scholarly journals Isolated superfused rats atrial model for the investigation of atrial fibrillation mechanisms and treatment

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Glatstein ◽  
M Ghiringhelli ◽  
L Maizels ◽  
E Heller ◽  
E Maor ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Resolution ◽  
Sinus Rhythm ◽  
Optical Mapping ◽  
Ex Vivo ◽  
Anatomical Landmarks ◽  
Ex Vivo Model ◽  
Electrophysiological Properties ◽  
Custom Made ◽  
Isolated Atria

Abstract Background One of the major barriers to an improved mechanistic understanding of atrial fibrillation (AF), and thus in the pipeline of drug development, has been a lack of appropriate tissue models, especially in small animals. Aim We propose an advanced anatomical ex-vivo model based on rat atria for acute assessment of AF susceptibility. This novel model could yield a better understanding of arrhythmia mechanisms as well as the development of potential therapeutic strategies for the prevention or termination of atrial arrhythmias. Methods Wistar rats atria (N=25) were isolated, flattened and pinned to a custom-made silicon plate. Atria were superfused with an oxygenized Tyrode's solution. Tissues were then loaded with a voltage-sensitive dye and mapped using a high-resolution optical mapping system. AF was induced with 1uM carbamylcholine (N=23) coupled with pacing maneuvers and treated with 30uM Vernakalant (N=10) or 10uM Flecainide (N=10). Finally, the feasibility of a new ablation technique (electroporation) was evaluated. Results Optical mapping results suggested that the superfusion procedure led to a fast atrial recovery. Sinus activity was conserved for all atria for a long period. All the anatomical landmarks were clearly visualized. The acquired optical signals were analyzed during sinus rhythm and pacing, which allowed the creation of detailed activation maps and measurements of action potential duration (APD) and conduction velocity (CV) at different pacing rates. The resulting APD restitution curves revealed electrical excitation at high pacing rates (cycle length between 50ms and 300ms) with a relatively flattened curve. AF was successfully induced and optically mapping confirmed the presence of reentrant activity. AF was successfully treated using Vernacalant and Flecainide. Finally, we demonstrated the feasibility of a new ablation approach (electroporation) for creation of a continuous linear lesion serving as a functional block. Conclusion The isolated superfused atria model, coupled with voltage-sensitive dyes, can be utilized for long-term high-resolution functional imaging of the atria during sinus rhythm, pacing and arrhythmogenic activity. This allows the study of the atrial electrophysiological properties, the mechanisms involved in AF initiation, perpetuation, and termination as well as the study of drug and new ablation modalities. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) Spontaneous activation of isolated atria

An experimental model of veno-venous arterial extracorporeal membrane oxygenation

2019 ◽  
Vol 43 (4) ◽  
pp. 268-276
Author(s):  
Mirko Belliato ◽  
Luca Caneva ◽  
Alessandro Aina ◽  
Antonella Degani ◽  
Silvia Mongodi ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Experimental Model ◽  
Ex Vivo ◽  
Venous Pressure ◽  
Ex Vivo Model ◽  
Membrane Oxygenation ◽  
Arterial Cannula ◽  
Venous Cannula ◽  
Custom Made ◽  
Aortic Impedance

Introduction: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. Aim: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump–driven circuit. Methods: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. Results: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. Conclusion: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings

A new implantable tool for repeated assessment of supraventricular electrophysiology and atrial fibrillation susceptibility in freely moving rats

2020 ◽  
Author(s):  
Michael Murninkas ◽  
Roni Gillis ◽  
Danielle I Lee ◽  
Sigal Elyagon ◽  
Nikhil Suresh Bhandarkar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ex Vivo ◽  
Adult Rats ◽  
Electrophysiological Properties ◽  
Multiple Risk Factors ◽  
Electrophysiological Studies ◽  
Cycle Lengths ◽  
Major Factors

