scholarly journals A novel computational sheep atria model for the study of atrial fibrillation

2013 ◽  
Vol 3 (2) ◽  
pp. 20120067 ◽  
Author(s):  
Timothy D. Butters ◽  
Oleg V. Aslanidi ◽  
Jichao Zhao ◽  
Bruce Smaill ◽  
Henggui Zhang
Keyword(s):  
Atrial Fibrillation ◽  
Animal Models ◽  
Pulmonary Veins ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Cell Types ◽  
Underlying Mechanisms ◽  
Detailed Computer ◽  
Atrial Cell ◽  
Atrial Excitation

Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types. The developed cell models were then incorporated into a three-dimensional anatomical model of the sheep atria, which was recently reconstructed and segmented based on anatomical features within different regions. This created a novel biophysically detailed computational model of the three-dimensional sheep atria. Using the model, we then investigated the mechanisms by which paroxysmal rapid focal activity in the pulmonary veins can transit to sustained atrial fibrillation. It was found that the anisotropic property of the atria arising from the fibre structure plays an important role in facilitating the development of fibrillatory atrial excitation waves, and the electrical heterogeneity plays an important role in its initiation.

scholarly journals Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation

2013 ◽  
Vol 3 (2) ◽  
pp. 20120069 ◽  
Author(s):  
Oleg V. Aslanidi ◽  
Michael A. Colman ◽  
Marta Varela ◽  
Jichao Zhao ◽  
Bruce H. Smaill ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Frequency ◽  
Computational Study ◽  
Pulmonary Veins ◽  
Three Dimensional ◽  
Primary Source ◽  
Integrative Model ◽  
Micro Computed Tomography ◽  
Three Dimensional Model ◽  
Arrhythmogenic Substrate

Mechanisms underlying the genesis of re-entrant substrate for the most common cardiac arrhythmia, atrial fibrillation (AF), are not well understood. In this study, we develop a multi-scale three-dimensional computational model that integrates cellular electrophysiology of the left atrium (LA) and pulmonary veins (PVs) with the respective tissue geometry and fibre orientation. The latter is reconstructed in unique detail from high-resolution (approx. 70 μm) contrast micro-computed tomography data. The model is used to explore the mechanisms of re-entry initiation and sustenance in the PV region, regarded as the primary source of high-frequency electrical activity in AF. Simulations of the three-dimensional model demonstrate that an initial break-down of normal electrical excitation wave-fronts can be caused by the electrical heterogeneity between the PVs and LA. High tissue anisotropy is then responsible for the slow conduction and generation of a re-entrant circuit near the PVs. Evidence of such circuits has been seen clinically in AF patients. Our computational study suggests that primarily the combination of electrical heterogeneity and conduction anisotropy between the PVs and LA tissues leads to the generation of a high-frequency (approx. 10 Hz) re-entrant source near the PV sleeves, thus providing new insights into the arrhythmogenic mechanisms of excitation waves underlying AF.

scholarly journals Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 217 ◽  
Author(s):  
Milic ◽  
Tian ◽  
Bernhagen
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Cop9 Signalosome ◽  
Ring E3 Ligase ◽  
Ubiquitin Proteasome ◽  
Underlying Mechanisms ◽  
Isopeptidase Activity

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is an evolutionarily conserved multi-protein complex, consisting of eight subunits termed CSN1-CSN8. The main biochemical function of the CSN is the control of protein degradation via the ubiquitin-proteasome-system through regulation of cullin-RING E3-ligase (CRL) activity by deNEDDylation of cullins, but the CSN also serves as a docking platform for signaling proteins. The catalytic deNEDDylase (isopeptidase) activity of the complex is executed by CSN5, but only efficiently occurs in the three-dimensional architectural context of the complex. Due to its positioning in a central cellular pathway connected to cell responses such as cell-cycle, proliferation, and signaling, the CSN has been implicated in several human diseases, with most evidence available for a role in cancer. However, emerging evidence also suggests that the CSN is involved in inflammation and cardiovascular diseases. This is both due to its role in controlling CRLs, regulating components of key inflammatory pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and complex-independent interactions of subunits such as CSN5 with inflammatory proteins. In this case, we summarize and discuss studies suggesting that the CSN may have a key role in cardiovascular diseases such as atherosclerosis and heart failure. We discuss the implicated molecular mechanisms ranging from inflammatory NF-κB signaling to proteotoxicity and necrosis, covering disease-relevant cell types such as myeloid and endothelial cells or cardiomyocytes. While the CSN is considered to be disease-exacerbating in most cancer entities, the cardiovascular studies suggest potent protective activities in the vasculature and heart. The underlying mechanisms and potential therapeutic avenues will be critically discussed.

