrophysiological models. The potential clinical applications include testing and predicting effects of pharmaceutical agents and performing patient-specific ablation and defibrillation. A review of studies involving these models and their major findings are provided.

  18. Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python bivittatus). (United States)

    Slay, Christopher E; Enok, Sanne; Hicks, James W; Wang, Tobias


    Physiological cardiac hypertrophy is characterized by reversible enlargement of cardiomyocytes and changes in chamber architecture, which increase stroke volume and via augmented convective oxygen transport. Cardiac hypertrophy is known to occur in response to repeated elevations of O2 demand and/or reduced O2 supply in several species of vertebrate ectotherms, including postprandial Burmese pythons (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P. bivittatus is a facultative rather than obligatory response to digestion, though the triggers of this response are unknown. Here, we hypothesized that an O2 supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese pythons. To test this hypothesis, we rendered animals anemic prior to feeding, essentially halving blood oxygen content during the postprandial period. Fed anemic animals had heart rates 126% higher than those of fasted controls, which, coupled with a 71% increase in mean arterial pressure, suggests fed anemic animals were experiencing significantly elevated cardiac work. We found significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles 39% larger than those of fasted controls and 28% larger than in fed controls. These findings support our hypothesis that those animals with a greater magnitude of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal' stimulating postprandial cardiac hypertrophy is likely mediated by elevated ventricular wall stress associated with postprandial hemodynamics.

  19. An update on insertable cardiac monitors

    DEFF Research Database (Denmark)

    Olsen, Flemming J; Biering-Sørensen, Tor; Krieger, Derk W


    Continuous cardiac rhythm monitoring has undergone compelling progress over the past decades. Cardiac monitoring has emerged from 12-lead electrocardiograms being performed at the discretion of the treating physician to in-hospital telemetry, Holter monitoring, prolonged external event monitoring...

  20. Complications after cardiac implantable electronic device implantations

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;


    Complications after cardiac implantable electronic device (CIED) treatment, including permanent pacemakers (PMs), cardiac resynchronization therapy devices with defibrillators (CRT-Ds) or without (CRT-Ps), and implantable cardioverter defibrillators (ICDs), are associated with increased patient...

  1. Clinical advances on Cardiac Insuffiency

    Directory of Open Access Journals (Sweden)

    Angel Julio Romero Cabrera


    Full Text Available Cardiac insuffiency is a complex clinical syndrome which constitutes a common final path to get in by the majority of the cardiac diseases. Studies based on the communitarian surveys shows that from 30 to 40 % of the patients decease within the first year of the diagnosis. The rest of the patients (from 60 to 70 % die within the 5 years after being diagnosed. For this reason it has been called as the ¨cancer of cardiology¨. The objective of this article is to update the advances reached in the clinical and therapeutic aspects of this important syndrome.

  2. Elevated sensitivity to cardiac ischemia in proteinuric rats is independent of adverse cardiac remodeling

    NARCIS (Netherlands)

    Szymanski, Mariusz K.; Hillege, Hans L.; Danser, A. H. Jan; Garrelds, Ingrid M.; Schoemaker, Regien G.


    Objectives: Chronic renal dysfunction severely increases cardiovascular risk. Adverse cardiac remodeling is suggested to play a major role as predisposition for increased cardiac ischemic vulnerability. The aim of the present study was to examine the role of adverse cardiac remodeling in cardiac sen

  3. Quasiperiodicity route to chaos in cardiac conduction model (United States)

    Quiroz-Juárez, M. A.; Vázquez-Medina, R.; Ryzhii, E.; Ryzhii, M.; Aragón, J. L.


    It has been suggested that cardiac arrhythmias are instances of chaos. In particular that the ventricular fibrillation is a form of spatio-temporal chaos that arises from normal rhythm through a quasi-periodicity or Ruelle-Takens-Newhouse route to chaos. In this work, we modify the heterogeneous oscillator model of cardiac conduction system proposed in Ref. [Ryzhii E, Ryzhii M. A heterogeneous coupled oscillator model for simulation of ECG signals. Comput Meth Prog Bio 2014;117(1):40-49. doi:10.1016/j.cmpb.2014.04.009.], by including an ectopic pacemaker that stimulates the ventricular muscle to model arrhythmias. With this modification, the transition from normal rhythm to ventricular fibrillation is controlled by a single parameter. We show that this transition follows the so-called torus of quasi-periodic route to chaos, as verified by using numerical tools such as power spectrum and largest Lyapunov exponent.

  4. Exploring the Role of Calcium in Cardiac Cell Dynamics (United States)

    Berger, Carolyn; Idriss, Salim; Rouze, Ned; Hall, David; Gauthier, Daniel


    Bifurcations in the electrical response of cardiac tissue can destabilize spatio-temporal waves of electrochemical activity in the heart, leading to tachycardia or even fibrillation. Therefore, it is important to understand the mechanisms that cause instabilities in cardiac tissue.Traditionally, researchers have focused on understanding how the transmembrane voltage is altered in response to an increase in pacing rate, i.e. a shorter time interval between propagating electrochemical waves. However, the dynamics of the transmembrane voltage are coupled to the activity of several ions that traverse the membrane. Therefore, to fully understand the mechanisms that drive these bifurcations, we must include an investigation of the ionic behavior. We will present our recent investigation of the role of intracellular calcium in an experimental testbed of frog ventricle. Calcium and voltage are measured simultaneously, allowing for the previous research regarding voltage to guide our understanding of the calcium dynamics.

  5. Abaqus/Standard-based quantification of human cardiac mechanical properties

    CERN Document Server

    Genet, Martin; Kuhl, Ellen; Guccione, Julius


    Computational modeling can provide critical insight into existing and potential new surgical procedures, medical or minimally-invasive treatments for heart failure, one of the leading causes of deaths in the world that has reached epidemic proportions. In this paper, we present our Abaqus/Standard-based pipeline to create subject-specific left ventricular models. We first review our generic left ventricular model, and then the personalization process based on magnetic resonance images. Identification of subject-specific cardiac material properties is done by coupling Abaqus/Standard to the python optimization library NL-Opt. Compared to previous studies from our group, the emphasis is here on the fully implicit solving of the model, and the two-parameter optimization of the passive cardiac material properties.

  6. Pregnancy as a cardiac stress model



    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women witho...

  7. Bifid cardiac apex in a 25-year-old male with sudden cardiac death. (United States)

    Wu, Annie; Kay, Deborah; Fishbein, Michael C


    Although a bifid cardiac apex is common in certain marine animals, it is an uncommon finding in humans. When present, bifid cardiac apex is usually associated with other congenital heart anomalies. We present a case of bifid cardiac apex that was an incidental finding in a 25-year-old male with sudden cardiac death from combined drug toxicity. On gross examination, there was a bifid cardiac apex with a 2-cm long cleft. There were no other significant gross or microscopic abnormalities. This case represents the very rare occurrence of a bifid cardiac apex as an isolated cardiac anomaly.

  8. Discovery and progress of direct cardiac reprogramming. (United States)

    Kojima, Hidenori; Ieda, Masaki


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

  9. Multimodality imaging to guide cardiac interventional procedures

    NARCIS (Netherlands)

    Tops, Laurens Franciscus


    In recent years, a number of new cardiac interventional procedures have been introduced. Catheter ablation procedures for atrial fibrillation (AF) have been refined and are now considered a good treatment option in patients with drug-refractory AF. In cardiac pacing, cardiac resynchronization therap

  10. Regulation of Cardiac Hypertrophy: the nuclear option

    NARCIS (Netherlands)

    D.W.D. Kuster (Diederik)


    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, c

  11. Cardiac manifestations of myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Petri, Helle; Vissing, John; Witting, Nanna;


    To estimate the degree of cardiac involvement regarding left ventricular ejection fraction, conduction abnormalities, arrhythmia, risk of sudden cardiac death (SCD) and the associations between cardiac involvement and cytosine-thymine-guanine (CTG)-repeat, neuromuscular involvement, age and gende...... in patients with myotonic dystrophy type 1 (MD1)....

  12. Cardiac anatomy and physiology: a review. (United States)

    Gavaghan, M


    This article reviews the normal anatomy and physiology of the heart. Understanding the normal anatomic and physiologic relationships described in this article will help perioperative nurses care for patients who are undergoing cardiac procedures. Such knowledge also assists nurses in educating patients about cardiac procedures and about activities that can prevent, reverse, or improve cardiac illness.

  13. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo


    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

  14. Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances.

    LENUS (Irish Health Repository)

    O'Donnell, David H


    OBJECTIVE: This article reviews the optimal cardiac MRI sequences for and the spectrum of imaging appearances of cardiac tumors. CONCLUSION: Recent technologic advances in cardiac MRI have resulted in the rapid acquisition of images of the heart with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MRI provides optimal assessment of the location, functional characteristics, and soft-tissue features of cardiac tumors, allowing accurate differentiation of benign and malignant lesions.

  15. Cardiac Electromechanical Models: From Cell to Organ

    Directory of Open Access Journals (Sweden)

    Natalia A Trayanova


    Full Text Available The heart is a multiphysics and multiscale system that has driven the development of the most sophisticated mathematical models at the frontiers of computation physiology and medicine. This review focuses on electromechanical (EM models of the heart from the molecular level of myofilaments to anatomical models of the organ. Because of the coupling in terms of function and emergent behaviors at each level of biological hierarchy, separation of behaviors at a given scale is difficult. Here, a separation is drawn at the cell level so that the first half addresses subcellular/single cell models and the second half addresses organ models. At the subcelluar level, myofilament models represent actin-myosin interaction and Ca-based activation. Myofilament models and their refinements represent an overview of the development in the field. The discussion of specific models emphasizes the roles of cooperative mechanisms and sarcomere length dependence of contraction force, considered the cellular basis of the Frank-Starling law. A model of electrophysiology and Ca handling can be coupled to a myofilament model to produce an EM cell model, and representative examples are summarized to provide an overview of the progression of field. The second half of the review covers organ-level models that require solution of the electrical component as a reaction-diffusion system and the mechanical component, in which active tension generated by the myocytes produces deformation of the organ as described by the equations of continuum mechanics. As outlined in the review, different organ-level models have chosen to use different ionic and myofilament models depending on the specific application; this choice has been largely dictated by compromises between model complexity and computational tractability. The review also addresses application areas of EM models such as cardiac resynchronization therapy and the role of mechano-electric coupling in arrhythmias and

  16. Electrical coupling between the human serotonin transporter and voltage-gated Ca(2+) channels. (United States)

    Ruchala, Iwona; Cabra, Vanessa; Solis, Ernesto; Glennon, Richard A; De Felice, Louis J; Eltit, Jose M


    Monoamine transporters have been implicated in dopamine or serotonin release in response to abused drugs such as methamphetamine or ecstasy (MDMA). In addition, monoamine transporters show substrate-induced inward currents that may modulate excitability and Ca(2+) mobilization, which could also contribute to neurotransmitter release. How monoamine transporters modulate Ca(2+) permeability is currently unknown. We investigate the functional interaction between the human serotonin transporter (hSERT) and voltage-gated Ca(2+) channels (CaV). We introduce an excitable expression system consisting of cultured muscle cells genetically engineered to express hSERT. Both 5HT and S(+)MDMA depolarize these cells and activate the excitation-contraction (EC)-coupling mechanism. However, hSERT substrates fail to activate EC-coupling in CaV1.1-null muscle cells, thus implicating Ca(2+) channels. CaV1.3 and CaV2.2 channels are natively expressed in neurons. When these channels are co-expressed with hSERT in HEK293T cells, only cells expressing the lower-threshold L-type CaV1.3 channel show Ca(2+) transients evoked by 5HT or S(+)MDMA. In addition, the electrical coupling between hSERT and CaV1.3 takes place at physiological 5HT concentrations. The electrical coupling between monoamine neurotransmitter transporters and Ca(2+) channels such as CaV1.3 is a novel mechanism by which endogenous substrates (neurotransmitters) or exogenous substrates (like ecstasy) could modulate Ca(2+)-driven signals in excitable cells.

  17. Molecular therapies for cardiac arrhythmias

    NARCIS (Netherlands)

    Boink, G.J.J.


    Despite the ongoing advances in pharmacology, devices and surgical approaches to treat heart rhythm disturbances, arrhythmias are still a significant cause of death and morbidity. With the introduction of gene and cell therapy, new avenues have arrived for the local modulation of cardiac disease. Th

  18. The cardiac patient in Ramadan. (United States)

    Chamsi-Pasha, Majed; Chamsi-Pasha, Hassan


    Ramadan is one of the five fundamental pillars of Islam. During this month, the majority of the 1.6 billion Muslims worldwide observe an absolute fast from dawn to sunset without any drink or food. Our review shows that the impact of fasting during Ramadan on patients with stable cardiac disease is minimal and does not lead to any increase in acute events. Most patients with the stable cardiac disease can fast safely. Most of the drug doses and their regimen are easily manageable during this month and may need not to be changed. Ramadan fasting is a healthy nonpharmacological means for improving cardiovascular risk factors. Most of the Muslims, who suffer from chronic diseases, insist on fasting Ramadan despite being exempted by religion. The Holy Quran specifically exempts the sick from fasting. This is particularly relevant if fasting worsens one's illness or delays recovery. Patients with unstable angina, recent myocardial infarction, uncontrolled hypertension, decompensated heart failure, recent cardiac intervention or cardiac surgery or any debilitating diseases should avoid fasting.

  19. Pseudothrombocytopenia in cardiac surgical practice. (United States)

    Nair, Sukumaran K; Shah, Roma; Petko, Matus; Keogh, Bruce E


    Pseudothrombocytopenia is observed occasionally in post-cardiac surgical patients. It is commonly due to EDTA-mediated immunological mechanisms, which lead to agglutination of functionally intact platelets. This condition is harmless and does not warrant platelet transfusion. We describe an instance of pseudothrombocytopenia in our practice and discuss its clinical relevance.

  20. Thoracocentesis in cardiac surgery patients. (United States)

    Wickbom, Anders; Cha, Soon Ok; Ahlsson, Anders


    Pleural effusion following cardiac surgery is a common complication that sometimes requires invasive treatment. Conventional methods for evacuation include needle aspiration and chest tube insertion. We present an effective, easy and potentially time-saving method of thoracocentesis, using a single-lumen central venous catheter.

  1. Reninoma presenting as cardiac syncope

    Directory of Open Access Journals (Sweden)

    Tak Shahid


    Full Text Available Reninoma, a renin-secreting tumor of the juxta-glomerular cells of the kidney, is a rare but surgically treatable cause of secondary hypertension in children. We report a case of reninoma presenting as cardiac syncope with long QTc on electrocardiogram due to hypokalemia.

  2. Cardiac leiomyosarcoma, a case report

    DEFF Research Database (Denmark)

    Andersen, Rikke; Kristensen, Bjarne W; Gill, Sabine


    In this case report we present the history of a patient admitted with recurrent pulmonary edema. Transesophageal chocardiography showed a tumour in the left atrium, occluding the ostium of the mitral valve and mimicking intermittent mitral stenosis. Cardiac surgery followed by pathological...

  3. Cardiac connexins and impulse propagation

    NARCIS (Netherlands)

    J.A. Jansen; T.A.B. van Veen; J.M.T. de Bakker; H.V.M. van Rijen


    Gap junctions form the intercellular pathway for cell-to-cell transmission of the cardiac impulse from its site of origin, the sinoatrial node, along the atria, the atrioventricular conduction system to the ventricular myocardium. The component parts of gap junctions are proteins called connexins (C

  4. [Acute cardiac failure in pheochromocytoma.

    DEFF Research Database (Denmark)

    Jønler, Morten; Munk, Kim


    Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...

  5. Cardiac resynchronization therapy in China

    Institute of Scientific and Technical Information of China (English)

    Wei HUA


    @@ Congestive heart failure (HF) is a major and growing public health problem. The therapeutic approach includes non-pharmacological measures, pharmacological therapy,mechanical devices, and surgery. Despite the benefits of optimal pharmacologic therapy, the prognosis is still not ideal. At this time, cardiac resynchronization therapy (CRT)has gained wide acceptance as an alternative treatment for HF patients with conduction delay.1

  6. Cardiac abnormalities after subarachnoid hemorrhage

    NARCIS (Netherlands)

    Bilt, I.A.C. van der


    Aneurysmal subarachnoid hemorrhage(aSAH) is a devastating neurological disease. During the course of the aSAH several neurological and medical complications may occur. Cardiac abnormalities after aSAH are observed often and resemble stress cardiomyopathy or Tako-tsubo cardiomyopathy(Broken Heart Syn

  7. Response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Schiffer, Angélique A; Widdershoven, Jos W


    Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10-40% of patients do not respond to this treatment and are labeled as nonresponders...

  8. Molecular Modeling of Cardiac Troponin (United States)

    Manning, Edward P.

    The cardiac thin filament regulates interactions of actin and myosin, the force-generating elements of muscular contraction. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components, including cardiac troponin (cTn). My hypothesis is that signal propagation occurs between distant ends of the cardiac troponin complex through calcium-dependent alterations in the dynamics of cTn and tropomyosin (Tm). I propose a model of the thin filament that encompasses known structures of cTn, Tm and actin to gain insight into cardiac troponin's allosteric regulation of thin filament dynamics. By performing molecular dynamics simulations of cTn in conjunction with overlapping Tm in two conditions, with and without calcium bound to site II of cardiac troponin C (cTnC), I found a combination of calcium-dependent changes in secondary structure and dynamics throughout the cTn-Tm complex. I then applied this model to investigate familial hypertrophic cardiomyopathy (FHC), a disease of the sarcomere that is one of the most commonly occurring genetic causes of heart disease. Approximately 15% of known FHC-related mutations are found in cardiac troponin T (cTnT), most of which are in or flank the alpha-helical N-tail domain TNT1. TNT1 directly interacts with overlapping Tm coiled coils. Using this model I identified effects of TNT1 mutations that propagate to the cTn core where site II of cTnC, the regulatory site of calcium binding in the thin filament, is located. Specifically, I found that mutations in TNT1 alter the flexibility of TNT1 and that the flexibility of TNT1 is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, I identified a pathway of propagation of structural and dynamic changes linking TNT1 to site II of cTnC. Mutation-induced changes at site II cTnC alter calcium coordination which corresponds to biophysical measurements of calcium

  9. An integrated platform for image-guided cardiac resynchronization therapy (United States)

    Ma, Ying Liang; Shetty, Anoop K.; Duckett, Simon; Etyngier, Patrick; Gijsbers, Geert; Bullens, Roland; Schaeffter, Tobias; Razavi, Reza; Rinaldi, Christopher A.; Rhode, Kawal S.


    Cardiac resynchronization therapy (CRT) is an effective procedure for patients with heart failure but 30% of patients do not respond. This may be due to sub-optimal placement of the left ventricular (LV) lead. It is hypothesized that the use of cardiac anatomy, myocardial scar distribution and dyssynchrony information, derived from cardiac magnetic resonance imaging (MRI), may improve outcome by guiding the physician for optimal LV lead positioning. Whole heart MR data can be processed to yield detailed anatomical models including the coronary veins. Cine MR data can be used to measure the motion of the LV to determine which regions are late-activating. Finally, delayed Gadolinium enhancement imaging can be used to detect regions of scarring. This paper presents a complete platform for the guidance of CRT using pre-procedural MR data combined with live x-ray fluoroscopy. The platform was used for 21 patients undergoing CRT in a standard catheterization laboratory. The patients underwent cardiac MRI prior to their procedure. For each patient, a MRI-derived cardiac model, showing the LV lead targets, was registered to x-ray fluoroscopy using multiple views of a catheter looped in the right atrium. Registration was maintained throughout the procedure by a combination of C-arm/x-ray table tracking and respiratory motion compensation. Validation of the registration between the three-dimensional (3D) roadmap and the 2D x-ray images was performed using balloon occlusion coronary venograms. A 2D registration error of 1.2 ± 0.7 mm was achieved. In addition, a novel navigation technique was developed, called Cardiac Unfold, where an entire cardiac chamber is unfolded from 3D to 2D along with all relevant anatomical and functional information and coupled to real-time device detection. This allowed more intuitive navigation as the entire 3D scene was displayed simultaneously on a 2D plot. The accuracy of the unfold navigation was assessed off-line using 13 patient data sets

  10. Can cardiac surgery cause hypopituitarism? (United States)

    Francis, Flverly; Burger, Ines; Poll, Eva Maria; Reineke, Andrea; Strasburger, Christian J; Dohmen, Guido; Gilsbach, Joachim M; Kreitschmann-Andermahr, Ilonka


    Apoplexy of pituitary adenomas with subsequent hypopituitarism is a rare but well recognized complication following cardiac surgery. The nature of cardiac on-pump surgery provides a risk of damage to the pituitary because the vascular supply of the pituitary is not included in the cerebral autoregulation. Thus, pituitary tissue may exhibit an increased susceptibility to hypoperfusion, ischemia or intraoperative embolism. After on-pump procedures, patients often present with physical and psychosocial impairments which resemble symptoms of hypopituitarism. Therefore, we analyzed whether on-pump cardiac surgery may cause pituitary dysfunction also in the absence of pre-existing pituitary disease. Twenty-five patients were examined 3-12 months after on-pump cardiac surgery. Basal hormone levels for all four anterior pituitary hormone axes were measured and a short synacthen test and a growth hormone releasing hormone plus arginine (GHRH-ARG)-test were performed. Quality of life (QoL), depression, subjective distress for a specific life event, sleep quality and fatigue were assessed by means of self-rating questionnaires. Hormonal alterations were only slight and no signs of anterior hypopituitarism were found except for an insufficient growth hormone rise in two overweight patients in the GHRH-ARG-test. Psychosocial impairment was pronounced, including symptoms of moderate to severe depression in 9, reduced mental QoL in 8, dysfunctional coping in 6 and pronounced sleep disturbances in 16 patients. Hormone levels did not correlate with psychosocial impairment. On-pump cardiac surgery did not cause relevant hypopituitarism in our sample of patients and does not serve to explain the psychosocial symptoms of these patients.

  11. Isoprenaline enhances local Ca2+ release in cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Jian-xin SHEN


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

  12. Cardiac troponin: an emerging cardiac biomarker in animal health

    Directory of Open Access Journals (Sweden)

    Vishal V. Undhad

    Full Text Available Analysis of cardiac troponin I (cTn I and T (cTnT are considered the “gold standard” for the non-invasive diagnosis of myocardial injury in human and animals. It has replaced traditionally used cardiac biomarkers such as myoglobin, lactate dehydrogenase (LDH, creatine kinase (CK and CK-MB due to its high sensitivity and specificity for the detection of myocardial injury. Cardiac troponins are proteins that control the calcium-mediated interaction between actin and myosin, allowing contraction at the sarcomere level. Concentration of the cTn can be correlated microscopic lesion and loss of immunolabeling in myocardium damage. Troponin concentration remains elevated in blood for 1-2wks so that wide window is available for diagnosis of myocardial damage. The cTn test has >95% specificity and sensitivity and test is less time consuming (10 to 15 minutes and less costly (INR 200 to INR 500. [Vet. World 2012; 5(8.000: 508-511

  13. Vasoactive substances in the circulatory dysfunction of cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens Henrik


    Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, and neurohumoral dysregulation. Moreover, the circulating levels of several vasoactive substances may be elevated....... Splanchnic vasodilatation is of pathogenic significance for the low systemic vascular resistance and abnormal volume distribution, which are important elements in the development of the concomitant cardiac dysfunction, recently termed cirrhotic cardiomyopathy. The systolic and diastolic functions...... are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms seem to include a reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators. such as nitric oxide...

  14. [Cardiac cephalgia: an underdiagnosed condition? ]. (United States)

    Gutiérrez Morlote, Jesús; Fernández García, José M; Timiraos Fernández, Juan J; Llano Cardenal, Miguel; Llano Catedral, Miguel; Rodríguez Rodríguez, Eloy; Pascual Gómez, Julio


    Cardiac cephalgia, or headache occurring as manifestation of myocardial ischemia, has only recently been recognized as a distinct entity. In patients with known ischemic cardiopathy, its diagnosis depends on the presence of severe headache that is accompanied by nausea, worsened by physical exercise, and only ceases with nitrate administration. We report on two patients who met diagnostic criteria for this entity. In both, headache was the only symptom of coronary ischemia, and delayed its diagnosis. Headache occurred both at rest and during exertion, and resolved only after the administration of nitrates. Cardiac cephalgia should be suspected in patients with a history of ischemic cardiopathy who present with de novo headache, even when thoracic pain is absent, especially if the headache improves with nitrates. Differential diagnosis with migraine is crucial to avoid the administration of vasoconstrictors.

  15. [Cardiac toxicity of 5-fluorouracil]. (United States)

    Fournier, C; Benahmed, M; Blondeau, M


    A 67 year-old patient receives 5-fluorouracil for vocal chord cancer. During the perfusion, atypical angina pain occurs, accompanied with offset of ST above the baseline in standard leads and in V4 through V6. The pain subsides spontaneously in 45 minutes. These ECG alterations are followed 48 hours later by diffuse inverted T waves with lengthened QT. Cardiac ultrasonography and isotopic angiography do not show any abnormality of the left ventricular function, but myocardial tomoscintigraphy with labelled thallium show a lower hypofixation on exertion. The cardiac toxicity of 5-fluorouracil is in frequent. It is usually believed that it involves a coronary spasm, as suggested by the ECG tracing in the reported cases. The incident, which may be painful or painless, may result in a myocardial infarction or even sudden death during the perfusion. Therefore, it is advisable to discontinue the treatment as soon as an angina-type pain occurs.

  16. Progeria syndrome with cardiac complications. (United States)

    Ilyas, Saadia; Ilyas, Hajira; Hameed, Abdul; Ilyas, Muhammad


    A case report of 6-year-old boy with progeria syndrome, with marked cardiac complications is presented. The boy had cardiorespiratory failure. Discoloured purpuric skin patches, alopecia, prominent forehead, protuberant eyes, flattened nasal cartilage, malformed mandible, hypodentition, and deformed rigid fingers and toes were observed on examination. The boy was unable to speak. A sclerotic systolic murmur was audible over the mitral and aortic areas. Chest x-rays showed cardiac enlargement and the electrocardiogram (ECG) showed giant peaked P waves (right atrial hypertrophy) and right ventricular hypertrophy. Atherosclerotic dilated ascending aorta, thickened sclerotic aortic, mitral, and tricuspid valves with increased echo texture, left and right atrial and right ventricular dilatation, reduced left ventricular cavity, and thickened speckled atrial and ventricular septa were observed on echocardiography.

