3,547 results on '"Purkinje fibers"'
Search Results
2. Partial and complete loss of myosin binding protein H-like cause cardiac conduction defects
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David Y. Barefield, Sean Yamakawa, Ibrahim Tahtah, Jordan J. Sell, Michael Broman, Brigitte Laforest, Sloane Harris, Alejandro Alvarez-Arce, Kelly N. Araujo, Megan J. Puckelwartz, J. Andrew Wasserstrom, Glenn I. Fishman, and Elizabeth M. McNally
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Arrhythmias, Cardiac ,Myosins ,Article ,Purkinje Fibers ,Cytoskeletal Proteins ,Mice ,Cardiac Conduction System Disease ,Contactins ,Tachycardia ,Animals ,Humans ,Calcium ,Heart Atria ,Cardiology and Cardiovascular Medicine ,Molecular Biology - Abstract
A premature truncation of MYBPHL in humans and a loss of Mybphl in mice is associated with dilated cardiomyopathy, atrial and ventricular arrhythmias, and atrial enlargement. MYBPHL encodes myosin binding protein H-like (MyBP-HL). Prior work in mice indirectly identified Mybphl expression in the atria and in small puncta throughout the ventricle. Because of its genetic association with human and mouse cardiac conduction system disease, we evaluated the anatomical localization of MyBP-HL and the consequences of loss of MyBP-HL on conduction system function. Immunofluorescence microscopy of normal adult mouse ventricles identified MyBP-HL-positive ventricular cardiomyocytes that co-localized with the ventricular conduction system marker contactin-2 near the atrioventricular node and in a subset of Purkinje fibers. Mybphl heterozygous ventricles had a marked reduction of MyBP-HL-positive cells compared to controls. Lightsheet microscopy of normal perinatal day 5 mouse hearts showed enrichment of MyBP-HL-positive cells within and immediately adjacent to the contactin-2-positive ventricular conduction system, but this association was not apparent in Mybphl heterozygous hearts. Surface telemetry of Mybphl-null mice revealed atrioventricular block and atrial bigeminy, while intracardiac pacing revealed a shorter atrial relative refractory period and atrial tachycardia. Calcium transient analysis of isolated Mybphl-null atrial cardiomyocytes demonstrated an increased heterogeneity of calcium release and faster rates of calcium release compared to wild type controls. Super-resolution microscopy of Mybphl heterozygous and homozygous null atrial cardiomyocytes showed ryanodine receptor disorganization compared to wild type controls. Abnormal calcium release, shorter atrial refractory period, and atrial dilation seen in Mybphl null, but not wild type control hearts, agree with the observed atrial arrhythmias, bigeminy, and atrial tachycardia, whereas the proximity of MyBP-HL-positive cells with the ventricular conduction system provides insight into how a predominantly atrial expressed gene contributes to ventricular arrhythmias and ventricular dysfunction.
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- 2022
3. Role of Purkinje‒muscle junction in early ventricular fibrillation in a porcine model: Beyond the trigger concept
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Robert D. Anderson, Stéphane Massé, John Asta, Patrick F.H. Lai, Praloy Chakraborty, Mohammed Ali Azam, Eugene Downar, and Kumaraswamy Nanthakumar
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Epicardial Mapping ,Purkinje Fibers ,Swine ,Muscles ,Ventricular Fibrillation ,Catheter Ablation ,Animals ,Humans ,General Medicine ,Cardiology and Cardiovascular Medicine ,Endocardium - Abstract
The role of the Purkinje network in triggering ventricular fibrillation (VF) has been studied; however, its involvement after onset and in early maintenance of VF is controversial.We studied the role of the Purkinje-muscle junctions (PMJ) on epicardial-endocardial activation gradients during early VF.In a healthy, porcine, beating-heart Langendorff model [control, n = 5; ablation, n = 5], simultaneous epicardial-endocardial dominant frequent mapping was used (224 unipolar electrograms) to calculate activation rate gradients during the onset and early phase of VF. Selective Purkinje ablation was performed using Lugol's solution, followed by VF re-induction and mapping and finally, histological evaluation.Epicardial activation rates were faster than endocardial rates for both onset and early VF. After PMJ ablation, activation rates decreased epicardially and endocardially for both onset and early VF [Epi: 9.7 ± 0.2 to 8.3 ± 0.2 Hz (p.0001) and 10.9 ± 0.4 to 8.8 ± 0.3 Hz (p.0001), respectively; Endo: 8.2 ± 0.3 Hz to 7.4 ± 0.2 Hz (p.0001) and 7.0 ± 0.4 Hz to 6.6 ± 0.3 Hz (p = .0002), respectively]. In controls, epicardial-endocardial activation rate gradients during onset and early VF were 1.7 ± 0.3 Hz and 4.5 ± 0.4 Hz (p.001), respectively. After endocardial ablation of PMJs, these gradients were reduced to 0.9 ± 0.3 Hz (onset VF, p.001) and to 2.2 ± 0.3 Hz (early VF, p.001). Endocardial-epicardial Purkinje fiber arborization and selective Purkinje fiber extinction after only endocardial ablation (not with epicardial ablation) was confirmed on histological analysis.Beyond the trigger paradigm, PMJs determine activation rate gradients during onset and during early maintenance of VF.
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- 2022
4. Morphology of septomarginal trabeculae in Hatay mountain gazelle (Gazella gazella)
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Baran Erdem, Tolga Tutar, Lutfi Takci, Yeşim Akaydin Bozkurt, and Sevinç Ateş
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Male ,Purkinje Fibers ,Antelopes ,General Veterinary ,Connective Tissue ,Heart Ventricles ,Myocardium ,Animals ,Female ,General Medicine - Abstract
This study was conducted to reveal the anatomical and histological features of left and right septomarginal trabeculae in the heart of the Hatay mountain gazelle. In the study, two female and two male adult Hatay mountain gazelle hearts were used. For this purpose, the materials detected in 10% formaldehyde solution were stained with Crossman's modified triple staining technique and examined under a light microscope after anatomical examinations and measurements were made. The presence of trabeculae in both ventricles was demonstrated. While the number of septomarginal trabeculae was 1 in each of the samples in the right ventricle, it was determined that it was 2 in each of three hearts and 3 in one heart in the left ventricle. It was observed that the right trabeculae were unbranched and fleshy, while the left trabeculae were filamentous and mostly branched. The lengths and thicknesses of the right trabeculae were measured 12-17 mm and 3-4 mm and the lengths and thicknesses of the left trabeculae were measured 6-15 mm and 0.5-1 mm. In the histological examination of both trabeculae, connective tissue, Purkinje fibres and blood vessels were observed, in addition, it was detected that the right trabeculae had myocardial fibres. Few capillaries were found in the left trabecula, while both more capillaries and blood vessels were found in the right trabeculae.
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- 2021
5. A novel transgenic Cre allele to label mouse cardiac conduction system
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Peter C Kahr, Shuang Li, Matthew C. Hill, Ge Tao, James F. Martin, Min Zhang, and Zachary A. Kadow
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Heart Injury ,Purkinje fibers ,Heart Ventricles ,Population ,Purkinje cell ,Myocardial Infarction ,Mice, Transgenic ,Biology ,Article ,Purkinje Fibers ,Mice ,Heart Conduction System ,medicine ,Animals ,Regeneration ,Ventricular Function ,Cell Lineage ,Myocytes, Cardiac ,RNA-Seq ,Myocardial infarction ,education ,Molecular Biology ,Alleles ,education.field_of_study ,Integrases ,Myocardium ,Regeneration (biology) ,Cell Biology ,medicine.disease ,Cardiovascular physiology ,Cell biology ,Tamoxifen ,medicine.anatomical_structure ,Animals, Newborn ,cardiovascular system ,Electrical conduction system of the heart ,Transcriptome ,Developmental Biology - Abstract
The cardiac conduction system is a network of heterogeneous cell population that initiates and propagates electric excitations in the myocardium. Purkinje fibers, a network of specialized myocardial cells, comprise the distal end of the conduction system in the ventricles. The developmental origins of Purkinje fibers and their roles during cardiac physiology and arrhythmia have been reported. However, it is not clear if they play a role during ischemic injury and heart regeneration. Here we introduce a novel tamoxifen-inducible Cre allele that specifically labels a broad range of components in the cardiac conduction system while excludes other cardiac cell types and vital organs. Using this new allele, we investigated the cellular and molecular response of Purkinje fibers to myocardial injury. In a neonatal mouse myocardial infarction model, we observed significant increase in Purkinje cell number in regenerating myocardium. RNA-Seq analysis using laser-captured Purkinje fibers showed a unique transcriptomic response to myocardial infarction. Our finds suggest a novel role of cardiac Purkinje fibers in heart injury.
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- 2021
6. Sex differences in the origin of Purkinje ectopy-initiated idiopathic ventricular fibrillation
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Estelle Gandjbakhch, Josselin Duchateau, Ghassen Cheniti, Elodie Surget, F. Daniel Ramirez, Fabrice Extramiana, Pierre Jaïs, Clémentine André, Yosuke Nakatani, Takashi Nakashima, Antoine Leenhardt, Akihiko Nogami, Philipp Krisai, Mélèze Hocini, Takamitsu Takagi, Olivier Bernus, Tsukasa Kamakura, Frederic Sacher, Françoise Hidden-Lucet, Romain Tixier, Michel Haïssaguerre, Nicolas Welte, Xavier Pillois, Remi Chauvel, Nicolas Derval, Thomas Pambrun, and David Benoist
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Adult ,Male ,medicine.medical_specialty ,Heart Ventricles ,Long QT syndrome ,medicine.medical_treatment ,Magnetic Resonance Imaging, Cine ,Catheter ablation ,Coronary Angiography ,Risk Assessment ,Sudden death ,Purkinje Fibers ,Electrocardiography ,Electrophysiology study ,Sex Factors ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Medical history ,Circadian rhythm ,Sex Distribution ,Retrospective Studies ,Brugada syndrome ,medicine.diagnostic_test ,business.industry ,Incidence ,medicine.disease ,Ventricular Premature Complexes ,medicine.anatomical_structure ,Echocardiography ,Ventricle ,Ventricular Fibrillation ,Cardiology ,Female ,France ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity. Objective The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF. Methods Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin. Results Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P Conclusion PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.
