Sostenuto in parte da sovvenzioni NHLBI-HL039707 P01 e P01-HL087226 e la Fondazione Leducq (JJ e OB), da una Società Spagnola di Cardiologia Fellowship, Fundación Pedro Barrie de la Maza e Fundación Alfonso Martín Escudero (DFR), dalla Fédération Française de Cardiologie (RPM), da una borsa di studio Premio Cuore Ritmo Società, La Compagnia del Giappone Heart Foundation / La società giapponese di elettrocardiologia (MIA).

1. Cuore rimozione e perfusione Langendorff Peso di 35-40 Kg pecore vengono anestetizzati con 4-6 mg / Kg di propofol e 60-100 mg / Kg di sodio pentobarbital. I cuori sono rimosse tramite toracotomia e collegato ad una Langendorff-perfusione con sistema di circolazione ossigenata (95% O2, 5% CO2) Tyrode soluzione è ad un flusso costante di 240-270 ml / min, pH 7.4 e 35,5-37,5 ° C. La composizione del Tyrode (in mm): NaCl 130, KCl 4.0, MgCl2 1, CaCl2 1.8, NaHCO3 24, NaH2PO4 1,2, 5,6 glucosio, albumina e 0,04 g / L. Blebbistatin 10 micron (Enzo Life Science International, Inc. Plymouth Meeting, PA, USA) viene utilizzato per ridurre la forza contrattile. 2. Stretch indotta fibrillazione atriale nel cuore perfuso Langendorff-pecora L&#39;isolato, coronarica perfuso sottoposto ad una atriale trans-settale foratura per permettere pareggio pressione intracavitaria in entrambi gli atri. Tutti gli orifizi vena vengono poi sigillate, ad eccezione della vena cava inferiore, che è cannulata e collegato ad un sensore digitale (Sistemi Biopac trasduttore-TSD104A; Biopac Systems, Inc., Goleta, CA, USA) e ad una cannula deflusso cui a tempo indeterminato altezza sopra gli atri controlla la pressione intra-atriale. La pressione viene poi aumentato a 12 cm H 2 O, che porta ad un aumento di circa il 30% in volume relativo al volume atriale a 6 cm H 2 O. La pressione viene mantenuta stabile durante l&#39;esperimento. Prima di sigillare le vene cateteri elettrodi tetrapolari (Torq, Medtronic Inc. / Minneapolis / MN / USA) sono collocati in ciascuna delle vene polmonari per registrare i segnali bipolari da due elettrodi distali (frequenza di campionamento, 1,0 kHz) usando un amplificatore Biopac Sistemi (DA100C; Biopac Systems, Inc., Goleta, CA, USA). Due ulteriori custum fatti elettrodi bipolari sono posizionati sul tetto della sinistra appendice atriale (LAA) e la parte superiore del diritto appendice atriale. 3. Mappatura ottica impostare <ol><li> Mappatura epicardici dell&#39;appendice atriale sinistra. Una iniezione in bolo da 5 a 10 ml Di-4-ANEPPS (10 mg / ml) (Sigma-Aldrich, St. Louis, MO, USA) e un periodo di carico di 10 minuti sono necessari per ottenere tensione sensibili alla fluorescenza eccitazione laser (532 nm) della superficie epicardico. La fluorescenza emessa viene poi trasmessa attraverso un lungo 600 nm filtro passa e proiettate su LittleJoe CCD videocamera (80x80 pixel, SciMeasure sistemi analitici, Inc. Decatur, Georgia, USA) e ha acquisito ad una velocità di 800 fotogrammi al secondo (vedi rappresentazione schematica nella Figura 1A). Cinque secondi di film sono ottenuti a intervalli di 2 min durante AF. L&#39;area della superficie mappata epicardico è ~ 14 cm 2. </li><li> Endocardica mappatura ottica del PLA del cuore intatto. Un secondo LittleJoe camera CCD (80x80 pixel) è sincronizzato con la fotocamera epicardico. A 10 mm di diametro a doppio canale boroscopio rigido (Everest VIT, Fiandre Inc., NJ, USA) con una di 90 gradi campo di vista viene introdotto attraverso la parete anteriore del ventricolo sinistro, attraverso la valvola mitrale e focalizzato sulla superficie endocardica del PLA. L&#39;area otticamente mappato sul PLA è ~ 4 cm 2, che consente di visualizzare le quattro vene polmonari e il setto atriale-polmonare fascio (Figura 1A, B). Il boroscopio è c montata sulla fotocamera CCD con una misura per oculare. Luce laser 532 nm è poi consegnato al canale eccitazione del boroscopio attraverso un liquido fibre ottiche (0,2 nel nucleo). </li></ol> 4. Protocollo fibrillazione atriale Sotto continuo tratto atriale AF è indotta attraverso stimolazione raffica (12 Hz, 5 ms legumi, soglia 2x diastolica) da un elettrodo di stimolazione situato sulla parte superiore del LAA. AF è permesso di continuare per 50 minuti e 5 secondi film ottici vengono acquisite a intervalli di due minuti. Registrazioni bipolari sono raccolti in modo continuo. Acquisizione del film ottica attiva acquisizione simultanea di 5-sec segmenti delle registrazioni bipolare. 