The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
R. A. Lefebvre - One of the best experts on this subject based on the ideXlab platform.
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Study of the regulation of the inotropic response to 5-HT_4 receptor activation via phosphodiesterases and its cross-talk with C-type natriuretic peptide in porcine left atrium
Naunyn-Schmiedeberg's Archives of Pharmacology, 2012Co-Authors: S. Weninger, J. H. Maeyer, R. A. LefebvreAbstract:We studied how 5-HT_4 receptor-mediated inotropic responses are regulated at the level of cAMP in porcine left atrium. We used selective phosphodiesterase (PDE) inhibitors to assess which PDE subtypes are responsible for the fade with time of inotropic responses to 5-HT_4 receptor activation with 5-HT and the 5-HT_4 receptor agonist prucalopride. A possible cross-talk via PDEs between cGMP and 5-HT_4 receptor-induced cAMP signalling was evaluated. Electrically paced left atrial Pectinate Muscles from young male pigs (15–25 kg) were studied in vitro. Simultaneous inhibition of PDE3 plus PDE4 subtypes was necessary to increase the amplitude and completely prevent the fade of the inotropic response to 5-HT and prucalopride. When responses to 5-HT or prucalopride had faded 1 h after addition, the nonspecific PDE-inhibitor IBMX still fully recovered inotropic responses. Stimulation of particulate guanylyl cyclase, together with PDE2 and PDE4 inhibition, delayed the fade of the response to 5-HT, while stimulation of soluble guanylyl cyclase independently of PDEs accelerated the fade of the response to 5-HT. In conclusion, both PDE3 and PDE4 subtypes are responsible for the suppression and the fade of the inotropic response to 5-HT and prucalopride. Signalling through the 5-HT_4 receptor remains fully active for at least 90 min with PDEs continuously regulating the response. cGMP levels, elevated by activation of particulate guanylyl cyclase under PDE2 inhibition, can indirectly enhance 5-HT_4 receptor-mediated signalling, at least when also PDE4 is inhibited, presumably through inhibition of PDE3. Elevation of cGMP generated by soluble guanylyl cyclase attenuates responses to 5-HT independently of PDEs.
S. Weninger - One of the best experts on this subject based on the ideXlab platform.
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Study of the regulation of the inotropic response to 5-HT_4 receptor activation via phosphodiesterases and its cross-talk with C-type natriuretic peptide in porcine left atrium
Naunyn-Schmiedeberg's Archives of Pharmacology, 2012Co-Authors: S. Weninger, J. H. Maeyer, R. A. LefebvreAbstract:We studied how 5-HT_4 receptor-mediated inotropic responses are regulated at the level of cAMP in porcine left atrium. We used selective phosphodiesterase (PDE) inhibitors to assess which PDE subtypes are responsible for the fade with time of inotropic responses to 5-HT_4 receptor activation with 5-HT and the 5-HT_4 receptor agonist prucalopride. A possible cross-talk via PDEs between cGMP and 5-HT_4 receptor-induced cAMP signalling was evaluated. Electrically paced left atrial Pectinate Muscles from young male pigs (15–25 kg) were studied in vitro. Simultaneous inhibition of PDE3 plus PDE4 subtypes was necessary to increase the amplitude and completely prevent the fade of the inotropic response to 5-HT and prucalopride. When responses to 5-HT or prucalopride had faded 1 h after addition, the nonspecific PDE-inhibitor IBMX still fully recovered inotropic responses. Stimulation of particulate guanylyl cyclase, together with PDE2 and PDE4 inhibition, delayed the fade of the response to 5-HT, while stimulation of soluble guanylyl cyclase independently of PDEs accelerated the fade of the response to 5-HT. In conclusion, both PDE3 and PDE4 subtypes are responsible for the suppression and the fade of the inotropic response to 5-HT and prucalopride. Signalling through the 5-HT_4 receptor remains fully active for at least 90 min with PDEs continuously regulating the response. cGMP levels, elevated by activation of particulate guanylyl cyclase under PDE2 inhibition, can indirectly enhance 5-HT_4 receptor-mediated signalling, at least when also PDE4 is inhibited, presumably through inhibition of PDE3. Elevation of cGMP generated by soluble guanylyl cyclase attenuates responses to 5-HT independently of PDEs.