  17. Sudden cardiac death in athletes

    Directory of Open Access Journals (Sweden)

    Fábio Camilo Pellegrino dos Santos


    Full Text Available ABSTRACT The most accepted definition of sudden cardiac death nowadays is an unexplained death occurred suddenly within one hour of symptom onset. If it was not witnessed, individuals need to had been observed for at least 24 hours before the event and should be discarded the possibility of non cardiac causes of sudden death, pulmonary embolism or extensive malignancy. The term athlete refers to individuals of any age who participate in collective or individual regular physical activity, as well as physical training program for regular competitions. The sudden death of a young athlete, whether amateur or professional, especially during competitions, is always dramatic, with strong negative social impact and in the media. The fact that sports are recommended as a formula for longevity and quality of life makes these events a cause for concern in sports and society in general.

  18. Heart fields and cardiac morphogenesis. (United States)

    Kelly, Robert G; Buckingham, Margaret E; Moorman, Antoon F


    In this review, we focus on two important steps in the formation of the embryonic heart: (i) the progressive addition of late differentiating progenitor cells from the second heart field that drives heart tube extension during looping morphogenesis, and (ii) the emergence of patterned proliferation within the embryonic myocardium that generates distinct cardiac chambers. During the transition between these steps, the major site of proliferation switches from progenitor cells outside the early heart to proliferation within the embryonic myocardium. The second heart field and ballooning morphogenesis concepts have major repercussions on our understanding of human heart development and disease. In particular, they provide a framework to dissect the origin of congenital heart defects and the regulation of myocardial proliferation and differentiation of relevance for cardiac repair.

  19. Respiratory gating in cardiac PET

    DEFF Research Database (Denmark)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E


    of our study was to compare the resulting imaging quality by the use of a time-based respiratory gating system in two groups administered either adenosine or dipyridamole as the pharmacological stress agent. METHODS AND RESULTS: Forty-eight patients were randomized to adenosine or dipyridamole cardiac...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4......BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...

  20. Systems biology and cardiac arrhythmias. (United States)

    Grace, Andrew A; Roden, Dan M


    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence.

  1. Nutritional Status and Cardiac Autophagy

    Directory of Open Access Journals (Sweden)

    Jihyun Ahn


    Full Text Available Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

  2. Pregnancy as a cardiac stress model. (United States)

    Chung, Eunhee; Leinwand, Leslie A


    Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation.


    Directory of Open Access Journals (Sweden)



    Full Text Available : Heart transplantation has emerged as the definitive therapy for patients with end-stage cardiomyopathy. The two most common forms of cardiac disease that lead to transplantation are ischemic cardiomyopathy and dilated cardiomyopathy, which together comprise approximately 90% of cases. The other less common forms of heart disease include viral cardiomyopathy, infiltrative cardiomyopathy, postpartum cardiomyopathy, valvular heart disease and congenital heart disease

  4. Chaos control of cardiac arrhythmias. (United States)

    Garfinkel, A; Weiss, J N; Ditto, W L; Spano, M L


    Chaos theory has shown that many disordered and erratic phenomena are in fact deterministic, and can be understood causally and controlled. The prospect that cardiac arrhythmias might be instances of deterministic chaos is therefore intriguing. We used a recently developed method of chaos control to stabilize a ouabain-induced arrhythmia in rabbit ventricular tissue in vitro. Extension of these results to clinically significant arrhythmias such as fibrillation will require overcoming the additional obstacles of spatiotemporal complexity.

  5. Fatty acids and cardiac disease: fuel carrying a message. (United States)

    van Bilsen, M; Planavila, A


    From the viewpoint of the prevention of cardiovascular disease (CVD) burden, there has been a continuous interest in the detrimental effects of the Western-type high-fat diet for more than half a century. More recently, this general view has been subject to change as epidemiological studies showed that replacing fat by carbohydrate may even be worse and that various polyunsaturated fatty acids (FA) have beneficial rather than detrimental effects on CVD outcome. At the same time, advances in lipid biology have provided insight into the mechanisms by which the different lipid components of the Western diet affect the cardiovascular system. In fact, this still is a rapidly growing field of research and in recent years novel FA derivatives and FA receptors have been discovered. This includes fish-oil derived FA-derivatives with anti-inflammatory properties, the so-called resolvins, and various G-protein-coupled receptors that recognize FA as ligands. In the present review, we will extensively discuss the role of FA and their metabolites on cardiac disease, with special emphasis on the role of the different saturated and polyunsaturated FA and their respective metabolites in cellular signal transduction and the possible implications for the development of cardiac hypertrophy and cardiac failure.

  6. Microfluidic cardiac cell culture model (μCCCM). (United States)

    Giridharan, Guruprasad A; Nguyen, Mai-Dung; Estrada, Rosendo; Parichehreh, Vahidreza; Hamid, Tariq; Ismahil, Mohamed Ameen; Prabhu, Sumanth D; Sethu, Palaniappan


    Physiological heart development and cardiac function rely on the response of cardiac cells to mechanical stress during hemodynamic loading and unloading. These stresses, especially if sustained, can induce changes in cell structure, contractile function, and gene expression. Current cell culture techniques commonly fail to adequately replicate physical loading observed in the native heart. Therefore, there is a need for physiologically relevant in vitro models that recreate mechanical loading conditions seen in both normal and pathological conditions. To fulfill this need, we have developed a microfluidic cardiac cell culture model (μCCCM) that for the first time allows in vitro hemodynamic stimulation of cardiomyocytes by directly coupling cell structure and function with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell culture chamber on a thin flexible silicone membrane. Integrating the cell culture chamber with a pump, collapsible pulsatile valve and an adjustable resistance element (hemostatic valve) in series allow replication of various loading conditions experienced in the heart. This paper details the design, modeling, fabrication and characterization of fluid flow, pressure and stretch generated at various frequencies to mimic hemodynamic conditions associated with the normal and failing heart. Proof-of-concept studies demonstrate successful culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an in vivo like phenotype within this system.

  7. Cardiac autonomic nerve distribution and arrhythmia

    Institute of Scientific and Technical Information of China (English)

    Quan Liu; Dongmei Chen; Yonggang Wang; Xin Zhao; Yang Zheng


    OBJECTIVE: To analyze the distribution characteristics of cardiac autonomic nerves and to explore the correlation between cardiac autonomic nerve distribution and arrhythmia.DATA RETRIEVAL: A computer-based retrieval was performed for papers examining the distribution of cardiac autonomic nerves, using "heart, autonomic nerve, sympathetic nerve, vagus nerve, nerve distribution, rhythm and atrial fibrillation" as the key words.SELECTION CRITERIA: A total of 165 studies examining the distribution of cardiac autonomic nerve were screened, and 46 of them were eventually included.MAIN OUTCOME MEASURES: The distribution and characteristics of cardiac autonomic nerves were observed, and immunohistochemical staining was applied to determine the levels of tyrosine hydroxylase and acetylcholine transferase (main markers of cardiac autonomic nerve distribution). In addition, the correlation between cardiac autonomic nerve distribution and cardiac arrhythmia was investigated.RESULTS: Cardiac autonomic nerves were reported to exhibit a disordered distribution in different sites, mainly at the surface of the cardiac atrium and pulmonary vein, forming a ganglia plexus. The distribution of the pulmonary vein autonomic nerve was prominent at the proximal end rather than the distal end, at the upper left rather than the lower right, at the epicardial membrane rather than the endocardial membrane, at the left atrium rather than the right atrium, and at the posterior wall rather than the anterior wall. The main markers used for cardiac autonomic nerves were tyrosine hydroxylase and acetylcholine transferase. Protein gene product 9.5 was used to label the immunoreactive nerve distribution, and the distribution density of autonomic nerves was determined using a computer-aided morphometric analysis system.CONCLUSION: The uneven distribution of the cardiac autonomic nerves is the leading cause of the occurrence of arrhythmia, and the cardiac autonomic nerves play an important role in the

  8. Mechanical modulation of cardiac microtubules. (United States)

    White, Ed


    Microtubules are a major component of the cardiac myocyte cytoskeleton. Interventions that alter it may influence cardiac mechanical and electrical activity by disrupting the trafficking of proteins to and from the surface membrane by molecular motors such as dynein, which use microtubules as tracks to step along. Free tubulin dimers may transfer GTP to the α-subunits of G-proteins, thus an increase in free tubulin could increase the activity of G-proteins; evidence for and against such a role exists. There is more general agreement that microtubules act as compression-resisting structures within myocytes, influencing visco-elasticity of myocytes and increasing resistance to shortening when proliferated and resisting deformation from longitudinal shear stress. In response to pressure overload, there can be post-translational modifications resulting in more stable microtubules and an increase in microtubule density. This is accompanied by contractile dysfunction of myocytes which can be reversed by microtubule disruption. There are reports of mechanically induced changes in electrical activity that are dependent upon microtubules, but at present, a consensus is lacking on whether disruption or proliferation would be beneficial in the prevention of arrhythmias. Microtubules certainly play a role in the response of cardiac myocytes to mechanical stimulation, the exact nature and significance of this role is still to be fully determined.

  9. Review Article of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Jittiporn PURATTANAMAL


    Full Text Available Cardiac amyloidosis is a term that means the deposit of abnormal proteins in the myocardium leading to global thickening of the heart walls. The clinical character is that of infiltrative cardiomyopathy. AL amyloidosis is the most common type that involves cardiac failure. Cardiac amyloid precedes clinical congestive heart failure, especially right-sided heart failure. Laboratory investigations have identified the amyloid fibril proteins deposited in the organ tissues. Immunofixation tests are the most sensitive that recognize the paraprotein mean light chain protein or immunoglobulin subtype deposit. Prognosis is poor if AL amyloidosis is untreated. Treatment of systemic involvement in AL amyloidosis is via chemotherapy such as melphalan and prednisolone. UK experts have reported the results of treatment in AL amyloidosis. Regardless of the use of adjunctive chemotherapy, the five-year survival after heart transplantation was generally poorer for AL (20 % at five years, but similar for non-AL amyloidosis (64 % at five years, than heart transplants in other cases. Progression of the systemic disease contributed to increased mortality. A specific treatment that increases the chances of survival is unknown.

  10. Sudden cardiac death risk stratification. (United States)

    Deyell, Marc W; Krahn, Andrew D; Goldberger, Jeffrey J


    Arrhythmic sudden cardiac death (SCD) may be caused by ventricular tachycardia/fibrillation or pulseless electric activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our healthcare and research resources to tackle this important public health issue. Although our understanding of SCD because of pulseless electric activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-ventricular tachycardia/ventricular fibrillation. This review focuses on existing and novel risk stratification tools for SCD-ventricular tachycardia/ventricular fibrillation. For patients with left ventricular dysfunction or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-ventricular tachycardia/ventricular fibrillation occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized.

  11. Neurologic management following cardiac arrest. (United States)

    Bircher, N G


    Optimal neurologic outcome after cardiac arrest requires careful attention to the details of both intracranial and extracranial homeostasis. A high index of suspicion regarding the potential causes and complications of cardiac arrest facilitates discovery and treatment of problems before they adversely affect neurologic outcome. The future is bright for resuscitation research: Our fundamental understanding of cerebral ischemia and its consequences has dramatically improved, and this knowledge can hopefully be transferred to clinical useful modes of therapy. However, the transition from a promising, therapeutically effective intervention in animals to the demonstration that treatment is effective following cardiac arrest in humans is an important and difficult step. The patient population is heterogeneous before the insult, the duration and severity of the insult are variable, and the effectiveness of cardiopulmonary resuscitation varies among institutions. Therefore, the only means of demonstrating clinical efficacy is the performance of a large clinical trial. The Resuscitation Research Center at the University of Pittsburgh has developed and coordinated a multicenter, multinational team of investigators who have completed one definitive trial of postarrest barbiturate therapy and are currently completing a similar trial using a calcium entry blocker. Despite the formidable obstacles posed by such comprehensive efforts, they provide the mechanism for determining whether the cost of a new treatment modality is justified by the likelihood of improved mortality or morbidity.

  12. Inherited arrhythmias: The cardiac channelopathies

    Directory of Open Access Journals (Sweden)

    Shashank P Behere


    Full Text Available Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information′s website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years and age (birth-18 years, yielding 47 results. The second search using the medical subject headings (MeSH database with the search terms "Long QT Syndrome" (MeSH and "Short QT Syndrome" (MeSH and "Brugada Syndrome" (MeSH and "Catecholaminergic Polymorphic Ventricular Tachycardia" (MeSH, applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full.

  13. Implementation study of an analog spiking neural network for assisting cardiac delay prediction in a cardiac resynchronization therapy device. (United States)

    Sun, Qing; Schwartz, François; Michel, Jacques; Herve, Yannick; Dalmolin, Renzo


    In this paper, we aim at developing an analog spiking neural network (SNN) for reinforcing the performance of conventional cardiac resynchronization therapy (CRT) devices (also called biventricular pacemakers). Targeting an alternative analog solution in 0.13- μm CMOS technology, this paper proposes an approach to improve cardiac delay predictions in every cardiac period in order to assist the CRT device to provide real-time optimal heartbeats. The primary analog SNN architecture is proposed and its implementation is studied to fulfill the requirement of very low energy consumption. By using the Hebbian learning and reinforcement learning algorithms, the intended adaptive CRT device works with different functional modes. The simulations of both learning algorithms have been carried out, and they were shown to demonstrate the global functionalities. To improve the realism of the system, we introduce various heart behavior models (with constant/variable heart rates) that allow pathologic simulations with/without noise on the signals of the input sensors. The simulations of the global system (pacemaker models coupled with heart models) have been investigated and used to validate the analog spiking neural network implementation.

  14. Modeling cardiac mechano-electrical feedback using reaction-diffusion-mechanics systems (United States)

    Keldermann, R. H.; Nash, M. P.; Panfilov, A. V.


    In many practically important cases, wave propagation described by the reaction-diffusion equation initiates deformation of the medium. Mathematically, such processes are described by coupled reaction-diffusion-mechanics (RDM) systems. RDM systems were recently used to study the effects of deformation on wave propagation in cardiac tissue, so called mechano-electrical feedback (MEF). In this article, we review the results of some of these studies, in particular those relating to the effects of deformation on pacemaker activity and spiral wave dynamics in the heart. We also provide brief descriptions of the numerical methods used, and the underlying cardiac physiology.

  15. Automatic right ventricle segmentation in cardiac MRI via anisotropic diffusion and SPCNN (United States)

    Wang, Kemin; Ma, Yurun; Lei, Ruoming; Yang, Zhen; Ma, Yide


    Cardiac Magnetic Resonance Image (CMRI) is a significant assistant for the cardiovascular disease clinical diagnosis. The segmentation of right ventricle (RV) is essential for cardiac function evaluation, especially for RV function measurement. Automatic RV segmentation is difficult due to the intensity inhomogeneity and the irregular shape. In this paper, we propose an automatic RV segmentation framework. Firstly, we use the anisotropic diffusion to filter the CMRI. And then, the endocardium is extracted by the simplified pulse coupled neural network (SPCNN) segmentation. At last, the morphologic processors are used to obtain the epicardium. The experiment results show that our method obtains a good performance for both the endocardium and the epicardium segmentation.

  16. Cardiac tamponade: contrast reflux as an indicator of cardiac chamber equalization

    Directory of Open Access Journals (Sweden)

    Nauta Foeke Jacob


    Full Text Available Abstract Background Traumatic hemopericardium remains a rare entity; it does however commonly cause cardiac tamponade which remains a major cause of death in traumatic blunt cardiac injury. Objectives We present a case of blunt chest trauma complicated by cardiac tamponade causing cardiac chamber equalization revealed by reflux of contrast. Case report A 29-year-old unidentified male suffered blunt chest trauma in a motor vehicle collision. Computed tomography (CT demonstrated a periaortic hematoma and hemopericardium. Significant contrast reflux was seen in the inferior vena cava and hepatic veins suggesting a change in cardiac chamber pressures. After intensive treatment including cardiac massage this patient expired of cardiac arrest. Conclusion Reflux of contrast on CT imaging can be an indicator of traumatic cardiac tamponade.

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

    NARCIS (Netherlands)

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


    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

  18. Cognitive impairment after sudden cardiac arrest


    Jaszke-Psonka, Magdalena; Piegza, Magdalena; Ścisło, Piotr; Pudlo, Robert; Piegza, Jacek; Badura-Brzoza, Karina; Leksowska, Aleksandra; Hese, Robert T.; Gorczyca, Piotr W.


    Aim To evaluate the incidence and severity of the impairment of selected cognitive functions in patients after sudden cardiac arrest (SCA) in comparison to patients after myocardial infarction without SCA and healthy subjects and to analyze the influence of sociodemographic and clinical parameters and the duration of cardiac arrest on the presence and severity of the described disorders. Material and methods The study group comprised 30 cardiac arrest survivors, the reference group comprised ...

  19. Surgical resection of a giant cardiac fibroma. (United States)

    Stamp, Nikki L; Larbalestier, Robert I


    A 42-year-old woman presented to a regional hospital emergency room with palpitations and was found to be in ventricular tachycardia. Chest radiography demonstrated a massively enlarged cardiac silhouette. Echocardiography and cardiac magnetic resonance imaging demonstrated a mass within the left ventricular free wall, consistent with a cardiac fibroma. The patient proceeded to have surgical resection of the mass. Left ventricular function was preserved postoperatively.

  20. Activation of cardiac ryanodine receptors by cardiac glycosides. (United States)

    Sagawa, Toshio; Sagawa, Kazuko; Kelly, James E; Tsushima, Robert G; Wasserstrom, J Andrew


    This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 channel activity. Digoxin and actodigin increased single-channel activity at low concentrations normally associated with therapeutic plasma levels, yielding a 50% of maximal effect of approximately 0.2 nM for each agent. Channel activation by glycosides did not require MgATP and occurred only when digoxin was applied to the cytoplasmic side of the channel. Similar results were obtained in human RyR2 channels; however, neither the crude skeletal nor the purified cardiac channel was activated by glycosides. Channel activation was dependent on [Ca2+] on the luminal side of the bilayer with maximal stimulation occurring between 0.3 and 10 mM. Rat RyR2 channels were activated by digoxin only at 1 microM, consistent with the lower sensitivity to glycosides in rat heart. These results suggest a model in which RyR2 channel activation by digoxin occurs only when luminal [Ca2+] was increased above 300 microM (in the physiological range). Consequently, increasing SR load (by Na+ pump inhibition) serves to amplify SR release by promoting direct RyR2 channel activation via a luminal Ca2+-sensitive mechanism. This high-affinity effect of glycosides could contribute to increased SR Ca2+ release and might play a role in the inotropic and/or toxic actions of glycosides in vivo.

  1. Cardiac Arrhythmias: Diagnosis, Symptoms, and Treatments. (United States)

    Fu, Du-Guan


    The cardiac arrhythmia is characterized by irregular rhythm of heartbeat which could be either too slow (100 beats/min) and can happen at any age. The use of pacemaker and defibrillators devices has been suggested for heart arrhythmias patients. The antiarrhythmic medications have been reported for the treatment of cardiac arrhythmias or irregular heartbeats. The diagnosis, symptoms, and treatments of cardiac arrhythmias as well as the radiofrequency ablation, tachycardia, Brugada syndrome, arterial fibrillation, and recent research on the genetics of cardiac arrhythmias have been described here.

  2. Multimodality imaging for resuscitated sudden cardiac death. (United States)

    Chen, Yingming Amy; Deva, Djeven; Kirpalani, Anish; Prabhudesai, Vikram; Marcuzzi, Danny W; Graham, John J; Verma, Subodh; Jimenez-Juan, Laura; Yan, Andrew T


    We present a case that elegantly illustrates the utility of two novel noninvasive imaging techniques, computed tomography (CT) coronary angiography and cardiac MRI, in the diagnosis and management of a 27-year-old man with exertion-induced cardiac arrest caused by an anomalous right coronary artery. CT coronary angiography with 3D reformatting delineated the interarterial course of an anomalous right coronary artery compressed between the aorta and pulmonary artery, whereas cardiac MRI showed a small myocardial infarction in the right coronary artery territory not detected on echocardiography. This case highlights the value of novel multimodality imaging techniques in the risk stratification and management of patients with resuscitated cardiac arrest.

  3. Tumors of the cardiac conduction system: are they an explanation for otherwise unexplained sudden cardiac death?

    Institute of Scientific and Technical Information of China (English)


    @@ Cardiac tumors are well described in the literature. The first reports of cardiac tumors date back hundreds of years.The prevalence of primary cardiac tumors at autopsy ranges from 0.001% to 0.3% with secondary tumors more common than in primary tumors.


    Directory of Open Access Journals (Sweden)



    Full Text Available Cardiovascular malformations are the most common cause of congenital malformations, the diagnosis of which requires a close observation in the neonatal period. Early recognition of CHD is important in the neonatal period, as many of them may be fatal if undiagnosed and may require immediate intervention. The objectives of this study are to study the epidemiology of neonatal cardiac murmurs, to identify clinical characteristics which differentiate pathological murmur from functional murmurs and to assess the reliability of clinical evaluation in diagnosing CHD. Method of study included all neonates admitted to the NICU, postnatal ward, attending pediatric OPD or neonatal follow up clinic and were detected to have cardiac murmurs. It was a cross sectional study over a period of 16months. A clinical diagnosis was made based on history and clinical examination. Then Chest X-ray and ECG, Echocardiography was done in all neonates for confirmation of the diagnosis. These neonates were again examined daily till they were in hospital and during the follow-up visit at 6 weeks. The results of 70 neonates in this study conducted over a period of 24 months included the incidence of cardiac murmurs among intramural neonates which was 13.5 for 1000 live births. Most frequent symptom was fast breathing in 10(14.3% cases. VSD was the most common diagnosis clinically in 23 (33% babies. The most frequent Echo diagnosis was acyanotic complex congenital heart disease in 25(36% cases followed by 12(17% cases each of VSD and ASD respectively. Overall in our study 77.1% (54cases of the murmurs were diagnosed correctly and confirmed by Echocardiography The study concluded that it is possible to make clinical diagnosis in many cases of congenital heart diseases, the functional murmurs could be differentiated from those arising from structural heart disease and evaluation of the infants based only on murmurs, few congenital heart diseases can be missed.

  5. ECLS in Pediatric Cardiac Patients (United States)

    Di Nardo, Matteo; MacLaren, Graeme; Marano, Marco; Cecchetti, Corrado; Bernaschi, Paola; Amodeo, Antonio


    Extracorporeal life support (ECLS) is an important device in the management of children with severe refractory cardiac and or pulmonary failure. Actually, two forms of ECLS are available for neonates and children: extracorporeal membrane oxygenation (ECMO) and use of a ventricular assist device (VAD). Both these techniques have their own advantages and disadvantages. The intra-aortic balloon pump is another ECLS device that has been successfully used in larger children, adolescents, and adults, but has found limited applicability in smaller children. In this review, we will present the “state of art” of ECMO in neonate and children with heart failure. ECMO is commonly used in a variety of settings to provide support to critically ill patients with cardiac disease. However, a strict selection of patients and timing of intervention should be performed to avoid the increase in mortality and morbidity of these patients. Therefore, every attempt should be done to start ECLS “urgently” rather than “emergently,” before the presence of dysfunction of end organs or circulatory collapse. Even though exciting progress is being made in the development of VADs for long-term mechanical support in children, ECMO remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation. With the increase in familiarity with ECMO, new indications have been added, such as extracorporeal cardiopulmonary resuscitation (ECPR). The literature supporting ECPR is increasing in children. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS have reduced in the last 5 years and many centers support patients with functionally univentricular circulations. Improved results have been recently achieved in this complex subset of patients. PMID

  6. Sudden Cardiac Death and Post Cardiac Arrest Syndrome. An Overview

    Directory of Open Access Journals (Sweden)

    Zima Endre


    Full Text Available A satisfactory neurologic outcome is the key factor for survival in patients with sudden cardiac death (SCD, however this is highly dependent on the haemodynamic status. Short term cardiopulmonary resuscitation and regained consciousness on the return of spontaneous circulation (ROSC is indicative of a better prognosis. The evaluation and treatment of SCD triggering factors and of underlying acute and chronic diseases will facilitate prevention and lower the risk of cardiac arrest. Long term CPR and a prolonged unconscious status after ROSC, in the Intensive Care Units or Coronary Care Units, indicates the need for specific treatment and supportive therapy including efforts to prevent hyperthermia. The prognosis of these patients is unpredictable within the first seventy two hours, due to unknown responses to therapeutic management and the lack of specific prognostic factors. Patients in these circumstances require the highest level of intensive care and aetiology driven treatment without any delay, independently of their coma state. Current guidelines sugest the use of multiple procedures in arriving at a diagnosis and prognosis of these critical cases.

  7. [Morgagni hernia causing cardiac tamponade]. (United States)

    S Breinig; Paranon, S; Le Mandat, A; Galinier, P; Dulac, Y; Acar, P


    Morgagni hernia is a rare malformation (3% of diaphragmatic hernias). This hernia is usually asymptomatic in children. We report on a case revealed by an unusual complication. Severe cyanosis was due to right-to-left atrial shunt through the foramen ovale assessed by 2D echocardiography. Diagnosis of the Morgagni hernia was made with CT scan. The intrathoracic liver compressed the right chambers of the heart causing tamponade. Cardiac compression was reversed after surgery and replacement of the liver in the abdomen. Six months after the surgery, the infant was symptom-free with normal size right chambers of the heart.