scholarly journals Fluoroless ablation of atrial fibrillation using intracardiac ultrasound integrated with 3D electroanatomical mapping system

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
B Antolic ◽  
M Jan ◽  
M Vrbajnscak ◽  
D Zizek ◽  
N Kajdic
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Veins ◽  
Three Dimensional ◽  
Intracardiac Echocardiography ◽  
High Rate ◽  
Integration System ◽  
Funding Sources ◽  
Automatic Integration ◽  
First Pass ◽  
Intracardiac Ultrasound

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Intracardiac echocardiography (ICE) is gaining increasingly wider adoption in interventional electrophysiology (EP) and represents an all-round tool for ablation of atrial fibrillation (AF). The key upgrade to the usefulness of ICE is its integration into three-dimensional (3D) electroanatomic mapping (EAM) system (ICE/EAM automatic integration system). Purpose The aim of this single-centre retrospective study was to evaluate feasibility, safety and acute efficacy of ICE/EAM automatic integration system guided fluoroless ablation of AF.  Methods Patients with symptomatic paroxysmal or persistent AF referred for first pulmonary vein isolation (PVI) radiofrequency catheter ablation (RFCA) from September 2017 to August 2020 were included in the study. Those who underwent additional ablations for concomitant arrhythmias were excluded from statistical analysis. All procedures were performed without the use of fluoroscopy. A detailed 3D virtual anatomy of the left atrium (LA) and structures relevant to AF ablation was constructed from ultrasound contours obtained with ICE probe inside the LA. Pulmonary veins (PVs) and antral regions were additionally mapped with fast anatomical mapping. PVI was performed with contact force (CF) sensing catheter. Procedural endpoint was successful PVI.  Results A total of 56 patients underwent RFCA (35.7% females, median age 62.7 years, 53.6% paroxysmal AF). Acute PVI was achieved in all patients (100%). Adverse events were detected in two patients (3.6%). The median procedure duration was 110.5 min (IQR 100.0-133.8). First-pass isolation was achieved in 50/56 LPVs (89.3%) and in 44/56 RPVs (78.6%). In patients where first-pass isolation was no achieved, intravenous carina had to be ablated in 3/6 (50%) of LPVs and 9/12 (75%) of RPVs.  Conclusions Flouroless PVI using ICE/EAM automatic integration system is feasible, safe and acutely effective. We achieved high rate of first-pass isolation.

scholarly journals Intracardiac Echocardiography during Catheter-Based Ablation of Atrial Fibrillation

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jürgen Biermann ◽  
Christoph Bode ◽  
Stefan Asbach
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Pulmonary Veins ◽  
Three Dimensional ◽  
Interatrial Septum ◽  
Intracardiac Echocardiography ◽  
Success Rates ◽  
Adjacent Structures ◽  
Intracardiac Ultrasound ◽  
Dimensional Object

Accurate delineation of the variable left atrial anatomy is of utmost importance during anatomically based ablation procedures for atrial fibrillation targeting the pulmonary veins and possibly other structures of the atria. Intracardiac echocardiography allows real-time visualisation of the left atrium and adjacent structures and thus facilitates precise guidance of catheter-based ablation of atrial fibrillation. In patients with abnormal anatomy of the atria and/or the interatrial septum, intracardiac ultrasound might be especially valuable to guide transseptal access. Software algorithms like CARTOSound (Biosense Webster, Diamond Bar, USA) offer the opportunity to reconstruct multiple two-dimensional ultrasound fans generated by intracardiac echocardiography to a three-dimensional object which can be merged to a computed tomography or magnetic resonance imaging reconstruction of the left atrium. Intracardiac ultrasound reduces dwell time of catheters in the left atrium, fluoroscopy, and procedural time and is invaluable concerning early identification of potential adverse events. The application of intracardiac echocardiography has the great capability to improve success rates of catheter-based ablation procedures.