The complex pathophysiology of atrial fibrillation (AF) is governed by multiple risk factors in ways that are still elusive. Basic electrophysiological properties including atrial effective refractory period (AERP) and conduction velocity are major factors determining the susceptibility of the atrial myocardium to AF. Although there is a great need for affordable animal models in this field of research, in-vivo rodent studies are limited by technical challenges. Recently, we introduced an implantable system for long-term assessment of AF susceptibility in ambulatory rats. However, technical considerations did not allow us to perform concomitant supraventricular electrophysiology measurements. Here, we designed a novel quadripolar-electrode specifically adapted for comprehensive atrial studies in ambulatory rats. Electrodes were fabricated from medical-grade silicone, four platinum-iridium poles and stainless steel fixating pins. Initial quality validation was performed ex-vivo, followed by implantation in adult rats and repeated electrophysiological studies 1, 4 and 8 weeks post implantation. Capture threshold was stable. Baseline AERP values (38.1±2.3 and 39.5±2.0 using 70ms and 120ms S1-S1 cycle lengths, respectively) confirmed the expected absence of rate-adaptation in the unanesthetized state and validated our prediction that markedly higher values reported under anesthesia are non-physiological. Evaluation of AF substrate in parallel with electrophysiological parameters validated our recent finding of a gradual increase in AF susceptibility over-time and demonstrated that this phenomenon is associated with an electrical remodeling process characterized by AERP shortening. Our findings indicate that the miniature quadripolar-electrode is a potent new tool, which opens a window of opportunities for better utilization of rats in AF research.

scholarly journals High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation

10.3791/3103 ◽  
2011 ◽  
Author(s):  
David Filgueiras-Rama ◽  
Raphael Pedro Martins ◽  
Steven R. Ennis ◽  
Sergey Mironov ◽  
Jiang Jiang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Resolution ◽  
Optical Mapping ◽  
Sheep Model

scholarly journals Extracellular vesicles secreted by human cardiosphere-derived cells attenuate electrophysiological remodelling in an in vitro model of atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Gomez-Cid ◽  
M Moro-Lopez ◽  
A S De La Nava ◽  
A I Fernandez ◽  
M E Fernandez-Santos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Conduction Velocity ◽  
Extracellular Vesicles ◽  
In Vitro Model ◽  
Optical Mapping ◽  
Rotor Dynamics ◽  
Antiarrhythmic Effect ◽  
Electrophysiological Properties ◽  
Vitro Model

Abstract Background Stem cells and their secreted extracellular vesicles (EVs) have shown different cardioprotective effects. However, their impact on the electrophysiological properties of the heart tissue remains controversial. While the use of some progenitor cells seems to have antiarrhythmic potential, the use of cardiomyocyte-like cells may be proarrhythmic. The mechanisms behind, and whether these effects are linked to cell engraftment and not to their secreted products is not fully known. Purpose The aim of this study was to investigate the electrophysiological modifications induced by extracellular vesicles secreted by human cardiosphere-derived cells (CDC-EVs) in an in vitro model of atrial fibrillation in order to explore their potential antiarrhythmic effect. Methods CDCs were derived from cardiac biopsies of patients who underwent cardiac surgery for other reasons. Purified CDC-EVs resuspended in serum-free media (SFM) vs. SFM alone were added to HL-1 atrial myocyte monolayers presenting spontaneous fibrillatory activity. After 48 hours, the monolayers were fully confluent, and the electrophysiological properties were analysed through optical mapping in both the treated (n=9) and control plates (n=9). Optical mapping recordings of the monolayers were analysed with Matlab for the activation frequency, activation complexity, rotor dynamics (curvature and meandering) and conduction velocity. Results CDC-EVs reduced activation complexity of the fibrillating atrial monolayers by ∼40% (2.74±0.59 vs. 1.61±0.16 PS/cm2, p<0.01). This reduction in activation complexity was accompanied by larger rotor meandering (1.47±0.82 vs. 4.32±2.25 cm/s, p<0.01) and decreased curvature (1.79±0.40 vs. 0.87±0.24 rad/cm, p<0.01) in the treated group. Despite reduction in the activation complexity, activation frequency did not change significantly between both groups. This could be in part because CDC-EVs increased conduction velocity by 80% (1.32±0.57 vs. 2.65±0.87 cm/s, p<0.01). Low conduction velocity has been linked to higher reentry recurrence, and lower meandering and higher curvature to higher rotor stability and harder AF termination. Therefore, CDC-EVs seem to drive cardiomyocytes to a less arrhythmic profile reducing activation complexity and preventing remodelling by increasing conduction velocity and modifying rotor dynamics. Conclusions CDC-EVs significantly modify conduction velocity and rotor dynamics, therefore reducing fibrillation complexity and remodelling to drive atrial myocytes to a less arrhythmogenic profile. Testing CDC-EVs in more robust models of atrial fibrillation, the most common sustained arrhythmia in humans with significant morbidity and mortality, is of special interest. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaciόn,CIBERCV, Spain Figure 1

scholarly journals In vivo ratiometric optical mapping enables high-resolution cardiac electrophysiology in pig models