  8. Cardiac imaging: does radiation matter? (United States)

    Einstein, Andrew J.; Knuuti, Juhani


    The use of ionizing radiation in cardiovascular imaging has generated considerable discussion. Radiation should not be considered in isolation, but rather in the context of a careful examination of the benefits, risks, and costs of cardiovascular imaging. Such consideration requires an understanding of some fundamental aspects of the biology, physics, epidemiology, and terminology germane to radiation, as well as principles of radiological protection. This paper offers a concise, contemporary perspective on these areas by addressing pertinent questions relating to radiation and its application to cardiac imaging. PMID:21828062

  9. 10.2.Cardiac arrhythmias

    Institute of Scientific and Technical Information of China (English)


    930257 Electrophysiologic study of reperfu-sion arrhythmias.YIN Hong (尹红),et al.Af-fil Hosp,Shandong Med Univ,Jinan.Chin CirJ 1993;8(1):37—39.Twenty dogs of experimental ischemic reper-fusion were studied with a three-dimensionalmapping system of cardiac electric activity andmultiple—level myocardial recordings by bipolarplunge—needle electrodes.27% of the nonsus-tained ventricular tachycardia (NSVT) of intra-mural reentry occurred in the ischemic subendo-

  10. Cerebral oximetry in cardiac anesthesia (United States)

    Vretzakis, George; Georgopoulou, Stauroula; Stamoulis, Konstantinos; Stamatiou, Georgia; Tsakiridis, Kosmas; Katsikogianis, Nikolaos; Kougioumtzi, Ioanna; Machairiotis, Nikolaos; Tsiouda, Theodora; Mpakas, Andreas; Beleveslis, Thomas; Koletas, Alexander; Siminelakis, Stavros N.; Zarogoulidis, Konstantinos


    Cerebral oximetry based on near-infrared spectroscopy (NIRS) is increasingly used during the perioperative period of cardiovascular operations. It is a noninvasive technology that can monitor the regional oxygen saturation of the frontal cortex. Current literature indicates that it can stratify patients preoperatively according their risk. Intraoperatively, it provides continuous information about brain oxygenation and allows the use of brain as sentinel organ indexing overall organ perfusion and injury. This review focuses on the clinical validity and applicability of this monitor for cardiac surgical patients. PMID:24672700

  11. Calmodulin kinase II inhibition protects against structural heart disease. (United States)

    Zhang, Rong; Khoo, Michelle S C; Wu, Yuejin; Yang, Yingbo; Grueter, Chad E; Ni, Gemin; Price, Edward E; Thiel, William; Guatimosim, Silvia; Song, Long-Sheng; Madu, Ernest C; Shah, Anisha N; Vishnivetskaya, Tatiana A; Atkinson, James B; Gurevich, Vsevolod V; Salama, Guy; Lederer, W J; Colbran, Roger J; Anderson, Mark E


    Beta-adrenergic receptor (betaAR) stimulation increases cytosolic Ca(2+) to physiologically augment cardiac contraction, whereas excessive betaAR activation causes adverse cardiac remodeling, including myocardial hypertrophy, dilation and dysfunction, in individuals with myocardial infarction. The Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a recently identified downstream element of the betaAR-initiated signaling cascade that is linked to pathological myocardial remodeling and to regulation of key proteins involved in cardiac excitation-contraction coupling. We developed a genetic mouse model of cardiac CaMKII inhibition to test the role of CaMKII in betaAR signaling in vivo. Here we show CaMKII inhibition substantially prevented maladaptive remodeling from excessive betaAR stimulation and myocardial infarction, and induced balanced changes in excitation-contraction coupling that preserved baseline and betaAR-stimulated physiological increases in cardiac function. These findings mark CaMKII as a determinant of clinically important heart disease phenotypes, and suggest CaMKII inhibition can be a highly selective approach for targeting adverse myocardial remodeling linked to betaAR signaling.

  12. More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. (United States)

    Kishore, Raj; Khan, Mohsin


    Stem cell therapy provides immense hope for regenerating the pathological heart, yet has been marred by issues surrounding the effectiveness, unclear mechanisms, and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been used with varied success. Cell-free components, such as exosomes enriched in proteins, messenger RNAs, and miRs characteristic of parental stem cells, represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively used to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes, including their potential benefits and limitations to develop a potentially viable therapy for cardiovascular problems.

  13. Light-sheet fluorescence imaging to localize cardiac lineage and protein distribution (United States)

    Ding, Yichen; Lee, Juhyun; Ma, Jianguo; Sung, Kevin; Yokota, Tomohiro; Singh, Neha; Dooraghi, Mojdeh; Abiri, Parinaz; Wang, Yibin; Kulkarni, Rajan P.; Nakano, Atsushi; Nguyen, Thao P.; Fei, Peng; Hsiai, Tzung K.


    Light-sheet fluorescence microscopy (LSFM) serves to advance developmental research and regenerative medicine. Coupled with the paralleled advances in fluorescence-friendly tissue clearing technique, our cardiac LSFM enables dual-sided illumination to rapidly uncover the architecture of murine hearts over 10 by 10 by 10 mm3 in volume; thereby allowing for localizing progenitor differentiation to the cardiomyocyte lineage and AAV9-mediated expression of exogenous transmembrane potassium channels with high contrast and resolution. Without the steps of stitching image columns, pivoting the light-sheet and sectioning the heart mechanically, we establish a holistic strategy for 3-dimentional reconstruction of the “digital murine heart” to assess aberrant cardiac structures as well as the spatial distribution of the cardiac lineages in neonates and ion-channels in adults.

  14. Assessment of cardiac sympathetic nerve integrity with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Raffel, David M. E-mail:; Wieland, Donald M


    The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation.

  15. 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.

  16. Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration. (United States)

    Zeng, Bin; Tong, Suiyang; Ren, Xiaofeng; Xia, Hao


    Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were co-localized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2'-deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury.

  17. Cardiac troponin elevations among critically ill patients.

    NARCIS (Netherlands)

    Klein Gunnewiek, J.M.T.; Hoeven, J.G. van der


    PURPOSE OF THE REVIEW: Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed. RE

  18. [Cardiac Pacemakers, implantable defibrillators and IRM]. (United States)

    Frank, R; Hidden-Lucet, F; Himbert, C; Petitot, J C; Fontaine, G


    The IRM is formally contraindicated to the pacemaker and cardiac defibrillator wearers because of the risk of inhibition or inappropriate stimulations during the examination. However if the examination is essential, suitable programming of the apparatus and a constant monitoring of the heartbeat rate by a qualified doctor in cardiac stimulation must make it possible to avoid any accident.

  19. Acute cardiac failure in neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Sparrow, Patrick


    We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

  20. Coagulopathy and hemostatic monitoring in cardiac surgery

    DEFF Research Database (Denmark)

    Johansson, Pär I; Sølbeck, Sacha; Genet, Gustav;


    Cardiac surgery with cardiopulmonary bypass (CPB) causes severe derangements in the hemostatic system, which in turn puts the patient at risks of microvascular bleeding. Excessive transfusion and surgical re-exploration after cardiac surgery are potentially associated with a number of adverse...

  1. Cardiac troponins in dogs and cats

    DEFF Research Database (Denmark)

    Langhorn, Rebecca; Willesen, Jakob


    . Conventionally, the cardiac troponins have been used for diagnosis of acute myocardial infarction in humans and have become the gold standard biomarkers for this indication. They have become increasingly recognized as an objective measure of cardiomyocyte status in both cardiac and noncardiac disease, supplying...

  2. Preoperative respiratory physical therapy in cardiac surgery

    NARCIS (Netherlands)

    Hulzebos, H.J.


    Cardiac surgery is one of the most common surgical procedures and accounts for more resources expended in cardiovascular medicine than any other single procedure. Because cardiac surgery involves sternal incision and cardiopulmonary bypass, patients usually have a restricted respiratory function in

  3. Cardiac MRI of the athlete's heart

    NARCIS (Netherlands)

    Prakken, N.H.J.


    The increase in pre-participation cardiovascular screening using the Lausanne protocol will ultimately lead to an increased use of cardiac MRI and MDCT in the cardiovascular work-up of athletes. The role of cardiac MRI is well established in the evaluation of cardiomyopathies, myocarditis, aortic st

  4. Cardiac manifestations of inborn errors of metabolism.

    NARCIS (Netherlands)

    Evangeliou, A.; Papadopoulou-Legbelou, K.; Daphnis, E.; Ganotakis, E.; Vavouranakis, I.; Michailidou, H.; Hitoglou-Makedou, A.; Nicolaidou, P.; Wevers, R.A.; Varlamis, G.


    AIM: The aim of the study was to investigate the frequency and type of cardiac manifestations in a defined group of patients with inborn errors of metabolism. This paper also explores the key role of cardiac manifestations in the diagnosis of inborn errors of metabolism in daily practice. METHODS: O

  5. Drugs, QTc prolongation and sudden cardiac death

    NARCIS (Netherlands)

    S.M.J.M. Straus (Sabine)


    textabstract__Abstract__ The term sudden cardiac death pertains to an unexpected death from cardiac causes within a short time period and has been described throughout history. The ancient Egyptians inscribed on the tomb of a nobleman some 4500 years ago that he had died suddenly and without appare

  6. Primary cardiac hemangioendothelioma: a case report

    Institute of Scientific and Technical Information of China (English)

    WANG Li-feng; LIU Ming; ZHU Hong; HAN Wei; HU Cheng-yi; QI Ji-ping; MEI Huan-lin; GE Re-le; ZHOU Min


    @@ Primary cardiac hemangioendothelioma is extremely rare.1-3 Up to now less than twenty cases have been reported in English literature, the data about this kind of cardiac tumors are scanty. In this report, a case of a huge hemangio-endothelioma that arose from the right atrium and was successfully resected is presented.

  7. Cardiac spindle cell hemangioma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Young; Lee, In Jae; Min, Kwang Sun; Jeon, Eui Yong; Lee, Yul; Bae, Sang Hoon [Hallym University College of Medicine, Anyang (Korea, Republic of)


    Spindle cell hemangioma is an uncommon vascular lesion histologically resembling a cavernous hemangioma and Kaposi's sarcoma with a predilection for the extremities. There are no radiologic reports concerning cardiac spindle cell hemangioma in the current literature. We report here a case of cardiac spindle cell hemangioma.

  8. Corticosteroids in cardiac surgery: a continuing controversy

    NARCIS (Netherlands)

    Dieleman, J.M.


    Cardiac surgery leads to significant improvements in symptoms of cardiac disease and quality of life, but is still associated with a substantial risk of adverse events and postoperative disability. The perioperative systemic inflammatory response syndrome (SIRS) likely plays a role in the developmen

  9. Update in cardiac arrhythmias and pacing. (United States)

    García-Bolao, Ignacio; Ruiz-Mateas, Francisco; Bazan, Victor; Berruezo, Antonio; Alcalde, Oscar; Leal del Ojo, Juan; Acosta, Juan; Martínez Sellés, Manuel; Mosquera, Ignacio


    This article discusses the main advances in cardiac arrhythmias and pacing published between 2013 and 2014. Special attention is given to the interventional treatment of atrial fibrillation and ventricular arrhythmias, and on advances in cardiac pacing and implantable cardioverter defibrillators, with particular reference to the elderly patient.

  10. Athletes at Risk for Sudden Cardiac Death (United States)

    Subasic, Kim


    High school athletes represent the largest group of individuals affected by sudden cardiac death, with an estimated incidence of once or twice per week. Structural cardiovascular abnormalities are the most frequent cause of sudden cardiac death. Athletes participating in basketball, football, track, soccer, baseball, and swimming were found to…

  11. Epicardial origin of cardiac CFU-Fs. (United States)

    Slukvin, Igor I


    The epicardium has been recognized as a source of cardiovascular progenitors during embryogenesis and postnatal life. In this issue of Cell Stem Cell, Chong et al. (2011) identify cardiac CFU-Fs as cardiac-resident cells of epicardial origin with broad multilineage differentiation potential.

  12. Cardiac Vagal Regulation and Early Peer Status (United States)

    Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.


    A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

  13. Ultrasound Imaging in Teaching Cardiac Physiology (United States)

    Johnson, Christopher D.; Montgomery, Laura E. A.; Quinn, Joe G.; Roe, Sean M.; Stewart, Michael T.; Tansey, Etain A.


    This laboratory session provides hands-on experience for students to visualize the beating human heart with ultrasound imaging. Simple views are obtained from which students can directly measure important cardiac dimensions in systole and diastole. This allows students to derive, from first principles, important measures of cardiac function, such…

  14. Stem cell sources for cardiac regeneration

    NARCIS (Netherlands)

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


    Cell-based cardiac repair has the ambitious aim to replace the malfunctioning cardiac muscle developed after myocardial infarction, with new contractile cardiomyocytes and vessels. Different stem cell populations have been intensively studied in the last decade as a potential source of new cardiomyo

  15. Cardiac Rehabilitation in Older Adults. (United States)

    Schopfer, David W; Forman, Daniel E


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

  16. Cardiac involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    V. De Gennaro Colonna


    Full Text Available Rheumatoid arthritis (RA is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It’s an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non- Hodgkin lymphoma. Among extra-articular complications, cardiovascular (CV involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

  17. Clofibrate, calcium and cardiac muscle. (United States)

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


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

  18. Cardiac safety of liposomal anthracyclines. (United States)

    Ewer, Michael S; Martin, Francis J; Henderson, Craig; Shapiro, Charles L; Benjamin, Robert S; Gabizon, Alberto A


    Conventional anthracyclines are active against many tumor types, but cardiotoxicity related to the cumulative dose may limit their use; this is particularly problematic for patients with risk factors for increased toxicity, for those who have received any anthracycline in the past, or for those who are to receive other cardiotoxic agents. Preclinical studies determined that encapsulating conventional anthracyclines in liposomes reduced the incidence and severity of cumulative dose-related cardiomyopathy while preserving antitumor activity. In controlled clinical trials, the risk of cardiotoxicity was significantly lower when nonpegylated liposomal doxorubicin (Myocet [NPLD]) was substituted for conventional doxorubicin, but the risk was not significantly different when NPLD was used in place of conventional epirubicin. Direct comparisons to conventional doxorubicin therapy showed comparable efficacy but significantly lower risk of cardiotoxicity with pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) therapy. Retrospective and prospective trials have not identified a maximum "cardiac safe" dose of PLD, despite use of cumulative doses exceeding 2,000 mg/m2 in some patients. Liposomal daunorubicin (DaunoXome [DNX]) may be associated with a lower risk of cardiotoxicity than conventional anthracyclines, but comparative trials are not available. With respect to combination chemotherapy, early results of clinical trials suggest that combining trastuzumab or a taxane with NPLD or PLD instead of a conventional anthracycline significantly reduces cardiotoxicity risk without reducing chemotherapeutic efficacy. Further results are eagerly awaited from ongoing controlled trials of cardiac safety with long-term liposomal anthracycline therapy, either alone or in combination with other potentially cardiotoxic agents.

  19. Paradoxical hypertension with cardiac tamponade. (United States)

    Argulian, Edgar; Herzog, Eyal; Halpern, Dan G; Messerli, Franz H


    Subacute (medical) tamponade develops over a period of days or even weeks. Previous studies have shown that subacute tamponade is uncommonly associated with hypotension. On the contrary, many of those patients are indeed hypertensive at initial presentation. We sought to determine the prevalence and predictors of hypertensive cardiac tamponade and hemodynamic response to pericardial effusion drainage. We conducted a retrospective study of patients who underwent pericardial effusion drainage for subacute pericardial tamponade. Diagnosis of pericardial tamponade was established by the treating physician based on clinical data and supportive echocardiographic findings. Patients were defined as hypertensive if initial systolic blood pressure (BP) was ≥140 mm Hg. Thirty patients with subacute tamponade who underwent pericardial effusion drainage were included in the analysis. Eight patients (27%) were hypertensive with a mean systolic BP of 167 compared to 116 mm Hg in 22 nonhypertensive patients. Hypertensive patients with tamponade were more likely to have advanced renal disease (63% vs 14%, p tamponade after pericardial effusion drainage. Those results are consistent with previous studies with an estimated prevalence of hypertensive tamponade from 27% to 43%. In conclusion, a hypertensive response was observed in approximately 1/3 of patients with subacute pericardial tamponade. Relief of cardiac tamponade commonly resulted in a decrease in BP.

  20. [Technologies for cardiac valve prostheses]. (United States)

    Nakano, Kiyoharu


    To show the technological development of cardiac valve prostheses, a historical review of both mechanical and biological valve prostheses and a current overview of modern cardiac valve devices are provided. Scince the 1st implantation of Starr-Edwards ball valve in 1960, both mechanical and biological valve prostheses have advanced. The valve design, the material of the leaflet and the hausing of mechanical prostheses have improved. Currently, the majority of the mechanical prostheses are bileaflet tilting disc valves made of pyrolytic carbon, which is antithromboembolic. However, anticoagulation therapy with warfarin is still required. As for the bioprostheses, although the fixation and anti-mineralization methods of the tissues improved, the durability of these valves is still limited. For the material of the current biological valves, the porcine aortic valve or bovine pericardium are used. The tissues are fixed by non-pressure or low-pressure method in glutaraldehyde solution. A stented and non-stented valves are available. Epoch-making events in this field are the implantation of new bioprosthetic valves using tissue engineering methods and the development of the transcatheter valve replacement therapies.

  1. Predictive Modeling of Cardiac Ischemia (United States)

    Anderson, Gary T.


    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  2. Gene transfer to promote cardiac regeneration. (United States)

    Collesi, Chiara; Giacca, Mauro


    There is an impelling need to develop new therapeutic strategies for patients with myocardial infarction and heart failure. Leading from the large quantity of new information gathered over the last few years on the mechanisms controlling cardiomyocyte proliferation during embryonic and fetal life, it is now possible to devise innovative therapies based on cardiac gene transfer. Different protein-coding genes controlling cell cycle progression or cardiomyocyte specification and differentiation, along with microRNA mimics and inhibitors regulating pre-natal and early post-natal cell proliferation, are amenable to transformation in potential therapeutics for cardiac regeneration. These gene therapy approaches are conceptually revolutionary, since they are aimed at stimulating the intrinsic potential of differentiated cardiac cells to proliferate, rather than relying on the implantation of exogenously expanded cells to achieve tissue regeneration. For efficient and prolonged cardiac gene transfer, vectors based on the Adeno-Associated Virus stand as safe, efficient and reliable tools for cardiac gene therapy applications.

  3. Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes

    Institute of Scientific and Technical Information of China (English)

    LIANG Jia-liang; FENG Zhi-kuan; LIU Xiao-ying; LIN Qiu-xiong; FU Yong-heng; SHAN Zhi-xin; ZHU Jie-ning; LIN Shu-guang; YU Xi-yong


    Background The effect of impaired glucose tolerance (IGT) on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography.Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor (MIF) and G-protein coupled receptor kinase 2 (GRK2) were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls,increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively (F=15.370, P=0.003). Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction (EF) being (68.59±6.62)% in IGT rats vs. (81.07±4.59)% in controls (t=4.020, P=0.002). There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.

  4. Cardiac molecular-acclimation mechanisms in response to swimming-induced exercise in Atlantic salmon.

    Directory of Open Access Journals (Sweden)

    Vicente Castro

    Full Text Available Cardiac muscle is a principal target organ for exercise-induced acclimation mechanisms in fish and mammals, given that sustained aerobic exercise training improves cardiac output. Yet, the molecular mechanisms underlying such cardiac acclimation have been scarcely investigated in teleosts. Consequently, we studied mechanisms related to cardiac growth, contractility, vascularization, energy metabolism and myokine production in Atlantic salmon pre-smolts resulting from 10 weeks exercise-training at three different swimming intensities: 0.32 (control, 0.65 (medium intensity and 1.31 (high intensity body lengths s(-1. Cardiac responses were characterized using growth, immunofluorescence and qPCR analysis of a large number of target genes encoding proteins with significant and well-characterized function. The overall stimulatory effect of exercise on cardiac muscle was dependent on training intensity, with changes elicited by high intensity training being of greater magnitude than either medium intensity or control. Higher protein levels of PCNA were indicative of cardiac growth being driven by cardiomyocyte hyperplasia, while elevated cardiac mRNA levels of MEF2C, GATA4 and ACTA1 suggested cardiomyocyte hypertrophy. In addition, up-regulation of EC coupling-related genes suggested that exercised hearts may have improved contractile function, while higher mRNA levels of EPO and VEGF were suggestive of a more efficient oxygen supply network. Furthermore, higher mRNA levels of PPARα, PGC1α and CPT1 all suggested a higher capacity for lipid oxidation, which along with a significant enlargement of mitochondrial size in cardiac myocytes of the compact layer of fish exercised at high intensity, suggested an enhanced energetic support system. Training also elevated transcription of a set of myokines and other gene products related to the inflammatory process, such as TNFα, NFκB, COX2, IL1RA and TNF decoy receptor. This study provides the first

  5. Exercises in anatomy: cardiac isomerism. (United States)

    Anderson, Robert H; Sarwark, Anne E; Spicer, Diane E; Backer, Carl L


    It is well recognized that the patients with the most complex cardiac malformations are those with so-called visceral heterotaxy. At present, it remains a fact that most investigators segregate these patients on the basis of their splenic anatomy, describing syndromes of so-called asplenia and polysplenia. It has also been known for quite some time, nonetheless, that the morphology of the tracheobronchial tree is usually isomeric in the setting of heterotaxy. And it has been shown that the isomerism found in terms of bronchial arrangement correlates in a better fashion with the cardiac anatomy than does the presence of multiple spleens, or the absence of any splenic tissue. In this exercise in anatomy, we use hearts from the Idriss archive of Lurie Children's Hospital in Chicago to demonstrate the isomeric features found in the hearts obtained from patients known to have had heterotaxy. We first demonstrate the normal arrangements, showing how it is the extent of the pectinate muscles in the atrial appendages relative to the atrioventricular junctions that distinguishes between morphologically right and left atrial chambers. We also show the asymmetry of the normal bronchial tree, and the relationships of the first bronchial branches to the pulmonary arteries supplying the lower lobes of the lungs. We then demonstrate that diagnosis of multiple spleens requires the finding of splenic tissue on either side of the dorsal mesogastrium. Turning to hearts obtained from patients with heterotaxy, we illustrate isomeric right and left atrial appendages. We emphasize that it is only the appendages that are universally isomeric, but point out that other features support the notion of cardiac isomerism. We then show that description also requires a full account of veno-atrial connections, since these can seemingly be mirror-imaged when the arrangement within the heart is one of isomerism of the atrial appendages. We show how failure to recognize the presence of such isomeric

  6. Nonlinear dynamics of the heartbeat II. Subharmonic bifurcations of the cardiac interbeat interval in sinus node disease (United States)

    Goldberger, Ary L.; Bhargava, Valmik; West, Bruce J.; Mandell, Arnold J.


    Changing the coupling of electronic relaxation oscillators may be associated with the emergence of complex periodic behavior. The electrocardiographic record of a patient with the “sick sinus syndrome” demonstrated periodic behavior including subharmonic bifurcations in an attractor of his interbeat interval. Such nonlinear dynamics which may emerge from alterations in the coupling of oscillating pacemakers are not predicted by traditional models in cardiac electrophysiology. An understanding of the nonlinear behavior of physical and mathematical systems may generalize to pathophysiological processes.

  7. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher


    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.


    Institute of Scientific and Technical Information of China (English)

    Yin-ping Chu; Jin-lian Cheng; Ru-kun Chen; Yu-bo Fan; Fang Pu


    Objective To assess the influence of mimic cardiac rate on hydrodynamics of different mechanical prosthetic cardiac valves.Methods US-made CarboMedics bileaflet valve, China-made Jiuling bileaflet valve and C-L tilting disc valve were tested via a pulsatile flow simulator in the aortic position. Testing conditions were set at mimic cardiac rates of 55 bpm, 75 bpm, 100bpm with a constant mimic cardiac output of 4 L/min. The mean pressure differences (△P), leakage volumes (LEV) and closing volumes (CLV) across each valve, and effective orifice areas (EOA) were analyzed.Results Within physiological range, △p, LEV, and CLV decreased as mimic cardiac rate increased, with a large extent of variance. EOA increased along with an increase in mimic cardiac rate. It was a different response in terms of cardiac rate alteration for different types of mechanical prosthetic cardiac valves.Conclusion Mimic cardiac rate change affects hydrodynamics of mechanical prosthetic cardiac valves. Within physiological range, the hydrodynamic of prosthetic bileaflet valve is better than that of tilting disc valve.

  9. Descartes, Cardiac Heat, and Alchemy. (United States)

    Heitsch, Dorothea


    René Descartes (1596-1650) insisted on a heat and light theory to explain cardiac movement, and used concepts such as distillation of the vital spirits, fermentation in the digestive process, and fermentation in the circulation of the blood. I argue that his theory of the body as a heat-exchange system was based on alchemical and natural philosophical notions of fire and light expounded by precursors and contemporaries who included Jean D'Espagnet, Jean Fernel, Jan Baptist van Helmont, and Andreas Libavius. Descartes endeavoured to mechanise their approaches, creating a theory in which fire and heat, a legacy from thermal explanations of physiology, were transformed into alchemical fire, and then into mechanistic or physicalist heat.

  10. [Cardiopulmonary resuscitation in cardiac arrest following trauma]. (United States)

    Leidel, B A; Kanz, K-G


    For decades, survival rates of cardiac arrest following trauma were reported between 0 and 2 %. Since 2005, survival rates have increased with a wide range up to 39 % and good neurological recovery in every second person injured for unknown reasons. Especially in children, high survival rates with good neurologic outcomes are published. Resuscitation following traumatic cardiac arrest differs significantly from nontraumatic causes. Paramount is treatment of reversible causes, which include massive bleeding, hypoxia, tension pneumothorax, and pericardial tamponade. Treatment of reversible causes should be simultaneous. Chest compression is inferior following traumatic cardiac arrest and should never delay treatment of reversible causes of the traumatic cardiac arrest. In massive bleeding, bleeding control has priority. Damage control resuscitation with permissive hypotension, aggressive coagulation therapy, and damage control surgery represent the pillars of initial treatment. Cardiac arrest due to hypoxia should be resolved by airway management and ventilation. Tension pneumothorax should be decompressed by finger thoracostomy, pericardial tamponade by resuscitative thoracotomy. In addition, resuscitative thoracotomy allows direct and indirect bleeding control. Untreated impact brain apnea may rapidly lead to cardiac arrest and requires quick opening of the airway and effective oxygenation. Established algorithms for treatment of cardiac arrest following trauma enable a safe, structured, and effective management.

