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  • 1
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    Increased Expression of HCN Channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts [Heart Failure] (2013)
    American Heart Association (AHA)
    Details
    Publication Date: 2013-06-27
    Description: Background The efficacy of pharmacological interventions to prevent sudden arrhythmic death in patients with chronic heart failure remains limited. Evidence now suggests increased ventricular expression of hyperpolarization-activated cation (HCN) channels in hypertrophied and failing hearts contributes to their arrythmicity. Still, the role of induced HCN channel expression in the enhanced arrhythmicity associated with heart failure and the capacity of HCN channel blockade to prevent lethal arrhythmias remains undetermined. Methods and Results We examined the effects of ivabradine, a specific HCN channel blocker, on survival and arrhythmicity in transgenic mice (dnNRSF-Tg) expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor, a useful mouse model of dilated cardiomyopathy leading to sudden death. Ivabradine (7 mg/kg per day orally) significantly reduced ventricular tachyarrhythmias and improved survival among dnNRSF-Tg mice while having no significant effect on heart rate or cardiac structure or function. Ivabradine most likely prevented the increase in automaticity otherwise seen in dnNRSF-Tg ventricular myocytes. Moreover, cardiac-specific overexpression of HCN2 in mice (HCN2-Tg) made hearts highly susceptible to arrhythmias induced by chronic β-adrenergic stimulation. Indeed, ventricular myocytes isolated from HCN2-Tg mice were highly susceptible to β-adrenergic stimulation-induced abnormal automaticity, which was inhibited by ivabradine. Conclusions HCN channel blockade by ivabradine reduces lethal arrhythmias associated with dilated cardiomyopathy in mice. Conversely, cardiac-specific overexpression of HCN2 channels increases arrhythmogenicity of β-adrenergic stimulation. Our findings demonstrate the contribution of HCN channels to the increased arrhythmicity seen in failing hearts and suggest HCN channel blockade is a potentially useful approach to preventing sudden death in patients with heart failure.
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 2
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    Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure (2014)
    Oxford University Press
    Details
    Publication Date: 2014-09-26
    Description: Aims Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca 2+ channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. Methods and results We compared the effects of cilnidipine, a dual N- and L-type Ca 2+ channel blocker, with those of nitrendipine, a selective L-type Ca 2+ channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B , which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg; CACNA1B +/– mice showed fewer malignant arrhythmias than dnNRSF-Tg; CACNA1B +/+ mice. Conclusions Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure.
    Print ISSN: 0008-6363
    Electronic ISSN: 1755-3245
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    Pro-B-type natriuretic peptide is cleaved intracellularly: impact of distance between O-glycosylation and cleavage sites (2015)
    The American Physiological Society (APS)
    Details
    Publication Date: 2015-09-17
    Description: We investigated the molecular mechanism underlying the processing of pro-B-type natriuretic peptide (proBNP). Rat neonatal atrial and ventricular myocytes were cultured separately. We examined the molecular forms of secreted and intracellular BNP in atrial and ventricular myocytes; levels of corin and furin mRNA in atrial and ventricular myocytes; the effect their knockdown on proBNP processing; plasma molecular forms of BNP from rats and humans with and without heart failure; and the impact of the distance between the glycosylation and cleavage sites in wild-type and mutant human proBNP, expressed in rat myocytes transfected with lentiviral vectors. BNP was the major molecular form secreted by atrial and ventricular myocytes. Transfection of furin siRNA reduced proBNP processing in both atrial and ventricular myocytes; however, transfection of corin siRNA did not reduce it. BNP was the major molecular form in rat plasma, whereas proBNP was the major form in human plasma. The relative fraction of human BNP in rat myocytes expressing human proBNP was about 60%, but increasing the distance between the glycosylation and cleavage sites through mutation, increased the processed fraction correspondingly. These results suggest that proBNP is processed into BNP intracellularly by furin. The level of proBNP processing is lower in humans than rats, most likely due to the smaller distance between the O -glycosylation and cleavage sites in humans.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
    Published by The American Physiological Society (APS)
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  • 4
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    The renin-angiotensin system promotes arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy (2015)
    Oxford University Press
    Details
    Publication Date: 2015-12-29
    Description: Aims The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin–angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias. Methods and results Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles. Conclusion Renin inhibition or genetic deletion of AT1aR suppresses pathological cardiac remodelling that leads to the generation of substrates maintaining VT/VF and reduces the occurrence of sudden death in dnNRSF-Tg mice. These findings demonstrate the significant contribution of RAS activation to the progression of arrhythmogenic substrates.