Henggui Zhang - One of the best experts on this subject based on the ideXlab platform.
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3D anatomical atria model and regional APs.
2017Co-Authors: Dominic G. Whittaker, Jules C. Hancox, Aziza El Harchi, Henggui ZhangAbstract:The anatomical atria geometry shown from two views–looking at the RA posterior wall and into the cavities (A), with regions of atrial septum (AS), atrio-ventricular ring (AVR), crista terminalis (CT), left atrium (LA), left atrial appendage (LAA), left pulmonary veins (LPV), Pectinate Muscles (PM), right atrium (RA), right atrial appendage (RAA), right pulmonary veins (RPV), and sinoatrial node (SAN) shown for reference. Action potentials for regional cell models including the Bachmann’s bundle (BB) at 1 Hz (B), with colours corresponding to tissue segmentation in (A). Activation sequence in the heterogeneous 3D anatomical atria model, following initiation of an AP in the SAN region (C).
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Regions of the atria included in each quadrant for the two positions inside the torso.
2015Co-Authors: Erick Perez A. Alday, Michael A. Colman, Philip Langley, Timothy D. Butters, Jonathan Higham, Antony J. Workman, Jules C. Hancox, Henggui ZhangAbstract:The regions of the atria are: Right atrium (RA), right atrial appendage (RAA), Pectinate Muscles (PM), cristal terminalis (CT), sinoatrial node (SAN), superior vena cava (SVC), atrio-ventricular ring (AVR), right pulmonary vein (RPV), bundle branch (BB), left atrium (LA), left atrial appendage (LAA), inferior vena cava (IVC) and left pulmonary veins (LPV). Position 1 is taken from [23]. Position 2 is taken from the actual position of the atria inside its torso.Regions of the atria included in each quadrant for the two positions inside the torso.
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Models and procedure used to develop the algorithm.
2015Co-Authors: Erick Perez A. Alday, Michael A. Colman, Philip Langley, Timothy D. Butters, Jonathan Higham, Antony J. Workman, Jules C. Hancox, Henggui ZhangAbstract:(A(i)) 3D Atrial model with the different regions of the atria included in this simulation: right atrium (RA, transparent purple), right atrial appendage (RAA, beige), Pectinate Muscles (PM, green), cristalterminalis (CT, solid purple), sinoatrial node (SAN, red), superior vena cava (SVC), atrio-ventricular ring (AVR, grey), right pulmonary vein (RPV, blue), Bachmann’s bundle (BB, orange), left atrium (LA, light blue), left atrial appendage (LAA, yellow), inferior vena cava (IVC) and left pulmonary veins (LPV, blue). A(ii) is a snapshot of the activation of the atria at 30ms after initiation. B(i) Torso model with all the considerations used in the simulation, we can observe the position of the atria as well. B(ii) BSP produced in our simulation, corresponding to the atrial snapshot in Aii. C(i) and (ii) indicate the different stimulated points across the surface of the atria, used for focal ectopic pacing. D Positions of the electrodes placement in the torso mesh from the front (i) and from the back (ii), for the 64-lead ECG system.