  11. Integrable Couplings of the Coupled Burgers Hierarchy

    Institute of Scientific and Technical Information of China (English)

    XIATie-Cheng; CHENXiao-Hong; CHENDeng-Yuan; ZHANGYu-Feng


    In this letter, a new loop algebra G is constructed, from which a new isospectral problem is established. It follows that integrable couplings of the well-known coupled Burgers hierarchy are obtained.

  12. Coupling strength versus coupling impact in nonidentical bidirectionally coupled dynamics (United States)

    Laiou, Petroula; Andrzejak, Ralph G.


    The understanding of interacting dynamics is important for the characterization of real-world networks. In general, real-world networks are heterogeneous in the sense that each node of the network is a dynamics with different properties. For coupled nonidentical dynamics symmetric interactions are not straightforwardly defined from the coupling strength values. Thus, a challenging issue is whether we can define a symmetric interaction in this asymmetric setting. To address this problem we introduce the notion of the coupling impact. The coupling impact considers not only the coupling strength but also the energy of the individual dynamics, which is conveyed via the coupling. To illustrate this concept, we follow a data-driven approach by analyzing signals from pairs of coupled model dynamics using two different connectivity measures. We find that the coupling impact, but not the coupling strength, correctly detects a symmetric interaction between pairs of coupled dynamics regardless of their degree of asymmetry. Therefore, this approach allows us to reveal the real impact that one dynamics has on the other and hence to define symmetric interactions in pairs of nonidentical dynamics.

  13. [Research progress of cardiac systems biology]. (United States)

    Wang, Juan; Shang, Tong


    Systems Biology is one of the most widely discussed fields among emerging post-genomic disciplines. Medical systems biology is an important component of systems biology. The goals of medical systems biology are gaining a complete understanding of human body in normal and disease states. Driven by the great importance of cardiovascular diseases, cardiac systems biology is improving rapidly. This review provides an overview of major themes in the developing field of cardiac systems biology, including some of the high-throughput experiments and strategies used to integrate the datasets, various types of computational approaches used for developing useful quantitative models, and successful examples, future directions of cardiac systems biology.

  14. Cardiac and Respiratory Disease in Aged Horses. (United States)

    Marr, Celia M


    Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids.

  15. Cardiac Electrophysiology: Normal and Ischemic Ionic Currents and the ECG (United States)

    Klabunde, Richard E.


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

  16. Coupling coefficients for coupled-cavity lasers

    Energy Technology Data Exchange (ETDEWEB)

    Lang, R.J.; Yariv, A.


    The authors derive simple, analytic formulas for the field coupling coefficients in a two-section coupled-cavity laser using a local field rate equation treatment. They show that there is a correction to the heuristic formulas based on power flow calculated by Marcuse; the correction is in agreement with numerical calculations from a coupled-mode approach.

  17. Cardiac carcinoid: tricuspid delayed hyperenhancement on cardiac 64-slice multidetector CT and magnetic resonance imaging.

    LENUS (Irish Health Repository)

    Martos, R


    INTRODUCTION: Carcinoid heart disease is a rare condition in adults. Its diagnosis can be easily missed in a patient presenting to a primary care setting. We revised the advantages of using coronary multidetector computed tomography (MDCT) and cardiac magnetic resonance imaging (MRI) in diagnosing this condition. MATERIALS AND METHODS: We studied a 65-year-old patient with carcinoid heart disease and right heart failure using transthoracic Doppler-echocardiogram, cardiac MDCT and MRI. Cardiac echocardiogram revealed marked thickening and retraction of the tricuspid leaflets with dilated right atrium and ventricle. Cardiac MDCT and MRI demonstrated fixation and retraction of the tricuspid leaflets with delayed contrast hyperenhancement of the tricuspid annulus. CONCLUSION: This case demonstrates fascinating imaging findings of cardiac carcinoid disease and highlights the increasing utility of contrast-enhanced MRI and cardiac MDCT in the diagnosis of this interesting condition.

  18. A severe penetrating cardiac injury in the absence of cardiac tamponade. (United States)

    Connelly, Tara M; Kolcow, Walenty; Veerasingam, Dave; DaCosta, Mark


    Penetrating cardiac injury is rare and frequently not survivable. Significant haemorrhage resulting in cardiac tamponade commonly ensues. Such cardiac tamponade is a clear clinical, radiological and sonographic indicator of significant underlying injury. In the absence of cardiac tamponade, diagnosis can be more challenging. In this case of a 26-year old sailor stabbed at sea, a significant pericardial effusion and cardiac tamponade did not occur despite an injury transversing the pericardium. Instead, the pericardial haemorrhage drained into the left pleural cavity resulting in a haemothorax. This case is notable due to a favourable outcome despite a delay in diagnosis due to a lack of pericardial effusion, a concomitant cerebrovascular event and a long delay from injury to appropriate medical treatment in the presence of a penetrating cardiac wound deep enough to cause a muscular ventricular septal defect and lacerate a primary chordae of the anterior mitral leaflet.

  19. Molecular Aspects of Exercise-induced Cardiac Remodeling. (United States)

    Bernardo, Bianca C; McMullen, Julie R


    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  20. Evaluation of a novel integrated sensor system for synchronous measurement of cardiac vibrations and cardiac potentials. (United States)

    Chuo, Yindar; Tavakolian, Kouhyar; Kaminska, Bozena


    The measurement of human body vibrations as a result of heart beating, simultaneously with cardiac potentials have been demonstrated in past studies to bring additional value to diagnostic cardiology through the detection of irregularities in the mechanical movement of the heart. The equipment currently available to the medical community is either large and bulky or difficult to synchronize. To address this problem, a novel integrated sensor system has been developed to record cardiac vibration and cardiac potential simultaneously and synchronously from a single compact site on the chest. The developed sensor system is lightweight, small in size, and suitable for mounting on active moving patients. The sensor is evaluated for its adequacy in measuring cardiac vibrations and potentials. In this evaluation, 45 independent signal recording are studied from 15 volunteers, and the morphology of the recorded signals are analyzed qualitatively (by visual inspection) and quantitatively (by computational methods) against larger devices used in established cardiac vibration studies (reference devices). It is found that the cardiac vibration signals acquired by the integrated sensor has 92.37% and 81.76% identically identifiable systolic and diastolic cardiac complexes, respectively, when compared to the cardiac vibration signals recorded simultaneously from the reference device. Further, the cardiac potential signals acquired by the integrated sensor show a high correlation coefficient of 0.8912 and a high estimated signal-to-noise-ratio of 22.00 dB when compared to the reference electrocardiograph (non-standard leads) acquired through a common clinical machine. The results suggest that the tiny, wearable, integrated sensor system that synchronously measures cardiac vibrations and cardiac potentials may be practical for use as an alternative or assistive cardiac diagnostic tool.

  1. Newton-Krylov-BDDC solvers for nonlinear cardiac mechanics

    KAUST Repository

    Pavarino, L.F.


    The aim of this work is to design and study a Balancing Domain Decomposition by Constraints (BDDC) solver for the nonlinear elasticity system modeling the mechanical deformation of cardiac tissue. The contraction–relaxation process in the myocardium is induced by the generation and spread of the bioelectrical excitation throughout the tissue and it is mathematically described by the coupling of cardiac electro-mechanical models consisting of systems of partial and ordinary differential equations. In this study, the discretization of the electro-mechanical models is performed by Q1 finite elements in space and semi-implicit finite difference schemes in time, leading to the solution of a large-scale linear system for the bioelectrical potentials and a nonlinear system for the mechanical deformation at each time step of the simulation. The parallel mechanical solver proposed in this paper consists in solving the nonlinear system with a Newton-Krylov-BDDC method, based on the parallel solution of local mechanical problems and a coarse problem for the so-called primal unknowns. Three-dimensional parallel numerical tests on different machines show that the proposed parallel solver is scalable in the number of subdomains, quasi-optimal in the ratio of subdomain to mesh sizes, and robust with respect to tissue anisotropy.

  2. Cardiac mechanical energy and effects on the arterial tree. (United States)

    Muñoz, H R; Sacco, C M


    Blood flow pulsatility is the result of the heart's activity as a pump unable to develop steady flow, and its interaction with the arterial tree. Thus, the heart is a cyclic energy generator whose adequate function requires the two phases of this cycle to be normal. Diastolic properties determine the degree of filling of the ventricles and the strength of the following systole. Systole, in turn, must generate enough energy to overcome forces opposing ejection. These can be divided into internal (the mechanical characteristics of the ventricle itself) and external loads (the characteristics of the arterial tree). As a result, hydraulic energy is imparted to blood (external ventricular work) that manifests itself as blood pressure and flow. Given the cyclic nature of cardiac activity, the external ventricular work has steady and pulsatile components. The steady component is energy lost during steady flow because of vascular resistance, and the pulsatile work is that lost in arterial pulsations and mainly depends on the aortic impedance. Thus, the characteristics of the arterial tree will determine the relative contribution of these two components to blood flow and the efficency of the heart. In addition, the arterial tree modifies the different waves (pressure and flow) traveling in the circulation. These modifications have important consequences for cardiac function. The ventricle and the arterial tree constitute a coupled biological system, and its overall performance is a function of the behavior of each unit at any given moment.

  3. Role of the intercalated disc in cardiac propagation and arrhythmogenesis. (United States)

    Kleber, Andre G; Saffitz, Jeffrey E


    This review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the "intercalated disc."The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called "electrical uncoupling") may either only slow, or additionally stabilize propagation and reverse unidirectional propagation block to bidirectional propagation. This is because the safety factor for propagation increases with decreasing intercellular electrical conductance. The role of heterogeneous connexin expression, which may be present in disease states, is also discussed. The hypothesis that so-called ephaptic impulse transmission plays a role in heart and can substitute for electrical coupling has been revived recently. Whereas ephaptic transmission can be demonstrated in theoretical simulations, direct experimental evidence has not yet been presented. The second part of this review deals with the interaction of three protein complexes at the intercalated disc: (1) desmosomal and adherens junction proteins, (2) ion channel proteins, and (3) gap junction channels consisting of connexins. Recent work has revealed multiple interactions between these three protein complexes which occur, at least in part, at the level of protein trafficking. Such interactions are likely to play an important role in the pathogenesis of arrhythmogenic cardiomyopathy, and may reveal new therapeutic concepts and targets.


    Directory of Open Access Journals (Sweden)

    Andre Georges Kleber


    Full Text Available AbstractThis review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the intercalated disc. The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called electrical uncoupling may either only slow, or additionally stabilize propagation and reverse unidirectional propagation block to bidirectional propagation. This is because the safety factor for propagation increases with decreasing intercellular electrical conductance. The role of heterogeneous connexin expression, which may be present in disease states, is also discussed. The hypothesis that so-called ephaptic impulse transmission plays a role in heart and can substitute for electrical coupling has been revived recently. Whereas ephaptic transmission can be demonstrated in theoretical simulations, direct experimental evidence has not yet been presented.The second part of this review deals with the interaction of three protein complexes at the intercalated disc: (1 desmosomal and adherers junction proteins, (2 ion channel proteins, and (3 gap junction channels consisting of connexins. Recent work has revealed multiple interactions between these three protein complexes which occur, at least in part, at the level of protein trafficking. Such interactions are likely to play an important role in the pathogenesis of arrhythmogenic cardiomyopathy, and may reveal new therapeutic concepts and targets.

  5. Cardiac Origins of the Postural Orthostatic Tachycardia Syndrome (United States)

    Fu, Qi; VanGundy, Tiffany B.; Galbreath, M. Melyn; Shibata, Shigeki; Jain, Manish; Hastings, Jeffrey L.; Bhella, Paul S.; Levine, Benjamin D.


    Objectives To test the hypothesis that a small heart coupled with reduced blood volume contributes to the Postural Tachycardia Syndrome (POTS), while exercise training improves this syndrome. Background Patients with POTS have marked increases in heart rate during orthostasis. However, the underlying mechanisms are unknown and the effective therapy is uncertain. Methods Twenty-seven POTS patients underwent autonomic function tests, cardiac MRI, and blood volume measurements. Twenty-five of them participated in a 3-mo specially designed exercise training program with 19 completing the program; these patients were reevaluated after training. Results were compared with those of 16 healthy controls. Results Upright heart rate and total peripheral resistance were greater, while stroke volume and cardiac output were smaller in patients than controls. Baroreflex function was similar between groups. Left ventricular mass (median [25%, 75%], 1.26 [1.12, 1.37] vs 1.45 [1.34, 1.57] g/kg; PSeuss, the main character had a heart that was “two sizes too small.” PMID:20579544

  6. Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis. (United States)

    Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V


    Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy.

  7. Action potential duration heterogeneity of cardiac tissue can be evaluated from cell properties using Gaussian Green's function approach.

    Directory of Open Access Journals (Sweden)

    Arne Defauw

    Full Text Available Action potential duration (APD heterogeneity of cardiac tissue is one of the most important factors underlying initiation of deadly cardiac arrhythmias. In many cases such heterogeneity can be measured at tissue level only, while it originates from differences between the individual cardiac cells. The extent of heterogeneity at tissue and single cell level can differ substantially and in many cases it is important to know the relation between them. Here we study effects from cell coupling on APD heterogeneity in cardiac tissue in numerical simulations using the ionic TP06 model for human cardiac tissue. We show that the effect of cell coupling on APD heterogeneity can be described mathematically using a Gaussian Green's function approach. This relates the problem of electrotonic interactions to a wide range of classical problems in physics, chemistry and biology, for which robust methods exist. We show that, both for determining effects of tissue heterogeneity from cell heterogeneity (forward problem as well as for determining cell properties from tissue level measurements (inverse problem, this approach is promising. We illustrate the solution of the forward and inverse problem on several examples of 1D and 2D systems.

  8. A smartphone based cardiac coherence biofeedback system. (United States)

    De Jonckheere, J; Ibarissene, I; Flocteil, M; Logier, R


    Cardiac coherence biofeedback training consist on slowing one's breathing to 0.1 Hz in order to simulate the baroreflex sensitivity and increase the respiratory sinus arrhythmia efficiency. Several studies have shown that these breathing exercises can constitute an efficient therapy in many clinical contexts like cardiovascular diseases, asthma, fibromyalgia or post-traumatic stress. Such a non-intrusive therapeutic solution needs to be performed on an 8 to 10 weeks period. Even if some heart rate variability based solutions exist, they presented some mobility constrain rendering these cardiac / respiratory control technologies more difficult to perform on a daily used. In this paper, we present a new simplified smartphone based solution allowing people to process efficient cardiac coherence biofeedback exercises. Based on photo-plethysmographic imaging through the smartphone camera, this sensor-less technology allows controlling cardiac coherence biofeedback exercises through a simplified heart rate variability algorithm.

  9. Depression After a Cardiac Event or Diagnosis (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Depression After A Cardiac Event or Diagnosis Updated:Jun 16,2014 Cardiovascular disease can trigger depression; counseling and medication can help beat it. When ...

  10. The Western Denmark Cardiac Computed Tomography Registry

    DEFF Research Database (Denmark)

    Nielsen, Lene Hüche; Nørgaard, Bjarne Linde; Tilsted, Hans Henrik;


    -CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%-100%), but was >85% for more than 70% of all variables. Using......BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We...... expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables. RESULTS: By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography...

  11. Cardiac Computed Tomography (Multidetector CT, or MDCT) (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Cardiac Computed Tomography (Multidetector CT, or MDCT) Updated:Sep 19, ... The ECG is also needed to help the computer that is connected to the CT scanner create ...

  12. Cardiac Imaging in Heart Failure with Comorbidities. (United States)

    Wong, Chiew; Chen, Sylvia; Iyngkaran, Pupalan


    Imaging modalities stand at the frontiers for progress in congestive heart failure (CHF) screening, risk stratification and monitoring. Advancements in echocardiography (ECHO) and Magnetic Resonance Imaging (MRI) have allowed for improved tissue characterizations, cardiac motion analysis, and cardiac performance analysis under stress. Common cardiac comorbidities such as hypertension, metabolic syndromes and chronic renal failure contribute to cardiac remodeling, sharing similar pathophysiological mechanisms starting with interstitial changes, structural changes and finally clinical CHF. These imaging techniques can potentially detect changes earlier. Such information could have clinical benefits for screening, planning preventive therapies and risk stratifying patients. Imaging reports have often focused on traditional measures without factoring these novel parameters. This review is aimed at providing a synopsis on how we can use this information to assess and monitor improvements for CHF with comorbidities.

  13. Cardiac tissue engineering: state of the art. (United States)

    Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas


    The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

  14. Incidental Cardiac Findings on Thoracic Imaging.

    LENUS (Irish Health Repository)

    Kok, Hong Kuan


    The cardiac structures are well seen on nongated thoracic computed tomography studies in the investigation and follow-up of cardiopulmonary disease. A wide variety of findings can be incidentally picked up on careful evaluation of the pericardium, cardiac chambers, valves, and great vessels. Some of these findings may represent benign variants, whereas others may have more profound clinical importance. Furthermore, the expansion of interventional and surgical practice has led to the development and placement of new cardiac stents, implantable pacemaker devices, and prosthetic valves with which the practicing radiologist should be familiar. We present a collection of common incidental cardiac findings that can be readily identified on thoracic computed tomography studies and briefly discuss their clinical relevance.

  15. Cardiac manifestations of Pallister-Killian syndrome. (United States)

    Tilton, Richard K; Wilkens, Alisha; Krantz, Ian D; Izumi, Kosuke


    Pallister-Killian syndrome (PKS) is a sporadic multisystem genetic diagnosis characterized by facial dysmorphia, variable developmental delay and intellectual impairment, hypotonia, hearing loss, seizures, differences in skin pigmentation, temporal alopecia, diaphragmatic hernia, congenital heart defects, and other systemic abnormalities. Although congenital heart defects have been described in association with PKS, the full spectrum of heart disease is still not entirely known. Here, we describe the pattern of cardiac findings of 81 probands with PKS who have had at least one cardiac evaluation, demonstrating structural heart difference in 37% of our cohort (n = 30). Septal defects such as atrial or ventricular septal defects (n = 12) were the most commonly seen congenital heart differences. Additional findings included the occasional occurrence of bicuspid aortic valve, aortic dilatation, and cardiac hypertrophy/cardiomyopathy. We suggest cardiac evaluation for all individuals with PKS at the time of diagnosis as well as subsequent longitudinal follow-up to monitor for the development of cardiomyopathy and aortic dilatation.

  16. Cardiac sarcoidosis. State of the art

    Directory of Open Access Journals (Sweden)

    Muñoz-Ortiz, Edison


    Full Text Available Sarcoidosis is a rare disease of unknown etiology, described over 80 years ago. It is a multisystemic disorder characterized by the presence of granulomatous lesions without caseation. Cardiac involvement varies according to the region, but it is generally accepted that 5 % of patients with systemic sarcoidosis have cardiac infiltration with clinical evidence; however, autopsy studies indicate that up to 20 % to 30 % of patients with sarcoidosis have myocardial involvement. Several factors -environmental, occupational and infectious- have been proposed as triggers of the process in individuals with genetic predisposition. Cardiac sarcoidosis may have a wide range of presentations and may even be asymptomatic; the most common manifestations are heart failure, abnormal heart rhythm and lethal ventricular arrhythmias. Treatment includes medications for heart failure, steroids and immune-suppressants, management of lethal arrhythmias with ablation and/or implantable cardioverter defibrillator and cardiac transplantation in severe cases.

  17. National Cardiac Device Surveillance Program Database (United States)

    Department of Veterans Affairs — The National Cardiac Device Surveillance Program Database supports the Eastern Pacemaker Surveillance Center (EPSC) staff in its function of monitoring some 11,000...

  18. Nanomaterials for Cardiac Myocyte Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Rodolfo Amezcua


    Full Text Available Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

  19. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I


    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac......, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), psmooth muscle (222±13; 115±2; 48±2 umol•g(-1)•min(-1), p

  20. Methemoglobinaemia in Cardiac Patients on Nitrate Therapy

    Directory of Open Access Journals (Sweden)

    Abdel Aziz A. Ghanem


    Full Text Available Background: Methaemoglobinaemia refers to the oxidation of ferrous iron to ferric iron within the haemoglobin molecule, which occurs following oxidative stresses. The subsequent impairment in oxygen transport may lead to progressive hypoxia that is highly dangerous condition especially in borderline patients like the cardiac patient.Objectives: In the present work, authors explore the extent of methaemoglobinaemia in cardiac patients receiving nitrate therapy.Methodology: The study included 970 cardiac patients presented in cardiology department, Mansoura Specialised Medical Hospital, Egypt, in the period from February to July 2009. Patients were taking oral, sublingual, dermal preparation or a combination of two preparations.Results: cases of the study had methemoglobin level 1.1782 ± 0.3476 g/dL with insignificant difference between males and females. Methemoglobin showed positive correlation with carboxyhemogloin and negative correlation with O2 content and O2 saturation. It was significantly higher in cardiac patient with chest infection, anaemia and diabetic patients but didn't differ in hepatic or non hepatic cardiac patients. 3.2% of cardiac patients who receive more than one nitrate preparation (either oral and dermal or oral and sublingual therapy have methemoglobin level significantly higher than those who receive single preparation. There is significant difference in methemoglobin level in cardiac patients complaining of myocardial infarction “MI”, unstable Angina, atrial fibrillation “AF” and hypertensive heart disease “HTN”.Conclusions: It is concluded that commonly used dosages of nitrates are capable of causing elevations of methemoglobin ranged from 0.9 – 5.3 g/dl. Although the elevation in methaemoglobin (MetHb levels was not of routine clinical significance, there was statistically significant increase in MetHb levels in cardiac patients with another pathologic condition as anaemia, diabetes mellitus or chest

  1. Blunt cardiac rupture in a toddler

    Directory of Open Access Journals (Sweden)

    Peep Talving


    Full Text Available Blunt cardiac rupture is typically a fatal injury with overall mortality exceeding 90%. Most of the patients never reach the hospital alive. In pediatric patients, only 0.03% of cases following blunt trauma admissions have a cardiac injury. This report presents a rare survivor of 16-months old toddler injured in a domestic accident suffering a right atrial rupture repaired through a median sternotomy. To the best of our knowledge this is the youngest case reported in the literature.

  2. The obesity paradox in cardiac arrest patients. (United States)

    Chalkias, Athanasios; Xanthos, Theodoros


    Evidence from clinical cohorts indicates an obesity paradox in overweight and obese patients who seem to have a more favorable short-term and long-term prognosis than leaner patients. Although obese cardiac arrest victims are theoretically more difficult to be resuscitated due to difficulties in providing adequate chest compressions, ventilation, and oxygenation, research so far has shown that there is an obesity paradox in cardiac arrest.

  3. Automated Segmentation of Cardiac Magnetic Resonance Images

    DEFF Research Database (Denmark)

    Stegmann, Mikkel Bille; Nilsson, Jens Chr.; Grønning, Bjørn A.


    is based on determination of the left-ventricular endocardial and epicardial borders. Since manual border detection is laborious, automated segmentation is highly desirable as a fast, objective and reproducible alternative. Automated segmentation will thus enhance comparability between and within cardiac...... studies and increase accuracy by allowing acquisition of thinner MRI-slices. This abstract demonstrates that statistical models of shape and appearance, namely the deformable models: Active Appearance Models, can successfully segment cardiac MRIs....

  4. Anesthetic issues for robotic cardiac surgery


    Wendy K Bernstein; Andrew Walker


    As innovative technology continues to be developed and is implemented into the realm of cardiac surgery, surgical teams, cardiothoracic anesthesiologists, and health centers are constantly looking for methods to improve patient outcomes and satisfaction. One of the more recent developments in cardiac surgical practice is minimally invasive robotic surgery. Its use has been documented in numerous publications, and its use has proliferated significantly over the past 15 years. The anesthesiolog...

  5. Cardiac CT Angiography in Congestive Heart Failure. (United States)

    Levine, Avi; Hecht, Harvey S


    Cardiac CT angiography has become an important tool for the diagnosis and treatment of congestive heart failure. Differentiation of ischemic from nonischemic cardiomyopathy; evaluation of myocardial perfusion; characterization of hypertrophic cardiomyopathy, left ventricular noncompaction, and arrhythmogenic right ventricular dysplasia; and delineation of congenital heart defects and valvular abnormalities are the primary diagnostic applications. Therapeutic use includes visualization of the coronary venous anatomy for optimal implementation of cardiac resynchronization therapy and evaluation of left ventricular assist devices and transplant vasculopathy.

  6. Management of Cardiac Electronic Device Infections

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nielsen, Jens Cosedis


    Cardiac implantable electronic device (CIED) infection is an increasing problem. Reasons for this are uncertain, but likely relate to an increasing proportion of implantable cardioverter defibrillator (ICD) and cardiac resynchronisation therapy (CRT) devices implanted, as well as implantations...... in 'higher risk' candidates, i.e. patients with heart failure, diabetes and renal failure. Challenges within the field of CIED infections are multiple with prevention being the most important challenge. Careful prescription of CIED treatment and careful patient preparation before implantation is important...

  7. Skeletal myoblasts for heart regeneration and repair: state of the art and perspectives on the mechanisms for functional cardiac benefits. (United States)

    Formigli, L; Zecchi-Orlandini, S; Meacci, E; Bani, D


    Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells in basic research and clinical trials of cell based therapy for cardiac repair and regeneration. Although SkMB engraftment into the post-infarcted heart has been consistently found to improve cardiac contractile function, the underlying therapeutic mechanisms remain still a matter of controversy and debate. This is basically because SkMBs do not attain a cardiac-like phenotype once homed into the diseased heart nor they form a contractile tissue functionally coupled with the surrounding viable myocardium. This issue of concern has generated the idea that the cardiotropic action of SkMBs may depend on the release of paracrine factors. However, the paracrine hypothesis still remains ill-defined, particularly concerning the identification of the whole spectrum of cell-derived soluble factors and details on their cardiac effects. In this context, the possibility to genetically engineering SkMBs to potentate their paracrine attitudes appears particularly attractive and is actually raising great expectation. Aim of the present review is not to cover all the aspects of cell-based therapy with SkMBs, as this has been the object of previous exhaustive reviews in this field. Rather, we focused on novel aspects underlying the interactions between SkMBs and the host cardiac tissues which may be relevant for directing the future basic and applied research on SkMB transplantation for post ischemic cardiac dysfunction.