5. Analisi in frequenza Analisi in frequenza consente l&#39;identificazione delle regioni con alto tasso di attivazione durante l&#39;AF, insieme con gradienti di frequenze comprese tra atrio destro e sinistro. Dominante frequenza (DF) le mappe sono ottenuti da ciascun film ottico dopo l&#39;applicazione di un veloce algoritmo di Fourier transform (FFT) per la serie temporale segnale di fluorescenza registrate in ciascun pixel. FFT 7 si applica anche ai 5 secondi segnali bipolari (filtro passa-alto a 3 Hz e filtro passa-basso a 35 Hz) sincronizzato con il film ottica. 6. Dinamiche di fibrillazione atriale <ol><li> Generazione di mappe di fase. Analisi delle dinamiche AF si avvale di filmati fase generato tramite la trasformazione di Hilbert. 14 In sintesi, la fase istantanea del potenziale d&#39;azione ha registrato per ogni pixel è determinata dalla trasformando l&#39;originale serie temporali di segnali in modo tale che ogni componente spettrale è spostato dal suo ciclo corrispondente trimestre . dopoguerra 15ds, la fase istantanea del segnale è ottenuto dalla arcotangente del rapporto tra il segnale trasformato al segnale originale. L&#39;angolo di fase, con valori compresi tra-π e π radianti è rappresentato come una combinazione di colori continua a costruire una mappa di fase, in cui il continuo cambiamento di fase spaziale riflette il processo di eccitazione, ripolarizzazione e recupero 14. </li><li> Caratterizzazione del pattern di attivazione. Varie classi di pattern di attivazione può essere identificato con i film di fase (Figura 2), inclusi i seguenti: <ul><li> Un rotore è identificato dalla presenza di tutte le fasi di convergere su un punto di singolarità della durata di più di una rotazione (Figura 2A). </li><li> Un passo avanti è definito come un fronte d&#39;onda che appare nel campo visivo e di propagazione verso l&#39;esterno (Figura 2B) in un obiettivo-come il modello. </li><li> Spatiotemporally organizzato onde periodiche sono definiti come un minimo di quattro onde in sequenza periodica che emergono dalla stessa posizione nel campo visivo, con la stessa direzione e inter-wave intervallo (Figura 2C). </li></ul></li></ol> Ulteriori quantificazione permette la correlazione spaziale dei domini più alta frequenza con il modello più comune di attivazione ottenute da quella particolare regione. Quest&#39;ultimo mette in evidenza il ruolo cruciale della cartografia della superficie endocardica del PLA, in quanto rappresenta comunemente la regione in cui i domini più alta frequenza si trovano durante acuta AF. 7. Rappresentante dei risultati: Dominante frequenza (DF) gradienti da PLA a LAA e RAA sono presenti durante acuta indotta tratto AF. La regione più alta DF è localizzata sia pari o vicino ad una delle vene polmonari o in qualche parte del PLA. Episodio 11 Un rappresentante AF è mostrato in figura 3, in cui il più alto DF è localizzato sul PLA (destro inferiore della vena polmonare). I risultati sostengono la presenza di sorgenti ad alta frequenza nella guida PLA AF coerente con la sinistra a gradienti DF destra osservate durante le procedure ablative in fibrillazione atriale parossistica umano 16. Quantificazione dei pattern di attivazione usando film mappa fase mostra che il maggior numero di rotori si trova alla PLA e la giunzione tra il PLA e il LAA. 8 volte è possibile identificare i rotori di lunga durata il cui centro di rotazione (punto di Singolarità) localizza con il dominio più alta frequenza. 10 Poiché il tessuto atriale rappresenta una struttura tridimensionale, identificando rotori sulla superficie mappata endocardica del PLA suggerisce che il centro di rotazione di quei rotori (filamento) è finalmente perpendicolare alla superficie della zona di mappatura . La Figura 4 mostra un rotore registrato dall&#39;endocardio del PLA con simultanea di conduzione fibrillatory verso il LAA, che correla anche con un gradiente di frequenza tra il PLA e il LAA (9 e 6,4 Hz rispettivamente). Il numero di rotori è costantemente superiore al PLA che il LAA, il che suggerisce un ruolo essenziale di rientro del PLA per mantenere l&#39;aritmia in questo modello. Nel complesso, i risultati confermano