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Research Article A Computer Simulation Study of Anatomy Induced Drift of Spiral Waves in the Human Atrium
2014Co-Authors: Sanjay R. Kharche, Henggui Zhang, Irina V. Biktasheva, Gunnar Seemann, Vadim N. BiktashevAbstract:Copyright © 2015 Sanjay R. Kharche et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The interaction of spiral waves of excitation with atrial anatomy remains unclear. This simulation study isolates the role of atrial anatomical structures on spiral wave spontaneous drift in the human atrium. We implemented realistic and idealised 3D human atria models to investigate the functional impact of anatomical structures on the long-term (∼40 s) behaviour of spiral waves. The drift of a spiral wave was quantified by tracing its tip trajectory, which was correlated to atrial anatomical features. The interaction of spiral waves with the following idealised geometries was investigated: (a) a wedge-like structure with a continuously varying atrial wall thickness; (b) a ridge-like structure with a sudden change in atrial wall thickness; (c) multiple bridge-like structures consisting of a bridge connected to the atrial wall. Spiral waves drifted from thicker to thinner regions and along ridge-like structures. Breakthrough patterns caused by Pectinate Muscles (PM) bridges were also observed, albeit infrequently. Apparent anchoring close to PM-atrial wall junctions was observed. These observations were similar in both the realistic and the idealised models. We conclude that spatially altering atrial wall thickness is a significant cause of drift of spiral waves. PM bridges cause breakthrough patterns and induce transient anchoring of spiral waves. 1
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mechanisms of transition from normal to reentrant electrical activity in a model of rabbit atrial tissue interaction of tissue heterogeneity and anisotropy
Biophysical Journal, 2009Co-Authors: Oleg Aslanidi, Mark R Boyett, Halina Dobrzynski, Jue Li, Henggui ZhangAbstract:Experimental evidence suggests that regional differences in action potential (AP) morphology can provide a substrate for initiation and maintenance of reentrant arrhythmias in the right atrium (RA), but the relationships between the complex electrophysiological and anatomical organization of the RA and the genesis of reentry are unclear. In this study, a biophysically detailed three-dimensional computer model of the right atrial tissue was constructed to study the role of tissue heterogeneity and anisotropy in arrhythmogenesis. The model of Lindblad et al. for a rabbit atrial cell was modified to incorporate experimental data on regional differences in several ionic currents (primarily, INa, ICaL, IK1, Ito, and Isus) between the crista terminalis and Pectinate muscle cells. The modified model was validated by its ability to reproduce the AP properties measured experimentally. The anatomical model of the rabbit RA (including tissue geometry and fiber orientation) was based on a recent histological reconstruction. Simulations with the resultant electrophysiologically and anatomically detailed three-dimensional model show that complex organization of the RA tissue causes breakdown of regular AP conduction patterns at high pacing rates (>11.75 Hz): as the AP in the crista terminalis cells is longer, and electrotonic coupling transverse to fibers of the crista terminalis is weak, high-frequency pacing at the border between the crista terminalis and Pectinate Muscles results in a unidirectional conduction block toward the crista terminalis and generation of reentry. Contributions of the tissue heterogeneity and anisotropy to reentry initiation mechanisms are quantified by measuring action potential duration (APD) gradients at the border between the crista terminalis and Pectinate Muscles: the APD gradients are high in areas where both heterogeneity and anisotropy are high, such that intrinsic APD differences are not diminished by electrotonic interactions. Thus, our detailed computer model reconstructs complex electrical activity in the RA, and provides new insights into the mechanisms of transition from focal atrial tachycardia into reentry.
Omer Berenfeld - One of the best experts on this subject based on the ideXlab platform.