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- 2021
7. Automated Framework for the Inclusion of a His–Purkinje System in Cardiac Digital Twins of Ventricular Electrophysiology
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Karli Gillette, Aurel Neic, Anton J. Prassl, Gernot Plank, Julien Bouyssier, Matthias A. F. Gsell, and Edward J. Vigmond
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Bundle of His ,medicine.medical_specialty ,Parameter identification ,Computer science ,Biomedical Engineering ,12 lead electrocardiogram ,Purkinje Fibers ,Ventricular myocardium ,Electrocardiography ,Heart Conduction System ,His–Purkinje system ,Internal medicine ,medicine ,Humans ,Sinus rhythm ,Precision Medicine ,Cardiac electrophysiology ,Computational cardiac modeling ,Models, Cardiovascular ,Magnetic Resonance Imaging ,Virtual Physiological Human ,Electrocardiogram ,Electrophysiology ,Ventricular activation ,Cardiology ,Electrophysiologic Techniques, Cardiac ,Algorithms ,Forward ECG modeling - Abstract
Personalized models of cardiac electrophysiology (EP) that match clinical observation with high fidelity, referred to as cardiac digital twins (CDTs), show promise as a tool for tailoring cardiac precision therapies. Building CDTs of cardiac EP relies on the ability of models to replicate the ventricular activation sequence under a broad range of conditions. Of pivotal importance is the His–Purkinje system (HPS) within the ventricles. Workflows for the generation and incorporation of HPS models are needed for use in cardiac digital twinning pipelines that aim to minimize the misfit between model predictions and clinical data such as the 12 lead electrocardiogram (ECG). We thus develop an automated two stage approach for HPS personalization. A fascicular-based model is first introduced that modulates the endocardial Purkinje network. Only emergent features of sites of earliest activation within the ventricular myocardium and a fast-conducting sub-endocardial layer are accounted for. It is then replaced by a topologically realistic Purkinje-based representation of the HPS. Feasibility of the approach is demonstrated. Equivalence between both HPS model representations is investigated by comparing activation patterns and 12 lead ECGs under both sinus rhythm and right-ventricular apical pacing. Predominant ECG morphology is preserved by both HPS models under sinus conditions, but elucidates differences during pacing. Supplementary Information The online version contains supplementary material available at 10.1007/s10439-021-02825-9.
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- 2021
8. Estimation of Personalized Minimal Purkinje Systems From Human Electro-Anatomical Maps
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Josselin Duchateau, Edward J. Vigmond, Michel Haïssaguerre, Fernando Barber, Mélèze Hocini, Rafael Sebastian, Miguel Lozano, Ignacio García-Fernández, and Peter Langfield
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Radiological and Ultrasound Technology ,business.industry ,Computer science ,Heart Ventricles ,Myocardium ,Network structure ,Therapy planning ,Pattern recognition ,Computer Science Applications ,Purkinje Fibers ,Electrocardiography ,Electrophysiology ,Humans ,Computer Simulation ,Time error ,Artificial intelligence ,Electrical and Electronic Engineering ,business ,Heart structure ,Contraction (operator theory) ,Software - Abstract
The Purkinje system is a heart structure responsible for transmitting electrical impulses through the ventricles in a fast and coordinated way to trigger mechanical contraction. Estimating a patient-specific compatible Purkinje Network from an electro-anatomical map is a challenging task, that could help to improve models for electrophysiology simulations or provide aid in therapy planning, such as radiofrequency ablation. In this study, we present a methodology to inversely estimate a Purkinje network from a patient's electro-anatomical map. First, we carry out a simulation study to assess the accuracy of the method for different synthetic Purkinje network morphologies and myocardial junction densities. Second, we estimate the Purkinje network from a set of 28 electro-anatomical maps from patients, obtaining an optimal conduction velocity in the Purkinje network of 1.95 ± 0.25 m/s, together with the location of their Purkinje-myocardial junctions, and Purkinje network structure. Our results showed an average local activation time error of 6.8±2.2 ms in the endocardium. Finally, using the personalized Purkinje network, we obtained correlations higher than 0.85 between simulated and clinical 12-lead ECGs.
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- 2021
9. Environmental Fe, Ti, Al, Cu, Hg, Bi, and Si Nanoparticles in the Atrioventricular Conduction Axis and the Associated Ultrastructural Damage in Young Urbanites: Cardiac Arrhythmias Caused by Anthropogenic, Industrial, E-Waste, and Indoor Nanoparticles
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Rafael Reynoso-Robles, Rafael Brito-Aguilar, José Luis Rodríguez-López, Carlos Gayosso-Chávez, H. G. Silva-Pereyra, Beatriz Pérez-Guillé, Gladis Judith Labrada-Delgado, Partha Sarathi Mukherjee, Ricardo Delgado-Chávez, Rosa Eugenia Soriano-Rosales, Lilian Calderón-Garcidueñas, Miguel Angel Jiménez-Bravo Luna, and Angélica González-Maciel
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Tachycardia ,Purkinje fibers ,Industrial Waste ,010501 environmental sciences ,01 natural sciences ,Sarcomere ,Electronic Waste ,Lipofuscin ,medicine ,Humans ,Tachycardia, Atrioventricular Nodal Reentry ,Environmental Chemistry ,Mexico ,Cell damage ,Aged ,0105 earth and related environmental sciences ,Titanium ,Chemistry ,Gap junction ,Arrhythmias, Cardiac ,Mercury ,General Chemistry ,medicine.disease ,Atrioventricular node ,medicine.anatomical_structure ,Transmission electron microscopy ,Atrioventricular Node ,cardiovascular system ,Biophysics ,Nanoparticles ,medicine.symptom - Abstract
Air pollution exposure is a risk factor for arrhythmia. The atrioventricular (AV) conduction axis is key for the passage of electrical signals to ventricles. We investigated whether environmental nanoparticles (NPs) reach the AV axis and whether they are associated with ultrastructural cell damage. Here, we demonstrate the detection of the shape, size, and composition of NPs by transmission electron microscopy (TEM) and energy-dispersive X-ray spectrometry (EDX) in 10 subjects from Metropolitan Mexico City (MMC) with a mean age of 25.3 ± 5.9 and a 71-year-old subject without cardiac pathology. We found that in every case, Fe, Ti, Al, Hg, Cu, Bi, and/or Si spherical or acicular NPs with a mean size of 36 ± 17 nm were present in the AV axis in situ, freely and as conglomerates, within the mitochondria, sarcomeres, lysosomes, lipofuscin, and/or intercalated disks and gap junctions of Purkinje and transitional cells, telocytes, macrophages, endothelium, and adjacent atrial and ventricular fibers. Erythrocytes were found to transfer NPs to the endothelium. Purkinje fibers with increased lysosomal activity and totally disordered myofilaments and fragmented Z-disks exhibited NP conglomerates in association with gap junctions and intercalated disks. AV conduction axis pathology caused by environmental NPs is a plausible and modifiable risk factor for understanding common arrhythmias and reentrant tachycardia. Anthropogenic, industrial, e-waste, and indoor NPs reach pacemaker regions, thereby increasing potential mechanisms that disrupt the electrical impulse pathways of the heart. The cardiotoxic, oxidative, and abnormal electric performance effects of NPs in pacemaker locations warrant extensive research. Cardiac arrhythmias associated with nanoparticle effects could be preventable.
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- 2021
10. [His-Purkinje system pacing: the latest journey and the original starting point]
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S L, Wu
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Purkinje Fibers ,Bundle of His ,Electrocardiography ,Bundle-Branch Block ,Cardiac Pacing, Artificial ,Humans - Published
- 2022
11. Reply to the Editor-The characteristics and potential origin of the proximal left anterior fascicle premature ventricular complexes
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Jinlin Zhang
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Purkinje Fibers ,Bundle of His ,Physiology (medical) ,Humans ,Cardiology and Cardiovascular Medicine ,Ventricular Premature Complexes - Published
- 2022
12. The change of cardiac axis deviation in catheter ablation of verapamil‐sensitive idiopathic left ventricular tachycardia
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Jian Wang, Ming Liang, Zulu Wang, Mingyu Sun, Guitang Yang, Han Yaling, Zhiqing Jin, and Yanchun Liang
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Purkinje fibers ,medicine.medical_treatment ,Catheter ablation ,030204 cardiovascular system & hematology ,Ventricular tachycardia ,Cardiac axis ,Purkinje Fibers ,Electrocardiography ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Sinus rhythm ,030212 general & internal medicine ,Child ,Aged ,business.industry ,General Medicine ,Middle Aged ,Ablation ,medicine.disease ,medicine.anatomical_structure ,Verapamil ,Child, Preschool ,Catheter Ablation ,Tachycardia, Ventricular ,Cardiology ,Left axis deviation ,Female ,sense organs ,Cardiology and Cardiovascular Medicine ,business ,Anti-Arrhythmia Agents ,medicine.drug - Abstract
Background The underlying mechanism of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) has been postulated to be reentrant activation in the Purkinje fiber network of the left posterior fascicle (LPF) or the left anterior fascicle (LAF). However, changing of cardiac axis deviation in sinus rhythm (SR) or during ILVT after radiofrequency catheter ablation (RFCA) has been rarely analyzed. Methods Of the 232 patients with sustained ILVT induced and surface electrocardiogram (ECG) in SR recorded before and after RFCA, the changes of ECG morphology in SR and during ILVT were analyzed. Results The surface ECG in SR changed in 114 (49.1%) patients after RFCA. ILVT could still be induced in 27 (23.7%) patients. In comparison with the original ILVT, 3 forms of ECG morphology were observed. In 8 patients the ILVT morphology was unchanged. In the 13 patients with ILVT axis deviation conversion after ablation, the successful target was more proximal. In the 6 patients with ILVT morphology change but without axis deviation conversion after ablation, the successful ablation site was more distal. Among 15 patients with recurrent ILVT during follow-up, 7 patients had previous axis deviation changes in SR after RFCA, the changes maintained in 4 patients and recovered in 3 patients. Conclusions The morphology changes on surface ECG in SR after RFCA wouldn't be a necessary prerequisite or a good endpoint for ILVT ablation. To analyze ILVT morphology changes after ablation would help to further clarify an appropriate approach for catheter ablation of ILVT. This article is protected by copyright. All rights reserved.
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- 2021
13. Muscarinic agonists inhibit the ATP-dependent potassium current and suppress the ventricle–Purkinje action potential dispersion
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Jozefina Szlovák, Norbert Jost, Tamás Árpádffy-Lovas, Norbert Nagy, István Koncz, Zsolt Gurabi, Zsófia Kohajda, Julius Gy. Papp, Balázs Györe, Péter Gazdag, András Gyökeres, Noémi Tóth, László Virág, Bence József Pászti, and Tibor Magyar
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Physiology ,Purkinje fibers ,Heart Ventricles ,Action Potentials ,Muscarinic Agonists ,Pharmacology ,Purkinje Fibers ,Parasympathetic nervous system ,Adenosine Triphosphate ,Dogs ,Physiology (medical) ,Muscarinic acetylcholine receptor ,medicine ,Animals ,Chemistry ,General Medicine ,Hypoxia (medical) ,Potassium current ,medicine.anatomical_structure ,Ventricle ,Potassium ,cardiovascular system ,medicine.symptom ,Acetylcholine ,medicine.drug - Abstract
Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia–reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent potassium current (I K-ATP), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified. Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch-clamp method. Acetylcholine at 5 μmol/L did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje–ventricle APD dispersion when it was administered after 5 μmol/L pinacidil application. Carbachol at 3 μmol/L reduced the pinacidil-activated I K-ATP under voltage-clamp conditions. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition. In this study, we found that acetylcholine inhibits the I K-ATP and thus suppresses the ventricle–Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions.
