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

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na⁺-channel blocker (5 μM) ranolazine or the intracellular Ca²⁺ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand

Quantification of the transmural dynamics of atrial fibrillation by simultaneous endocardial and epicardial optical mapping in an acute sheep model

BACKGROUND: Therapy strategies for atrial fibrillation based on electrical characterization are becoming viable personalized medicine approaches to treat a notoriously difficult disease. In light of these approaches that rely on high-density surface mapping, this study aims to evaluate the presence of three-dimensional electrical substrate variations within the transmural wall during acute episodes of atrial fibrillation. METHODS AND RESULTS: Optical signals were simultaneously acquired from the epicardial and endocardial tissue during acute fibrillation in ovine isolated left atria. Dominant frequency, regularity index, propagation angles and phase dynamics were assessed and correlated across imaging planes to gauge the synchrony of the activation patterns compared to paced rhythms. Static frequency parameters were well correlated spatially between the endocardium and the epicardium (dominant frequency, 0.79+/-0.06 and regularity index, 0.93+/-0.009). However, dynamic tracking of propagation vectors and phase singularity trajectories revealed discordant activity across the transmural wall. The absolute value of the difference in the number, spatial stability, and temporal stability of phase singularities between the epicardial and endocardial planes was significantly greater than 0 with a median difference of 1.0, 9.27%, and 19.75%, respectively. The number of wavefronts with respect to time was significantly less correlated and the difference in propagation angle was significantly larger in fibrillation compared to paced rhythms. CONCLUSIONS: Atrial fibrillation substrates are dynamic three-dimensional structures with a range of discordance between the epicardial and endocardial tissue. The results of this study suggest that transmural propagation may play a role in AF maintenance mechanisms

INPOP Planetary ephemerides and applications in the frame of the BepiColombo mission including new constraints on the graviton mass and dilaton parameters

We present here the new results obtained with the INPOP planetary ephemerides and BepiColombo radio-science simulations. We give new constraints for the classic General Relativity tests in terms of violation of the PPN parameters $\beta$ and $\gamma$ and the time variation of the gravitational constant G. We also present new limits for the mass of the graviton and finally we obtain new acceptable intervals for the dilaton parameters $\alpha_{0}$, $\alpha_{T}$ and $\alpha_{G}$. Besides these tests of gravitation, we also study the possibility of detecting the Sun core rotation.Comment: arXiv admin note: substantial text overlap with arXiv:2111.0449

Simplified approach to the application of the geometric collective model

The predictions of the geometric collective model (GCM) for different sets of Hamiltonian parameter values are related by analytic scaling relations. For the quartic truncated form of the GCM -- which describes harmonic oscillator, rotor, deformed gamma-soft, and intermediate transitional structures -- these relations are applied to reduce the effective number of model parameters from four to two. Analytic estimates of the dependence of the model predictions upon these parameters are derived. Numerical predictions over the entire parameter space are compactly summarized in two-dimensional contour plots. The results considerably simplify the application of the GCM, allowing the parameters relevant to a given nucleus to be deduced essentially by inspection. A precomputed mesh of calculations covering this parameter space and an associated computer code for extracting observable values are made available through the Electronic Physics Auxiliary Publication Service. For illustration, the nucleus 102Pd is considered.Comment: RevTeX 4, 15 pages, to be published in Phys. Rev.

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

OBJECTIVE: The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF). METHODS AND RESULTS: Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV. CONCLUSION: Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF

Influence of Filtering Techniques on Holographic Images

Broadband Holography has become a powerful tool in computerized non-destructive testing. Interpretation of images, however, is difficult due to the fact that perfect imaging of flaw sizes is impossible until now. The situation is even more complex, since multiple scattering, wave mode conversions, and inhomogeneities in the material give rise to artifacts in the holographic image. Thus, signal and data processing techniques at different levels of the signal flow path may help improve the situation. Within this paper the following methods are discussed: (1) Inverse filtering. Inverse filters improve echo shape and duration. This in turn influences lateral and axial resolutions of the image. Since inverse filtering is known to be an ill posed problem we apply a standard Tychonoff regularization. It turns out to be equivalent to Wiener filtering in its simplest form.; (2) The ALOK i, k-filter. This is a non linear filter mainly used for data reduction purposes during the inspection of large scale components. An attempt is made to at least partly recover the original signal from ALOK data.; (3) Image processing. Using the holographic image of a natural crack we show different image processing techniques. This may be a tool to gain more insight into the flaw size and geometry under test

Endocardial role in arrhythmias induced by acute ventricular stretch and the involvement of Purkinje fibres, in isolated rat hearts

Purkinje fibres (PFs) play an important role in some ventricular arrhythmias and acute ventricular stretch can evoke mechanically-induced arrhythmias. We tested whether PFs and specifically TRPM4 channels, play a role in these mechanically-induced arrhythmias. Pseudo-ECGs and left ventricular (LV) activation, measured by optical mapping, were recorded in isolated, Langendorff-perfused, rat hearts. The LV endocardial surface was irrigated with experimental agents, via an indwelling catheter. The number and period of ectopic activations was measured during LV lumen inflation via an indwelling fluid-filled balloon (100 μL added over 2 s, maintained for 38 s). Mechanically-induced arrhythmias occurred during balloon inflation: they were multifocal, maximal in the first 5 s and ceased within 20 s. Optical mapping revealed activation patterns indicating PF-mediated and ectopic focal sources. Irrigation of the LV lumen with Lugol solution (IK/I2) for 10s reduced ectopics by 93% (n = 16, P < 0.001); with ablation of endocardial PFs confirmed by histology. Five min irrigation of the LV lumen with 50 μM 9-Phenanthrol, a blocker of TRPM4 channels, reduced ectopics by 39% (n = 15, P < 0.01). Immunohistochemistry confirmed that TRPM4 was more abundant in PFs than myocardium. Our results show that the endocardial surface plays an important role in these mechanically-induced ectopic activations. Ectopic activation patterns indicate a participation of PFs in these arrhythmias, with a potential involvement of TRPM4 channels, shown by the reduction of arrhythmias by 9-Phenanthrol