    Print ISSN: 0008-6363
    Electronic ISSN: 1755-3245
    Topics: Medicine
    Published by Oxford University Press
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  • 5
    Electronic Resource
    Electronic Resource
    Flux pinning and dissipation in textured multifilamentary (Bi–Pb)2Sr2Ca2Cu3Ox/Ag tapes (2001)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 89 (2001), S. 3861-3867 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We have studied the magnetotransport, magnetization properties, and microstructure of multifilamentary (Bi–Pb)2Sr2Ca2Cu3Ox (Bi-2223)/Ag tapes with varying filaments from 1 to 37 to explore the energy dissipation, reversible flux motion, and flux pinning related to the microstructure. Our results show that the dissipation is temperature, current, and magnetic field induced. The dissipation is thermally activated and the vortex liquid state is plastically deformed. The dissociation of vortex–antivortex pairs by current, magnetic field, and temperature plays a major role in enhancing the dissipation process, resulting in large broadening in the transition. We observed a reversible fluxoid motion of vortices. The critical current density follows an exponential dependence on the magnetic field. The weak links seem to be broken even for a field as low as 5 G even 12 K below the transition temperature. However, at low temperature, the weak links behave as superconducting. The microscopic characterizations show evidence for the dislocations, stacking faults, and misorientation of grains and grain boundaries that control the critical current in tapes. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1353560
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  • 6
    Electronic Resource
    Electronic Resource
    Flux pinning in melt-processed ternary (Nd–Eu–Gd)Ba2Cu3Oy superconductors with Gd2BaCuO5 addition (1999)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 86 (1999), S. 5705-5711 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The flux pinning behavior of ternary melt-processed (Nd–Eu–Gd)Ba2Cu3Oy superconductors is studied with varying Gd2BaCuO5 second-phase (Gd-211) defect concentrations using magnetotransport and magnetization measurements. The critical current density, Jc increases with the addition of Gd-211 particles displaying a maximum value of Jc for 30% at zero and in intermediate field range and decreases on further addition of Gd-211 particles. A pronounced field-induced bump feature in the resistivity was observed. The dynamic scaling of the resistance suggests the low temperature phase as the vortex-glass phase. The current–voltage characteristics over the whole transition temperature regime show a linear flux–flow type behavior that favors the phenomenon of vortex entanglement in the liquid phase. The Nd/Ba substitution sites along with Gd-211 second-phase particles refined by the addition of a small amount of Pt are one of the possible reasons for the vortex entanglement in the liquid phase. The in-plane and out-of-plane resistance measurements clearly show the correlation of the vortices in the liquid state favoring some influence of twin planes and occasionally occurring natural grain boundaries on the liquid state as well. These defects give rise to high critical current density at low temperature with significant enhancement in pinning favoring the glassy phase to occur. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.371582
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  • 7
    Electronic Resource
    Electronic Resource
    Temperature effects on charge retention characteristics of integrated SrBi2(Ta,Nb)2O9 capacitors (1997)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 71 (1997), S. 2538-2540 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Temperature effects on charge retention characteristics of integrated SrBi2(Ta,Nb)2O9 thin film capacitors were examined in the temperature range of 27–150°C. The decay in remanent polarization at 27°C was linear in logarithmic time from 10−3 to 105 s with a decay rate of 0.24 μC/cm2 per decade. The elevation of storage temperature resulted in an instantaneous decrease in remanent polarization, while the decay rate at elevated temperatures after the instantaneous decrease was as small as that at 27°C. The instantaneous decrease in remanent polarization caused by elevating the temperature was explained by the temperature dependence of spontaneous polarization in the vicinity of the second order transition temperature. The development of asymmetry in the hysteresis loop during high temperature storing indicates that the logarithmic time dependence of the decay in remanent polarization is due to redistribution of space charges rather than polarization reversal. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.120110
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  • 8
    Electronic Resource
    Electronic Resource
    Rotational viscosity in ferroelectric liquid crystals estimated from transient light scattering and dielectric properties (1989)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 65 (1989), S. 3602-3605 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A new method for the estimation of rotational viscosity of ferroelectric liquid crystals using transient light scattering (TSM) is reported. The relation between rotational viscosity, spontaneous polarization, and dielectric dispersion frequency is studied as a function of the racemization. The rotational viscosity is almost independent of spontaneous polarization and there is no obvious correlation between rotational viscosity and dispersion frequency. The dispersion frequency is confirmed to be inversely proportional to the square of the helical pitch. The rotational viscosity calculated from this relation is consistent with that from the new TSM method.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.342639
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  • 9
    Electronic Resource
    Electronic Resource
    Dynamical properties of magneto-optical effect in magnetic fluid thin films (1988)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 64 (1988), S. 5846-5848 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The dynamical properties of the magneto-optical effects of magnetic fluids thin films were investigated. The thin films, 12 μm thick, of magnetite colloidal particles in water solvents and alkylnaphthalene one were prepared. A pulsed magnetic field H(t) was generated in a single turn coil by discharging a 40-kV capacitor bank. The intensity I(t) of the transmitted light through the two crossed polarizers and the films located in the coil was measured. The relaxation process of the magneto-optical effect can be described in terms of a single relaxation time, τ=3 μs, for a water-based magnetic fluid, while the relaxation time constant for alkylnaphthalene one depends on the field strength. These dynamical properties can be interpreted by the time-dependent Ginzburg–Landau theory by introducing the order parameter of the colloidal particles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.342231
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  • 10
    Electronic Resource
    Electronic Resource
    Evidence of strong flux pinning in melt-processed ternary (Nd–Eu–Gd)Ba2Cu3Oy superconductors (1999)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 75 (1999), S. 253-255 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The flux pinning behavior of ternary melt-processed (Nd–Eu–Gd)Ba2Cu3Oy superconductors is studied with varying defect concentrations using magnetotransport and magnetization measurements. A huge field-induced bump feature in the resistivity with increasing defect density, field-induced magnetization kink and linear voltage-current (V-I) characteristics over the whole transition temperature regime favor the phenomenon of vortex entanglement in the liquid phase. The Nd/Ba substitution sites along with the fine second-phase particles are one of the possible reasons for the vortex entanglement and these defects give rise to high critical current density and reduced dissipation at low temperature with significant enhancement in pinning. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.124339
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