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- 2021
14. Three‐dimensional visualization of the bovine cardiac conduction system and surrounding structures compared to the arrangements in the human heart
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Marcos C. de Almeida, Robert H. Anderson, and Shumpei Mori
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0301 basic medicine ,Histology ,Purkinje fibers ,03 medical and health sciences ,Imaging, Three-Dimensional ,0302 clinical medicine ,Species Specificity ,Heart Conduction System ,medicine ,Animals ,Humans ,Ventricular outflow tract ,cardiovascular diseases ,Molecular Biology ,Aorta ,Ecology, Evolution, Behavior and Systematics ,Sinus (anatomy) ,business.industry ,Human heart ,Heart ,Cell Biology ,Anatomy ,Original Papers ,Atrioventricular node ,Bundle branches ,Apex (geometry) ,030104 developmental biology ,medicine.anatomical_structure ,cardiovascular system ,Cattle ,Electrical conduction system of the heart ,Tomography, X-Ray Computed ,business ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
In the human heart, the atrioventricular node is located toward the apex of the triangle of Koch, which is also at the apex of the inferior pyramidal space. It is adjacent to the atrioventricular portion of the membranous septum, through which it penetrates to become the atrioventricular bundle. Subsequent to its penetration, the conduction axis is located on the crest of the ventricular septum, sandwiched between the muscular septum and ventricular component of the membranous septum, where it gives rise to the ramifications of the left bundle branch. In contrast, the bovine conduction axis has a long non‐branching component, which penetrates into a thick muscular atrioventricular septum having skirted the main cardiac bone and the rightward half of the non‐coronary sinus of the aortic root. It commonly gives rise to both right and left bundle branches within the muscular ventricular septum. Unlike the situation in man, the left bundle branch is long and thin before it branches into its fascicles. These differences from the human heart, however, have yet to be shown in three‐dimensions relative to the surrounding structures. We have now achieved this goal by injecting contrast material into the insulating sheaths that surround the conduction network, evaluating the results by subsequent computed tomography. The fibrous atrioventricular membranous septum of the human heart is replaced in the ox by the main cardiac bone and the muscular atrioventricular septum. The apex of the inferior pyramidal space, which in the bovine, as in the human, is related to the atrioventricular node, is placed inferiorly relative to the left ventricular outflow tract. The bovine atrioventricular conduction axis, therefore, originates from a node itself located inferiorly compared to the human arrangement. The axis must then skirt the non‐coronary sinus of the aortic root prior to penetrating the thicker muscular ventricular septum, thus accounting for its long non‐branching course. We envisage that our findings will further enhance comparative anatomical research.
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- 2021
15. Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: possible implication to enhanced proarrhythmic risk
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Péter Gazdag, István Koncz, Bence József Pászti, Tibor Magyar, András Varró, Jozefina Szlovák, Norbert Jost, László Virág, János Prorok, Tamás Árpádffy-Lovas, Leila Topal, Balázs Györe, Norbert Nagy, and Muhammad Naveed
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Male ,Drug ,Patch-Clamp Techniques ,Physiology ,Heart Ventricles ,media_common.quotation_subject ,Action Potentials ,Ibuprofen ,030204 cardiovascular system & hematology ,Pharmacology ,030226 pharmacology & pharmacy ,Purkinje Fibers ,03 medical and health sciences ,chemistry.chemical_compound ,Dogs ,0302 clinical medicine ,Levofloxacin ,Physiology (medical) ,Animals ,Humans ,Medicine ,Myocytes, Cardiac ,Repolarization reserve ,media_common ,Nonsteroidal ,Dose-Response Relationship, Drug ,business.industry ,organic chemicals ,Anti-Inflammatory Agents, Non-Steroidal ,Arrhythmias, Cardiac ,Rabbit (nuclear engineering) ,General Medicine ,Electrophysiology ,chemistry ,Rabbits ,business ,Microelectrodes ,medicine.drug - Abstract
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM; n = 6) and rabbit (100 µM; n = 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (n = 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence IK1, but decreased the amplitude of Ito and IKr potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed INaL and ICa currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.
- Published
- 2021
16. Different effects of amiodarone and dofetilide on the dispersion of repolarization between well-coupled ventricular and Purkinje fibers1
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András Varró, István Baczkó, Zoltán Husti, László Virág, and Tamás Árpádffy-Lovas
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Pharmacology ,medicine.medical_specialty ,Physiology ,Chemistry ,Purkinje fibers ,Ventricular Tachyarrhythmias ,Transmural dispersion ,Dofetilide ,General Medicine ,Amiodarone ,medicine.anatomical_structure ,Physiology (medical) ,Internal medicine ,Dispersion (optics) ,cardiovascular system ,medicine ,Ventricular muscle ,Cardiology ,Repolarization ,medicine.drug - Abstract
Increased transmural dispersion of repolarization is an established contributing factor to ventricular tachyarrhythmias. In this study, we evaluated the effect of chronic amiodarone treatment and acute administration of dofetilide in canine cardiac preparations containing electrotonically coupled Purkinje fibers (PFs) and ventricular muscle (VM) and compared the effects to those in uncoupled PF and VM preparations using the conventional microelectrode technique. Dispersion between PFs and VM was inferred from the difference in the respective action potential durations (APDs). In coupled preparations, amiodarone decreased the difference in APDs between PFs and VM, thus decreasing dispersion. In the same preparations, dofetilide increased the dispersion by causing a more pronounced prolongation in PFs. This prolongation was even more emphasized in uncoupled PF preparations, while the effect in VM was the same. In uncoupled preparations, amiodarone elicited no change on the difference in APDs. In conclusion, amiodarone decreased the dispersion between PFs and VM, while dofetilide increased it. The measured difference in APD between cardiac regions may be the affected by electrotonic coupling; thus, studying PFs and VM separately may lead to an over- or underestimation of dispersion.
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- 2021
17. Ventricular fibrillation after ablation of a benign arrhythmia. Angry Purkinje syndrome?
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Raphael Rosso, Arie Lorin Schwartz, Sami Viskin, Yuval Levi, and Aviram Hochstadt
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Quinidine ,medicine.medical_specialty ,Polymorphic ventricular tachycardia ,Purkinje fibers ,business.industry ,medicine.medical_treatment ,Case Report ,Cardiac arrest ,Ablation ,medicine.disease ,medicine.anatomical_structure ,Internal medicine ,Ventricular fibrillation ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Published
- 2020
18. Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation
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Machteld J. Boonstra, Rob W. Roudijk, Rolf Brummel, Wil Kassenberg, Lennart J. Blom, Thom F. Oostendorp, Anneline S. J. M. te Riele, Jeroen F. van der Heijden, Folkert W. Asselbergs, Peter Loh, and Peter M. van Dam
- Subjects
Diagnostic Imaging ,Purkinje Fibers ,Electrocardiography ,Heart Conduction System ,Body Surface Potential Mapping ,Image Interpretation, Computer-Assisted ,Biomedical Engineering ,Humans ,Arrhythmias, Cardiac ,cardiovascular diseases ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Ventricular Function, Left - Abstract
Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicateiECG. To improve the estimation of normal ventricular activation, theiECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focaliECG. Therefore, we introduce the novel multi-waveiECG method and report on its performance. Multi-waveiECG and multi-focaliECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for bothiECG methods. TheiECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-waveiECG versus multi-focaliECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.
- Published
- 2022
19. Idiopathic multifocal myocardial atrophy with fibrosis and fatty infiltration involving Purkinje fibres in a 13‐year‐old Arabian broodmare: Histopathological features
- Author
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Mohammad Ali, Wasiq Mehmood, Masa-aki Oikawa, and Midori Goto Asakawa
- Subjects
Pathology ,medicine.medical_specialty ,Myocarditis ,sudden death ,Case Report ,Autopsy ,Case Reports ,Arabian horses ,Sudden death ,Purkinje Fibers ,cardiopathology ,Atrophy ,Fibrosis ,medicine ,Animals ,Horses ,Interventricular septum ,Myocardial Degeneration ,General Veterinary ,business.industry ,medicine.disease ,Purkinje fibres ,medicine.anatomical_structure ,cardiac conduction system ,histopathology ,Female ,Horse Diseases ,Myocardial fibrosis ,Cardiomyopathies ,business - Abstract
Myocardial atrophy with fibrosis and fatty infiltration involving the cardiac conduction system is relatively unusual in horses. We herein report of such a case in a 13‐year‐old Arabian broodmare that had spontaneously died on a paddock. An autopsy revealed multifocal myocardial atrophy with concomitant fibrosis and fatty infiltration in both the ventricles and interventricular septum. The Purkinje fibres in the ventricles and interventricular septum were surrounded by thick fibrous or adipose tissues adjacent to atrophic myocardial cells. Myocardial fibrosis and fatty infiltration were likely secondary to myocardial atrophy, occurring as a pathological response triggered by the repair of muscular wall injury. However, there were no major vascular pathologies (e.g. atherosclerosis and arteriosclerosis); hence, the pathogenesis of myocardial atrophy was unclear. There was no evidence of myocardial atrophy - induced pathologies such as infarct, ischaemic lesions, myocardial degeneration, myocarditis and endocarditis. However, such an unusual histopathological pattern may be associated with rapid clinical deterioration and death., Idiopathic multifocal myocardial atrophy.
- Published
- 2020
20. Vascular supply of the anterior interventricular epicardial nerves and ventricular Purkinje fibers in the porcine hearts
- Author
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Vladimir Musil, Josef Sach, Vaclav Kudrna, Jana Vranova, Petr Zach, Jana Mrzilkova, J Stingl, Zdenek Suchomel, and David Kachlik
- Subjects
0106 biological sciences ,0301 basic medicine ,Purkinje fibers ,Left Ventricles ,Anatomy ,Biology ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Adventitia ,Vasa nervorum ,cardiovascular system ,medicine ,Porcine heart ,Animal Science and Zoology ,Anterior interventricular artery ,Vein ,Vascular supply ,Developmental Biology - Abstract
The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.