la teoria che rotori stabile e veloce in atrio sinistro può guidare tratto acuta indotta AF e le onde che emanano subiscono complessi, spazialmente distribuiti i modelli blocco di conduzione come si dirigono verso l&#39;atrio destro, che si manifesta come conduzione fibrillatory e diminuire progressivamente dominante frequenza. <img src="/files/ftp_upload/3103/3103fig1.jpg" alt="Figura 1" /> Figura 1. Rappresentazione schematica di sperimentale istaurato. R: Un boroscopio rigido viene introdotto attraverso la parete anteriore del ventricolo sinistro e l&#39;orifizio della valvola mitrale e focalizzato sulla superficie endocardica dell&#39;atrio posteriore sinistra (PLA). Una telecamera CCD è accoppiato al boroscopio e l&#39;illuminazione laser è fornita attraverso una guida laser liquidi collegato alla parte inferiore del boroscopio. Mappatura epicardico viene eseguita sul LAA. Elettrodi bipolari sono immessi sul atrio destro e il tetto dell&#39;atrio sinistro. Ulteriori segnali bipolari si ottengono dalle vene polmonari. B: vista laterale delle seguenti atrio sinistro aprendo la parete laterale a scopo illustrativo. La punta del boroscopio illumina la superficie endocardica della PLA. Un elettrodo bipolare si trova sul tetto dell&#39;atrio sinistro. LAA: appendice atriale sinistra. LV: ventricolo sinistro. RA: atrio destro. RV: ventricolo destro. <img src="/files/ftp_upload/3103/3103fig2.jpg" alt="Figura 2" /> Figura 2. Diversi modelli di attivazione identificato dopo la generazione di film fase. R: istantanee sequenziale dell&#39;appendice atriale sinistra (LAA) mostrano la rotazione di un rotore attorno al suo centro di rotazione (punto di singolarità). Da sinistra a destra, una rotazione completa è stata completata. B: Un passo avanti modello campione di attivazione sul LAA. L&#39;onda appare in crescitaper angolo destro del campo di vista e si propaga verso l&#39;esterno. C: Quattro onde spatiotemporally organizzati periodici (A 0, 182, 352 e 512 ms, rispettivamente) provenienti dalla regione PLA verso il LAA. Isocrone sono tracciate a intervalli di 10 ms. Fondo, la chiave per le varie fasi del potenziale d&#39;azione è un colore. <img src="/files/ftp_upload/3103/3103fig3.jpg" alt="Figura 3" /> Figura 3. Identificazione delle regioni con l&#39;attività più alta frequenza durante la fase acuta indotta tratto AF in una Langendorff-perfusione cardiaca pecore isolate. A: visione anatomica dell&#39;appendice atriale sinistra (LAA), a destra appendice atriale (RAA) e posteriore dell&#39;atrio sinistro (PLA). PLA immagine è una visione endoscopica della regione mappata con le quattro vene polmonari (PV). B: mappe DF ottenuto mappando ottico sul LAA e PLA. Valore di frequenza nel RAA è stato ottenuto da elettrogrammi bipolare. La regione più alta frequenza si trova in PLA. C: spettri di potenza Rappresentante, in cui il DF massima corrisponde al 12,4 Hz nella regione PLA del PV destra. LSPV: a sinistra della vena polmonare superiore. LIPV: a sinistra della vena polmonare inferiore. RSPV: a destra della vena polmonare superiore. RIPV: a destra della vena polmonare inferiore. Tratto da riferimento 11 (David Filgueiras Rama e José Jalife. Meccanismi alla base fibrillazione atriale. In Scienze di base per Elettrofisiologo Clinica, vol. 3 (a cura di Carlo Antzelevitch) 141-156 (Saunders, 2011). <img src="/files/ftp_upload/3103/3103fig4.jpg" alt="Figura 4" /> Figura 4. Simultaneousphase mappe (A, B) e mappe delle frequenze dominanti (C) dal posteriore dell&#39;atrio sinistro (PLA) e appendice atriale sinistro (LAA). R: istantanee in sequenza dal PLA mostrando un rotore e la deriva del suo punto di singolarità. B: simultanea scatti fase di scatto dalla LAA. Pattern di attivazione mostrare le onde di propagazione compatibile con conduzione fibrillatory. Punti di singolarità sono presenti anche in correlazione con wavebreaks nella regione di conduzione fibrillatory. (Vedi anche il video 4) C: simultanea mappe delle frequenze dominante dal PLA e il LAA. Il più veloce regione si trova al PLA (9 Hz), che è correlato con la presenza di un rotore in fase di analisi delle mappe. La frequenza più alta al LAA è di 6 Hz, che è correlato con la conduzione fibrillatory. Sul lato destro del pannello C, attivazioni singolo pixel ottiche da PLA e LAA sono mostrati.