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endoscopic fluorescence mapping of the left atrium a novel experimental approach for high resolution endocardial mapping in the intact heart
Heart Rhythm, 2007Co-Authors: Jerome Kalifa, Jose Jalife, Sergey Mironov, Matthew Klos, Sharon Zlochiver, Kazuhiko Tanaka, Netha Ulahannan, Masatoshi Yamazaki, Omer BerenfeldAbstract:Background Despite the availability of several mapping technologies for investigating the electrophysiologic mechanisms of atrial fibrillation (AF), an experimental tool enabling high-resolution mapping of electrical impulses on the endocardial surface of the intact left atrium is lacking. Objective The purpose of this report is to present a new optical mapping approach implementing a steerable cardio-endoscope in isolated hearts. Methods The system consists of a direct or side-view endoscope coupled to a 532-nm excitation laser for illumination and a CCD camera for imaging of potentiometric dye fluorescence (di-4-ANEPPS, 80 × 80 pixels, 200–800 frames/s). The cardio-endoscope was aimed successively at diverse posterior left atrial locations to obtain high-resolution movies of electrical wave propagation and detailed endocardial anatomic features in the presence and absence of atrial stretch. Results We present several examples of high-resolution endoscopic posterior left atrial recordings of wave propagation patterns during both sinus rhythm and AF with signal-to-noise ratio similar to conventional optical mapping systems. We demonstrate the endoscope's ability to visualize highly organized AF sources (rotors) at specific locations on the posterior left atrium and posterior left atrium–pulmonary vein junctions. We present video images of waves emanating from such sources as they propagate into Pectinate Muscles in the left atrial appendage. In particular, we demonstrate this approach is ideally suited for studying the effects of atrial stretch on AF dynamics. Conclusion In isolated hearts, cardio-endoscopic optical mapping of electrical activity should enable comprehensive evaluation of AF activity in the posterior left atrium, the role of local anatomy on AF dynamics, and the efficacy of pharmacologic and ablative interventions.
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frequency dependent breakdown of wave propagation into fibrillatory conduction across the Pectinate muscle network in the isolated sheep right atrium
Circulation Research, 2002Co-Authors: Omer Berenfeld, Alexey V Zaitsev, Sergey Mironov, Arkady M Pertsov, Jose JalifeAbstract:Atrial fibrillation (AF) may result from stationary reentry in the left atrium (LA), with fibrillatory conduction toward the right atrium (RA). We hypothesize that periodic input to the RA at an exceedingly high frequency results in disorganized wave propagation, compatible with fibrillatory conduction. Simultaneous endocardial and epicardial optical mapping (di-4-ANEPPS) was performed in isolated, coronary-perfused sheep RA. Rhythmic pacing of Bachmann’s bundle allowed well-controlled and realistic conditions for LA-driven RA. Pacing at increasingly higher frequencies (2.0 to 6.0 Hz) led to increasing delays in activation distal to major branching sites of the crista terminalis and Pectinate bundles, culminating in spatially distributed intermittent blockade at or above ≈6.5 Hz. At this “breakdown frequency,” the direction of RA propagation became completely variable from beat to beat and thus transformed into fibrillatory conduction. Such frequency-dependent changes were independent of action potential duration. Rather, the spatial boundaries between proximal and distal frequencies correlated well with branch sites of the Pectinate musculature. Thus, there exists a breakdown frequency in the sheep RA below which activity is periodic throughout the atrium and above which it is fibrillation-like. The data are consistent with the ideas that during AF, high-frequency activation initiated in the LA undergoes fibrillatory conduction toward the RA, and that sink-to-source effect at branch points of the crista terminalis and Pectinate Muscles is important in determining the complexity of the arrhythmia.
Jose Jalife - One of the best experts on this subject based on the ideXlab platform.