- Published
- 2020
21. Clinical outcomes of His‐Purkinje conduction system pacing
- Author
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Amal Muthumala and Pugazhendhi Vijayaraman
- Subjects
Bradycardia ,Bundle of His ,medicine.medical_specialty ,medicine.medical_treatment ,Bundle-Branch Block ,Cardiac resynchronization therapy ,030204 cardiovascular system & hematology ,Cardiac Resynchronization Therapy ,Purkinje Fibers ,03 medical and health sciences ,0302 clinical medicine ,Cardiac Conduction System Disease ,Heart Conduction System ,Atrioventricular node ablation ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,His-Purkinje conduction ,business.industry ,Cardiac Pacing, Artificial ,General Medicine ,medicine.disease ,Ventricular activation ,Heart failure ,Cardiology ,Implant ,medicine.symptom ,Electrical conduction system of the heart ,Cardiology and Cardiovascular Medicine ,business - Abstract
His-Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing (HBP) and left bundle branch pacing (LBBP) allows normal left ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. HBP has been established for several years with centers from China, Europe, and North America reporting their experience. There is international guidance as to how to implant such systems with the differing patterns of His bundle capture clearly described. LBBP is a more recent innovation with potential advantages including improved pacing parameters. HPCSP has been extensively studied in a variety of indications including cardiac resynchronization therapy, atrioventricular node ablation, and bradycardia pacing. This review will focus on the clinical outcomes of HPCSP including mortality and morbidity of heart failure hospitalization and symptoms.
- Published
- 2020
22. Investigating cardiac stimulation limits of MRI gradient coils using electromagnetic and electrophysiological simulations in human and canine body models
- Author
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Lothar R. Schad, Bastien Guerin, Valerie Klein, Mathias Davids, and Lawrence L. Wald
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Purkinje fibers ,heart model ,Solenoid ,Slew rate ,Parameter space ,Article ,030218 nuclear medicine & medical imaging ,Switching time ,03 medical and health sciences ,Dogs ,Electromagnetic Fields ,0302 clinical medicine ,cardiac stimulation ,electromagnetic exposure safety ,Electric field ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,MRI gradient field switching ,Physics ,magnetostimulation thresholds ,Magnetic Resonance Imaging ,Amplitude ,medicine.anatomical_structure ,Electromagnetic coil ,electromagnetic field simulation ,Cardiac Electrophysiology ,Electromagnetic Phenomena ,Algorithms ,030217 neurology & neurosurgery ,Biomedical engineering - Abstract
Purpose Cardiac stimulation (CS) limits to gradient coil switching speed are difficult to measure in humans; instead, current regulatory guidelines (IEC 60601-2-33) are based on animal experiments and electric field-to-dB/dt conversion factors computed for a simple, homogeneous body model. We propose improvement to this methodology by using more detailed CS modeling based on realistic body models and electrophysiological models of excitable cardiac fibers. Methods We compute electric fields induced by a solenoid, coplanar loops, and a commercial gradient coil in two human body models and a canine model. The canine simulations mimic previously published experiments. We generate realistic fiber topologies for the cardiac Purkinje and ventricular muscle fiber networks using rule-based algorithms, and evaluate CS thresholds using validated electrodynamic models of these fibers. Results We were able to reproduce the average measured canine CS thresholds within 5%. In all simulations, the Purkinje fibers were stimulated before the ventricular fibers, and therefore set the effective CS threshold. For the investigated gradient coil, simulated CS thresholds for the x-, y-, and z-axis were at least one order of magnitude greater than the International Electrotechnical Commission limit. Conclusion We demonstrate an approach to simulate gradient-induced CS using a combination of electromagnetic and electrophysiological modeling. Pending additional validation, these simulations could guide the assessment of CS limits to MRI gradient coil switching speed. Such an approach may lead to less conservative, but still safe, operation limits, enabling the use of the maximum gradient amplitude versus slew rate parameter space of recent, powerful gradient systems.
- Published
- 2020
23. Purkinje Fibers in Canine False Tendons: New Anatomical and Electrophysiological Findings
- Author
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Yanchun Liang, Zhang Qi, Sainan Li, Junqi Wang, Jing-Jing Rong, Guitang Yang, Xunzhang Wang, Ming Liang, Yaling Han, Zulu Wang, Yang Lv, Yi Li, Mingyu Sun, and Yuji Zhang
- Subjects
Decremental conduction ,Article Subject ,Purkinje fibers ,business.industry ,Anatomy ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Electrophysiology ,0302 clinical medicine ,medicine.anatomical_structure ,RC666-701 ,Mitral valve ,cardiovascular system ,medicine ,Diseases of the circulatory (Cardiovascular) system ,cardiovascular diseases ,030212 general & internal medicine ,Chordae tendineae ,Cardiology and Cardiovascular Medicine ,business ,Papillary muscle ,Endocardium ,Research Article - Abstract
Introduction. Purkinje system and false tendons (FTs) are related to ventricular arrhythmia, but the association between Purkinje fibers and FTs is not clear. This study investigated the associations of anatomical and electrophysiological characteristics between Purkinje fibers and FTs. Methods and Results. We optimized the protocol of Lugol’s iodine solution staining of Purkinje fibers to study the anatomical structure and originated a novel electrophysiological mapping method, named the direct visual mapping (DVM) method, to study the electrophysiological characteristics. By using the above-mentioned innovations in 12 dogs, we found the following. (1) There was no Purkinje fiber found 0.5 cm–1.0 cm below the valve annulus or on the leaflets or chordae tendineae of the mitral valve or adjacent to the top 1/3 of the papillary muscle. (2) Purkinje fibers existed in all FTs, including smaller and tiny FTs. (3) The Purkinje fibers contained in the FTs extended from the proximal to the distal end, and their electrophysiological characteristics were similar to the fibers on the endocardium, including anterograde, retrograde, and decremental conduction and automaticity. Conclusions. Purkinje fibers are commonly found in FTs. The electrophysiological characteristics of the Purkinje fibers contained in FTs are similar to the fibers on the endocardium. FTs might have an anatomical and electrophysiological basis for ventricular arrhythmia.
- Published
- 2020
24. Reduced Na+ current in Purkinje fibers explains cardiac conduction defects and arrhythmias in Duchenne muscular dystrophy
- Author
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Bruno K. Podesser, Attila Kiss, Janine Ebner, Hannes Todt, Xaver Koenig, Petra L. Szabo, Karlheinz Hilber, and Pavel Uhrin
- Subjects
medicine.medical_specialty ,biology ,Physiology ,Purkinje fibers ,Chemistry ,Duchenne muscular dystrophy ,Connexin ,Decreased cardiac output ,medicine.disease ,Green fluorescent protein ,medicine.anatomical_structure ,Physiology (medical) ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,biology.protein ,cardiovascular diseases ,Patch clamp ,Cardiology and Cardiovascular Medicine ,Dystrophin ,Perfusion - Abstract
Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a degenerative muscle disease triggered by mutations in the gene encoding for the intracellular protein dystrophin. A major source for the arrhythmias in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant mechanisms. The reason for ventricular conduction impairments and the associated arrhythmias in the dystrophic heart has remained unidentified. In the present study, we explored the hypothesis that dystrophin-deficient cardiac Purkinje fibers have reduced Na+ currents (INa), which would represent a potential mechanism underlying slowed ventricular conduction in the dystrophic heart. Therefore, by using a Langendorff perfusion system, we isolated Purkinje fibers from the hearts of adult wild-type control and dystrophin-deficient mdx mice. Enhanced green fluorescent protein (eGFP) expression under control of the connexin 40 gene allowed us to discriminate Purkinje fibers from eGFP-negative ventricular working cardiomyocytes after cell isolation. Finally, we recorded INa from wild-type and dystrophic mdx Purkinje fibers for comparison by means of the whole cell patch clamp technique. We found substantially reduced INa densities in mdx compared with wild-type Purkinje fibers, suggesting that dystrophin deficiency diminishes INa. Because Na+ channels in the Purkinje fiber membrane represent key determinants of ventricular conduction velocity, we propose that reduced INa in Purkinje fibers at least partly explains impaired ventricular conduction and the associated arrhythmias in the dystrophic heart.NEW & NOTEWORTHY Dystrophic cardiac Purkinje fibers have abnormally reduced Na+ current densities. This explains impaired ventricular conduction in the dystrophic heart.
- Published
- 2020
25. Voltage dependent conduction abnormalities in His bundle pacing in patients without His Purkinje system disease
- Author
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Mohamed Musheinesh, Rehan Mahmud, and Shakeel Jamal
- Subjects
Bundle of His ,medicine.medical_specialty ,business.industry ,Cardiac Pacing, Artificial ,Stimulation ,High voltage ,030204 cardiovascular system & hematology ,Purkinje Fibers ,Electrocardiography ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Bundle ,Internal medicine ,Cardiology ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Abnormality ,Cardiology and Cardiovascular Medicine ,Lead (electronics) ,business ,Low voltage ,Voltage - Abstract
Background During His bundle (HB) pacing, the active fixation of HB lead may cause disruption of the enclosed conduction fibers and cause conduction delay. His Purkinje conduction delays have been shown to revert to normal with higher voltage pacing. Objective To determine if conduction delays seen with penetrative HB pacing are voltage dependent and can resolve with higher stimulus voltage. Methods In 17 patients undergoing HBP, the effect of voltage on a composite His Purkinje system-ventricular activation time (hVAT) as well as electrocardiographic (ECG) evidence of conduction delay, was systematically evaluated. Results There was highly significant prolongation of hVAT indicative of conduction delay in 13/17 patients. ECG changes of rightward delay were also seen in 9/13 patients. Both types of delays we manifest at lower voltages and we uniquely resolved by higher stimulation voltage. A pre-excitation like abnormality was also seen in 15/17 patients. This conduction abnormality was manifest at higher voltage without prolongation of hVAT. In 6/15 patients the pre-excitation like abnormality ceased at lower voltage. Conclusion HB pacing is associated with evidence of significant conduction delay noted at low voltage, which resolves with higher stimulation voltage. The more common pre-excitation like abnormality appears to occur at high voltage and, in of itself, does not appear to prolong hVAT.
- Published
- 2020
26. Towards chamber specific heart-on-a-chip for drug testing applications
- Author
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Milica Radisic, Benjamin F.L. Lai, Yimu Zhao, Erika Yan Wang, Qinghua Wu, Naimeh Rafatian, Houman Savoji, and Rick Xing Ze Lu
- Subjects
Purkinje fibers ,Induced Pluripotent Stem Cells ,Pharmaceutical Science ,02 engineering and technology ,Disease ,Organ-on-a-chip ,Article ,03 medical and health sciences ,Lab-On-A-Chip Devices ,Drug Discovery ,medicine ,Humans ,Myocytes, Cardiac ,Induced pluripotent stem cell ,030304 developmental biology ,0303 health sciences ,Tissue Engineering ,Drug discovery ,Sinoatrial node ,business.industry ,Heart ,021001 nanoscience & nanotechnology ,Atrioventricular node ,medicine.anatomical_structure ,Microtechnology ,0210 nano-technology ,business ,Neuroscience ,Biofabrication - Abstract
Modelling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modelling. Innovative biofabrication techniques have facilitated the development of organ-on-a-chip technology that has great potential to complement conventional animal models. However, human organ as a whole, more specifically the human heart, is difficult to regenerate in vitro, in terms of its chamber specific orientation and its electrical functional complexity. Recent progress with the development of induced pluripotent stem cell differentiation protocols, made recapitulating the complexity of the human heart possible through the generation of cells representative of atrial & ventricular tissue, the sinoatrial node, atrioventricular node and Purkinje fibers. Current heart-on-a-chip approaches incorporate biological, electrical, mechanical, and topographical cues to facilitate tissue maturation, therefore improving the predictive power for the chamber-specific therapeutic effects targeting adult human. In this review, we will give a summary of current advances in heart-on-a-chip technology and provide a comprehensive outlook on the challenges involved in the development of human physiologically relevant heart-on-a-chip.