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Nessun conflitto di interessi dichiarati.

Le caratteristiche del tratto acuta indotta AF nel cuore pecore isolate ricordano alcune delle proprietà delle risorse umane fibrillazione atriale parossistica. Un aumento acuto della pressione intra-atriale nel cuore pecore consente il mantenimento della fibrillazione atriale per lunghi periodi di tempo, simile a un più alto rischio di fibrillazione atriale osservata in pazienti con dilatazione atriale. 1 La presenza della sinistra a destra gradienti nel DF pecore atri è simili a quelli registrati nel uma...

<table border="1"><tbody><tr><td> Nome del materiale </td><td> Azienda </td><td> Numero di catalogo </td></tr><tr><td> Eutanasia </td><td></td><td></td></tr><tr><td> Eparina </td><td> Sigma </td><td> H3393 </td></tr><tr><td> Propofol </td><td> Abbott </td><td> 5206-04-03 </td></tr><tr><td> Pentobarbital </td><td> Lundbeck Inc </td><td> NDC 67386-501-55 </td></tr><tr><td> Introduttore 18 Gauge </td><td> Terumo </td><td> SS * FF1832 </td></tr><tr><td> Con risvolto tubo endotracheale (9 mm) </td><td> DRE Veterinaria </td><td> # 9440 </td></tr><tr><td> Custodia in fibra ottica Laringoscopio </td><td> DRE Veterinaria </td><td> # 991 </td></tr><tr><td> Fibra ottica Lama </td><td> DRE Veterinaria </td><td> N ° 984 </td></tr><tr><td> Forbici di funzionamento </td><td> DRE Veterinaria </td><td> # 9702 # 1944 </td></tr><tr><td> Manico bisturi # 3 Solid 4 &quot; </td><td> Roboz Surgical Instrument Co., Inc. </td><td> RS-9843 </td></tr><tr><td> Lame bisturi sterile </td><td> Roboz Surgical Instrument Co., Inc. </td><td> RS-9801-10 </td></tr><tr><td> Ventilazione borsa </td><td> Westmed </td><td> 562013 </td></tr><tr><td> Forbici sims curvo Sharp / Blunt </td><td> Roboz Surgical Instrument Co., Inc. </td><td> RS-7035 </td></tr><tr><td> Pinze tessuto (× 2) </td><td> DRE Veterinaria </td><td> # 1895 </td></tr><tr><td> Pinze Kantrowitz Toracica, 11 &quot; </td><td> Biomedical Research Instruments, Inc. </td><td> 34-1980 </td></tr><tr><td> Finochietto Spreader grande cassa </td><td> Kapp Surgical Instrument Inc. </td><td> KS-7301 </td></tr><tr><td> Toracotomia cesoie </td><td> Rostfrei Solingen </td><td></td></tr><tr><td> Vassoio di plastica </td><td> Nalgene </td><td> Fischer </td></tr><tr><td> Mappatura ottica </td><td></td><td></td></tr><tr><td> Forbici Bonn (× 2) </td><td> Roboz Surgical Instrument Co., Inc </td><td> RS-5840SC </td></tr><tr><td> Seta chirurgica </td><td> Fischer </td><td> 50-900-04214 </td></tr><tr><td> Micro dissettore </td><td> Roboz Surgical Instrument Co., Inc </td><td> RS-5130 </td></tr><tr><td> Cateteri elettrodi tetrapolari (Torq) (× 4) </td><td> Medtronic Inc. </td><td> 05580SP </td></tr><tr><td> Sensore digitale. Biopac Sistemi trasduttore </td><td> Biopac Systems, Inc. </td><td> RX104A </td></tr><tr><td> Biopac sistemi di amplificazione </td><td> Biopac Systems, Inc. </td><td> DA-100C </td></tr><tr><td> Di-4-ANEPPS </td><td> Sigma-Aldrich, S. </td><td> D8604-5mg </td></tr><tr><td> Blebbistatin </td><td> Enzo Life Science International, Inc. </td><td> BML-E1315-0025 </td></tr><tr><td> LittleJoe CCD videocamera (× 2) </td><td> SciMeasure sistemi analitici, Inc. </td><td></td></tr><tr><td> Dual-channel boroscopio rigido </td><td> Everest VIT, Inc. </td><td> R10-25-0-90 </td></tr><tr><td> Pompe di perfusione (× 2) </td><td> Cole Parmer </td><td> GK-77920-30 </td></tr><tr><td> Sonda di temperatura </td><td> Cole Parmer </td><td> R-08491-02 </td></tr><tr><td> pH-metro </td><td> Fischer </td><td> 01-913-806 </td></tr><tr><td> Indicatore