  8. Cardiac electromechanics and the forward/inverse problems of electrocardiology. (United States)

    Buist, M; Smith, N P; Pullan, A J


    The mechanical motion of the heart plays a role in determining the waveforms observed in an ECG. This study is designed to ascertain, from a theoretical perspective, the influence of this motion. This is achieved through an analysis of a detailed forward model including a full bidomain description and a strongly coupled model of cardiac electromechanics. Simulations were run on identical problems with and without the inclusion of mechanical deformation and the results were analyzed with a view towards the inverse problem of electrocardiology. Initial results have shown the QRS complex to be largely invariant under deformation, but significant changes in T wave morphology have been observed. Further analysis has revealed that it is the effect of the cell-level mechanics on repolarization that is primarily responsible for these changes as opposed to the tissue deformation.

  9. Inscribing Optical Excitability to Non-Excitable Cardiac Cells: Viral Delivery of Optogenetic Tools in Primary Cardiac Fibroblasts (United States)

    Yu, Jinzhu; Entcheva, Emilia


    We describe in detail a method to introduce optogenetic actuation tools, a mutant version of channelrhodopsin- 2, ChR2(H134R), and archaerhodopsin (ArchT), into primary cardiac fibroblasts (cFB) in vitro by adenoviral infection to yield quick, robust, and consistent expression. Instructions on adjusting infection parameters such as the multiplicity of infection and virus incubation duration are provided to generalize the method for different lab settings or cell types. Specific conditions are discussed to create hybrid co-cultures of the optogenetically modified cFB and non-transformed cardiomyocytes to obtain light- sensitive excitable cardiac syncytium, including stencil-patterned cell growth. We also describe an all-optical framework for the functional testing of responsiveness of these opsins in cFB. The presented methodology provides cell-specific tools for the mechanistic investigation of the functional bioelectric contribution of different non-excitable cells in the heart and their electrical coupling to cardiomyocytes under different conditions. PMID:26965132

  10. A review: trichloroethylene metabolites: potential cardiac teratogens. (United States)

    Johnson, P D; Dawson, B V; Goldberg, S J


    This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have reported an increased number of congenital cardiac defects when exposed to TCE or DCE during fetal development. Metabolites of TCE and DCE studied in the drinking-water exposure study include trichloroacetic acid TCAA), monochloroacetic acid, trichloroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacetaldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart development. Rats receiving 2730 ppm TCAA in drinking water were the only metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p = 0.0004 Wilcoxon test and p =0.0015 exact permutation test). Maternal and fetal variables showed no statistically significant differences between treated and untreated groups. When treated with TCAA the increased cardiac defects, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific cardiac teratogen. Further studies of drinking-water exposure and potential mechanisms of action on the developing heart are proceeding.

  11. Role of Circulating Fibrocytes in Cardiac Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Rong-Jie Lin; Zi-Zhuo Su; Shu-Min Liang; Yu-Yang Chen; Xiao-Rong Shu; Ru-Qiong Nie; Jing-Feng Wang


    Objective: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis.Data Sources: This review is based on the data from 1994 to present obtained from PubMed.The search terms were "circulating fibrocytes" and "cardiac fibrosis".Study Selection: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected.Results: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics ofhematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+).They can produce extracellular matrix and many cytokines.It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis.Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts.Conclusions: Circulating fibrocytes are effector cells in cardiac fibrosis.

  12. Surface Electrocardiogram Predictors of Sudden Cardiac Arrest (United States)

    Abdelghani, Samy A.; Rosenthal, Todd M.; Morin, Daniel P.


    Background: Heart disease is a major cause of death in industrialized nations, with approximately 50% of these deaths attributable to sudden cardiac arrest. If patients at high risk for sudden cardiac arrest can be identified, their odds of surviving fatal arrhythmias can be significantly improved through prophylactic implantable cardioverter defibrillator placement. This review summarizes the current knowledge pertaining to surface electrocardiogram (ECG) predictors of sudden cardiac arrest. Methods: We conducted a literature review focused on methods of predicting sudden cardiac arrest through noninvasive electrocardiographic testing. Results: Several electrocardiographic-based methods of risk stratification of sudden cardiac arrest have been studied, including QT prolongation, QRS duration, fragmented QRS complexes, early repolarization, Holter monitoring, heart rate variability, heart rate turbulence, signal-averaged ECG, T wave alternans, and T-peak to T-end. These ECG findings have shown variable effectiveness as screening tools. Conclusion: At this time, no individual ECG finding has been found to be able to adequately stratify patients with regard to risk for sudden cardiac arrest. However, one or more of these candidate surface ECG parameters may become useful components of future multifactorial risk stratification calculators. PMID:27660578

  13. Ultrasound assessment of fetal cardiac function (United States)

    Crispi, Fàtima; Valenzuela‐Alcaraz, Brenda; Cruz‐Lemini, Monica


    Abstract Introduction: Fetal heart evaluation with US is feasible and reproducible, although challenging due to the smallness of the heart, the high heart rate and limited access to the fetus. However, some cardiac parameters have already shown a strong correlation with outcomes and may soon be incorporated into clinical practice. Materials and Methods: Cardiac function assessment has proven utility in the differential diagnosis of cardiomyopathies or prediction of perinatal mortality in congenital heart disease. In addition, some cardiac parameters with high sensitivity such as MPI or annular peak velocities have shown promising results in monitoring and predicting outcome in intrauterine growth restriction or congenital diaphragmatic hernia. Conclusion: Cardiac function can be adequately evaluated in most fetuses when appropriate expertise, equipment and time are available. Fetal cardiac function assessment is a promising tool that may soon be incorporated into clinical practice to diagnose, monitor or predict outcome in some fetal conditions. Thus, more research is warranted to further define specific protocols for each fetal condition that may affect cardiac function. PMID:28191192

  14. Epigenetic mechanisms in cardiac development and disease

    Institute of Scientific and Technical Information of China (English)

    Marcus Vallaster; Caroline Dacwag Vallaster; Sean M. Wu


    During mammalian development,cardiac specification and ultimately lineage commitment to a specific cardiac cell type is accomplished by the action of specific transcription factors (TFs) and their meticulous control on an epigenetic level.In this review,we detail how cardiacspecific TFs function in concert with nucleosome remodeling and histone-modifying enzymes to regulate a diverse network of genes required for processes such as cell growth and proliferation,or epithelial to mesenchymal transition (EMT),for instance.We provide examples of how several cardiac TFs,such as Nkx2.5,WHSC1,Tbx5,and Tbx1,which are associated with developmental and congenital heart defects,are required for the recruitment of histone modifiers,such as Jarid2,p300,and Ash21,and components of ATP-dependent remodeling enzymes like Brg1,Baf60c,and Baf180.Binding of these TFs to their respective sites at cardiac genes coincides with a distinct pattern of histone marks,indicating that the precise regulation of cardiac gene networks is orchestrated by interactions between TFs and epigenetic modifiers.Furthermore,we speculate that an epigenetic signature,comprised of TF occupancy,histone modifications,and overall chromatin organization,is an underlying mechanism that governs cardiac morphogenesis and disease.

  15. Stem cell sources for cardiac regeneration. (United States)

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


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

  16. Role of Circulating Fibrocytes in Cardiac Fibrosis (United States)

    Lin, Rong-Jie; Su, Zi-Zhuo; Liang, Shu-Min; Chen, Yu-Yang; Shu, Xiao-Rong; Nie, Ru-Qiong; Wang, Jing-Feng; Xie, Shuang-Lun


    Objective: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis. Data Sources: This review is based on the data from 1994 to present obtained from PubMed. The search terms were “circulating fibrocytes” and “cardiac fibrosis”. Study Selection: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected. Results: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts. Conclusions: Circulating fibrocytes are effector cells in cardiac fibrosis. PMID:26831236

  17. Biomimetic materials design for cardiac tissue regeneration. (United States)

    Dunn, David A; Hodge, Alexander J; Lipke, Elizabeth A


    Cardiovascular disease is the leading cause of death worldwide. In the absence of sufficient numbers of organs for heart transplant, alternate approaches for healing or replacing diseased heart tissue are under investigation. Designing biomimetic materials to support these approaches will be essential to their overall success. Strategies for cardiac tissue engineering include injection of cells, implantation of three-dimensional tissue constructs or patches, injection of acellular materials, and replacement of valves. To replicate physiological function and facilitate engraftment into native tissue, materials used in these approaches should have properties that mimic those of the natural cardiac environment. Multiple aspects of the cardiac microenvironment have been emulated using biomimetic materials including delivery of bioactive factors, presentation of cell-specific adhesion sites, design of surface topography to guide tissue alignment and dictate cell shape, modulation of mechanical stiffness and electrical conductivity, and fabrication of three-dimensional structures to guide tissue formation and function. Biomaterials can be engineered to assist in stem cell expansion and differentiation, to protect cells during injection and facilitate their retention and survival in vivo, and to provide mechanical support and guidance for engineered tissue formation. Numerous studies have investigated the use of biomimetic materials for cardiac regeneration. Biomimetic material design will continue to exploit advances in nanotechnology to better recreate the cellular environment and advance cardiac regeneration. Overall, biomimetic materials are moving the field of cardiac regenerative medicine forward and promise to deliver new therapies in combating heart disease.

  18. Inhomogeneity of action potential waveshape assists frequency entrainment of cardiac pacemaker cells. (United States)

    Cloherty, S L; Lovell, N H; Celler, B G; Dokos, S


    In this paper, we have employed ionic models of sinoatrial node cells to investigate the synchronization of a pair of coupled cardiac pacemaker cells from central and peripheral regions of the sinoatrial node. The free-running cycle length of the cell models was perturbed using two independent techniques and the minimum coupling conductance required to achieve frequency entrainment was used to assess the relative ease with which various cell pairs achieve entrainment. The factors effecting entrainment were further investigated using single-cell models paced with an artificial biphasic coupling current. Our simulation results suggest that dissimilar cell types, those with largely different upstroke velocities entrain more easily, that is, they require less coupling conductance to achieve 1:1 frequency entrainment. We, therefore, propose that regional variation in action-potential waveshape within the sinoatrial node assists frequency synchronization in vivo.

  19. RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Yong-Hui Mu

    Full Text Available In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from the sarcoplasmic reticulum (SR and cardiac contraction. Previous research has documented the molecular coupling of small-conductance Ca2+-activated K+ channels (SK channels to VDCCs in mouse cardiac muscle. Little is known regarding the role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated K+ current (IK,Ca recorded from isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2, or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium ATPase (SERCA (p<0.05, p<0.01, respectively. The activation of RyR2 by caffeine increased the IK,Ca in the cardiac cells (p<0.05, p<0.01, respectively. We further analyzed the effect of RyR2 knockdown on IK,Ca and Ca2+ in isolated adult mouse cardiomyocytes using a whole-cell patch clamp technique and confocal imaging. RyR2 knockdown in mouse atrial cells transduced with lentivirus-mediated small hairpin interference RNA (shRNA exhibited a significant decrease in IK,Ca (p<0.05 and [Ca2+]i fluorescence intensity (p<0.01. An immunoprecipitated complex of SK2 and RyR2 was identified in native cardiac tissue by co-immunoprecipitation assays. Our findings indicate that RyR2-mediated Ca2+ release is responsible for the activation and modulation of SK channels in cardiac myocytes.

  20. Hindlimb unloading results in increased predisposition to cardiac arrhythmias and alters left ventricular connexin 43 expression. (United States)

    Moffitt, Julia A; Henry, Matthew K; Welliver, Kathryn C; Jepson, Amanda J; Garnett, Emily R


    Hindlimb unloading (HU) is a well-established animal model of cardiovascular deconditioning. Previous data indicate that HU results in cardiac sympathovagal imbalance. It is well established that cardiac sympathovagal imbalance increases the risk for developing cardiac arrhythmias. The cardiac gap junction protein connexin 43 (Cx43) is predominately expressed in the left ventricle (LV) and ensures efficient cell-to-cell electrical coupling. In the current study we wanted to test the hypothesis that HU would result in increased predisposition to cardiac arrhythmias and alter the expression and/or phosphorylation of LV-Cx43. Electrocardiographic data using implantable telemetry were obtained over a 10- to 14-day HU or casted control (CC) condition and in response to a sympathetic stressor using isoproterenol administration and brief restraint. The arrhythmic burden was calculated using a modified scoring system to quantify spontaneous and provoked arrhythmias. In addition, Western blot analysis was used to measure LV-Cx43 expression in lysates probed with antibodies directed against the total and an unphosphorylated form of Cx43 in CC and HU rats. HU resulted in a significantly greater total arrhythmic burden during the sympathetic stressor with significantly more ventricular arrhythmias occurring. In addition, there was increased expression of total LV-Cx43 observed with no difference in the expression of unphosphorylated LV-Cx43. Specifically, the increased expression of LV-Cx43 was consistent with the phosphorylated form. These data taken together indicate that cardiovascular deconditioning produced through HU results in increased predisposition to cardiac arrhythmias and increased expression of phosphorylated LV-Cx43.

  1. Molecular dynamics simulations of the cardiac troponin complex performed with FRET distances as restraints.

    Directory of Open Access Journals (Sweden)

    Jayant James Jayasundar

    Full Text Available Cardiac troponin (cTn is the Ca(2+-sensitive molecular switch that controls cardiac muscle activation and relaxation. However, the molecular detail of the switching mechanism and how the Ca(2+ signal received at cardiac troponin C (cTnC is communicated to cardiac troponin I (cTnI are still elusive. To unravel the structural details of troponin switching, we performed ensemble Förster resonance energy transfer (FRET measurements and molecular dynamic (MD simulations of the cardiac troponin core domain complex. The distance distributions of forty five inter-residue pairs were obtained under Ca(2+-free and saturating Ca(2+ conditions from time-resolved FRET measurements. These distances were incorporated as restraints during the MD simulations of the cardiac troponin core domain. Compared to the Ca(2+-saturated structure, the absence of regulatory Ca(2+ perturbed the cTnC N-domain hydrophobic pocket which assumed a closed conformation. This event partially unfolded the cTnI regulatory region/switch. The absence of Ca(2+, induced flexibility to the D/E linker and the cTnI inhibitory region, and rotated the cTnC N-domain with respect to rest of the troponin core domain. In the presence of saturating Ca(2+ the above said phenomenon were absent. We postulate that the secondary structure perturbations experienced by the cTnI regulatory region held within the cTnC N-domain hydrophobic pocket, coupled with the rotation of the cTnC N-domain would control the cTnI mobile domain interaction with actin. Concomitantly the rotation of the cTnC N-domain and perturbation of the D/E linker rigidity would control the cTnI inhibitory region interaction with actin to effect muscle relaxation.

  2. Troponin not just a simple cardiac marker: prognostic significance of cardiac troponin

    Institute of Scientific and Technical Information of China (English)

    Benny Mulyanto Setiadi; LEI Han; CHANG Jing


    Objective The object of this study was to review the role of cardiac troponin as a prognostic factor in acute coronary syndrome patients of varying circumstances.Data sources The data used in this review were obtained mainly from the studies of cardiac troponin reported in pubmed from 1981 to 2006.Study selection Relevant articles on studies of cardiac troponin were selected.Results Elevated cardiac troponin in patients with ST elevation and non ST elevation myocardial infarction was associated with adverse outcomes, including a higher incidence of congestive heart failure, shock, and death. Patients with elevated cardiac troponin value seemed to benefit more from invasive strategies including a percutaneous coronary intervention and bypass surgery, but elevated cardiac troponin was also correlated with adverse outcomes, including a higher degree of failure, shock, and mortality in patients undergoing percutaneous coronary intervention; a higher degree of perioperative myocardial infarction, low cardiac output syndrome, cardiopulmonary resuscitation, and new-onset ventricular arrhythmia in patients undergoing bypass surgery were also observed. Elevated troponin after a percutaneous coronary intervention seemed to be associated with short-term adverse outcomes rather than long-term adverse outcomes, unless the elevation of the troponin post percutaneous coronary intervention was quite high (about 5 times above normal). On the contrary, elevated cardiac troponin after bypass surgery was more confusing to analyze since it happened in almost all patients. Furthermore, differences in cutoff values and time measurements in some studies add more confusion; thus, further research is warranted.Conclusions The prognostic value of cardiac troponin is demonstrated in almost all acute coronary syndrome patients. In addition to its high sensitivity and specificity, the prognostic value of cardiac troponin is another reason to make it the "golden cardiac marker' of this time.

  3. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan


    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  4. Microwave Treatment for Cardiac Arrhythmias (United States)

    Hernandez-Moya, Sonia


    NASA seeks to transfer the NASA developed microwave ablation technology, designed for the treatment of ventricular tachycardia (irregular heart beat), to industry. After a heart attack, many cells surrounding the resulting scar continue to live but are abnormal electrically; they may conduct impulses unusually slowly or fire when they would typically be silent. These diseased areas might disturb smooth signaling by forming a reentrant circuit in the muscle. The objective of microwave ablation is to heat and kill these diseased cells to restore appropriate electrical activity in the heart. This technology is a method and apparatus that provides for propagating microwave energy into heart tissues to produce a desired temperature profile therein at tissue depths sufficient for thermally ablating arrhythmogenic cardiac tissue while preventing excessive heating of surrounding tissues, organs, and blood. A wide bandwidth double-disk antenna is effective for this purpose over a bandwidth of about six gigahertz. A computer simulation provides initial screening capabilities for an antenna such as antenna, frequency, power level, and power application duration. The simulation also allows optimization of techniques for specific patients or conditions. In comparison with other methods that involve direct-current pulses or radio frequencies below 1 GHz, this method may prove more effective in treating ventricular tachycardia. This is because the present method provides for greater control of the location, cross-sectional area, and depth of a lesion via selection of the location and design of the antenna and the choice of microwave power and frequency.

  5. Future of cardiac computed tomography

    Institute of Scientific and Technical Information of China (English)

    Carlo N De Cecco; U Joseph Schoepf


    Coronary computed tomography angiography(CCTA)has become an integral tool in the noninvasive diagnostic workup of patients with suspected coronary artery disease in both elective and emergency settings. Today, it represents a mature technique providing accurate, non-invasive morphological assessment of the coronary arteries and atherosclerotic plaque burden. Iterative reconstruction algorithms, low kV imaging, and single-heart beat acquisitions hold promise to further reduce dose requirements and improve the safety and robustness of the technique in several circumstances including imaging of heavily calcified vessels, patients with morbid obesity or irregular heart rates, and assessment in the emergency setting. However, it has become clear over recent years that cardiac radiologists need to take further steps towards the development and integration of functional imaging with morphological CCTA assessment to truly provide a comprehensive evaluation of the heart. Computed tomography myocardial perfusion imaging, including both dynamic and static dual-energy approaches, has demonstrated the ability to directly assess and quantify myocardial ischemia with simultaneous CCTA acquisition with a reasonable contrast medium volume and radiation dose delivered to the patient. In order to promote CCTA in the clinical and research environments, radiologists should prepare to embrace the change from morphological to functional imaging, furnishing all the necessary resources and information to referring clinicians.

  6. Psychosocial aspects in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Pogosova, N. V.; Saner, H.; Pedersen, S. S.


    A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health- related quality ......, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.......A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health- related quality...... questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention...

  7. Psychosocial aspects in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Pogosova, Nana; Saner, Hugo; Pedersen, Susanne S.


    A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality o......, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.......A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality...... questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention...

  8. Different aspects of the effects of thapsigargin on automatism, contractility and responsiveness to phenylephrine in cardiac preparations from rats and guinea pigs. (United States)

    Kocic, I; Dworakowska, D; Dworakowski, R


    Sarcoplasmic reticulum (SR) Ca(2+)-ATPase play a very important role in excitation-contraction coupling in the heart. The effects of thapsigargin (TG), a selective inhibitor of SR Ca(2+)-ATPase in the heart muscle, on automatism and contractility of the rat and guinea pig heart were examined. Experiments were performed on isolated right auricula and right ventricle papillary muscle. The following parameters were registered: force of contraction (Fc); rate of rise of force (+dF/dt); rate of fall of force (-dF/dt); time to peak contraction (ttp); duration of relaxation phase of contraction at the level of 10% of total amplitude (tt10); and automatism (b.p.m.). Additionally, the influence of thapsigargin on the effects of phenylephrine on the above mentioned parameters were studied. It was found that TG (1 microM) decreased only the automatism in rat heart, but increased automatism and ttp duration and decreased Fc in guinea pig heart. The positive force-frequency relation in the guinea pig heart was attenuated. The effects of phenylephrine in the rat heart were not significantly different before and after pretreatment with TG. Alternatively, pretreatment with TG exerted a profound influence on the effects of phenylephrine in the guinea pig heart. The results indicate that TG has different effects on the guinea pig and rat hearts. The reason for this could be due to species differences, i.e. the weaker crossing of TG through the membrane of rat myocytes or a different mechanism of Ca2+ homeostasis in rat and guinea pig hearts.

  9. Cardiac Complications after Non-cardiac Surgery: Perioperative Risk Prediction and Reduction Strategies

    NARCIS (Netherlands)

    E.J. Bakker (Erik Jan)


    markdownabstract__Abstract__ Introduction | 9 I More than 200 million people worldwide undergo non-cardiac surgery annually. It is estimated that 2-5 percent of these patients suffer a cardiac complication (i.e. myocardial infarction, congestive heart failure, arrhythmia), resulting in death in app

  10. 42 CFR 410.49 - Cardiac rehabilitation program and intensive cardiac rehabilitation program: Conditions of coverage. (United States)


    ... section. Intensive cardiac rehabilitation site means a hospital outpatient setting or physician's office... combined with other types of exercise (that is, strengthening, stretching) as determined to be appropriate... cardiac rehabilitation in one of the following settings: (A) A physician's office. (B) A...

  11. Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death

    NARCIS (Netherlands)

    Straus, SMJM; Sturkenboom, MCJM; Bleumink, GS; van der Lei, J; de Graeff, PA; Kingma, JH; Stricker, BHC


    Aims To assess the association between the use of non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death. Methods and results A population-based case-control study was performed in the Integrated Primary Care Information (IPCI) project, a longitudinal observational database with compl

  12. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)


    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  13. Effects of subdiaphragmatic cardiac compression on cardiac arrest during liver transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Li-xiang; JI Zhi-xin; LIU Ya-hua; ZHOU Man-hong; SHI Hong-zhi; GUO Xiao-dong; SUN Kun; MA Li-zhi; CHEN Xin-guo; SHEN Zhong-yang


    Cardiac arrest during upper abdominal surgery such as liver transplantation is a rare but very severe complication.Traditional external cardiac compression has been the mainstay of basic life support in general circumstances.Subdiaphragmatic cardiac compression (SDCC),with no incision in the diaphragm,may be a more effective measure.This maneuver can provide more effective and timely cardiac compression via the already open abdomen in surgery and not add extra trauma.This method can provide a quicker and more effective means of circulation support for intraoperative cardiac arrest patients without adding new injuries.Five cases are reported and all the patients had return of spontaneous circulation (ROSC).This is the first report of the SDCC method.

  14. A comparison of genetic findings in sudden cardiac death victims and cardiac patients

    DEFF Research Database (Denmark)

    Hertz, Christin L; Ferrero-Miliani, Laura; Frank-Hansen, Rune;


    previously characterized as unexplained. Additionally, a genetic diagnose in a SCD victim with a structural disease may not only add to the differential diagnosis, but also be of importance for pre-symptomatic family screening. In the case of SCD, the optimal establishment of the cause of death...... systematically identified and reviewed. The frequencies of disease-causing mutation were on average between 16 and 48% in the cardiac patient studies, compared with ∼10% in the post-mortem studies. The frequency of pathogenic mutations in heart genes in cardiac patients is up to four-fold higher than that in SCD......Sudden cardiac death (SCD) is responsible for a large proportion of non-traumatic, sudden and unexpected deaths in young individuals. Sudden cardiac death is a known manifestation of several inherited cardiac diseases. In post-mortem examinations, about two-thirds of the SCD cases show structural...

  15. Calcium quarks. (United States)

    Niggli, Ernst; Egger, Marcel


    Elementary subcellular Ca2+ signals arising from the opening of single ion channels may offer the possibility to examine the stochastic behavior and the microscopic chemical reaction rates of these channel proteins in their natural environment. Such an analysis can yield detailed information about the molecular function that cannot be derived from recordings obtained from an ensemble of channels. In this review, we summarize experimental evidence suggesting that Ca2+ sparks, elementary Ca2+ signaling events of cardiac and skeletal muscle excitation contraction coupling, may be comprised of a number of smaller Ca2+ signaling events, the Ca2+ quarks.

  16. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier


    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  17. Hemoglobin Drift after Cardiac Surgery (United States)

    George, Timothy J.; Beaty, Claude A.; Kilic, Arman; Haggerty, Kara A.; Frank, Steven M.; Savage, William J.; Whitman, Glenn J.