- Published
- 2020
27. Die Entdeckung des AV-Knotens des Herzens durch Sunao Tawara und Ludwig Aschoff
- Author
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Gerhard Aumüller
- Subjects
business.industry ,Purkinje fibers ,General Medicine ,Anatomy ,030204 cardiovascular system & hematology ,Functional interpretation ,Atrioventricular node ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,Atrioventricular bundle ,Electrical conduction system of the heart ,business - Abstract
Already in 1664, the Danish anatomist and naturalist Niels Stensen proved that the heart is a muscle. But for a long time it remained unclear what triggered the heart contractions.The Dutch physiologist Willem Einthoven registered the electrical processes in the contraction of the heart muscle and thus provided the first electrophysiological basis of cardiac muscle activity. Since 1903, Sunao Tawara was assistant to Ludwig Aschoff in Marburg. Both left Marburg in 1906: Tawara went back to Japan and Aschoff to Freiburg. In 1905, Tawara discovered the connections of the His’ bundle to the AV node and the Purkinje fibers. At that time, there was no thought of a functional interpretation. Tawara discovered a kind of “knot” that linked to the adjacent myocardial cells, as well as the “Tawara thighs”, which frayed and went into structures known as Purkinje fibers. Tawara detected the tree-like structure he had discovered as a muscle-fiber system that controlled the arousal of the heart’s musculature. Thus the old dispute between myogenic and neurogenic arousal of the heart was decided in favor of the myogenic excitation conduction. The atrioventricular node described by Tawara was given the eponym “Aschoff-Tawara node”. Tawara’s groundbreaking work on the conduction system was the basis for the discovery of the sinus node and the interpretation of the heart’s electrophysiology.
- Published
- 2019
28. SCN5A variant R222Q generated abnormal changes in cardiac sodium current and action potentials in murine myocytes and Purkinje cells
- Author
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Brett M. Kroncke, Tao Yang, Dan M. Roden, Lynn Hall, Laura L. Daniel, and Dina Myers Stroud
- Subjects
Purkinje fibers ,Mutant ,Action Potentials ,Mice, Transgenic ,Sodium Channels ,Article ,NAV1.5 Voltage-Gated Sodium Channel ,Electrocardiography ,Mice ,Purkinje Cells ,Physiology (medical) ,Animals ,Medicine ,Repolarization ,Myocyte ,Myocytes, Cardiac ,Alleles ,business.industry ,Sodium channel ,Dilated cardiomyopathy ,medicine.disease ,Cell biology ,Disease Models, Animal ,Electrophysiology ,medicine.anatomical_structure ,Echocardiography ,Heterologous expression ,Cardiology and Cardiovascular Medicine ,business - Abstract
BACKGROUND: The cardiac sodium channel (SCN5A) mutation, R222Q, neutralizes a positive charge in the domain I voltage sensor. Mutation carriers display very frequent ectopy and dilated cardiomyopathy (DCM). OBJECTIVES: To describe the effect of SCN5A R222Q on murine myocyte and Purkinje fiber electrophysiology, and identify underlying mechanisms. METHODS: We generated mice carrying humanized wild-type (H) and mutant (RQ) SCN5A channels. We characterized whole heart and isolated ventricular and Purkinje myocyte properties. RESULTS: RQ/RQ mice were not viable. I(Na) from RQ/H ventricular myocytes displayed increased “window current” and hyperpolarizing shifts in both inactivation and activation compared to H/H, as previously reported in heterologous expression systems. Surprisingly, action potentials were markedly abbreviated in RQ/H myocytes (APD90: 12.6±1.3 ms versus 29.1±1.0 ms in H/H, p
- Published
- 2019
29. Identification through action potential clamp of proarrhythmic consequences of the short QT syndrome T618I hERG 'hotspot' mutation
- Author
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Chunyun Du, Henggui Zhang, Stephen C. Harmer, and Jules C. Hancox
- Subjects
ERG1 Potassium Channel ,ERG1 Potassium Channel/genetics ,Patch-Clamp Techniques ,Electrocardiography/methods ,Patch-Clamp Techniques/methods ,Heart Ventricles ,Biophysics ,Heart Ventricles/metabolism ,Action Potentials ,Arrhythmias, Cardiac ,Cell Biology ,Purkinje Fibers/metabolism ,Biochemistry ,Heart Atria/metabolism ,Purkinje Fibers ,Electrocardiography ,HEK293 Cells ,Action Potentials/genetics ,Mutation ,Humans ,Arrhythmias, Cardiac/genetics ,Heart Atria ,Molecular Biology - Abstract
The T618I KCNH2-encoded hERG mutation is the most frequently observed mutation in genotyped cases of the congenital short QT syndrome (SQTS), a cardiac condition associated with ventricular fibrillation and sudden death. Most T618I hERG carriers exhibit a pronounced U wave on the electrocardiogram and appear vulnerable to ventricular, but not atrial fibrillation (AF). The basis for these effects is unclear. This study used the action potential (AP) voltage clamp technique to determine effects of the T618I mutation on hERG current (IhERG) elicited by APs from different cardiac regions. Whole-cell patch-clamp recordings were made at 37 °C of IhERG from hERG-transfected HEK-293 cells. Maximal IhERG during a ventricular AP command was increased ∼4-fold for T618I IhERG and occurred much earlier during AP repolarization. The mutation also increased peak repolarizing currents elicited by Purkinje fibre (PF) APs. Maximal wild-type (WT) IhERG current during the PF waveform was 87.2 ± 4.5% of maximal ventricular repolarizing current whilst for the T618I mutant, the comparable value was 47.7 ± 2.7%. Thus, the T618I mutation exacerbated differences in repolarizing IhERG between PF and ventricular APs; this could contribute to heterogeneity of ventricular-PF repolarization and consequently to the U waves seen in T618I carriers. The comparatively shorter duration and lack of pronounced plateau of the atrial AP led to a smaller effect of the T618I mutation during the atrial AP, which may help account for the lack of reported AF in T618I carriers. Use of a paired ventricular AP protocol revealed an alteration to protective IhERG transients that affect susceptibility to premature excitation late in AP repolarization/early in diastole. These observations may help explain altered arrhythmia susceptibility in this form of the SQTS.
- Published
- 2021
30. Anatomy and Pathology of the Cardiac Conduction System
- Author
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Melanie C. Bois, Fatima M. Ezzeddine, Anvi Raina, Roshan Karki, and Samuel J. Asirvatham
- Subjects
Heart Failure ,Pathology ,medicine.medical_specialty ,Bundle of His ,business.industry ,Cardiac electrophysiology ,Purkinje fibers ,medicine.medical_treatment ,Developmental Anatomy ,Human heart ,Anatomy ,Ablation ,medicine.disease ,Atrioventricular node ,medicine.anatomical_structure ,Heart Conduction System ,Physiology (medical) ,Heart failure ,cardiovascular system ,medicine ,Atrioventricular Node ,Humans ,Electrical conduction system of the heart ,Cardiology and Cardiovascular Medicine ,business - Abstract
The cardiac conduction system is formed of histologically and electrophysiologically distinct specialized tissues uniquely located in the human heart. Understanding the anatomy and pathology of the cardiac conduction system is imperative to an interventional electrophysiologist to perform safe ablation and device therapy for the management of cardiac arrhythmias and heart failure. The current review summarizes the normal and developmental anatomy of the cardiac conduction system, its variation in the normal heart and congenital anomalies, and its pathology and discusses important clinical pearls for the proceduralist.
- Published
- 2021
31. To the Editor— The characteristics and potential origin of the proximal left anterior fascicle premature ventricular complexes
- Author
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Songwen Chen, Yong Wei, Genqing Zhou, Xiaofeng Lu, and Shaowen Liu
- Subjects
Purkinje Fibers ,Bundle of His ,Electrocardiography ,Physiology (medical) ,Catheter Ablation ,Humans ,Cardiology and Cardiovascular Medicine ,Ventricular Premature Complexes - Published
- 2022
32. A review of cardiac autonomics: from pathophysiology to therapy
- Author
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Blaine Prichard, Rahul Jain, Katherine Julian, Joseph Raco, and Rohit Jain
- Subjects
Cardiac function curve ,Heart Failure ,Baroreceptor ,Purkinje fibers ,business.industry ,medicine.medical_treatment ,Arrhythmias, Cardiac ,Heart ,medicine.disease ,Autonomic Nervous System ,Cardiac pacemaker ,Vagus nerve ,Autonomic nervous system ,medicine.anatomical_structure ,Heart Conduction System ,Heart failure ,cardiovascular system ,medicine ,Molecular Medicine ,Humans ,Myocytes, Cardiac ,Electrical conduction system of the heart ,Cardiology and Cardiovascular Medicine ,business ,Neuroscience - Abstract
The effective management of cardiovascular diseases requires knowledge of intrinsic and extrinsic innervation of the heart and an understanding of how perturbations of said components affect cardiac function. The innate cardiac conduction system, which begins with cardiac pacemaker cells and terminates with subendocardial Purkinje fibers, is modulated by said systems. The intrinsic component of the cardiac autonomic nervous system, which remains incompletely elucidated, consists of intracardiac ganglia and interconnecting neurons that tightly regulate cardiac electrical activity. Extrinsic components of the autonomic nervous system, such as carotid baroreceptors and renin-angiotensin-aldosterone system, modulate sympathetic input to the heart through the stellate ganglion and parasympathetic input via the vagus nerve. There remains a need for additional therapies to treat conditions, such as advanced heart failure and refractory arrhythmias, and a better understanding of autonomics may be key to their development.