2019 ◽  
Vol 115 (11) ◽  
pp. 1659-1671 ◽  
Author(s):  
Peter Lee ◽  
Jorge G Quintanilla ◽  
José M Alfonso-Almazán ◽  
Carlos Galán-Arriola ◽  
Ping Yan ◽  
...  
Keyword(s):  
High Resolution ◽  
Cardiac Electrophysiology ◽  
High Speed ◽  
Near Infrared ◽  
Optical Mapping ◽  
Ex Vivo ◽  
Average Rate ◽  
Camera System ◽  
Epicardial Surface

Abstract Aims Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. Methods and results First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63–138) cm/s vs. 51 (41–64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217–254) ms vs. 192 (182–233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min−1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA. Conclusions In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models.

P988Classification of sinus rhythm potential morphology in patients with mitral valve disease

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M S Van Schie ◽  
R Starreveld ◽  
M C Roos-Serote ◽  
Y J H J Taverne ◽  
F R N Van Schaagen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Resolution ◽  
Mitral Valve ◽  
Sinus Rhythm ◽  
Mitral Valve Disease ◽  
Electrical Signal ◽  
Valve Disease ◽  
S Wave ◽  
S Waves ◽  
History Of

Abstract Funding Acknowledgements CVON-AFFIP [grant number 914728], NWO-Vidi [grant number 91717339], Biosense Webster USA [ICD 783454] and Medical Delta Background The morphology of atrial electrograms (EGMs) contains information on intra-atrial conduction and hence conduction disorders giving rise to development of atrial fibrillation (AF). Prior studies have indeed demonstrated that areas of abnormal EGM morphologies are indicators of electropathology underlying AF. By creating an electrical signal profile obtained from high-resolution mapping data of the entire atria during AF -a so-called AF Fingerprint- the severity and extensiveness of electropathology can be determined. The first step towards development of an AF Fingerprint, is understanding characteristics of EGM morphology during sinus rhythm (SR). Objective The goal of this study is to examine EGM morphology at a high resolution scale during SR in patients with mitral valve disease (MVD). Methods Intra-operative epicardial mapping (interelectrode distance 2mm) of the right and left atrium (RA, LA), Bachmann’s Bundle (BB) and pulmonary vein area (PVA) was performed during SR in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal atrial fibrillation (PAF). Unipolar single potentials (SPs) were classified according to their differences in relative R- and S-wave amplitude ratios. Results Epicardial EGMs revealed a wide variation of R/S ratios. A clear predominance of S-waves was observed at BB and the RA in both the no history of AF (no AF) and PAF group (BB 88.8% vs. 85.9%, RA: 92.1% vs. 85.1%, respectively). Differences between both groups were found at the RA, BB and LA (P = 0.021, P = 0.003 and P = 0.013, respectively). EGM voltages of the RA, BB and PVA in the no AF group were significantly higher compared to the PAF group (P < 0.001, P < 0.001 and P < 0.001, respectively), and are mainly determined by the size of the S-waves amplitudes. Conclusions Though excitation of the atria during SR is heterogeneously disrupted in patients with MVD, a history of AF in this patient group is characterized by decreased SP amplitudes at BB due to loss of S-wave amplitudes. This, together with our findings that variation in EGM morphologies in our population is considerable, emphasizes the need for a diagnostic tool enabling identification of electropathology in the individual patient. Abstract Figure. Potential morphology distribution

scholarly journals Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter

2021 ◽  
Author(s):  
M. Liebregts ◽  
M. C. E. F. Wijffels ◽  
M. N. Klaver ◽  
V. F. van Dijk ◽  
J. C. Balt ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Resolution ◽  
Sinus Rhythm ◽  
Atrial Flutter ◽  
Persistent Atrial Fibrillation ◽  
Limited Experience ◽  
Mapping System ◽  
Acute Success ◽  
Resolution Imaging ◽  
Selection Of

Abstract Introduction The AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface. Methods We evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter. Results A total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred. Conclusion The AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.

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