di temperatura digitale </td><td> Cole Parmer </td><td> GK89000-10 </td></tr><tr><td> Ossigenatore filtri </td><td> Sorin </td><td> 05318 </td></tr><tr><td> Tubi di perfusione di silicio (L / S 15) </td><td> Masterflex </td><td> 96410-15 </td></tr><tr><td> Guide di luce laser (× 6) </td><td> Oriel Corporation </td><td> 77536 </td></tr><tr><td> Liquido fibre ottiche (0,2 nel nucleo) </td><td> Newport Corporation </td><td> 77556 </td></tr><tr><td> Generatore laser (1 watt) (× 1) </td><td> Shanghai Sogno Lsaer Tecchnology </td><td> SDL-532-1000T </td></tr><tr><td> Generatore laser (5 watt) (× 1) </td><td> Spectra Physics Laser </td><td> MILL 5sJ </td></tr></tbody></table>

high-resolution endocardial and epicardial optical mapping in a sheep model of stretch-induced atrial fibrillation

Fibrillazione atriale (FA) è un&#39;aritmia cardiaca complessa con alta morbilità e mortalità. 1,2 E &#39;il più comune disturbo del ritmo cardiaco sostenuta osservata nella pratica clinica e la sua prevalenza è previsto un aumento nei prossimi anni. 3 Aumento della pressione intra-atriale e la dilatazione sono stati da tempo riconosciuto a portare a AF, 1,4 che evidenzia l&#39;importanza di utilizzare modelli animali e si estendono per studiare la dinamica AF. Comprendere i meccanismi alla base AF richiede la visualizzazione delle onde cardiaco elettrico ad alta risoluzione spaziale e temporale. Mentre ad alta risoluzione temporale può essere ottenuto mediante la mappatura elettrica convenzionale tradizionalmente utilizzate nella umane studi elettrofisiologici, il piccolo numero di intra-atriale elettrodi che possono essere utilizzati contemporaneamente limita la risoluzione spaziale e preclude ogni monitoraggio dettagliato delle onde elettriche durante l&#39;aritmia. L&#39;introduzione di mappatura ottica nei primi anni 90 ha consentito a grande campo caratterizzazione di attività fibrillatory insieme con sub-millimetrica risoluzione spaziale in modelli animali 5,6 e ha portato alla identificazione di rapida rotazione modelli di onda elettrica (rotori) come le sorgenti del fibrillatory attività che possono verificarsi nei ventricoli e atri. 7-9 Con il tempo-e combinati dominio della frequenza analisi di mappatura ottica è possibile dimostrare siti discreti di attività ad alta frequenza periodici durante la fibrillazione atriale, con gradienti di frequenze comprese tra atrio destro e sinistro . La regione con il più veloce rotori si attiva a frequenza più alta e le unità l&#39;aritmia generale. 10,11 Le onde provenienti dal rotore ad interagire con gli ostacoli sia funzionale o anatomica nel loro percorso, provocando il fenomeno della conduzione fibrillatory 12. Mappatura della superficie endocardica di l&#39;atrio posteriore sinistro (PLA) consente il tracciamento di AF dinamica onda nella regione con la frequenza più alta del rotore. È importante sottolineare che il PLA è la regione dove intracavitaria procedure ablative catetere sono di maggior successo nei pazienti con fibrillazione atriale terminazione, 13 che sottolinea l&#39;importanza di studiare le dinamiche AF dall&#39;interno dell&#39;atrio sinistro. Qui si descrive un modello di pecora tratto acuta indotta da AF, che ricorda alcune delle caratteristiche umane di fibrillazione atriale parossistica. Mappatura epicardico sulla atrio sinistro è completato con la mappatura endocardiche del PLA utilizzando un dual-channel boroscopio rigido c-montato una telecamera CCD, che rappresenta l&#39;approccio più diretto di visualizzare il pattern di attivazione nella regione più rilevanti per la manutenzione AF.

