Person: Kleber, Andre
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Kleber
First Name
Andre
Name
Kleber, Andre
3 results
Search Results
Now showing 1 - 3 of 3
Publication Activation During Sinus Rhythm in Ventricles With Healed Infarction(Ovid Technologies (Wolters Kluwer Health), 2019-10) Rottmann, Markus; Kleber, Andre; Barkagan, Michael; Sroubek, Jakub; Leshem, Eran; Shapira-Daniels, Ayelet; Buxton, Alfred; Anter, EladBackground: In infarct-related ventricular tachycardia (VT), the circuit often corresponds to a location characterized by activation slowing during sinus rhythm (SR). However, the relationship between activation slowing during SR and vulnerability for reentry and correlation to components of the VT circuit are unknown. This study examined the relationship between activation slowing during SR and vulnerability for reentry and correlated these areas with components of the circuit. Methods: In a porcine model of healed infarction, the spatial distribution of endocardial activation velocity was compared between SR and VT. Isthmus sites were defined using activation and entrainment mapping as areas exhibiting diastolic activity within the circuit while bystanders were defined as areas displaying diastolic activity outside the circuit. Results: Of 15 swine, 9 had inducible VT (5.2±3.0 per animal) while in 6 swine VT could not be induced despite stimulation from 4 RV and LV sites at 2 drive trains with 6 extra-stimuli down to refractoriness. Infarcts with VT had a greater magnitude of activation slowing during SR. A minimal endocardial activation velocity cutoff ≤0.1m/sec differentiated inducible from non-inducible infarctions (p=0.015). Regions of maximal endocardial slowing during SR corresponded to the VT isthmus (AUC=0.84 [95% CI 0.78-0.90) while bystander sites exhibited near-normal activation during SR. VT circuits were complex with 41.7% exhibiting discontinuous propagation with intramural bridges of slow conduction and delayed quasi-simultaneous endocardial activation. Regions forming the VT isthmus borders had faster activation during SR while regions forming the inner isthmus were activated faster during VT. Conclusions: Endocardial activation slowing during SR may differentiate infarctions vulnerable for VT from those less vulnerable for VT. Sites of slow activation during SR correspond to sites forming the VT isthmus but not to bystander sites.Publication Role of the intercalated disc in cardiac propagation and arrhythmogenesis(Frontiers Media S.A., 2014) Kleber, Andre; Saffitz, JeffreyThis 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.Publication Cell-to-cell coupling in engineered pairs of rat ventricular cardiomyocytes: relation between Cx43 immunofluorescence and intercellular electrical conductance(American Physiological Society, 2012) McCain, Megan; Desplantez, Thomas; Geisse, Nicholas A.; Rothen-Rutishauser, Barbara; Oberer, Helene; Parker, Kevin; Kleber, AndreGap junctions are composed of connexin (Cx) proteins, which mediate intercellular communication. Cx43 is the dominant Cx in ventricular myocardium, and Cx45 is present in trace amounts. Cx43 immunosignal has been associated with cell-to-cell coupling and electrical propagation, but no studies have directly correlated Cx43 immunosignal to electrical cell-to-cell conductance, \(g_j\), in ventricular cardiomyocyte pairs. To assess the correlation between Cx43 immunosignal and \(g_j\), we developed a method to determine both parameters from the same cell pair. Neonatal rat ventricular cardiomyocytes were seeded on micropatterned islands of fibronectin. This allowed formation of cell pairs with reproducible shapes and facilitated tracking of cell pair locations. Moreover, cell spreading was limited by the fibronectin pattern, which allowed us to increase cell height by reducing the surface area of the pattern. Whole cell dual voltage clamp was used to record \(g_j\) of cell pairs after 3–5 days in culture. Fixation of cell pairs before removal of patch electrodes enabled preservation of cell morphology and offline identification of patched pairs. Subsequently, pairs were immunostained, and the volume of junctional Cx43 was quantified using confocal microscopy, image deconvolution, and three-dimensional reconstruction. Our results show a linear correlation between gj and Cx43 immunosignal within a range of 8–50 nS.