- Published
- 2021
33. Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit
- Author
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Sunil Jit R. J. Logantha, Joseph Yanni, Ashraf Kitmitto, Oliver J. Monfredi, Luke Stuart, Akbar Vohra, Shu Nakao, R Hutcheon, Tobias Starborg, Caroline Jones, GM Quigley, George Hart, Robert S. Stephenson, Jonathan C. Jarvis, X. Cai, Antonio F. Corno, Il Young Oh, Halina Dobrzynski, and Mark R. Boyett
- Subjects
Male ,rabbits ,Action Potentials ,Purkinje fibers ,030204 cardiovascular system & hematology ,RC1200 ,Electrocardiography ,0302 clinical medicine ,Heart Rate ,Tomography ,0303 health sciences ,Ventricular Remodeling ,Cardiac Pacing, Artificial ,ion channels ,Rabbit (nuclear engineering) ,medicine.anatomical_structure ,Ion channels ,Models, Animal ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Cardiology ,Rabbits ,Cardiology and Cardiovascular Medicine ,RM ,medicine.medical_specialty ,Heart Ventricles ,Heart failure ,tomography ,03 medical and health sciences ,Internal medicine ,Electron microscopy ,medicine ,Animals ,Ventricular conduction ,Ion channel ,030304 developmental biology ,Heart Failure ,electron microscopy ,business.industry ,Original Articles ,X-Ray Microtomography ,medicine.disease ,R1 ,business - Abstract
Supplemental Digital Content is available in the text., Background: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. Methods: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. Results: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P
- Published
- 2021
34. Activation Propagation in Cardiac Ventricles Using the Model of the Normal and Disrupted Conduction System
- Author
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Elena Cocherova
- Subjects
Physics ,QRS complex ,medicine.anatomical_structure ,Nuclear magnetic resonance ,Purkinje fibers ,Multiphysics ,Bundle ,medicine ,Cardiac Ventricle ,Right bundle branch block ,Electrical conduction system of the heart ,medicine.disease ,Bundle branches - Abstract
The goal of the article was to design a model of cardiac ventricles with analytical geometry that enables simulation of normal and disrupted conduction system functions. The conduction system model comprised the His bundle, left and right bundle branches and an endocardial layer with higher conductivity representing the Purkinje fibers. While QRS duration relating to the total activation time of the whole ventricles lies in the physiological range of about 80 to 120 ms for the normal activation, it is more than 120 ms in the case of left or right bundle branch block (LBBB, RBBB). The propagated electrical activation in the model was described by the monodomain reaction-diffusion (RD) equation with the ionic transmembrane current density defined by the modified FitzHugh-Nagumo equations. This RD model of cardiac ventricles was numerically solved in the Comsol Multiphysics environment. Realistic activation time of the whole ventricles of about 98 ms was obtained for the model with a normal conduction system, while 151 ms and 129 ms were obtained for the model with LBBB and RBBB, respectively.
- Published
- 2021
35. New Onset Recurrent Syncope Triggered by Fever
- Author
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Marta Pachón, Miguel A. Arias, and Gerard Loughlin
- Subjects
Coronary angiography ,medicine.medical_specialty ,Fever ,Electric Countershock ,MEDLINE ,Amiodarone ,Electric countershock ,Coronary Angiography ,Syncope ,New onset ,Purkinje Fibers ,Electrocardiography ,Text mining ,Pharmacotherapy ,Recurrence ,Torsades de Pointes ,Streptococcal Infections ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,medicine.diagnostic_test ,biology ,business.industry ,Syncope (genus) ,Lidocaine ,Pharyngitis ,Middle Aged ,biology.organism_classification ,Ventricular Premature Complexes ,Tonsillitis ,Ventricular Fibrillation ,Cardiology ,Drug Therapy, Combination ,Female ,Cardiology and Cardiovascular Medicine ,business - Published
- 2020
36. Longitudinal dissociation and transition in thickness of the His‐Purkinje system cause various QRS waveforms of surface ECG under His bundle pacing: A simulation study based on clinical observations
- Author
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Takumi Washio, Jun-ichi Okada, Katsuhito Fujiu, Toshiaki Hisada, Issei Komuro, Seiryo Sugiura, and Eriko Hasumi
- Subjects
Bundle of His ,medicine.medical_specialty ,Bundle-Branch Block ,Longitudinal dissociation ,030204 cardiovascular system & hematology ,Purkinje Fibers ,Electrocardiography ,03 medical and health sciences ,Surface ecg ,QRS complex ,Imaging, Three-Dimensional ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Left bundle branch ,medicine ,Humans ,Waveform ,Computer Simulation ,cardiovascular diseases ,030212 general & internal medicine ,Right bundle branch ,Bundle branch block ,business.industry ,Cardiac Pacing, Artificial ,Models, Cardiovascular ,medicine.disease ,Bundle ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims His bundle pacing (HBP) is a feasible and reliable alternative to conventional right ventricular pacing (RVP), but associated ECG (electrocardiogram) changes have not been well-studied. This study aimed to determine the mechanisms underlying ECG changes associated with HBP using patient-specific multiscale heart simulations. Methods ECGs were recorded in two patients who were treated by HBP under a native rhythm and HBP at high and low voltages. We created patient-specific multiscale simulation heart models of these patients and performed ECG simulation under these conditions. Using these results and detailed information on the electrical field around the pacing lead, we investigated mechanisms underlying the observed ECG changes. Results Heart simulations successfully reproduced ECGs under a native rhythm for both cases. In case 1, nonselective HBP produced a left bundle branch (LBB) block pattern, which was reproduced as a selective right bundle branch (RBB) pacing. However, in case 2, ECG under nonselective HBP showed an RBB block pattern, which could not be reproduced by the commonly used framework. Findings on the electrical field and anatomy of the His bundle and its branches suggested that longitudinal dissociation of the His bundle and transition of thickness in the stem of the LBB caused a conduction delay in the RBB to produce these ECG changes in this patient. Conclusion Variations in the anatomy of the His bundle and its branches may underlie the diverse ECG responses to HBP. These variations should be taken into account when performing this therapy.
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- 2019
37. Prevention of ventricular fibrillation through de‐networking of the Purkinje system
- Author
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Guram Imnadze and Thomas Zerm
- Subjects
Epicardial Mapping ,Male ,medicine.medical_specialty ,Heart disease ,Purkinje fibers ,medicine.medical_treatment ,Catheter ablation ,030204 cardiovascular system & hematology ,Ventricular tachycardia ,ablation ,Proof of Concept Study ,Sudden cardiac death ,Purkinje Fibers ,Electrocardiography ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Purkinje network ,Radiofrequency Ablation ,Ischemic cardiomyopathy ,business.industry ,Dilated cardiomyopathy ,General Medicine ,Middle Aged ,medicine.disease ,Ventricular Premature Complexes ,Defibrillators, Implantable ,Electrophysiology ,Death, Sudden, Cardiac ,medicine.anatomical_structure ,Ventricular Fibrillation ,Ventricular fibrillation ,Cardiology ,Female ,ventricular tachycardia ,Cardiology and Cardiovascular Medicine ,business - Abstract
Introduction Sudden cardiac death from ventricular fibrillation (VF) remains a major health problem worldwide. Currently, there are limited treatment options available to patients who suffer from episodes of VF. Because Purkinje fibers have been implicated as a source of initiation of VF, we are presenting the first paper of a series highlighting the promising results of substrate modulation through “De‐Networking” of the Purkinje system preventing VF in patients without an alternative ablation strategy. Methods and Results We studied 10 consecutive patients (two female) all but one implanted with an ICD with documented VF or fast polymorphic Ventricular tachycardia (VT) (five patients without history of structural heart disease, two with ischemic cardiomyopathy, one with hypertrophic obstructive cardiomyopathy, one with dilated cardiomyopathy, and one with aortic valve disease). After 3D electroanatomical mapping, the left bundle branch (LBB) and left ventricular Purkinje potentials were annotated creating a virtual triangle with the apex formed by the distal LBB and the base by the most distal Purkinje potentials. Linear radiofrequency catheter ablation at the base of the triangle was performed, followed by ablation within the virtual triangle sparing the LBB and both fascicles (“de‐networking”). All patients were treated without complications. During 1‐year follow‐up, only 2/10(20%) patients experienced recurrence in form of a single episode of polymorphic VT/VF. Conclusion Catheter ablation of VF through “de‐networking” of the Purkinje system in patients without overt arrhythmia substrate or trigger appears safe and effective and will require further study in a larger patient cohort.
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- 2019
38. Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution
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Guang Li, Joseph C. Wu, David T. Paik, Shannon S. Choi, Jan W. Buikema, Lei Tian, Sneha Venkatraman, Eliza L. Adams, Benjamin Beyersdorf, Marc Tessier-Lavigne, William R. Goodyer, Orlando Chirikian, and Sean M. Wu
- Subjects
Physics ,Physiology ,Sinoatrial node ,Purkinje fibers ,fungi ,Cell ,Bundle branches ,Atrioventricular node ,Article ,Transcriptome ,Mice ,medicine.anatomical_structure ,Heart Conduction System ,Bundle ,medicine ,Animals ,RNA-Seq ,Single-Cell Analysis ,Electrical conduction system of the heart ,Cardiology and Cardiovascular Medicine ,Neuroscience - Abstract
Rationale: The cardiac conduction system (CCS) consists of distinct components including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers. Despite an essential role for the CCS in heart development and function, the CCS has remained challenging to interrogate because of inherent obstacles including small cell numbers, large cell-type heterogeneity, complex anatomy, and difficulty in isolation. Single-cell RNA-sequencing allows for genome-wide analysis of gene expression at single-cell resolution. Objective: Assess the transcriptional landscape of the entire CCS at single-cell resolution by single-cell RNA-sequencing within the developing mouse heart. Methods and Results: Wild-type, embryonic day 16.5 mouse hearts (n=6 per zone) were harvested and 3 zones of microdissection were isolated, including: Zone I—sinoatrial node region; Zone II—atrioventricular node/His region; and Zone III—bundle branch/Purkinje fiber region. Tissue was digested into single-cell suspensions, cells isolated, mRNA reverse transcribed, and barcoded before high-throughput sequencing and bioinformatics analyses. Single-cell RNA-sequencing was performed on over 22 000 cells, and all major cell types of the murine heart were successfully captured including bona fide clusters of cells consistent with each major component of the CCS. Unsupervised weighted gene coexpression network analysis led to the discovery of a host of novel CCS genes, a subset of which were validated using fluorescent in situ hybridization as well as whole-mount immunolabeling with volume imaging (iDISCO+) in 3 dimensions on intact mouse hearts. Further, subcluster analysis unveiled isolation of distinct CCS cell subtypes, including the clinically relevant but poorly characterized transitional cells that bridge the CCS and surrounding myocardium. Conclusions: Our study represents the first comprehensive assessment of the transcriptional profiles from the entire CCS at single-cell resolution and provides a characterization in the context of development and disease.