    Introduction Recent literature suggests that a restrictive approach to red blood cell transfusions is associated with improved outcomes in cardiac surgery (CS) patients. Even in the absence of bleeding, intravascular fluid shifts cause hemoglobin levels to drift postoperatively, possibly confounding the decision to transfuse. We undertook this study to define the natural progression of hemoglobin levels in postoperative CS patients. Methods We included all CS patients from 10/10-03/11 who did not receive a postoperative transfusion. Primary stratification was by intraoperative transfusion status. Change in hemoglobin was evaluated relative to the initial postoperative hemoglobin. Maximal drift was defined as the maximum minus the minimum hemoglobin for a given hospitalization. Final drift was defined as the difference between initial and discharge hemoglobin. Results Our final cohort included 199 patients, 71(36%) received an intraoperative transfusion while 128(64%) did not. The average initial and final hemoglobin for all patients were 11.0±1.4g/dL and 9.9±1.3g/dL, respectively, an final drift of 1.1±1.4g/dL. The maximal drift was 1.8±1.1g/dL and was similar regardless of intraoperative transfusion status(p=0.9). Although all patients’ hemoglobin initially dropped, 79% of patients reached a nadir and experienced a mean recovery of 0.7±0.7g/dL by discharge. On multivariable analysis, increasing CPB time was significantly associated with total hemoglobin drift(Coefficient/hour: 0.3[0.1–0.5]g/dL, p=0.02). Conclusions In this first report of hemoglobin drift following CS, although all postoperative patients experienced downward hemoglobin drift, 79% of patients exhibited hemoglobin recovery prior to discharge. Physicians should consider the eventual upward hemoglobin drift prior to administering red cell transfusions. PMID:22609121

  18. [Effects of temporary dual-chamber cardiac pacing in refractory cardiac failure]. (United States)

    Scanu, P; Lecluse, E; Michel, L; Bureau, G; Saloux, E; Cleron, S; Valette, B; Grollier, G; Potier, J C; Foucault, J P


    The authors studied 18 patients (15 men, 3 women) with an average age of 67 +/- 8 years with refractory cardiac failure. In order to determine the potential of pacing to raise cardiac output in severe cardiac failure. The average ejection fraction was 26 +/- 6.5%. All patients were in sinus rhythm:resting cardiac output was 3.35 l/min. Two temporary pacing catheters were positioned in the right atrium and at the apex of the right ventricle for dual-chamber mode pacing triggered by the spontaneous P waves. Changes in cardiac output were measured by Doppler echocardiography at different values of atrioventricular delay. Patients were considered to be responders if their cardiac outputs rose by 15%. In 7 patients meeting this criterion, the average increase in cardiac output was 27% (2.99 +/- 0.7 to 3.81 +/- 0.86 l/mn; p < 0.01); all had dilated cardiomyopathies with left bundle branch block and the optimal AV delay was 103 +/- 21 ms (80-140 ms); the duration of diastolic filling increased from 212 +/- 98 to 292 +/- 116 ms (p = 0.02). In the non-responding group (11 patients with an increase of cardiac output of only 3.6 +/- 0.09 to 3.9 +/- 0.92 l/mn; p < 0.01), the underlying disease process was mainly ischaemic. Two predictive factors of efficacy of dual-chamber pacing were identified: a short ventricular filling period (29 +/- 8% of the RR interval in the responders vs 44 +/- 9% in the non-responders; p < 0.01) and the presence of 1st degree atrioventricular block. Dual-chamber pacing could be a valuable method of increasing resting cardiac outputs in a selected group of patients with severe, refractory, cardiac failure.

  19. Recent advances in animal and human pluripotent stem cell modeling of cardiac laminopathy. (United States)

    Lee, Yee-Ki; Jiang, Yu; Ran, Xin-Ru; Lau, Yee-Man; Ng, Kwong-Man; Lai, Wing-Hon Kevin; Siu, Chung-Wah; Tse, Hung-Fat


    Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.

  20. Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity (United States)

    Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.; Stock, Ann M.


    Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin.

  1. Evidence of epigenetic tags in cardiac fibrosis. (United States)

    Grimaldi, Vincenzo; De Pascale, Maria Rosaria; Zullo, Alberto; Soricelli, Andrea; Infante, Teresa; Mancini, Francesco Paolo; Napoli, Claudio


    In cardiac fibrosis, following an injury or a stress, non-functional fibrotic tissue substitutes normal myocardium, thus leading to progressive heart failure. Activated fibroblasts are principal determinants of cardiac fibrosis by producing excessive fibrotic extracellular matrix and causing hypertrophy of cardiomyocytes. Epigenetic changes, such as DNA methylation, histone modifications, and miRNAs have been involved in these mechanisms. Therefore, there is a strong interest in reverting such epigenetic transformations in order to arrest myocardial fibrotic degeneration. Demethylating agents, such as 5-aza-2'-deoxycytidine, 5-azacytidine, some selective histone deacetylase inhibitors, including mocetinostat, trichostatin A, and MPT0E014, have a direct action on important inducers of cardiac fibrosis. Also dietary compounds, such as resveratrol, can suppress the differentiation of fibroblasts to myofibroblasts. Although in vivo and in vitro studies suggest specific epigenetic therapies to treat cardiac fibrosis, the related clinical trials are still lacking. A better understanding of the epigenetic effects of dietary compounds (e.g. curcumin and green tea catechins) on the onset and progression of cardiac fibrosis, will allow the identification of protective dietary patterns and/or the generation of novel potential epidrugs.

  2. Practical textbook of cardiac CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Tae-Hwan (ed.) [ASAN Medical Center, Seoul (Korea, Republic of). Dept. of Radiology


    Guide to the interpretation of cardiac CT and MRI for the purposes of diagnosis, treatment planning, and follow-up. Emphasis on applications in a wide range of real clinical situations. Numerous informative illustrations. Summarizing sections permitting rapid retrieval of information. QR codes allowing access to references, additional figures, and motion pictures from the internet. This up-to-date textbook comprehensively reviews all aspects of cardiac CT and MRI and demonstrates the value of these techniques in clinical practice. A wide range of applications are considered, including imaging of atherosclerotic and non-atherosclerotic coronary artery disease, coronary revascularization, ischemic heart disease, non-ischemic cardiomyopathy, valvular heart disease, cardiac tumors, and pericardial disease. The numerous high-quality images illustrate how to interpret cardiac CT and MRI correctly for the purposes of diagnosis, treatment planning, and follow-up. Helpful summarizing sections in every chapter will facilitate rapid retrieval of information. This book will be of great value to radiologists and cardiologists seeking a reliable guide to the optimal use of cardiac CT and MRI in real clinical situations.

  3. Heart-brain interactions in cardiac arrhythmia. (United States)

    Taggart, P; Critchley, H; Lambiase, P D


    This review examines current knowledge of the effects of higher brain centres and autonomic control loops on the heart with particular relevance to arrhythmogenesis. There is now substantial evidence that higher brain function (cortex), the brain stem and autonomic nerves affect cardiac electrophysiology and arrhythmia, and that these may function as an interactive system. The roles of mental stress and emotion in arrhythmogenesis and sudden cardiac death are no longer confined to the realms of anecdote. Advances in molecular cardiology have identified cardiac cellular ion channel mutations conferring vulnerability to arrhythmic death at the myocardial level. Indeed, specific channelopathies such as long QT syndrome and Brugada syndrome are selectively sensitive to either sympathetic or vagal stimulation. There is increasing evidence that afferent feedback from the heart to the higher centres may affect efferent input to the heart and modulate the cardiac electrophysiology. The new era of functional neuroimaging has identified the central neural circuitry in this brain-heart axis. Since precipitants of sudden fatal arrhythmia are frequently environmental and behavioural, central pathways translating stress into autonomic effects on the heart might be considered as therapeutic targets. These brain-heart interactions help explain the apparent randomness of sudden cardiac events and provide new insights into future novel therapies to prevent sudden death.

  4. Cardiac involvement in canine babesiosis : review article

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti


    Full Text Available Cardiac dysfunction in canine babesiosis has traditionally been regarded as a rare complication, with the majority of lesions reported as incidental findings at post-mortem examination. Recent studies have, however, demonstrated cardiac lesions in canine babesiosis. Cardiac troponins, especially troponin I, are sensitive markers of myocardial injury in canine babesiosis, and the magnitude of elevation of plasma troponin I concentrations appears to be proportional to the severity of the disease. ECG changes in babesiosis are similar to the pattern described for myocarditis and myocardial ischaemia and together with histopathological findings indicate that the heart suffers from the same pathological processes described in other organs in canine babesiosis, namely inflammation and hypoxia. The clinical application of the ECG appears to be limited and thus cardiovascular assessment should be based on functional monitoring rather than an ECG tracing. On cardiac histopathology from dogs that succumbed to babesiosis, haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium were documented, all of which would have resulted in ECG changes and elevations in cardiac troponin. Myocardial damage causes left ventricular failure, which will result in hypotension and an expansion of the plasma volume due to homeostatic mechanisms.

  5. Does organophosphate poisoning cause cardiac injury? (United States)

    Aghabiklooei, Abbas; Mostafazadeh, Babak; Farzaneh, Esmaeil; Morteza, Afsaneh


    Organophosphates are insecticides which are widely used as a suicidal agent in Iran. They are associated with different types of cardiac complications including cardiac arrest and arrhythmia, however their role in cardiac injury is not known yet. The aim of this study was to investigate the presence of myocardial damage in patients with cholinesterase poisoning.It was a prospective study conducted from January 2008 to March 2010. Cohorts of patients with cholinesterase poisoning due to suicidal attempt who have been referred to Loghman hospital were selected. Patients who have taken more than one poison or were used concomitant drugs were excluded. Physical examination was performed on admission to discover warning sign. Peripheral arterial blood gases, creatine kinase, creatine kinase-myocardial band, troponin-T measurements were performed in all cases. There were 24 patients, 7 of them women, with the mean age of 41.2±15.05 who were included in this study. Non-survivors had significantly higher levels of systolic blood pressure, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, bicarbonate Glasgow Coma Scale scoring and longer duration of mechanical ventilation. Our findings showed that cardiac injury is an important cause of death in organophosphate poisoning. It could be hypothesized that cardiac injury is a strong predictor of death in patients with organophosphate poisoning.

  6. Almanac 2013: cardiac arrhythmias and pacing. (United States)

    Liew, Reginald


    Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management. This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.


    Directory of Open Access Journals (Sweden)

    N Safai


    Full Text Available "nAcute renal failure (ARF following cardiac surgery occurs in 1 to 10% of patients. Patients who develop ARF have higher rates of mortality. This study was undertaken to estimate the role of perioperative variables in predicting of post cardiac surgery ARF. We studied a cohort of 398 adult patients who underwent cardiac surgery at our institution from February 2004 to February 2006. Adult patients who were scheduled for cardiac valvular surgery, coronary artery bypass grafting (CABG or both, with or without cardiopulmonary bypass (CPB were included. Exclusion criteria were death within two days of operation (n= 8, incomplete patient data, and preexisting renal dysfunction and dialysis requirement or a baseline serum creatinine > 4 mg/dl. Age, sex, left ventricular ejection fraction, diabetes, preoperative, presence of proteinuria (on dipstick, type of surgery, use of CPB and duration of surgery were recorded. A logistic regression analysis was performed to assess independent contribution of variables in the risk of ARF. A binary logistic regression revealed age was an independent predictor of ARF (P < 0.05. When both all variables were included in a multinominal logistic regression model, preoperative proteinuria independently predicted ARF (Odds ratio= 3.91, 95% CI: 1.55-9.91, P = 0.004. Our results revealed that special considerations should be given to elderly and patients with proteinuria when managing post cardiac surgery ARF.

  8. Biomarkers for cardiac cachexia: reality or utopia. (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita


    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related.

  9. Cardiac fluid dynamics anticipates heart adaptation. (United States)

    Pedrizzetti, Gianni; Martiniello, Alfonso R; Bianchi, Valter; D'Onofrio, Antonio; Caso, Pio; Tonti, Giovanni


    Hemodynamic forces represent an epigenetic factor during heart development and are supposed to influence the pathology of the grown heart. Cardiac blood motion is characterized by a vortical dynamics, and it is common belief that the cardiac vortex has a role in disease progressions or regression. Here we provide a preliminary demonstration about the relevance of maladaptive intra-cardiac vortex dynamics in the geometrical adaptation of the dysfunctional heart. We employed an in vivo model of patients who present a stable normal heart function in virtue of the cardiac resynchronization therapy (CRT, bi-ventricular pace-maker) and who are expected to develop left ventricle remodeling if pace-maker was switched off. Intra-ventricular fluid dynamics is analyzed by echocardiography (Echo-PIV). Under normal conditions, the flow presents a longitudinal alignment of the intraventricular hemodynamic forces. When pacing is temporarily switched off, flow forces develop a misalignment hammering onto lateral walls, despite no other electro-mechanical change is noticed. Hemodynamic forces result to be the first event that evokes a physiological activity anticipating cardiac changes and could help in the prediction of longer term heart adaptations.

  10. Ultrasensitive cardiac troponin I antibody based nanohybrid sensor for rapid detection of human heart attack. (United States)

    Bhatnagar, Deepika; Kaur, Inderpreet; Kumar, Ashok


    An ultrasensitive cardiac troponin I antibody conjugated with graphene quantum dots (GQD) and polyamidoamine (PAMAM) nanohybrid modified gold electrode based sensor was developed for the rapid detection of heart attack (myocardial infarction) in human. Screen printed gold (Au) electrode was decorated with 4-aminothiophenol for amine functionalization of the Au surface. These amino groups were further coupled with carboxyl functionalities of GQD with EDC-NHS reaction. In order to enhance the sensitivity of the sensor, PAMAM dendrimer was successively embedded on GQD through carbodiimide coupling to provide ultra-high surface area for antibody immobilization. The activated cardiac troponin I (cTnI) monoclonal antibody was immobilized on PAMAM to form nanoprobe for sensing specific heart attack marker cTnI. Various concentrations of cardiac marker, cTnI were electrochemically measured using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in human blood serum. The modifications on sensor surface were characterized by FTIR and AFM techniques. The sensor is highly specific to cTnI and showed negligible response to non-specific antigens. The sensitivity of the sensor was 109.23μAcm(-2)μg(-1) and lower limit of detection of cTnI was found 20fgmL(-1).

  11. Position Control of Motion Compensation Cardiac Catheters (United States)

    Kesner, Samuel B.; Howe, Robert D.


    Robotic catheters have the potential to revolutionize cardiac surgery by enabling minimally invasive structural repairs within the beating heart. This paper presents an actuated catheter system that compensates for the fast motion of cardiac tissue using 3D ultrasound image guidance. We describe the design and operation of the mechanical drive system and catheter module and analyze the catheter performance limitations of friction and backlash in detail. To mitigate these limitations, we propose and evaluate mechanical and control system compensation methods, including inverse and model-based backlash compensation, to improve the system performance. Finally, in vivo results are presented that demonstrate that the catheter can track the cardiac tissue motion with less than 1 mm RMS error. The ultimate goal of this research is to create a fast and dexterous robotic catheter system that can perform surgery on the delicate structures inside of the beating heart. PMID:21874124

  12. Fractal fluctuations in cardiac time series (United States)

    West, B. J.; Zhang, R.; Sanders, A. W.; Miniyar, S.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)


    Human heart rate, controlled by complex feedback mechanisms, is a vital index of systematic circulation. However, it has been shown that beat-to-beat values of heart rate fluctuate continually over a wide range of time scales. Herein we use the relative dispersion, the ratio of the standard deviation to the mean, to show, by systematically aggregating the data, that the correlation in the beat-to-beat cardiac time series is a modulated inverse power law. This scaling property indicates the existence of long-time memory in the underlying cardiac control process and supports the conclusion that heart rate variability is a temporal fractal. We argue that the cardiac control system has allometric properties that enable it to respond to a dynamical environment through scaling.

  13. Significance of Cardiac Rehabilitation on Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Krutika Gajjar


    Full Text Available Considering the high mortality and morbidity rate associated with cardiovascular diseases, Cardiacrehabilitation (CR is regarded for prevention and management of cardiovascular diseases. CR servicesare generally provided in an outpatient as comprehensive, long-term programs involving medicalevaluation, prescribed exercise, cardiac risk factor modification, education and counseling. This includesnutritional therapies, weight loss program management of lipid abnormalities with diet and medication,blood pressure control, diabetes management and stress management. The exercise component of a totalapproach to rehabilitation helps to overcome the fears and anxieties that so many people experience aftera heart attack. Aerobic exercise training program improves cardiovascular fitness in both healthyindividual and cardiac patients. Cardiac rehabilitation prevents and treat cardiovascular disease, reducescardiac risk factors, improving patient’s exercise capacity and enhancing quality of life. Aerobicexercise with intensity of approximately 60 to 70% of the maximal heart rate for 30 to 60 minutes, 3 to 4times a week, for 4 to 6 weeks enhances exercise capacity.

  14. Cardiac arrhythmias associated with spinal cord injury

    DEFF Research Database (Denmark)

    Hector, Sven Magnus; Biering-Sørensen, Tor; Krassioukov, Andrei;


    CONTEXT/OBJECTIVES: To review the current literature to reveal the incidence of cardiac arrhythmias and its relation to spinal cord injury (SCI). METHODS: Data source: MEDLINE database, 304 hits, and 32 articles were found to be relevant. The relevant articles all met the inclusion criteria: (1......) contained original data (2) on cardiac arrhythmias (3) in humans with (4) traumatic SCI. RESULTS: In the acute phase of SCI (1-14 days after injury) more cranial as well as more severe injuries seemed to increase the incidence of bradycardia. Articles not covering the first 14 days after injury, thus...... as during procedures such as penile vibro-stimulation and tracheal suction. These episodes of bradycardia were seen more often in individuals with cervical injuries. Longitudinal studies with continuous electrocardiogram recordings are needed to uncover the true relation between cardiac arrhythmias and SCI....

  15. Cardiac nonrigid motion analysis from image sequences

    Institute of Scientific and Technical Information of China (English)

    LIU Huafeng


    Noninvasive estimation of the soft tissue kinematics properties from medical image sequences has many important clinical and physiological implications, such as the diagnosis of heart diseases and the understanding of cardiac mechanics. In this paper, we present a biomechanics based strategy, framed as a priori constraints for the ill-posed motion recovery problema, to realize estimation of the cardiac motion and deformation parameters. By constructing the heart dynamics system equations from biomechanics principles, we use the finite element method to generate smooth estimates.of heart kinematics throughout the cardiac cycle. We present the application of the strategy to the estimation of displacements and strains from in vivo left ventricular magnetic resonance image sequence.

  16. Improving cardiac myocytes performance by CNTs platforms

    Directory of Open Access Journals (Sweden)

    Valentina eMartinelli


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

  17. Extracorporeal life support in pediatric cardiac patients

    Directory of Open Access Journals (Sweden)

    Matteo Di NARDO


    Full Text Available Extracorporeal Life Support (ECLS is a valuable tool in the management of neonates and older children with severe cardiac or respiratory failure. In this review, we focus on ECLS when used for neonatal and pediatric cardiac disease. Strict selection of patients and timely deployment are necessary to optimize outcomes. Although every attempt should be made to deploy ECLS urgently rather than emergently, extracorporeal cardiopulmonary resuscitation (ECPR is being increasingly used and reasonable survival rates have been achieved after initiation of ECLS during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS are falling over time, although lethal chromosomal abnormalities, severe irreversible brain injury, and extremely low gestational age and weight (<32 weeks gestation or <1.5 kg remain firm contraindications.

  18. Electrical stimulation systems for cardiac tissue engineering. (United States)

    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana


    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures.

  19. William Harvey, Peter Lauremberg and cardiac output. (United States)

    Teichmann, G


    In 1636, the Rostock professor of medicine and the art of poetry, Peter Lauremberg (1585-1639), was one of the earliest to mention circulation which had been discovered by William Harvey and documented in his anatomical manual. In 1628 William Harvey proved the existence of the blood circulation by calculating the "cardiac output in a half an hour (semihora)". The answer to the question why Harvey chose half an hour as the time range can be found in the way of measuring time usual at that period. The sandglasses were turned half-hourly in maritime navigation and the wheel-clocks on shore had only the hour-hand. Improved chronometry was one of the prerequisites for measuring cardiac output. The minute-hand became usual after 1700 and the second-hand later on. Taking into consideration the alterations of cardiac output made the latter one of the most important circulation parameters in diagnostics, prognostication and therapeutics.

  20. The value of cardiac genetic testing. (United States)

    Ingles, Jodie; Semsarian, Christopher


    Genetic testing is an important and necessary aspect of the management of families with cardiac genetic conditions. Commercial genetic tests are available for most cardiac genetic diseases, and increasing uptake amongst patients has contributed to a vastly improved knowledge of the genetic basis of these diseases. The incredible advances in genetic technologies have translated to faster, more comprehensive, and inexpensive commercial genetic tests and has completely changed the landscape of commercial genetic testing in recent years. While there are enormous challenges, mostly relating to interpretation of variants, the value of a genetic diagnosis should not be underestimated. In almost all cases, the single greatest utility is for the predictive genetic testing of family members. This review will describe the value of cardiac genetic testing in the current climate of rapid genetic advancements.

  1. Clinical skills: cardiac rhythm recognition and monitoring. (United States)

    Sharman, Joanna

    With technological advances, changes in provision of healthcare services and increasing pressure on critical care services, ward patients' severity of illness is ever increasing. As such, nurses need to develop their skills and knowledge to care for their client group. Competency in cardiac rhythm monitoring is beneficial to identify changes in cardiac status, assess response to treatment, diagnosis and post-surgical monitoring. This paper describes the basic anatomy and physiology of the heart and its conduction system, and explains a simple and easy to remember process of analysing cardiac rhythms (Resuscitation Council UK, 2000) that can be used in first-line assessment to assist healthcare practitioners in providing care to their patients.

  2. Risk factors of cardiac allograft vasculopathy. (United States)

    Szyguła-Jurkiewicz, Bożena; Szczurek, Wioletta; Gąsior, Mariusz; Zembala, Marian


    Despite advances in prevention and treatment of heart transplant rejection, development of cardiac allograft vasculopathy (CAV) remains the leading factor limiting long-term survival of the graft. Cardiac allograft vasculopathy etiopathogenesis is not fully understood, but a significant role is attributed to endothelial cell damage, caused by immunological and non-immunological mechanisms. Immunological factors include the differences between the recipient's and the donor's HLA systems, the presence of alloreactive antibodies and episodes of acute rejection. Among the non-immunological factors the most important are the age of the donor, ischemia-reperfusion injury and cytomegalovirus infection. The classical cardiovascular risk factors (diabetes, hypertension, obesity and hyperlipidemia) are also important. This study presents an up-to-date overview of current knowledge on the vasculopathy etiopathogenesis and the role played by endothelium and inflammatory processes in CAV, and it also investigates the factors which may serve as risk markers of cardiac allograft vasculopathy.

  3. Renal-sparing strategies in cardiac transplantation

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Ross, Heather J


    PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...... of sirolimus or everolimus. However, studies that use very early CNI discontinuation have found an increased risk of allograft rejection, and this strategy requires further study before it can be routinely recommended. CNI discontinuation late after cardiac transplantation seems more effective than CNI...


    Directory of Open Access Journals (Sweden)

    Nutan Nalini


    Full Text Available BACKGROUND This article is about the stillbirth in which we found significant numbers of cardiac as well as extracardiac defects, in combination or separately. In this article, we would like to emphasize the anomalies found in consanguineous marriages. AIM To correlate the prevalence of cardiac as well as extracardiac anomalies in consanguineous marriages. Especially, here we would like to focus on the cardiac lesions. MATERIAL AND METHOD The study was carried out in 44 still birth foetuses with detailed account of parentage. Significant number of cases with cardiac and extracardiac anomalies was found. RESULTS Out of total 44 stillbirth foetuses, 13 stillbirths were from consanguineous marriages in which 09 had cardiac anomalies. Interrupted aortic arch-02, Abnormal origin of right Subclavian artery- 01, Tetralogy of Fallot- 01, VSD- 04, ASD-01. The extra cardiac findings included Gastroschisis-01, Anencephaly with spina bifida-01, cleft lip/palate-01, polydactyly and syndactyly of ring and little finger-01, limb deformity-01, hydrocephalus-01, craniothoracopagus-01. CONCLUSION Considering the high incidence of cardiac and extracardiac anomalies in consanguineous parentage we must try to create an awareness to avoid the practice of consanguineous marriages in society.

  5. The cardiac patient during Ramadan and Hajj. (United States)

    Chamsi-Pasha, Hassan; Ahmed, Waqar H; Al-Shaibi, Khaled F


    The holy month of Ramadan is one of the five pillars of Islam. During this month, fasting Muslims refrain from eating, drinking, smoking, and sex from dawn until sunset. Although the Quran exempts sick people from the duty of fasting, it is not uncommon for many heart disease patients to fast during Ramadan. Despite the fact that more than a billion Muslims worldwide fast during Ramadan, there is no clear consensus on its effects on cardiac disease. Some studies have shown that the effects of fasting on stable patients with cardiac disease are minimal and the majority of patients with stable cardiac illness can endure Ramadan fasting with no clinical deterioration. Fasting during Ramadan does not seem to increase hospitalizations for congestive heart failure. However, patients with decompensated heart failure or those requiring large doses of diuretics are strongly advised not to fast, particularly when Ramadan falls in summer. Patients with controlled hypertension can safely fast. However, patients with resistant hypertension should be advised not to fast until their blood pressure is reasonably controlled. Patients with recent myocardial infarction, unstable angina, recent cardiac intervention or cardiac surgery should avoid fasting. Physician advice should be individualized and patients are encouraged to seek medical advice before fasting in order to adjust their medications, if required. The performance of the Hajj pilgrimage is another pillar of Islam and is obligatory once in the lifetime for all adult Muslims who are in good health and can afford to undertake the journey. Hajj is a physically, mentally, emotionally, and spiritually demanding experience. Medical checkups one or two months before leaving for Hajj is warranted, especially for those with chronic illnesses such as cardiovascular disease. Patients with heart failure, uncontrolled hypertension, serious arrhythmias, unstable angina, recent myocardial infarction, or cardiac surgery should be

  6. Stroke of a cardiac myxoma origin

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan


    Full Text Available AbstractObjective:The clinical features of cardiac myxoma stroke have not been sufficiently described. Debates remain concerning the options and timing of treatment and the clinical outcomes are unknown. This article aims to highlight the pertinent aspects of this rare condition.Methods:Data source of the present study came from a comprehensive literature collection of cardiac myxoma stroke in PubMed, Google search engine and Highwire Press for the year range 2000-2014.Results:Young adults, female predominance, single cerebral vessel (mostly the middle cerebral artery, multiple territory involvements and solitary left atrial myxoma constituted the outstanding characteristics of this patient setting. The most common affected cerebral vessel (the middle cerebral artery and areas (the basal ganglion, cerebellum and parietal and temporal regions corresponded well to the common manifestations of this patient setting, such as conscious alteration, ataxia, hemiparesis and hemiplegia, aphasia and dysarthria. Initial computed tomography scan carried a higher false negative rate for the diagnosis of cerebral infarction than magnetic resonance imaging did. A delayed surgical resection of cardiac myxoma was associated with an increased risk of potential consequences in particular otherwise arterial embolism. The mortality rate of this patient population was 15.3%.Conclusion:Cardiac myxoma stroke is rare. Often does it affect young females. For an improved diagnostic accuracy, magnetic resonance imaging of the brain and echocardiography are imperative for young stroke patients in identifying the cerebral infarct and determining the stroke of a cardiac origin. Immediate thrombolytic therapy may completely resolve the cerebral stroke and improve the neurologic function of the patients. An early surgical resection of cardiac myxoma is recommended in patients with not large territory cerebral infarct.