Watch this Scientific Journal Video about High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation at JoVE.com

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

Questo rapporto fornisce una descrizione dettagliata della metodologia e dei risultati della mappatura simultanea endocardici ed epicardici ottica di eccitazione elettrica nell&#39;atrio intatto sinistra di un Langendorff-perfusione cardiaca pecore durante tratto indotta fibrillazione atriale.

Ad alta risoluzione Mappatura endocardica e epicardici ottico in un modello di pecora Stretch indotta fibrillazione atriale

 Atrial fibrillation (AF) is a complex cardiac arrhythmia with high morbidity and mortality.1,2 It is the most common sustained cardiac rhythm disturbance ...

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Medicine

14.7K Views.  University of Michigan. Questo rapporto fornisce una descrizione dettagliata della metodologia e dei risultati della mappatura simultanea endocardici ed epicardici ottica di eccitazione elettrica nell'atrio intatto sinistra di un Langendorff-perfusione cardiaca pecore durante tratto indotta fibrillazione atriale.

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

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 2. Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke 3.
The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF 3. Rate control is achieved by administration of pharmacological agents, such as &beta;-blockers, that lower the heart rate until it reaches a less symptomatic state 3. Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods 4-6. In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects 3, or even increases in mortality in patients with structural heart defects 7. Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue 8, but don't reliably prevent thromboembolic events 6.
Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism 9,10. However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding 2. As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke 10. Other alternatives to warfarin, such as dabigatran 11 or rivaroxaban 12 demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue 13-15.
Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) 2, one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released.

The accompanying video describes a procedure for percutaneous placement of the WATCHMAN Left Atrial Appendage (LAA) Device. The WATCHMAN is a nitinol device designed to be permanently implanted at, or slightly distal to, the opening of the left atrial appendage (LAA) to trap blood clots before they exit the LAA, preventing thromboembolic stroke.

Il GUARDIANO atriale sinistra Appendage dispositivo di chiusura per la fibrillazione atriale

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily ...

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Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

Ablazione transcatetere in combinazione con i tasti chiusura appendice atriale per la fibrillazione atriale

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes &#8211; but is not limited to &#8211; hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation.

This article describes a rat model of electrically-induced ventricular fibrillation and resuscitation by chest compression, ventilation, and delivery of electrical shocks that simulates an episode of sudden cardiac arrest and conventional cardiopulmonary resuscitation. The model enables gathering insights on the pathophysiology of cardiac arrest and exploration of new resuscitation strategies.