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- 2019
39. Idiopathic ventricular fibrillation with repetitive activity inducible within the distal Purkinje system
- Author
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Olivier Bernus, Michel Haïssaguerre, William Escande, Mélèze Hocini, Ghassen Cheniti, and Alexandre Zhao
- Subjects
Adult ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Purkinje system ,Sudden death ,Article ,Purkinje Fibers ,Electrocardiography ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Physiology (medical) ,Internal medicine ,Humans ,Medicine ,Idiopathic ventricular fibrillation ,business.industry ,Reentry ,Middle Aged ,medicine.disease ,Premature beat ,Ventricular Fibrillation ,Ventricular fibrillation ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Published
- 2019
40. Towards the modeling of the Purkinje/myocardium coupled problem: A well-posedness analysis
- Author
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S. Mani Aouadi, W. Mbarki, Nejib Zemzemi, Université de Tunis El Manar (UTM), Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), LIRIMA, Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, and Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]
- Subjects
Discretization ,Purkinje fibers ,Quantitative Biology::Tissues and Organs ,Physics::Medical Physics ,030204 cardiovascular system & hematology ,Space (mathematics) ,Discrete problem ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Weighted Sobolev spaces ,[MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP] ,Uniqueness ,[MATH]Mathematics [math] ,Purkinje/myocardium ,030304 developmental biology ,Mathematics ,0303 health sciences ,Applied Mathematics ,Mathematical analysis ,Semi-implicit scheme ,[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation ,Finite element method ,Coupling (electronics) ,Sobolev space ,Computational Mathematics ,medicine.anatomical_structure ,2010 MSC: 92B05, 35K55, 35K57, 65N38 ,Electrical conduction system of the heart ,Monodomain/bidomain - Abstract
The Purkinje network is the specialized conduction system in the heart. It ensures the physiological spread of the electrical wave in the ventricles. In this work, in an insulated heart framework, we model the free running Purkinje system, using the monodomain equation. The intra-myocardium part of the Purkinje fiber is coupled to the ventricular tissue using the bidomain equation. The coupling is performed through the extracellular potential. We discretize the problem in time using a semi-implicit scheme. Then, we write a variational formulation of the semi discrete problem in a non standard weighted Sobolev functional spaces. We prove the existence and uniqueness of the solution of the Purkinje/myocardium semi-discretized problem. We discretize in space by the finite element P 1 − L a g r a n g e and conduct some numerical tests showing the anterograde and retrograde propagation of the electrical wave between the tissue and the Purkinje fibers.
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- 2019
41. Mechanisms of in utero cortisol effects on the newborn heart revealed by transcriptomic modeling
- Author
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Charles E. Wood, Celia W Curtis, Elaine M. Richards, Mengchen Li, Maureen Keller-Wood, and Andrew Antolic
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Male ,0301 basic medicine ,Hydrocortisone ,Microarray ,Physiology ,Heart Ventricles ,Apoptosis ,030204 cardiovascular system & hematology ,Purkinje Fibers ,Transcriptome ,Andrology ,03 medical and health sciences ,Fetal Heart ,0302 clinical medicine ,Pregnancy ,Physiology (medical) ,Heart Septum ,Animals ,Medicine ,Sheep, Domestic ,Muscle Cells ,Fetus ,Models, Genetic ,business.industry ,Cell Cycle ,Arrhythmias, Cardiac ,Heart ,medicine.disease ,030104 developmental biology ,Animals, Newborn ,In utero ,Female ,business ,Research Article - Abstract
We have identified effects of elevated maternal cortisol (induced by maternal infusion 1 mg·kg−1·day−1) on fetal cardiac maturation and function using an ovine model. Whereas short-term exposure (115–130-day gestation) increased myocyte proliferation and Purkinje fiber apoptosis, infusions until birth caused bradycardia with increased incidence of arrhythmias at birth and increased perinatal death, despite normal fetal cortisol concentrations from 130 days to birth. Statistical modeling of the transcriptomic changes in hearts at 130 and 140 days suggested that maternal cortisol excess disrupts cardiac metabolism. In the current study, we modeled pathways in the left ventricle (LV) and interventricular septum (IVS) of newborn lambs after maternal cortisol infusion from 115 days to birth. In both LV and IVS the transcriptomic model indicated over-representation of cell cycle genes and suggested disruption of cell cycle progression. Pathways in the LV involved in cardiac architecture, including SMAD and bone morphogenetic protein ( BMP) were altered, and collagen deposition was increased. Pathways in IVS related to metabolism, calcium signaling, and the actin cytoskeleton were altered. Comparison of the effects of maternal cortisol excess to the effects of normal maturation from day 140 to birth revealed that only 20% of the genes changed in the LV were consistent with normal maturation, indicating that chronic elevation of maternal cortisol alters normal maturation of the fetal myocardium. These effects of maternal cortisol on the cardiac transcriptome, which may be secondary to metabolic effects, are consistent with cardiac remodeling and likely contribute to the adverse impact of maternal stress on perinatal cardiac function.
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- 2019
42. Early transient recurrence of ventricular fibrillation after catheter ablation of premature ventricular contraction from Purkinje fibers in two patients with myocardial infarction
- Author
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Masahiro Maruyama, Yoshitaka Iwanaga, Naotaka Hashiguchi, Ryobun Yasuoka, Takashi Kurita, Yasuhito Kotake, Masafumi Ueno, and Shunichi Miyazaki
- Subjects
medicine.medical_specialty ,business.industry ,Purkinje fibers ,medicine.medical_treatment ,Percutaneous coronary intervention ,Catheter ablation ,030204 cardiovascular system & hematology ,medicine.disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Refractory ,Internal medicine ,Conventional PCI ,Ventricular fibrillation ,Cardiology ,Medicine ,cardiovascular diseases ,030212 general & internal medicine ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Artery - Abstract
Catheter ablation (CA) targeting premature ventricular contraction (PVC) from Purkinje fibers can be an effective therapy for refractory ventricular fibrillation (VF) after myocardial infarction (MI). We experienced two cases in which catheter ablation targeting PVC initiating VF after percutaneous coronary intervention (PCI) in post-MI patients was effective despite transient early recurrences of VF. The first patient (a 68-year-old woman with MI) developed drug-refractory VF 3 days after PCI to the left anterior descending artery (LAD) and left circumflex artery. CA targeting Purkinje potential preceding PVC at the infarcted area eliminated both the PVCs and VF. Three days after the procedure, the VF attacks relapsed by a different type of PVC. However, the VF responded to conventional treatments and disappeared thereafter. In the second patient (an 83-year-old woman with old MI), refractory VF attacks occurred after PCI to the LAD. CA targeting Purkinje potential preceding two distinct types of PVC successfully suppressed the VF. Although the VF relapsed 2 days after CA, it was suppressed by conventional treatment and disappeared the next day.
- Published
- 2019
43. TRANSCRIPTOMIC HETEROGENEITY OF THE POSTNATAL ATRIOVENTRICULAR CONDUCTION SYSTEM AT A SINGLE-CELL RESOLUTION
- Author
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N Munshi, K Kim, and Y Oh
- Subjects
business.industry ,Purkinje fibers ,Gap junction ,Cell sorting ,Bundle branches ,Nerve conduction velocity ,Cell biology ,PCP4 ,medicine.anatomical_structure ,Medicine ,Myocyte ,Cardiology and Cardiovascular Medicine ,business ,NODAL - Abstract
BACKGROUND The atrioventricular conduction system (AVCS) is a network of specialized cardiomyocytes responsible for coordinated spreading of electrical impulses throughout the ventricles to allow synchronized contractions. Specifically, it is composed of the AV node (AVN), which delays the electrical signal, and the ventricular conduction system (VCS) (i.e. His bundle, bundle branches and Purkinje fibers), which rapidly propagates the signal throughout the ventricles. Different AVCS regions possess different electrophysiological properties, such as conduction velocity. Overlapping and nonoverlapping expression patterns of some key developmental transcription factors (TFs), including Irx3, Tbx3, Etv1 and Nkx2.5 within the AVCS, suggest heterogeneous gene expression profiles. Although these structures of the AVCS were discovered >100 years ago, our understanding about its molecular constituents remains largely limited. METHODS AND RESULTS AVCS cells, which make up ∼0.05% of myocytes (∼500 cells/1 million cardiomyocytes), were isolated from early postnatal hearts (P1 to P4) of fluorescent reporter mice (Cntn2-Cre;Rosa26TdTomato), purified using fluorescence-activated cell sorting, and were subjected to single-cell RNA-sequencing. Unbiased cluster analysis on ∼7000 AVCS cells demonstrated distinct transcriptomic profiles in the AVN, proximal-VCS (i.e. His bundle and bundle branches) and distal-VCS (i.e. Purkinje fibers). Conforming to previous studies, well-known conduction markers, such as Etv1 and Kcne1, were present throughout the entire AVCS, whereas a VCS-specific TF, Irx3, was expressed throughout only the VCS. Additionally, Tbx3, Pcp4, Nppa and Lyz2 were enriched in the proximal, not distal, VCS. Sub-clustering analysis of AVN and proximal-VCS further identified unique expression patterns of molecular markers, such as Shox2 (exclusively in compact AVN) and Rspo3 (likely in lower nodal region connecting AVN and proximal-VCS). Moreover, we uncovered a potential regulatory relationship between Irx3 and Tbx3 in mediating their downstream targets, gap junction Gja5 (Cx40) and Gja1 (Cx43). In Irx3- and Tbx3-positive proximal-VCS, Gja5 and Gja1 expressions were lower compared to Irx3-positive/Tbx3-negative distal-VCS. In only Irx3-negative/Tbx3-positive AVN, both Gja5 and Gja1 expressions were undetected. Importantly, this regulatory relationship was recapitulated in cultured neonatal mouse atrial and ventricular myocytes overexpressing Irx3 and/or Tbx3. We also identified a cluster of cells which co-expressed conductive genes (i.e. Irx3, Kcne1, Gja5, Etv1) as well as G2/M cell cycle genes (i.e. Birc5, Ube2c, Cdk1, Ccnb1/2), suggesting the presence of committed conduction cells undergoing proliferation after birth. CONCLUSION Our study provides a comprehensive view of the cellular and molecular heterogeneity within the postnatal AVCS at a high-resolution and identifies potential novel markers with unique and overlapping transcriptomic patterns.