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

    Directory of Open Access Journals (Sweden)

    A. Medeiros


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

  8. An integrated bioimpedance—ECG gating technique for respiratory and cardiac motion compensation in cardiac PET (United States)

    Koivumäki, Tuomas; Nekolla, Stephan G.; Fürst, Sebastian; Loher, Simone; Vauhkonen, Marko; Schwaiger, Markus; Hakulinen, Mikko A.


    Respiratory motion may degrade image quality in cardiac PET imaging. Since cardiac PET studies often involve cardiac gating by ECG, a separate respiratory monitoring system is required increasing the logistic complexity of the examination, in case respiratory gating is also needed. Thus, we investigated the simultaneous acquisition of both respiratory and cardiac gating signals using II limb lead mimicking electrode configuration during cardiac PET scans of 11 patients. In addition to conventional static and ECG-gated images, bioimpedance technique was utilized to generate respiratory- and dual-gated images. The ability of the bioimpedance technique to monitor intrathoracic respiratory motion was assessed estimating cardiac displacement between end-inspiration and -expiration. The relevance of dual gating was evaluated in left ventricular volume and myocardial wall thickness measurements. An average 7.6  ±  3.3 mm respiratory motion was observed in the study population. Dual gating showed a small but significant increase (4 ml, p = 0.042) in left ventricular myocardial volume compared to plain cardiac gating. In addition, a thinner myocardial wall was observed in dual-gated images (9.3  ±  1.3 mm) compared to cardiac-gated images (11.3  ±  1.3 mm, p = 0.003). This study shows the feasibility of bioimpedance measurements for dual gating in a clinical setting. The method enables simultaneous acquisition of respiratory and cardiac gating signals using a single device with standard ECG electrodes.

  9. Acute tryptophan depletion attenuates brain-heart coupling following external feedback

    Directory of Open Access Journals (Sweden)

    Erik M Mueller


    Full Text Available External and internal performance feedback triggers neural and visceral modulations such as reactions in the medial prefrontal cortex and insulae or changes of heart period (HP. The functional coupling of neural and cardiac responses following feedback (cortico-cardiac connectivity is not well understood. While linear time-lagged within-subjects correlations of single-trial EEG and HP (cardio-electroencephalographic covariance-tracing, CECT indicate a robust negative coupling of EEG magnitude 300 ms after presentation of an external feedback stimulus with subsequent alterations of heart period (the so-called N300H phenomenon, the neurotransmitter systems underlying feedback-evoked cortico-cardiac connectivity are largely unknown. Because it has been shown that acute tryptophan depletion (ATD, attenuating brain serotonin (5-HT, decreases cardiac but not neural correlates of feedback processing, we hypothesized that 5-HT may be involved in feedback-evoked cortico-cardiac connectivity. In a placebo-controlled double-blind crossover design, twelve healthy participants received a tryptophan-free amino-acid drink at one session and a balanced amino-acid control-drink on another and twice performed a time-estimation task with feedback presented after each trial. N300H magnitude and plasma tryptophan levels were assessed. Results indicated a robust N300H after the control drink, which was significantly attenuated following ATD. Moreover, plasma tryptophan levels during the control session were correlated with N300H amplitude such that individuals with lower tryptophan levels showed reduced N300H. Together, these findings indicate that 5-HT is important for feedback-induced covariation of cortical and cardiac activity. Because individual differences in anxiety have previously been linked to 5-HT, cortico-cardiac coupling and feedback processing, the present findings may be particularly relevant for futures studies linking 5-HT to anxiety.

  10. Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart. (United States)

    Meyers, Tatyana A; Townsend, DeWayne


    Duchenne muscular dystrophy (DMD) is a progressive disease of striated muscle deterioration. Respiratory and cardiac muscle dysfunction are particularly clinically relevant because they result in the leading causes of death in DMD patients. Despite the clinical and physiological significance of these systems, little has been done to understand the cardiorespiratory interaction in DMD. We show here that prior to the onset of global cardiac dysfunction, dystrophin-deficient mdx mice have increased cardiac fibrosis with the right ventricle being particularly affected. Using a novel biventricular cardiac catheterization technique coupled with cardiac stress testing, we demonstrate that both the right and left ventricles have significant reductions in both systolic and diastolic function in response to dobutamine. Unstimulated cardiac function is relatively normal except for a significant reduction in the ventricular pressure transient duration compared with controls. These biventricular analyses also reveal the absence of a dobutamine-induced increase in isovolumic relaxation in the right ventricle of control hearts. Simultaneous assessment of biventricular pressure demonstrates a dobutamine-dependent enhancement of coupling between the ventricles in control mice, which is absent in mdx mice. Furthermore, studies probing the passive-extension properties of the left ventricle demonstrate that the mdx heart is significantly more compliant compared with age-matched C57BL/10 hearts, which have an age-dependent stiffening that is completely absent from dystrophic hearts. These new results indicate that right ventricular fibrosis is an early indicator of the development of dystrophic cardiomyopathy, suggesting a mechanism by which respiratory insufficiency may accelerate the development of heart failure in DMD.

  11. Is there a future for neuroprotective agents in cardiac surgery?

    NARCIS (Netherlands)

    van den Bergh, Walter M


    This article gives an overview of neuroprotective drugs that were recently tested in clinical trials in cardiac surgery. Also, recommendations are given for successful translational research and considerations for management during cardiac surgery.

  12. Preoperative physical therapy for elective cardiac surgery patients

    NARCIS (Netherlands)

    Hulzebos, E.H.J.; Smit, Y.; Helders, P.P.J.M.; Meeteren, N.L.U. van


    BACKGROUND: After cardiac surgery, physical therapy is a routine procedure delivered with the aim of preventing postoperative pulmonary complications. OBJECTIVES: To determine if preoperative physical therapy with an exercise component can prevent postoperative pulmonary complications in cardiac sur

  13. Controlled exposures to air pollutants and risk of cardiac arrhythmia

    NARCIS (Netherlands)

    Langrish, Jeremy P; Watts, Simon J; Hunter, Amanda J; Shah, Anoop S V; Bosson, Jenny A; Unosson, Jon; Barath, Stefan; Lundbäck, Magnus; Cassee, Flemming R; Donaldson, Ken; Sandström, Thomas; Blomberg, Anders; Newby, David E; Mills, Nicholas L


    BACKGROUND: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias,

  14. Chest pain of cardiac and noncardiac origin. (United States)

    Lenfant, Claude


    Chest pain is one of the most common symptoms driving patients to a physician's office or the hospital's emergency department. In approximately half of the cases, chest pain is of cardiac origin, either ischemic cardiac or nonischemic cardiac disease. The other half is due to noncardiac causes, primarily esophageal disorder. Pain from either origin may occur in the same patient. In addition, psychological and psychiatric factors play a significant role in the perception and severity of the chest pain, irrespective of its cause. Chest pain of ischemic cardiac disease is called angina pectoris. Stable angina may be the prelude of ischemic cardiac disease; and for this reason, it is essential to ensure a correct diagnosis. In most cases, further testing, such as exercise testing and angiography, should be considered. The more severe form of chest pain, unstable angina, also requires a firm diagnosis because it indicates severe coronary disease and is the earliest manifestation of acute myocardial infarction. Once a diagnosis of stable or unstable angina is established, and if a decision is made not to use invasive therapy, such as coronary bypass, percutaneous transluminal coronary angioplasty, or stent insertion, effective medical treatment of associated cardiac risk factors is a must. Acute myocardial infarction occurring after a diagnosis of angina greatly increases the risk of subsequent death. Chest pain in women warrants added attention because women underestimate their likelihood to have coronary heart disease. A factor that complicates the clinical assessment of patients with chest pain (both cardiac and noncardiac in origin) is the relatively common presence of psychological and psychiatric conditions such as depression or panic disorder. These factors have been found to cause or worsen chest pain; but unfortunately, they may not be easily detected. Noncardiac chest pain represents the remaining half of all cases of chest pain. Although there are a number of

  15. Dynamic NMR cardiac imaging in a piglet

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, M.; Rzedzian, R.; Mansfield, P. (Nottingham Univ. (UK). Dept. of Physics); Coupland, R.E. (Nottingham Univ. (UK). Queen' s Medical Centre)


    NMR echo-planar imaging (EPI) has been used in a real-time mode to visualise the thorax of a live piglet. Moving pictures are available on an immediate image display system which demonstrates dynamic cardiac function. Frame rates vary from one per cardiac cycle in a prospective stroboscopic mode with immediate visual output to a maximum of 10 frames per second yielding up to six looks in one piglet heart cycle, but using a visual playback mode. A completely new system has been used to obtain these images, features of which include a probe assembly with 22 cm access and an AP400 array processor for real-time data processing.

  16. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D


    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  17. Common cardiac arrhythmias: recognition and treatment. (United States)

    Talmers, F N; Kinhal, V; Sabharwal, S; Weissler, A M


    Cardiac arrhythmias are commonly seen in the everyday practice of medicine by the physician. Although certain arrhythmias may be suspected clinically, precise diagnosis is made by electrocardiographic recording of the abnormal rhythm. Once the arrhythmia has been recorded, the next steps are proper electrocardiographic diagnosis and selection of proper treatment. The specific mode of therapy and the speed with which it is delivered will depend not only on the type of arrhythmia, but also on the hemodynamic consequences of the rhythm abnormality on the patient's cardiovascular system. The purpose of this paper is to discuss the electrocardiographic criteria of common cardiac arrhythmias as well as current concepts regarding therapy.

  18. Supravalvular aortic stenosis with sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Pradeep Vaideeswar


    Full Text Available Sudden cardiac death (SCD most commonly results from previously undiagnosed congenital, acquired, or hereditary cardiac diseases. Congenital aortic valvular, subvalvular, and supravalvular disease with left ventricular outflow tract obstruction is an important preventable cause of sudden death. This report documents sudden death presumably due to acute myocardial ischemia in a young male with an undiagnosed supravalvular aortic stenosis (SVAS due to a rare association of isolation of coronary sinuses of Valsalva. Congenital supravalvular pulmonary stenosis and mitral valvular dysplasia were also present.

  19. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I


    with non-invasive measurements done both pre- and post-operatively and published in English. All types of non-cardiac surgery and both men and women of all ages were included. RESULTS: We found 1722 eligible studies in our search, and of these, five studies fulfilled our inclusion and exclusion criteria....... Endothelial function was disturbed in patients after non-cardiac surgery. Three studies found a significant decrease in the endothelial function immediately after surgery (2 and 24 h post-operatively). Two studies found that patients with previous endothelial dysfunction and scheduled for surgery (renal...... of post-operative myocardial damage....

  20. Postmortem cardiac imaging in fetuses and children

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Andrew M. [Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiorespiratory Division, Level 7, Old Nurses Home, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); Sebire, Neil J. [UCL Institute of Cardiovascular Science, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom)


    Fetal and pediatric cardiac autopsies have a crucial role in the counseling of parents with regard to both the cause of death of their child and the implications of such findings for future pregnancies, as well as for quality assurance of antenatal screening programs and antemortem diagnostic procedures. Postmortem imaging allows an opportunity to investigate the heart in situ prior to dissection, and both postmortem CT and postmortem MRI have shown excellent accuracy in detecting the majority of clinically significant cardiac lesions in the perinatal and pediatric population. As less-invasive autopsy becomes increasingly popular, clinical guidelines for maximal diagnostic yield in specific circumstances can be developed. (orig.)

  1. [Experimental simulation of blunt cardiac trauma]. (United States)

    Tumanov, E V


    This paper was designed to analyse the main experimental models of blunt cardiac trauma proposed during a period of more than 100 years beginning from the study of the Italian scientist Felice Meola dated to the 1870s till the present time. The analysis demonstrated that even a mild injury to the anterior chest wall in the projection of the heart may cause serious changes in hemodynamics and ECG characteristics. It was shown that various methods employed to simulate blunt cardiac trauma place potential constraints related to the design of experiments.

  2. Cardiac MRI and CT features of inheritable and congenital conditions associated with sudden cardiac death

    Energy Technology Data Exchange (ETDEWEB)

    Sparrow, Patrick; Merchant, Naeem; Provost, Yves; Doyle, Deirdre; Nguyen, Elsie; Paul, Narinder [University Health Network and Mount Sinai Hospital, Division of Cardiothoracic Imaging, Department of Medical Imaging, Toronto, Ontario (Canada)


    Cardiac MRI (CMR) and electrocardiogram (ECG)-gated multi-detector computed tomography (MDCT) are increasingly important tools in the identification and assessment of cardiac-related disease processes, including those associated with sudden cardiac death (SCD). While the commonest cause of SCD is coronary artery disease (CAD), in patients under 35 years inheritable cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are important aetiologies. CMR in particular offers both accurate delineation of the morphological abnormalities associated with these and other conditions and the possibility for risk stratification for development of ventricular arrhythmias with demonstration of macroscopic scar by delayed enhancement imaging with intravenous gadolinium. (orig.)

  3. Cardiac contraction and calcium transport function aftersevere burn injury in rats

    Institute of Scientific and Technical Information of China (English)


    Objective: To examine the function change of myocardial calcium transports and determined what role the change plays in cardiac dysfunction after severe burn injury in rats. Methods: The contraction and relaxation properties of the left ventricle (LV) were studied in the isolated hearts preparations of Wistar rats at 3, 8, and 24 h after a 30%TBSA (total body surface area) full-thickness burn. The calcium transport function of the sarcoplasmic reticulum (SR) was measured by the millipore filtration technique. Results: The maximal rate of LV pressure (± dp/dtmax) of the burn group was significantly lower than that of the control group (P < 0.01). In addition, the calciumdependent ATPase activity and the coupling ratio of SR were also markedly depressed. Conclusions: It indicates that the decrease in the SR calcium transport function is one of the important mechanisms for the cardiac contractile dysfunction after severe burn injury.


    Directory of Open Access Journals (Sweden)

    Pasam Naga Abhinay


    Full Text Available The cardiac pacemaker controls the rhythmicity of heart contractions and these can be substituted by battery-operated devices as last resource. Optogenetics involves insertion of light-sensitive proteins into human embryonic stem cell to encode DNA making mammalian tissues light-sensitive. The first discovered protein of this type is Channelrhodopsin2 (ChR2, which is widely used in neuroscience. The limitation of electrical stimulation of heart, a standard technique can be overcome by using ChR2.The various methods involved in optogenetics and energy needs were discussed in this section. Initially, optogenetics is confined only to neuronal system, later on extended to heart and other organs. This method involves precise localized stimulation and constant prolonged depolarization of cardiomyocytes and cardiac tissue resulting in alterations of pacemaking, Ca2+ homeostasis, electrical coupling and arrhythmogenic spontaneous extra beats.

  5. Age-associated alternations in cardiac β-adrenergic receptor signaling

    Institute of Scientific and Technical Information of China (English)

    Jing MA; Shiwen WANG; Ruiping XIAO


    During aging, cardiac contractile response to β-AR stimulation is decreased in humans and animal models. Recent studies demonstrate that the positive inotropic effects of both β1-AR and β2-AR stimulation are significantly decreased with aging.This is accompanied by decreases in both β-AR subtype densities and a reduction in membrane adenylyl cyclase activity. However,neither G protein-coupled receptor kinases (GRKs) nor inhibitory G proteins (Gi) appears to contribute to the age-associated reduction in the β-AR modulation of contraction. Thus, while both aging and chronic heart failure exhibit a diminution in cardiac β-AR responsiveness, only heart failure exhibits increased GRK-mediated desensitization ofβ-Ars and an upregulation of Gi proteins.

  6. Unidirectional Pinning and Hysteresis of Spatially Discordant Alternans in Cardiac Tissue

    CERN Document Server

    Skardal, Per Sebastian; Restrepo, Juan G


    Spatially discordant alternans is a widely observed pattern of voltage and calcium signals in cardiac tissue that can precipitate lethal cardiac arrhythmia. Using spatially coupled iterative maps of the beat-to-beat dynamics, we explore this pattern's dynamics in the regime of a calcium-dominated period-doubling instability at the single cell level. We find a novel nonlinear bifurcation associated with the formation of a discontinuous jump in the amplitude of calcium alternans at nodal lines separating discordant regions. We show that this jump unidirectionally pins nodal lines by preventing their motion away from the pacing site following a pacing rate decrease, but permitting motion towards this site following a rate increase. This unidirectional pinning leads to strongly history-dependent nodal line motion that is strongly arrhythmogenic.

  7. Hurricane Katrina: Impact on Cardiac Surgery Case Volume and Outcomes


    Bakaeen, Faisal G.; Huh, Joseph; Chu, Danny; Coselli, Joseph S.; LeMaire, Scott A.; Mattox, Kenneth L.; Wall, Matthew J.; Wang, Xing Li; Shenaq, Salwa A.; Atluri, Prasad V.; Awad, Samir S.; Berger, David H.


    Hurricane Katrina produced a surge of patient referrals to our facility for cardiac surgery. We sought to determine the impact of this abrupt volume change on operative outcomes. Using our cardiac surgery database, which is part of the Department of Veterans Affairs' Continuous Improvement in Cardiac Surgery Program, we compared procedural outcomes for all cardiac operations that were performed in the year before the hurricane (Year A, 29 August 2004–28 August 2005) and the year after (Year B...

  8. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues. (United States)

    Marsano, Anna; Conficconi, Chiara; Lemme, Marta; Occhetta, Paola; Gaudiello, Emanuele; Votta, Emiliano; Cerino, Giulia; Redaelli, Alberto; Rasponi, Marco


    In the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions. For this purpose, we developed a heart-on-a-chip platform, which recapitulates the physiologic mechanical environment experienced by cells in the native myocardium. The device includes an array of hanging posts to confine cell-laden gels, and a pneumatic actuation system to induce homogeneous uniaxial cyclic strains to the 3D cell constructs during culture. The device was used to generate mature and highly functional micro-engineered cardiac tissues (μECTs), from both neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), strongly suggesting the robustness of our engineered cardiac micro-niche. Our results demonstrated that the cyclic strain was effectively highly uniaxial and uniformly transferred to cells in culture. As compared to control, stimulated μECTs showed superior cardiac differentiation, as well as electrical and mechanical coupling, owing to a remarkable increase in junction complexes. Mechanical stimulation also promoted early spontaneous synchronous beating and better contractile capability in response to electric pacing. Pacing analyses of hiPSC-CM constructs upon controlled administration of isoprenaline showed further promising applications of our platform in drug discovery, delivery and toxicology fields. The proposed heart-on-a-chip device represents a relevant step forward in the field, providing a standard functional three-dimensional cardiac model to possibly predict signs of hypertrophic changes in cardiac phenotype by mechanical and biochemical co-stimulation.

  9. Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis. (United States)

    Schneider, Johanna; Lother, Achim; Hein, Lutz; Gilsbach, Ralf


    Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine storage. In the medulla, TAC caused an increase in chromaffin cell size but did not result in chromaffin cell proliferation. Ablation of chromaffin α(2C)-adrenoceptors did not affect adrenal weight or epinephrine synthesis. However, unilateral denervation of the adrenal gland completely prevented adrenal hypertrophy and increased catecholamine synthesis. Transcriptome analysis of microdissected adrenal medulla identified 483 up- and 231 downregulated, well-annotated genes after TAC. Among these genes, G protein-coupled receptor kinases 2 (Grk2) and 6 and phenylethanolamine N-methyltransferase (Pnmt) were significantly upregulated by TAC. In vitro, acetylcholine-induced Pnmt and Grk2 expression as well as enhanced epinephrine content was prevented by inhibition of nicotinic acetylcholine receptors and Ca(2+)/calmodulin-dependent signaling. Thus, activation of preganglionic sympathetic nerves innervating the adrenal medulla plays an essential role in inducing adrenal hypertrophy, enhanced catecholamine synthesis and induction of Grk2 expression after cardiac pressure overload.

  10. Evaluation of /sup 99m/Tc-albumin distribution ratio in cardiac chambers and lungs

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tadashige; Kanai, Hisakata; Tanaka, Masao and others


    In order to assess blood volume of the cardiac chambers and lungs, distribution ratio of /sup 99m/Tc-albumin (HSA) was obtained from radionuclide angiocardiogram and non-gated or gated equilibrium cardiac pool scintigram, using a scintillation camera coupled to a minicomputer. The radioactivity of /sup 99m/Tc of the entire cardiac blood pool including the large vessels (T), the right ventricle including the right atrium (RV) and the left ventricle (LV) was calculated from the 30deg anterior oblique cardiac pool scintigram. That of the both lungs (Lu) was calculated from the anterior cardiac pool scintigram. The radioactivity of total injected dose of HSA (H) was estimated from the initial transit of the tracer obtained by the radionuclide angiocardiogram. Then, distribution ratio of HSA of the each region of interest was expressed as RV/H, LV/H, T/H and Lu/H. RV/H, LV/H and T/H were 3.4+-0.6%, 3.1+-0.5% and 10.4+-2.0% in controls, 6.0+-0.8%, 2.6+-0.8% and 14.2+-2.4% in cor pulmonale, and 7.9+-1.7%, 7.7+-3.5% and 20.7+-4.3% in heart diseases with left heart failure, respectively. Lu/H was 4.9+-1.4% in controls, 4.4+-1.1% in cor pulmonale and 6.6+-1.9% in heart diseases without left heart failure. LV/H was correlated with left ventricular end-diastolic volume by contrast ventriculography. LV/H and RV/H were related with functional classification of NYHA. In conclusion, these parameters may be utilized as indices of the volume of blood pool of the heart chambers and lungs, and this method seems to be clinically applicable for the evaluation of pathophysiology in heart diseases.

  11. Cardiac imaging in patients with chronic liver disease

    DEFF Research Database (Denmark)

    Wiese, Signe; Hove, Jens D; Møller, Søren


    dysfunction at rest by application of new myocardial strain techniques. Experience with other modalities such as cardiac magnetic resonance imaging and cardiac computed tomography is limited. Future studies exploring these imaging modalities are necessary to characterize and monitor the cardiac changes...

  12. Genetic and environmental factors in cardiac sodium channel disease

    NARCIS (Netherlands)

    Mizusawa, Y.


    Cardiac sodium channelopathies, such as long QT syndrome type3 (LQT3), Brugada syndrome (BrS) and cardiac conduction disease (CCD), are heritable diseases associated with mutations in the SCN5A gene and sudden cardiac death. They were classically thought to be a monogenic disease. However, while LQT

  13. Improved detection of cardiac fibrosis : Biomarkers and novel imaging techniques

    NARCIS (Netherlands)

    Jong, S. de


    Cardiac cells are embedded in a collagen network that provides strength in the heart against tension that occurs during contraction and relaxation. In almost every cardiac disease increased collagen (fibrosis) is observed. Fibrosis has adverse effects on cardiac pump function and increases the risk

  14. Modes of induced cardiac arrest: hyperkalemia and hypocalcemia - Literature review


    Oliveira,Marcos Aurélio Barboza de; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseini; Cortez, José Luis Lasso; Braile, Domingo Marcolino


    The entry of sodium and calcium play a key effect on myocyte subjected to cardiac arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused by hypocalcemia maintains intracellular adenosine triphosphate levels, improves diastolic performance and reduces oxygen consumption, which can be translated into better protection to myocyte injury induced by cardiac arrest.

  15. Optogenetic control of the cardiac conduction system (Conference Presentation) (United States)

    Crocini, Claudia; Ferrantini, Cecilia; Coppini, Raffaele; Loew, Leslie M.; Cerbai, Elisabetta; Poggesi, Corrado; Pavone, Francesco S.; Sacconi, Leonardo


    Fatal cardiac arrhythmias are a major medical and social issue in Western countries. Current implantable pacemaker/defibrillators have limited effectiveness and are plagued by frequent malfunctions and complications. Here, we aim at setting up a new method to map and control the electrical activity of whole isolated mouse hearts. We employ a transgenic mouse model expressing Channel Rhodopsin-2 (ChR2) in the heart coupled with voltage optical mapping to monitor and control action potential propagation. The whole heart is loaded with the fluorinated red-shifted voltage sensitive dye (di-4-ANBDQPQ) and imaged with the central portion (128 x 128 pixel) of sCMOS camera operating at frame rate of 1.6 kHz. The wide-field imaging system is implemented with a random access ChR2 activation developed using two orthogonally-mounted acousto-optical deflectors (AODs). AODs rapidly scan different sites of the sample with a commutation time of 4 μs, allowing us to design ad hoc ChR2-stimulation pattern. First, we demonstrate the capability of our system in manipulating the conduction system of the whole mouse heart by changing the electrical propagation features. Then, we explore the efficacy of the random access ChR2 stimulation in inducing arrhythmias as well as to restore the cardiac sinus rhythm during an arrhythmic event. This work shows the potentiality of this new method for studying the mechanisms of arrhythmias and reentry in healthy and diseased hearts, as well as the basis of intra-ventricular dyssynchrony.

  16. Critical role of bicarbonate and bicarbonate transporters in cardiac function

    Institute of Scientific and Technical Information of China (English)

    Hong-Sheng; Wang; Yamei; Chen; Kanimozhi; Vairamani; Gary; E; Shull


    Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.