scholarly journals Ultrafast immunostaining of organ-scale tissues for scalable proteomic phenotyping

2019 ◽  
Author(s):  
Dae Hee Yun ◽  
Young-Gyun Park ◽  
Jae Hun Cho ◽  
Lee Kamentsky ◽  
Nicholas B. Evans ◽  
...  
Keyword(s):  
Animal Models ◽  
Three Dimensional ◽  
Chemical Transport ◽  
Cell Types ◽  
Spatial Context ◽  
Disease Models ◽  
Comprehensive Understanding ◽  
Wide Range ◽  
Unique Approach ◽  
Uniform Labeling

ABSTRACTStudying the function and dysfunction of complex biological systems necessitates comprehensive understanding of individual cells. Advancements in three-dimensional (3D) tissue processing and imaging modalities have enabled rapid visualization and phenotyping of cells in their spatial context. However, system-wide interrogation of individual cells within large intact tissue remains challenging, low throughput, and error-prone owing to the lack of robust labeling technologies. Here we introduce a rapid, versatile, and scalable method, eFLASH, that enables complete and uniform labeling of organ-scale tissue within one day. eFLASH dynamically modulates chemical transport and reaction kinetics to establish system-wide uniform labeling conditions throughout the day-long labeling period. This unique approach enables the same protocol to be compatible with a wide range of tissue types and probes, enabling combinatorial molecular phenotyping across different organs and species. We applied eFLASH to generate quantitative maps of various cell types in mouse brains. We also demonstrated multidimensional cell profiling in a marmoset brain block. We envision that eFLASH will spur holistic phenotyping of emerging animal models and disease models to help assess their functions and dysfunctions.

Non Anticoagulant Effects of Heparin: Implications for Animal Models of Peritoneal Dialysis

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 354-356 ◽  
Author(s):  
An S. De Vriese ◽  
Siska Mortier ◽  
Norbert H. Lameire
Keyword(s):  
Peritoneal Dialysis ◽  
Animal Models ◽  
Anticoagulant Activity ◽  
Experimental Studies ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Correct Interpretation ◽  
Peritoneal Membrane ◽  
Peritoneal Adhesions ◽  
Antiproliferative Effects

Heparin is a glycosaminoglycan with well-known anticoagulant activity. That property is used in animal models of peritoneal dialysis to maintain catheter patency and to prevent the development of peritoneal adhesions. However, heparin has a host of biologic actions beyond its role as an anticoagulant. Heparin modulates the activity of various inflammatory cells, affects the synthesis of extracellular matrix, has antiproliferative effects on several cell types, and influences neoangiogenesis. By virtue of those actions, intraperitoneally administered heparin may interfere with peritoneal membrane homeostasis. The potential side effects of heparin use in animal models of peritoneal dialysis should be recognized to permit correct interpretation of experimental studies conducted in those models.

scholarly journals Balloon Devices for Atrial Fibrillation Therapy

2015 ◽  
Vol 4 (1) ◽  
pp. 58 ◽  
Author(s):  
Andreas Metzner ◽  
Erik Wissner ◽  
Tina Lin ◽  
Feifan Ouyang ◽  
Karl-Heinz Kuck ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Alternative Energy ◽  
Pulmonary Veins ◽  
Balloon Catheter ◽  
Three Dimensional ◽  
Single Shot ◽  
Alternative Energy Sources ◽  
First Line Therapy ◽  
Three Dimensional Mapping ◽  
Endoscopic Ablation

Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients refractory to antiarrhythmic medication. In patients with paroxysmal AF, ablation can be offered as first-line therapy when performed in an experienced centre. The accepted cornerstone for all ablation strategies is isolation of the pulmonary veins. However, it is still challenging to achieve contiguous, transmural, permanent lesions using radio-frequency current (RFC) based catheters in conjunction with a three-dimensional mapping system and the learning curve remains long. These limitations have kindled interest in developing and evaluating novel catheter designs that incorporate alternative energy sources. Novel catheters include balloon-based ablation systems, incorporating different energy modalities such as laser (HeartlightTM, CardioFocus, Marlborough, MA, US), RFC (Hot Balloon Catheter, Hayama Arrhythmia Institute, Kanagawa, Japan) and cryo-energy (ArcticFront, Medtronic, Inc., Minneapolis, MN, US). While the cryoballoon (CB) and the radiofrequency hot balloon (RHB) are single-shot devices, the endoscopic ablation system (EAS) allows for point-by-point ablation. The CB and EAS are well established as safe, time-efficient and effective ablation tools. Initial studies using the RHB could also demonstrate promising results. However, more data are required.

scholarly journals Age and impaired left atrial performance are associated with increased atrial fibrosis in patients with paroxysmal and persistent atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
V Traykov ◽  
R Radoslavova ◽  
D Boychev ◽  
V Konstantinova ◽  
D Marchov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Low Voltage ◽  
Pulmonary Veins ◽  
Three Dimensional ◽  
Persistent Atrial Fibrillation ◽  
Strain Imaging ◽  
Electroanatomical Mapping ◽  
Custom Made ◽  
The Difference

Abstract Background Atrial performance assessed by strain imaging is used as a surrogate for left atrial (LA) structural remodelling. Presence of low voltage zones (LVZs) detected by three-dimensional electroanatomical mapping in patients with atrial fibrillation (AF) denotes more expressed extrapulmonary substrate potentially leading to worse outcomes following pulmonary vein isolation (PVI) for the treatment of AF. Purpose The current study aims to investigate the association between strain imaging parameters from echocardiography and the presence and extent of LVZs derived from LA electroanatomical mapping in patients undergoing AF ablation. Methods Seventy-eight patients (58 males, 74%) aged 59±9.48 years undergoing PVI for paroxysmal (35 patients, 49%) or persistent AF were prospectively studied. Preprocedural echocardiography included LA strain imaging assessing global LA strain (LAS) and regional strain of the basolateral region (RSLB). During the procedure, LA electroanatomical mapping during paced atrial rhythm was performed in all patients obtaining a LA voltage map. All LA maps were analysed offline using a custom-made software calculating the zone of low bipolar voltage <0.5 mV (LVZ<0.5mV) and the total LA endocardial area excluding pulmonary veins antra. LVZ<0.5mv was expressed as an absolute value and as percentage of the whole LA area. Results Patients aged more than 65 years (N=21, 27%) demonstrated a larger area of LVZ<0.5mV: 25.5±17.8 cm2 vs. 9.4±10.6 cm2 in those younger than 65 years, P=0.001. This corresponded to a higher proportion of the LA area demonstrating LVZ<0.5mV in patients older than 65 years: 22.6±14.6% vs. 8.9±11.8% in those younger than 65 years, P<0.0001. Twenty-nine of 78 patients (37.1%) had preprocedural LAS<20% and 23 (29.5%) demonstrated RSLB of <21%. Patients with LAS <20% had a higher total LVZ<0.5mV: 20.3±16.6 cm2 vs. 9.8±12.1 cm2 in patients with LAS≥20% at baseline, P=0.004. This equaled to 17.7±15.6% vs. 9.5±11.9% of total LA area, respectively (P=0.011). Patients with RSLB<21% also demonstrated larger areas of LVZ<0.5mV in the LA: 21.6±17.9 cm2 vs. 10.39±11.83 cm2 in the patients with RSLB ≥21%, P=0.012. Expressed as a proportion of the whole LA area the difference remained significant: 18.8±17.1% vs. 9.9±11.6%, respectively P=0.01. Conclusion Older age and impaired LA performance assessed by LA strain imaging are associated with larger areas of LVZ<0.5mV possibly reflecting more expressed LA fibrotic changes in patients with paroxysmal and persistent AF. These findings might serve in the preprocedural selection of the patients undergoing catheter ablation of AF. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Bulgarian Society of Cardiology

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