- Published
- 2021
44. Disturbances in the intraventricular conduction system in teenagers with type 1 diabetes. A pilot study
- Author
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Joanna Chrzanowska, Anna Noczyńska, Małgorzata Poręba, Anna Janocha, Rafał Poręba, Monika Seifert, Agnieszka Zubkiewicz-Kucharska, Krystyna Laszki-Szcząchor, and Małgorzata Sobieszczańska
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Purkinje fibers ,Endocrinology, Diabetes and Metabolism ,Heart Ventricles ,Pilot Projects ,Electrocardiography ,Endocrinology ,Cardiac Conduction System Disease ,Heart Conduction System ,Internal medicine ,Internal Medicine ,Medicine ,Humans ,Child ,Glycated Hemoglobin ,Type 1 diabetes ,business.industry ,Body Surface Potential Mapping ,Arrhythmias, Cardiac ,Intraventricular conduction ,medicine.disease ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,Ventricle ,Heart failure ,Cardiology ,Female ,Electrical conduction system of the heart ,business ,Autonomic neuropathy ,Standard ECG - Abstract
Body Surface Potential Mapping (BSPM) is a multi-electrode synchronous method for examining electrocardiographic records on the patients’ body surface that allows the assessment of changes in the heart conduction system. The aim of the study was to visualize and evaluate changes in the intraventricular system in adolescents with T1D. Patients and methods Inclusion criteria: age > 12 years, T1D duration >3 years, HbA1c >8%. Exclusion criteria: diagnosis of autonomic neuropathy, heart structural defects, heart failure. BSPM data were processed into map plotting to illustrate differences in ventricular activation time (VAT, isochron lines). Results 33 teenagers (20 boys), mean age 15.0 ± 2.1 years, T1D from 6.8 ± 4.1 years were included. Mean HbA1c was 9.6 ± 2.0%. In the standard ECG recording abnormalities were not present. The distribution of isolines on the group-mean map plotted for T1D patients only initially resembles the course of isolines on the group-map for normal subjects (N = 30), in whom the electrical impulse stimulating the heart ventricles passes through the atrio-ventricular node, then symmetrically excites the branches of His bundle and finally the Purkinje fibers. In T1D patients, after proper onset of intraventricular stimulation, the isolines reflecting the both ventricles reach higher time values, which indicates problems in the propagation of the ventricular depolarization. Conclusions 1. The time values of ventricular stimulation on the maps in T1D indicate a delayed and distorted propagation of activation in the heart conduction system over the left and right ventricle. 2. The observed changes occurred mostly outside the thoracic area covered by the standard 12-lead ECG registration.
- Published
- 2021
45. Human influenza a virus causes myocardial and cardiac-specific conduction system infections associated with early inflammation and premature death
- Author
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Ana Falcón, Celia Gutierrez, Guadalupe Guerrero-Serna, Sami F. Noujaim, Christopher Pablo Cop, Noelia Zamarreño, José Ángel Nicolás-Ávila, José Jalife, Manuel Desco, Alejandro Bernabe, Andrés Hidalgo, Daniela Ponce-Balbuena, Jesús Ruiz-Cabello, David Filgueiras-Rama, Jasmina Vasilijevic, Amelia Nieto, Jose Manuel Alfonso, Daniel Calle, Fundación La Caixa, European Molecular Biology Organization, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomedica en Red - CIBER, Fundación ProCNIC, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Frankel Cardiovascular Centre, Michigan Medicine (Estados Unidos), and NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos)
- Subjects
0301 basic medicine ,Influenzavirus A ,Physiology ,030204 cardiovascular system & hematology ,Recombinant virus ,Virus Replication ,Connexins ,Madin Darby Canine Kidney Cells ,0302 clinical medicine ,Myocytes, Cardiac ,Lung ,Mice, Inbred BALB C ,Virulence ,Heart Infection ,Viral Load ,Extracellular Matrix ,Myocarditis ,medicine.anatomical_structure ,Host-Pathogen Interactions ,Cytokines ,Human Influenza A Virus ,Female ,medicine.symptom ,Electrical conduction system of the heart ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,Green Fluorescent Proteins ,Inflammation ,Mice, Transgenic ,Virus ,Proinflammatory cytokine ,Purkinje Fibers ,03 medical and health sciences ,Dogs ,Orthomyxoviridae Infections ,Heart Conduction System ,Physiology (medical) ,Cardiac conduction ,medicine ,Animals ,Humans ,Biología y Biomedicina ,business.industry ,Premature Death ,Editorials ,Fibrosis ,Viral Replication ,Disease Models, Animal ,Kinetics ,030104 developmental biology ,Viral replication ,Immunology ,Mutation ,business - Abstract
Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations. We evaluated lung and heart viral titres in mice infected with either one of several hIAV strains inoculated intranasally. 3D reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells, and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titres did not statistically correlate with viral titres in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titres in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut-attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4-day post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase. Human IAV can infect the heart and cardiac-specific conduction system, which may contribute to cardiac complications and premature death. JV is a PhD fellow of the La Caixa Foundation International Fellowship Programme (La Caixa/CNB). This work was supported by the European Molecular Biology Organizat ion (STF-7649 to AF), the Spanish Ministry of Science, Innovation and Universities (MCIU), (BFU2011-26175 and BFU2014-57797-R to AN), and the network Ciber de Enfermedades Respiratorias (CIBERES) including the Improvement and Mobilit y Programme. The CNIC is a Severo Ochoa Center of Excellence (SEV-2015-0505). CNIC is supported by MCIU and the Pro CNIC Foundation. This study was supported by grants from Fondo Europeo de Desarrollo Regional (CB16/11/00458), grants SAF2015-65607-R and SAF2016-80324-R from MCIU (A.H. and D.F-R.) and fellowship SVP-2014-068595 to J.A.N-A. This study was supported by Frankel Cardiovascular Centre, Michigan Medicine (Grant 332475). JJ is supported in part by the National Heart, Lung, and Blood Institute (R01 Grant HL122352). S.F.N is supported in part by the National Heart, Lung, and Blood Institute grants R21HL138064 and R01HL129136. Sí
- Published
- 2021
46. Demystifying the Heart
- Author
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J. Anthony Gomes
- Subjects
Cell physiology ,Coronary arteries ,medicine.anatomical_structure ,Purkinje fibers ,business.industry ,medicine ,Human heart ,Cardiac action potential ,business ,Neuroscience - Abstract
The heart is a dynamic electrical cum mechanical organ, a true engineering masterpiece. In this chapter, the modern understanding of the anatomy, cellular physiology, and mechanics of the human heart is presented.
- Published
- 2021
47. Further Insights Into a Classic Arrhythmia: The Long Journey Involving P1 and P2 Potentials
- Author
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Shumpei, Mori and Osamu, Fujimura
- Subjects
Purkinje Fibers ,Tachycardia, Ventricular ,Humans - Published
- 2020
48. On the nature of delays allowing anatomical re-entry involving the Purkinje network: a simulation study
- Author
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Julien Bouyssier, Jason D. Bayer, Michel Haïssaguerre, Edward J. Vigmond, and Hiroshi Ashikaga
- Subjects
0303 health sciences ,Refractory period ,business.industry ,medicine.medical_treatment ,Re entry ,Gap junction ,Arrhythmias, Cardiac ,030204 cardiovascular system & hematology ,Nerve conduction velocity ,Lesion ,Coupling (electronics) ,Purkinje Fibers ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,medicine ,Humans ,Computer Simulation ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Neuroscience ,Ion channel ,Reduction (orthopedic surgery) ,030304 developmental biology - Abstract
Aims Clinical observations suggest that the Purkinje network can be part of anatomical re-entry circuits in monomorphic or polymorphic ventricular arrhythmias. However, significant conduction delay is needed to support anatomical re-entry given the high conduction velocity within the Purkinje network. Methods and results We investigated, in computer models, whether damage rendering the Purkinje network as either an active lesion with slow conduction or a passive lesion with no excitable ionic channel, could explain clinical observations. Active lesions had compromised sodium current and a severe reduction in gap junction coupling, while passive lesions remained coupled by gap junctions, but modelled the membrane as a fixed resistance. Both types of tissue could provide significant delays of over 100 ms. Electrograms consistent with those obtained clinically were reproduced. However, passive tissue could not support re-entry as electrotonic coupling across the delay effectively increased the proximal refractory period to an extremely long interval. Active tissue, conversely, could robustly maintain re-entry. Conclusion Formation of anatomical re-entry using the Purkinje network is possible through highly reduced gap junctional coupling leading to slowed conduction.
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- 2020
49. Regulation of HCN2 Current by PI3K/Akt Signaling
- Author
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Zhongju Lu, Hong Zhan Wang, Chris R. Gordon, Lisa M. Ballou, Richard Z. Lin, and Ira S. Cohen
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0301 basic medicine ,Physiology ,Purkinje fibers ,030204 cardiovascular system & hematology ,sinus node ,PI3K ,lcsh:Physiology ,03 medical and health sciences ,Pacemaker potential ,chemistry.chemical_compound ,0302 clinical medicine ,pacemaker current ,Physiology (medical) ,medicine ,Myocyte ,Phosphatidylinositol ,HCN2 ,Protein kinase A ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Original Research ,lcsh:QP1-981 ,Chemistry ,Akt ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Second messenger system - Abstract
It has long been known that heart rate is regulated by the autonomic nervous system. Recently, we demonstrated that the pacemaker current, I f , is regulated by phosphoinositide 3-kinase (PI3K) signaling independently of the autonomic nervous system. Inhibition of PI3K in sinus node (SN) myocytes shifts the activation of I f by almost 16 mV in the negative direction. I f in the SN is predominantly mediated by two members of the HCN gene family, HCN4 and HCN1. Purkinje fibers also possess I f and are an important secondary pacemaker in the heart. In contrast to the SN, they express HCN2 and HCN4, while ventricular myocytes, which do not normally pace, express HCN2 alone. In the current work, we investigated PI3K regulation of HCN2 expressed in HEK293 cells. Treatment with the PI3K inhibitor PI-103 caused a negative shift in the activation voltage and a dramatic reduction in the magnitude of the HCN2 current. Similar changes were also seen in cells treated with an inhibitor of the protein kinase Akt, a downstream effector of PI3K. The effects of PI-103 were reversed by perfusion of cells with phosphatidylinositol 3,4,5-trisphosphate (the second messenger produced by PI3K) or active Akt protein. We identified serine 861 in mouse HCN2 as a putative Akt phosphorylation site. Mutation of S861 to alanine mimicked the effects of Akt inhibition on voltage dependence and current magnitude. In addition, the Akt inhibitor had no effect on the mutant channel. These results suggest that Akt phosphorylation of mHCN2 S861 accounts for virtually all of the observed actions of PI3K signaling on the HCN2 current. Unexpectedly, Akt inhibition had no effect on I f in SN myocytes. This result raises the possibility that diverse PI3K signaling pathways differentially regulate HCN-induced currents in different tissues, depending on the isoforms expressed.
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- 2020
50. High-Resolution Mapping to Unmask and Localize Presystolic Purkinje Potentials During Idiopathic Verapamil-Sensitive Left Anterior Papillary Muscle Fascicular-Purkinje Ventricular Tachycardia
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Akihiko Nogami, Yasunori Kanzaki, and Itsuro Morishima
- Subjects
Male ,medicine.medical_specialty ,business.industry ,High resolution ,General Medicine ,Papillary Muscles ,Ventricular tachycardia ,medicine.disease ,Purkinje Fibers ,Electrocardiography ,Young Adult ,medicine.anatomical_structure ,Text mining ,Verapamil ,Internal medicine ,medicine ,Cardiology ,Catheter Ablation ,Tachycardia, Ventricular ,Humans ,Cardiology and Cardiovascular Medicine ,business ,Papillary muscle ,medicine.drug - Published
- 2020
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