  17. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy (United States)

    Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th


    We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on

  18. Current role of cardiac and extra-cardiac pathologies in clinically indicated cardiac computed tomography with emphasis on status before pulmonary vein isolation

    Energy Technology Data Exchange (ETDEWEB)

    Sohns, J.M.; Lotz, J. [Goettingen University Medical Center (Germany). Inst. for Diagnostic and Interventional Radiology; German Center for Cardiovascular Research (DZHK), Goettingen (Germany); Menke, J.; Staab, W.; Fasshauer, M.; Kowallick, J.T.; Zwaka, P.A.; Schwarz, A. [Goettingen University Medical Center (Germany). Inst. for Diagnostic and Interventional Radiology; Spiro, J. [Koeln University Hospital (Germany). Radiology; Bergau, L.; Unterberg-Buchwald, C. [Goettingen University Medical Center (Germany). Cardiology and Pneumology


    Purpose: The aim of this study was to assess the incidence of cardiac and significant extra-cardiac findings in clinical computed tomography of the heart in patients with atrial fibrillation before pulmonary vein isolation (PVI). Materials and Methods: 224 patients (64 ± 10 years; male 63%) with atrial fibrillation were examined by cardiac 64-slice multidetector CT before PVI. Extra-cardiac findings were classified as 'significant' if they were recommended to additional diagnostics or therapy, and otherwise as 'non-significant'. Additionally, cardiac findings were documented in detail. Results: A total of 724 cardiac findings were identified in 203 patients (91% of patients). Additionally, a total of 619 extra-cardiac findings were identified in 179 patients (80% of patients). Among these extra-cardiac findings 196 (32%) were 'significant', and 423 (68%) were 'non-significant'. In 2 patients (1%) a previously unknown malignancy was detected (esophageal cancer and lung cancer, local stage, no metastasis). 203 additional imaging diagnostics followed to clarify the 'significant' findings (124 additional CT, costs 38,314.69 US dollars). Overall, there were 3.2 cardiac and 2.8 extra-cardiac findings per patient. Extra-cardiac findings appear significantly more frequently in patients over 60 years old, in smokers and in patients with a history of cardiac findings (p < 0.05). Conclusion: Cardiac CT scans before PVI should be screened for extracardiac incidental findings that could have important clinical implications for each patient. (orig.)

  19. Complete cardiac rupture associated with closed chest cardiac massage: case report and review of the literature. (United States)

    Tattoli, Lucia; Maselli, Eloisa; Romanelli, Maria Carolina; Di Vella, Giancarlo; Solarino, Biagio


    Chest skeletal injuries are the most frequent complications of external chest massage (ECM) during cardiopulmonary resuscitation, but heart and great vessels lacerations that are indeed very rare. We report the case of a 35-year-old workman who collapsed and underwent ECM by his co-workers for almost 30 min. At autopsy, no external injuries, fractures or bruises of the ribs or sternum, were observed. A hemopericardium with a rupture of the heart was found, with no signs of pre-existent cardiac disease. Bruises of thoracic aortic wall, lung petechiae, a contusion of the liver, and bruises of lumbar muscles were found. The cause of death was due to sudden cardiac death with an extensive cardiac rupture. This is an unusual report of massive heart damage without any skeletal or muscle chest injuries, secondary to cardiopulmonary resuscitation. This kind of cardiac lesions may be considered when thoracic–abdominal trauma, or medical history, is unclear.

  20. Cardiac rehabilitation in Europe: results from the European Cardiac Rehabilitation Inventory Survey

    DEFF Research Database (Denmark)

    Bjarnason-Wehrens, Birna; McGee, Hannah; Zwisler, Ann-Dorthe


    Cardiac rehabilitation (CR) programmes support patients to achieve professionally recommended cardiovascular prevention targets and thus good clinical status and improved quality of life and prognosis. Information on CR service delivery in Europe is sketchy....

  1. The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation. (United States)

    Waldron, Lauren; Steimle, Jeffrey D; Greco, Todd M; Gomez, Nicholas C; Dorr, Kerry M; Kweon, Junghun; Temple, Brenda; Yang, Xinan Holly; Wilczewski, Caralynn M; Davis, Ian J; Cristea, Ileana M; Moskowitz, Ivan P; Conlon, Frank L


    Human mutations in the cardiac transcription factor gene TBX5 cause congenital heart disease (CHD), although the underlying mechanism is unknown. We report characterization of the endogenous TBX5 cardiac interactome and demonstrate that TBX5, long considered a transcriptional activator, interacts biochemically and genetically with the nucleosome remodeling and deacetylase (NuRD) repressor complex. Incompatible gene programs are repressed by TBX5 in the developing heart. CHD mis-sense mutations that disrupt the TBX5-NuRD interaction cause depression of a subset of repressed genes. Furthermore, the TBX5-NuRD interaction is required for heart development. Phylogenetic analysis showed that the TBX5-NuRD interaction domain evolved during early diversification of vertebrates, simultaneous with the evolution of cardiac septation. Collectively, this work defines a TBX5-NuRD interaction essential to cardiac development and the evolution of the mammalian heart, and when altered may contribute to human CHD.

  2. The European cardiac resynchronization therapy survey

    NARCIS (Netherlands)

    Dickstein, Kenneth; Bogale, Nigussie; Priori, Silvia; Auricchio, Angelo; Cleland, John G.; Gitt, Anselm; Limbourg, Tobias; Linde, Cecilia; van Veldhuisen, Dirk J.; Brugada, Josep


    Aims The European cardiac resynchronization therapy (CRT) survey is a joint initiative taken by the Heart Failure Association and the European Heart Rhythm Association of the European Society of Cardiology. The primary aim of this survey is to describe current European practice associated with CRT i

  3. Exosomes in cardiac injury and repair

    NARCIS (Netherlands)

    Vrijsen, K.R.


    Stem cell therapy has been proposed as a strategy to regenerate the damaged myocardium after myocardial infarction. The differentiation capacity of many different stem cells to cardiomyocytes and blood vessels and their effect on cardiac function has been studied. Despite low retention and engraftme

  4. Cardiac effects of sertindole and quetiapine

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Matz, Jørgen; Mittoux, Aurelia;


    The QT interval is the most widely used surrogate marker for predicting TdP; however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a quantitative T-wave morphology combination score (MCS) have emerged. This study investigated the cardiac effects of sertindole and quetiapin...

  5. Fibrinogen Concentrate Therapy in Complex Cardiac Surgery

    NARCIS (Netherlands)

    Bilecen, Suleyman; Peelen, Linda M.; Kalkman, Cor J.; Spanjersberg, Alexander J.; Moons, Karel G. M.; Nierich, Arno P.


    Objectives: Fibrinogen concentrate increasingly is used to treat coagulopathic bleeding in cardiac surgery although its effectiveness and safety have not been shown. The authors conducted a cohort study to quantify the effects of fibrinogen concentrate on postoperative blood loss and transfusion and

  6. SIRT3 in cardiac physiology and disease

    Directory of Open Access Journals (Sweden)

    Christoph Koentges


    Full Text Available Functional defects in mitochondrial biology causally contribute to various human diseases, including cardiovascular disease. Impairment in oxidative phosphorylation, mitochondrial oxidative stress and increased opening of the mitochondrial permeability transition pore add to the underlying mechanisms of heart failure or myocardial ischemia reperfusion (IR injury. Recent evidence demonstrated that the mitochondrial NAD+-dependent deacetylase sirtuin 3 (SIRT3 may regulate these mitochondrial functions by reversible protein lysine deacetylation. Loss of function studies demonstrated a role of impaired SIRT3 activity in the pathogenesis of myocardial IR injury as well as in the development of cardiac hypertrophy and the transition into heart failure. Gain of function studies and treatment approaches increasing mitochondrial NAD+ availability that ameliorate these cardiac pathologies have led to the proposal that activation of SIRT3 may represent a promising therapeutic strategy to improve mitochondrial derangements in various cardiac pathologies. In the current review, we will present and discuss the available literature on the role of SIRT3 in cardiac physiology and disease.

  7. Neurohumoral indicators of efficacy radiofrequency cardiac denervation

    Energy Technology Data Exchange (ETDEWEB)

    Evtushenko, A. V., E-mail:; Evtushenko, V. V. [National Research Tomsk State University, Tomsk (Russian Federation); Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Saushkina, Yu. V.; Gusakova, A. M.; Suslova, T. E.; Dymbrylova, O. N.; Smyshlyaev, K. A.; Kurlov, I. O. [Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Lishmanov, Yu. B.; Anfinogenova, Ya. D. [National Research Tomsk Polytechnic University, Tomsk (Russian Federation); Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Sergeevichev, D. S. [Academician E.N. Meshalkin State Research Institute of Circulation Pathology, Novosibirsk (Russian Federation); Bykov, A. N.; Syryamkin, V. I.; Kistenev, Yu. V. [National Research Tomsk State University, Tomsk (Russian Federation); Lotkov, A. I. [Institute of Strength Physics and Materials Science of the Siberian Branch of the RAS, Tomsk (Russian Federation); Pokushalov, E. A.


    In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes. The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using {sup 123}I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.

  8. Reoperation for bleeding in cardiac surgery

    DEFF Research Database (Denmark)

    Kristensen, Katrine Lawaetz; Rauer, Line Juul; Mortensen, Poul Erik;


    At Odense University Hospital (OUH), 5-9% of all unselected cardiac surgical patients undergo reoperation due to excessive bleeding. The reoperated patients have an approximately three times greater mortality than non-reoperated. To reduce the rate of reoperations and mortality due to postoperati...

  9. Minimally invasive cardiac surgery and transesophageal echocardiography

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Jha


    Full Text Available Improved cosmetic appearance, reduced pain and duration of post-operative stay have intensified the popularity of minimally invasive cardiac surgery (MICS; however, the increased risk of stroke remains a concern. In conventional cardiac surgery, surgeons can visualize and feel the cardiac structures directly, which is not possible with MICS. Transesophageal echocardiography (TEE is essential during MICS in detecting problems that require immediate correction. Comprehensive evaluation of the cardiac structures and function helps in the confirmation of not only the definitive diagnosis, but also the success of surgical treatment. Venous and aortic cannulations are not under the direct vision of the surgeon and appropriate positioning of the cannulae is not possible during MICS without the aid of TEE. Intra-operative TEE helps in the navigation of the guide wire and correct placement of the cannulae and allows real-time assessment of valvular pathologies, ventricular filling, ventricular function, intracardiac air, weaning from cardiopulmonary bypass and adequacy of the surgical procedure. Early detection of perioperative complications by TEE potentially enhances the post-operative outcome of patients managed with MICS.

  10. Neurohumoral indicators of efficacy radiofrequency cardiac denervation (United States)

    Evtushenko, A. V.; Evtushenko, V. V.; Saushkina, Yu. V.; Lishmanov, Yu. B.; Pokushalov, E. A.; Sergeevichev, D. S.; Gusakova, A. M.; Suslova, T. E.; Dymbrylova, O. N.; Bykov, A. N.; Syryamkin, V. I.; Kistenev, Yu. V.; Anfinogenova, Ya. D.; Smyshlyaev, K. A.; Lotkov, A. I.; Kurlov, I. O.


    In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes. The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using 123I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.

  11. Cardiac troponins in dogs and cats

    DEFF Research Database (Denmark)

    Langhorn, Rebecca; Willesen, Jakob


    Cardiac troponins are sensitive and specific markers of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart, however, it provides no information on the cause of injury or the mechanism of troponin release. Conven...

  12. Anaesthesia in the cardiac catheterization laboratory

    NARCIS (Netherlands)

    Braithwaite, Sue; Kluin, Jolanda; Buhre, Wolfgang F.; de Waal, Eric E. C.


    Purpose of review Interventions in the cardiac catheterization laboratory (CCL) requiring anaesthetic expertise are becoming routine. These interventions involve a heterogeneous patient population and take place in an offsite location. This review aims to give an insight into anaesthetic issues surr

  13. Cardiac arrhythmias during or after epileptic seizures (United States)

    van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D


    Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: ‘cardiac arrhythmias’ and ‘epilepsy’. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP. PMID:26038597

  14. Fast Registration of Cardiac Perfusion MRI

    DEFF Research Database (Denmark)

    Stegmann, Mikkel Bille; Larsson, Henrik B. W.


    This abstract presents a novel method for registration of cardiac perfusion MRI sequences. By performing complex analyses of variance and clustering in an annotated training set off-line, our method provides real-time segmentation in an on-line setting. This renders the method feasible for live...

  15. Cancer chemotherapy and cardiac arrhythmias: a review. (United States)

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva


    Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.

  16. Cardiac arrhythmias during or after epileptic seizures. (United States)

    van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D


    Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: 'cardiac arrhythmias' and 'epilepsy'. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP.

  17. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

    Clur, S. A. B.; Rengerink, K. Oude; Ottenkamp, J.; Bilardo, C. M.


    Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether

  18. Dermatoglyphic’s in Congenital Cardiac Disease

    Directory of Open Access Journals (Sweden)

    Singh Brijendra


    Full Text Available Various dermatoglyphic parameters like finger print pattern, atd angle, absolute ridge count & ab, bc ,cd, and ad ridge counts were observed in 150 cases of congenital cardiac disease, comprising of 72 cases of Ventricular Septal Defects (VSD, 60 cases of Atrial Septal Defects (ASD, 9 cases of Coarctation of Aorta (COA & 9 cases of Tetralogy of Fallot’s (TOF. Same dermatoglyphic parameters were also studied in 300 controls and statistical comparison of cases and controls was done. In our study it was observed that the congenital cardiac disease cases exhibited preponderance of whorls (55.8% with decrease in loop pattern (36.2% as compared to those of controls and the difference was highly significant (P<0.001. The difference in the mean total finger ridge count (TFRC of the controls and of the cases of Congenital Cardiac Diseases (CCD was found to be highly significant (P<0.001, while the  mean atd angle in the cases of Congenital Cardiac Disease (CCD was widen up and was statistically significant too. The mean ab, the mean bc ridge, the mean cd ridge and the mean ad ridge counts were also higher in the various type of CCD as compared to that controls and on statistical comparison, the difference was found to be highly significant.

  19. Cardiac arrhythmias in adult patients with asthma

    DEFF Research Database (Denmark)

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


    OBJECTIVE: The pathogenesis of cardiac arrhythmias in asthma patients has not been fully elucidated. Adverse drug effects, particularly those of β2-mimetics, may play a role. The aim of this study was to determine whether asthma is associated with the risk of cardiac arrhythmias and electrocardio......OBJECTIVE: The pathogenesis of cardiac arrhythmias in asthma patients has not been fully elucidated. Adverse drug effects, particularly those of β2-mimetics, may play a role. The aim of this study was to determine whether asthma is associated with the risk of cardiac arrhythmias...... and electrocardiographic characteristics of arrhythmogenicity (ECG) and to explore the role of β2-mimetics. METHODS: A cross-sectional study was conducted among 158 adult patients with a diagnosis of asthma and 6303 participants without asthma from the cohort of the Utrecht Health Project-an ongoing, longitudinal, primary...... or flutter). Secondary outcomes were tachycardia, bradycardia, PVC, atrial fibrillation or flutter, mean heart rate, mean corrected QT (QTc) interval length, and prolonged QTc interval. RESULTS: Tachycardia and PVCs were more prevalent in patients with asthma (3% and 4%, respectively) than those without...

  20. Measuring temporal resolution of cardiac CT reconstructions (United States)

    Matthews, David; Heuscher, Dominic


    Multi-slice CT today is capable of imaging the heart with excellent temporal resolution. Algorithms have been developed to perform reconstructions combining data from multiple cardiac cycles. This paper presents a simulation phantom that enables a direct measurement of the actual temporal resolution achieved by these algorithms. This is not only useful for assessing the temporal resolution but also for validating the algorithms themselves. A simulation phantom was developed that consists of a 20 cm. diameter water phantom containing an array of cylinders whose intensities are pulsed for various durations ranging from 10 msec. to 250 msec. The intensity varied between the background value of water (0 HU) and 800 HU. By measuring the nominal attenuation value at the center of each cylinder, a curve can be derived representing the response over the given temporal range. A temporal resolution representing the FWHM value is determined based on the half-max value of this curve. Reconstructions were performed using a multi-cycle cardiac algorithm described previously in the literature. The measured FWHM values agree quite well to the temporal resolution predicted by the cardiac algorithm itself. Even the variation along the longitudinal axis can be accounted for by the predicted values. A simulated phantom can be used to accurately assess the temporal resolution of cardiac reconstruction algorithms. Excellent agreement was achieved between the predicted and measured temporal resolution values for the multi-cycle algorithm used in this study.

  1. Antimyosin imaging in cardiac transplant rejection

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.L.; Cannon, P.J. (Department of Medicine, College of Physicians and Surgeons, Columbia University, New York (United States))


    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references.

  2. Sudden cardiac death in young adults

    DEFF Research Database (Denmark)

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


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

  3. Modular assembly of thick multifunctional cardiac patches (United States)

    Fleischer, Sharon; Shapira, Assaf; Feiner, Ron; Dvir, Tal


    In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues. PMID:28167795

  4. Technical solutions to improve cardiac regenerative therapy

    NARCIS (Netherlands)

    van Slochteren, F.J.


    The therapeutic options for patients suffering from ischemic heart disease (IHD) are limited, and worldwide 23 million patients suffer from heart failure (HF). Therefore there is a strong need for alternative therapies for IHD. Since cardiac regenerative therapies have shown promising results in bas

  5. Congenital cardiac anomalies in an English bulldog. (United States)

    McConkey, Marina J


    A 4-year-old male castrated English bulldog was referred to the Atlantic Veterinary College for evaluation of exercise intolerance, multiple syncopal episodes, and a grade IV/VI heart murmur. The dog was shown to have 3 congenital cardiac anomalies: atrial septal defect, mitral valve dysplasia, and subaortic stenosis. Medical management consisted of exercise restriction, atenolol, pimobendan, and taurine.

  6. Cardiac retractor for coronary bypass operations. (United States)

    Rousou, J A; Engelman, R M; Flack, J E; Deaton, D W


    The Thompson retractor, used mainly for abdominal procedures, has been used to retract the heart and facilitate exposure for the performance of inferior wall or posterolateral wall coronary anastomoses. It has been found to be very effective and can replace a second assistant to retract the heart or avoid other cumbersome methods of cardiac retraction.

  7. Electromagnetic clutches and couplings

    CERN Document Server

    Vorob'Yeva, T M; Fry, D W; Higinbotham, W


    Electromagnetic Clutches and Couplings contains a detailed description of U.S.S.R. electromagnetic friction clutches, magnetic couplings, and magnetic particle couplings. This book is divided into four chapters. The first chapter discusses the design and construction of magnetic (solenoid-operated) couplings, which are very quick-acting devices and used in low power high-speed servo-systems. Chapter 2 describes the possible fields of application, design, construction, and utilization of magnetic particle couplings. The aspects of construction, design, and utilization of induction clutches (sli

  8. Perceptions of cardiac rehabilitation patients, specialists and rehabilitation programs regarding cardiac rehabilitation wait times

    Directory of Open Access Journals (Sweden)

    Grace Sherry L


    Full Text Available Abstract Background In 2006, the Canadian Cardiovascular Society (CCS Access to Care Working Group recommended a 30-day wait time benchmark for cardiac rehabilitation (CR. The objectives of the current study were to: (1 describe cardiac patient perceptions of actual and ideal CR wait times, (2 describe and compare cardiac specialist and CR program perceptions of wait times, as well as whether the recommendations are appropriate and feasible, and (3 investigate actual wait times and factors that CR programs perceive to affect these wait times. Methods Postal and online surveys to assess perceptions of CR wait times were administered to CR enrollees at intake into 1 of 8 programs, all CCS member cardiac specialists treating patients indicated for CR, and all CR programs listed in Canadian directories. Actual wait times were ascertained from the Canadian Cardiac Rehabilitation Registry. The design was cross-sectional. Responses were described and compared. Results Responses were received from 163 CR enrollees, 71 cardiac specialists (9.3% response rate, and 92 CR programs (61.7% response rate. Patients reported that their wait time from hospital discharge to CR initiation was 65.6 ± 88.4 days (median, 42 days, while their ideal median wait time was 28 days. Most patients (91.5% considered their wait to be acceptable, but ideal wait times varied significantly by the type of cardiac indication for CR. There were significant differences between specialist and program perceptions of the appropriate number of days to wait by most indications, with CR programs perceiving shorter waits as appropriate (p  Conclusions Wait times following access to cardiac rehabilitation are prolonged compared with consensus recommendations, and yet are generally acceptable to most patients. Wait times following percutaneous coronary intervention in particular may need to be shortened. Future research is required to provide an evidence base for wait time

  9. High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery

    NARCIS (Netherlands)

    Noordzij, P. G.; van Geffen, O.; Dijkstra, I. M.; Boerma, D.; Meinders, A. J.; Rettig, T. C D; Eefting, F. D.; van Loon, D.; van de Garde, E. M W; van Dongen, E. P A


    BACKGROUND: Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the rel

  10. Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection.

    Directory of Open Access Journals (Sweden)

    Yasir Alhamdi


    Full Text Available Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY. Using a mouse model of invasive pneumococcal disease (IPD, we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns, well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001 and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB, induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with

  11. Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury (United States)

    Biswas, Hirak; Longmore, Gregory D.


    Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis. PMID:27706205

  12. Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Leela K Lella

    Full Text Available The significance of right ventricular ejection fraction (RVEF, independent of left ventricular ejection fraction (LVEF, following isolated coronary artery bypass grafting (CABG and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR, independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery.From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered 30 days outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months.Forty-eight patients had reduced RVEF (mean 25% and 61 patients had normal RVEF (mean 50% (p<0.001. Fifty-four patients had reduced LVEF (mean 30% and 55 patients had normal LVEF (mean 59% (p<0.001. Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05. Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03. Reduced LVEF did not influence long-term cardiac re-hospitalization.Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures.

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

    Directory of Open Access Journals (Sweden)

    Quan He


    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.

  14. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue. (United States)

    Mayorga, Maritza; Finan, Amanda; Penn, Marc


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

  15. Influence of cardiac decentralization on cardioprotection.

    Directory of Open Access Journals (Sweden)

    John G Kingma

    Full Text Available The role of cardiac nerves on development of myocardial tissue injury after acute coronary occlusion remains controversial. We investigated whether acute cardiac decentralization (surgical modulates coronary flow reserve and myocardial protection in preconditioned dogs subject to ischemia-reperfusion. Experiments were conducted on four groups of anesthetised, open-chest dogs (n = 32: 1- controls (CTR, intact cardiac nerves, 2- ischemic preconditioning (PC; 4 cycles of 5-min IR, 3- cardiac decentralization (CD and 4- CD+PC; all dogs underwent 60-min coronary occlusion and 180-min reperfusion. Coronary blood flow and reactive hyperemic responses were assessed using a blood volume flow probe. Infarct size (tetrazolium staining was related to anatomic area at risk and coronary collateral blood flow (microspheres in the anatomic area at risk. Post-ischemic reactive hyperemia and repayment-to-debt ratio responses were significantly reduced for all experimental groups; however, arterial perfusion pressure was not affected. Infarct size was reduced in CD dogs (18.6 ± 4.3; p = 0.001, data are mean ± 1 SD compared to 25.2 ± 5.5% in CTR dogs and was less in PC dogs as expected (13.5 ± 3.2 vs. 25.2 ± 5.5%; p = 0.001; after acute CD, PC protection was conserved (11.6 ± 3.4 vs. 18.6 ± 4.3%; p = 0.02. In conclusion, our findings provide strong evidence that myocardial protection against ischemic injury can be preserved independent of extrinsic cardiac nerve inputs.

  16. [Berberine inhibits cardiac fibrosis of diabetic rats]. (United States)

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei


    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  17. Measuring cardiac efficiency using PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Gullberg, Grand [Lawrence Berkeley National Laboratory (United States); Aparici, Carina Mari; Brooks, Gabriel [University of California San Francisco (United States); Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes [Lawrence Berkeley National Laboratory (United States)


    Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

  18. Ischemic Stroke Due to Cardiac Involvement: Emery Dreifuss Patient

    Directory of Open Access Journals (Sweden)

    Ersin Kasım Ulusoy


    Full Text Available Emery-Dreifuss muscular dystrophy (EDMD is a hereditary disease. It is characterized by early-onset contractures, slowly progressive weakness, fatigue related to skapulo-humero-peroneal muscle weakness, cardiomyopathy which develops in adulthood and cardiac conduction system block. Cardiac involvement has a prognostic significance in patients with EDMD and even sudden cardiac death may be the first clinical presentation. In this article, an EDMD patient with ischemic stroke clinic who didn’t have regular cardiac follow-up was reported and the importance of the treatment of cardiac diseases which could play a role in ischemic stroke etiology and the implantation of pace-maker was mentioned.

  19. Matrix identity and tractional forces influence indirect cardiac reprogramming (United States)

    Kong, Yen P.; Carrion, Bita; Singh, Rahul K.; Putnam, Andrew J.


    Heart regeneration through in vivo cardiac reprogramming has been demonstrated as a possible regenerative strategy. While it has been reported that cardiac reprogramming in vivo is more efficient than in vitro, the influence of the extracellular microenvironment on cardiac reprogramming remains incompletely understood. This understanding is necessary to improve the efficiency of cardiac reprogramming in order to implement this strategy successfully. Here we have identified matrix identity and cell-generated tractional forces as key determinants of the dedifferentiation and differentiation stages during reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure are also important, but play lesser roles. Our results suggest that the extracellular microenvironment can be optimized to enhance cardiac reprogramming.

  20. Cardiac ryanodine receptor gene (hRyR2) mutation underlying catecholaminergic polymorphic ventricular tachycardia in a Chinese adolescent presenting with sudden cardiac arrest and cardiac syncope

    Institute of Scientific and Technical Information of China (English)

    Ngai-Shing Mok; Ching-Wan Lam; Nai-Chung Fong; Yim-Wo Hui; Yuen-Choi Choi; Kwok-Yin Chan


    @@ Sudden cardiac death (SCD) in children and adolescents is uncommon and yet it is devastating for both victim's family and the society.Recently, it was increasingly recognized that SCD in young patients with structurally normal heart may be caused by inheritable primary electrical diseases due to the malfunction of cardiac ion channels, a disease entity known as the ion channelopathies.Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a specific form of ion channelopathy which can cause cardiac syncope or SCD in young patients by producing catecholamine-induced bi-directional ventricular tachycardia (BiVT), polymorphic VT and ventricular fibrillation (VF) during physical exertion or emotion.1-7 We reported here an index case of CPVT caused by cardiac ryanodine receptor gene (hRyR2)mutation which presented as cardiac syncope and sudden cardiac arrest in a Chinese adolescent female.