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endoscopic fluorescence mapping of the left atrium a novel experimental approach for high resolution endocardial mapping in the intact heart
Heart Rhythm, 2007Co-Authors: Jerome Kalifa, Jose Jalife, Sergey Mironov, Matthew Klos, Sharon Zlochiver, Kazuhiko Tanaka, Netha Ulahannan, Masatoshi Yamazaki, Omer BerenfeldAbstract:Background Despite the availability of several mapping technologies for investigating the electrophysiologic mechanisms of atrial fibrillation (AF), an experimental tool enabling high-resolution mapping of electrical impulses on the endocardial surface of the intact left atrium is lacking. Objective The purpose of this report is to present a new optical mapping approach implementing a steerable cardio-endoscope in isolated hearts. Methods The system consists of a direct or side-view endoscope coupled to a 532-nm excitation laser for illumination and a CCD camera for imaging of potentiometric dye fluorescence (di-4-ANEPPS, 80 × 80 pixels, 200–800 frames/s). The cardio-endoscope was aimed successively at diverse posterior left atrial locations to obtain high-resolution movies of electrical wave propagation and detailed endocardial anatomic features in the presence and absence of atrial stretch. Results We present several examples of high-resolution endoscopic posterior left atrial recordings of wave propagation patterns during both sinus rhythm and AF with signal-to-noise ratio similar to conventional optical mapping systems. We demonstrate the endoscope's ability to visualize highly organized AF sources (rotors) at specific locations on the posterior left atrium and posterior left atrium–pulmonary vein junctions. We present video images of waves emanating from such sources as they propagate into Pectinate Muscles in the left atrial appendage. In particular, we demonstrate this approach is ideally suited for studying the effects of atrial stretch on AF dynamics. Conclusion In isolated hearts, cardio-endoscopic optical mapping of electrical activity should enable comprehensive evaluation of AF activity in the posterior left atrium, the role of local anatomy on AF dynamics, and the efficacy of pharmacologic and ablative interventions.
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frequency dependent breakdown of wave propagation into fibrillatory conduction across the Pectinate muscle network in the isolated sheep right atrium
Circulation Research, 2002Co-Authors: Omer Berenfeld, Alexey V Zaitsev, Sergey Mironov, Arkady M Pertsov, Jose JalifeAbstract:Atrial fibrillation (AF) may result from stationary reentry in the left atrium (LA), with fibrillatory conduction toward the right atrium (RA). We hypothesize that periodic input to the RA at an exceedingly high frequency results in disorganized wave propagation, compatible with fibrillatory conduction. Simultaneous endocardial and epicardial optical mapping (di-4-ANEPPS) was performed in isolated, coronary-perfused sheep RA. Rhythmic pacing of Bachmann’s bundle allowed well-controlled and realistic conditions for LA-driven RA. Pacing at increasingly higher frequencies (2.0 to 6.0 Hz) led to increasing delays in activation distal to major branching sites of the crista terminalis and Pectinate bundles, culminating in spatially distributed intermittent blockade at or above ≈6.5 Hz. At this “breakdown frequency,” the direction of RA propagation became completely variable from beat to beat and thus transformed into fibrillatory conduction. Such frequency-dependent changes were independent of action potential duration. Rather, the spatial boundaries between proximal and distal frequencies correlated well with branch sites of the Pectinate musculature. Thus, there exists a breakdown frequency in the sheep RA below which activity is periodic throughout the atrium and above which it is fibrillation-like. The data are consistent with the ideas that during AF, high-frequency activation initiated in the LA undergoes fibrillatory conduction toward the RA, and that sink-to-source effect at branch points of the crista terminalis and Pectinate Muscles is important in determining the complexity of the arrhythmia.
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Ventricular fibrillation and atrial fibrillation are two different beasts.
Chaos, 1998Co-Authors: Richard A. Gray, Jose JalifeAbstract:Although the mechanisms of fibrillation are no doubt multi-faceted, the geometry of the heart may play a major role in the dynamics of wave propagation during fibrillation [A. T. Winfree, Science 266, 1003–1006 (1994)]. The ventricles are thick chambers made up of sheets of parallel muscle fibers with the direction of fibers rotating across the ventricular walls (rotational anisotropy). The thick walls of the ventricles allow reentry to develop transmurally, provided the wavelength is sufficiently small. Depending on the kinetics of heart cells, the dynamics of rotating waves in three dimensions may be fundamentally different than in two dimensions, leading to destabilization of reentry and ventricular fibrillation (VF) in thick ventricles. The atria have an intricate geometry comprised of a thin sheet of cardiac tissue attached to a very complex network of Pectinate Muscles. The branching geometry of the Pectinate Muscles may lead to destabilization of two-dimensional reentry via “long-distance” electric...