Un modello di ratto di fibrillazione ventricolare e Rianimazione dal convenzionale chiuso petto Tecnica

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

Robotic Ablation of Atrial Fibrillation

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between pulmonary vein (PV) and left atrium (LA) is created. This conduction block prevents AF, which is triggered by irregular electric activity originating from the PV. However, transmural atrial lesions are required which can be challenging. Re-conduction and AF recurrence occur in 20 - 40% of the cases. Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new remote catheter system (RCS), is presented. Objective of this article is to show feasibility of robotic AF ablation with a novel system. Materials and Methods: After interatrial trans-septal puncture is performed using a long sheath and needle under fluoroscopic guidance. The needle is removed and a guide wire is placed in the left superior PV. Then an ablation catheter is positioned in the LA, using the sheath and wire as guide to the LA. LA angiography is performed over the sheath. A circular mapping catheter is positioned via the long sheath into the LA and a three-dimensional (3-D) anatomical reconstruction of the LA is performed. The handle of the ablation catheter is positioned in the robotic arm of the Amigo system and the ablation procedure begins. During the ablation procedure, the operator manipulates the ablation catheter via the robotic arm with the use of a remote control. The ablation is performed by creating point-by-point lesions around the left and right PV ostia. Contact force is measured at the catheter tip to provide feedback of catheter-tissue contact. Conduction block is confirmed by recording the PV potentials on the circular mapping catheter and by pacing maneuvers. The operator stays out of the radiationfield during ablation. Conclusion: The novel catheter system allows ablation with high stability on low operator fluoroscopy exposure.

Pulmonary vein isolation (PVI) with an ablation catheter is a curative treatment for atrial fibrillation (AF). Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new robotic catheter system is presented. The goal of the procedure is electrical block between pulmonary vein and left atrium.

Robotic Ablazione della fibrillazione atriale

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between ...

Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm &#215; 2 mm or 10 mm x 10 mm, with a 100 &#215; 100 resolution (20 &#181;m/pixel or 100 &#181;m/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

This protocol describes the electrophysiological evaluation of murine atria utilizing an optical mapping system with a high temporal and spatial resolution, including dual recordings of the membrane voltage and Ca2+ transient under programmed stimulation through a specialized electrode catheter.

Valutazione elettrofisiologica di Atria murino con Mapping ottico ad alta risoluzione

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and ...

High-Throughput Analysis of Optical Mapping Data Using ElectroMap

Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we present, in a step-by-step guide, the use of ElectroMap for analysis, quantification, and mapping of high-resolution voltage and calcium datasets acquired by optical mapping. ElectroMap analysis options cover a wide variety of key electrophysiological parameters, and the graphical user interface allows straightforward modification of pre-processing and parameter definitions, making ElectroMap applicable to a wide range of experimental models. We show how built-in pacing frequency detection and signal segmentation allows high-throughput analysis of entire experimental recordings, acute responses, and single beat-to-beat variability. Additionally, ElectroMap incorporates automated multi-beat averaging to improve signal quality of noisy datasets, and here we demonstrate how this feature can help elucidate electrophysiological changes that might otherwise go undetected when using single beat analysis. Custom modules are included within the software for detailed investigation of conduction, single file analysis, and alternans, as demonstrated here. This software platform can be used to enable and accelerate the processing, analysis, and mapping of complex cardiac electrophysiology.

This protocol describes the setup and use of ElectroMap, a MATLAB-based open-source software platform for analysis of cardiac optical mapping data. ElectroMap provides a versatile high-throughput tool for analysis of optical mapping voltage and calcium datasets across a wide range of cardiac experimental models.

Analisi ad alta velocità effettiva dei dati di mappatura ottica tramite ElectroMapHigh-Throughput Analysis of Optical Mapping Data Using ElectroMap

Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we ...

Cooling or Warming the Esophagus to Reduce Esophageal Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most frequent type of cardiac ablation procedure performed. Although generally safe, collateral injury to surrounding structures, particularly the esophagus, remains a concern. Cooling or warming the esophagus to counteract the heat from RF ablation, or the cold from cryoablation, is a method that is used to reduce thermal esophageal injury, and there are increasing data to support this approach. This protocol describes the use of a commercially available esophageal temperature management device to cool or warm the esophagus to reduce esophageal injury during left atrial ablation. The temperature management device is powered by standard water-blanket heat exchangers, and is shaped like a standard orogastric tube placed for gastric suctioning and decompression. Water circulates through the device in a closed-loop circuit, transferring heat across the silicone walls of the device, through the esophageal wall. Placement of the device is analogous to the placement of a typical orogastric tube, and temperature is adjusted via the external heat-exchanger console.

The goal of this protocol is to describe the use of esophageal temperature modulation to counteract esophageal thermal injury from left atrial ablation for the treatment of atrial fibrillation.

Raffreddamento o riscaldamento dell'esofago per ridurre le lesioni esofagehe durante l'ablazione atriale sinistra nel trattamento della fibrillazione atriale

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most ...

Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only target the electrical abnormalities and not the underlying atrial myopathy. For the development of novel therapies, a reproducible large animal model of atrial myopathy is necessary. This paper presents a model of sterile pericarditis-induced atrial myopathy in Aachener minipigs. Sterile pericarditis was induced by spraying sterile talcum and leaving a layer of sterile gauze over the atrial epicardial surface. This led to inflammation and fibrosis, two crucial components of the pathophysiology of atrial myopathy, making the atria susceptible to the induction of AF. Two pacemaker electrodes were positioned epicardially on each atrium and connected to two pacemakers from different manufacturers. This strategy allowed for repeated non-invasive atrial programmed stimulation to determine the inducibility of AF at specified time points after surgery. Different protocols to test AF inducibility were used. The advantages of this model are its clinical relevance, with AF inducibility and the rapid induction of inflammation and fibrosis-both present in atrial myopathy-and its reproducibility. The model will be useful in the development of novel therapies targeting atrial myopathy and AF.

We describe a sterile pericarditis model in minipigs to study atrial myopathy and atrial fibrillation (AF). We present surgical and anesthetic techniques, strategies for vascular access, and a protocol to study the inducibility of AF.

Pericardite sterile in Aachener Minipigs come modello per la miopatia atriale e la fibrillazione atriale

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only ...

High-Resolution Three-Dimensional Imaging of the Footpad Vasculature in a Murine Hindlimb Gangrene Model

Peripheral arterial disease (PAD) is a significant cause of morbidity resulting from chronic exposure to atherosclerotic risk factors. Patients suffering from its most severe form, chronic limb-threatening ischemia (CLTI), face substantial impairments to daily living, including chronic pain, limited walking distance without pain, and nonhealing wounds. Preclinical models have been developed in various animals to study PAD, but mouse hindlimb ischemia remains the most widely used. There can be significant variation in response to ischemic insult in these models depending on the mouse strain used and the site, number, and means of arterial disruption. This protocol describes a unique method combining femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase (NOS) inhibitor to reliably induce footpad gangrene in Friend Virus B (FVB) mice that resembles the tissue loss of CLTI. While traditional means of assessing reperfusion such as laser Doppler perfusion imaging (LDPI) are still recommended, intracardiac perfusion of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) is used to label the vasculature. Subsequent whole-mount confocal laser scanning microscopy allows for high-resolution, three-dimensional (3D) reconstruction of footpad vascular networks that complements traditional means of assessing reperfusion in hindlimb ischemia models.

The present protocol describes a unique, clinically relevant model of peripheral arterial disease that combines femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase inhibitor to induce hindlimb gangrene in FVB mice. Intracardiac DiI perfusion is then used for high-resolution, three-dimensional imaging of the footpad vasculature.

Imaging tridimensionale ad alta risoluzione della vascolarizzazione del footpad in un modello di cancrena posteriore murina

Peripheral arterial disease (PAD) is a significant cause of morbidity resulting from chronic exposure to atherosclerotic risk factors. Patients suffering ...

Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats

Animal studies have brought important insights into our understanding regarding atrial fibrillation (AF) pathophysiology and therapeutic management. Reentry, one of the main mechanisms involved in AF pathogenesis, requires a certain mass of myocardial tissue in order to occur. Due to the small size of the atria, rodents have long been considered 'resistant' to AF. Although spontaneous AF has been shown to occur in rats, long-term follow-up (up to 50 weeks) is required for the arrhythmia to occur in those models. The present work describes an experimental protocol of transesophageal atrial burst pacing for rapid and efficient induction of AF in rats. The protocol can be successfully used in rats with healthy or remodeled hearts, in the presence of a wide variety of risk factors, allowing the study of AF pathophysiology, identification of novel therapeutic targets, and evaluation of novel prophylactic and/or therapeutic strategies.

The present work describes an experimental protocol of transesophageal atrial burst pacing for efficient induction of atrial fibrillation (AF) in rats. The protocol can be used in rats with healthy or remodeled hearts, allowing the study of AF pathophysiology, identification of novel therapeutic targets, and evaluation of new therapeutic strategies.

Stimolazione atriale transesofagea per l'induzione della fibrillazione atriale nei ratti

Animal studies have brought important insights into our understanding regarding atrial fibrillation (AF) pathophysiology and therapeutic management. ...