Apoiado em parte pelo NHLBI Grants P01-P01-HL039707 e HL087226 ea Fundação Leducq (JJ e OB), por uma Sociedade Espanhola de Cardiologia Fellowship, Fundación Pedro Barrie de la Maza e Alfonso Martín Escudero Fundación (DFR), pela Fédération Française de cardiologie (RPM), por um coração Award comunhão Rhythm Society, The Fellowship of Japan Heart Foundation / A Sociedade Japonesa de Eletrocardiologia (MY).

1. Remoção do coração e perfusão Langendorff Ovelhas pesando 35-40 kg são anestesiados com propofol 4-6 mg / Kg e 60-100 mg / Kg de pentobarbital sódico. Corações são removidos através de toracotomia e conectado a um sistema de perfusão Langendorff com circulação oxigenada (95% O2, 5% CO2) solução de Tyrode a uma taxa constante fluxo de 240-270 ml / min, pH 7,4 e 35,5-37,5 ° C. Composição do Tyrode (em mM) é: NaCl 130, KCl 4.0, MgCl2 1, CaCl2 1,8, NaHCO3 24, NaH2PO4 1.2, Glicose 5,6 e albumina 0,04 g / L. Blebbistatin 10 mM (Enzo Life Science International, Inc. Plymouth Meeting, PA, EUA) é usado para reduzir a força contrátil. 2. Estiramento induzida fibrilação atrial no coração ovelhas Langendorff-perfundidos O isolado, coração de perfusão coronariana submetido a uma punção trans-septal atrial para habilitar empatou pressão intracavitária em ambos os átrios. Todos os orifícios das veias são então selados, com exceção da veia cava inferior, que é canulada e conectada a um sensor digital (Biopac Sistemas transdutor-TSD104A; Biopac Systems, Inc., Goleta, CA, EUA) e uma cânula cuja saída open-ended altura acima do átrios controla a pressão intra-atrial. A pressão é então aumentado para 12 cm H 2 O, o que leva a um aumento de ~ 30% em relação ao volume atrial o volume de 6 cm H 2 O. A pressão é mantida estável durante todo o experimento. Antes de selar as veias cateteres-eletrodos tetrapolar (Torq, Medtronic Inc. / Minneapolis / MN / EUA) são colocados em cada uma das veias pulmonares para gravar sinais bipolar dos dois eletrodos distal (taxa de amostragem, 1,0 kHz) usando um amplificador de Sistemas Biopac (DA100C; Biopac Systems, Inc., Goleta, CA, EUA). Mais dois eletrodos custum-made bipolar são colocados no teto do apêndice atrial esquerdo (AAE) e no topo da aurícula direita. 3. Mapeamento óptico configurado <ol><li> Mapeamento epicárdico do apêndice atrial esquerdo. A injeção em bolus de 5 a 10 ml Di-4-ANEPPS (10 mg / mL) (Sigma-Aldrich, St. Louis, MO, EUA) e um período de carga de 10 min são necessárias para obter fluorescência sensíveis à voltagem sobre a excitação do laser (532 nm) da superfície epicárdica. A fluorescência emitida é então transmitida através de uma longa 600 nm e filtro passa projetada LittleJoe CCD da câmera de vídeo (80x80 pixels, SciMeasure Analytical Systems, Inc. Decatur, GA, EUA) e adquiridas a uma taxa de 800 quadros por segundo (veja representação esquemática na Figura 1A). Cinco segundos filmes são obtidas em intervalos de 2 min durante AF. A área da superfície mapeada epicárdica é ~ 14 cm 2. </li><li> Mapeamento endocárdico óptica do PLA do coração intacto. Um segundo LittleJoe câmera CCD (80x80 pixels) é sincronizada com a câmera do epicárdio. A 10 milímetros de diâmetro borescope canal dual-rígida (VIT Everest, Inc. Flanders, NJ, EUA) com um campo de 90 graus de vista é introduzido através da parede anterior do ventrículo esquerdo, através da válvula mitral e incidiu sobre a superfície do endocárdio do PLA. A área mapeada opticamente na PLA é de aproximadamente 4 cm 2, que permite visualizar as quatro veias pulmonares e do pacote de septo atrial-pulmonar (Figura 1A, B). A borescope é c-montados para a câmera CCD por meio de um adaptador de ocular feito por encomenda. A luz do laser 532 nm é então entregue ao canal de excitação do borescope através de um líquido luz-guia (0,2 no core). </li></ol> 4. Protocolo de fibrilação atrial Sob estiramento atrial contínua AF é induzida através de pacing explosão (12 Hz, 5 ms pulsos, limiar 2x diastólica) por um eletrodo de marcapasso localizado no topo da LAA. AF é autorizado a continuar por 50 minutos e 5-sec filmes ópticos são adquiridos em intervalos de dois minutos. Gravações bipolares são coletados de forma contínua. Aquisição dos filmes ópticos triggers aquisição simultânea de 5-sec segmentos das gravações bipolar. 5. Análise de freqüência Análise de freqüência permite a identificação de regiões com alta taxa de activação durante a AF, juntamente com gradientes de frequência entre átrio esquerdo e direito. Dominante freqüência (DF) mapas são obtidos a partir de cada filme óptico depois de aplicar um algoritmo de transformação rápida de Fourier (FFT) ao sinal de fluorescência de séries temporais registrados a cada pixel. 7 FFT também é aplicado para os 5 sinais segunda bipolar (High-pass filtrada em 3 Hz e passa-baixa filtrada a 35 Hz) sincronizado com os filmes ópticos. 6. Atrial dinâmica fibrilação <ol><li> Geração de mapas de fase. Análise da dinâmica AF aproveita filmes fase gerada através de transformação de Hilbert. 14 Resumidamente, a fase instantânea do potencial de ação registrado em cada pixel é determinada pela transformação do original de séries temporais de sinais de tal forma que cada componente espectral é desviado por seu ciclo de trimestre correspondente 15. Afterwards, a fase instantânea do sinal é obtida a partir da tangente inversa da razão entre o sinal transformado do sinal original. O ângulo de fase, com valores entre-π e π radianos é representado como um esquema de cor contínua para construir um mapa de fase, em que a mudança de fase espacial contínua reflete o processo de repolarização excitação, e recuperação. 14 </li><li> Caracterização dos padrões de ativação. Várias classes de padrões de ativação podem ser identificadas usando filmes de fase (Figura 2), incluindo o seguinte: <ul><li> Um rotor é identificada pela presença de todas as fases convergindo para um ponto de singularidade que durou mais de uma rotação (Figura 2A). </li><li> A descoberta é definida como uma frente de onda que aparecem no campo de visão e propagar para fora (Figura 2B) em um padrão meta-like. </li><li> Espaço-temporalmente organizada ondas periódicas são definidos como um mínimo de quatro seqüencial ondas periódicas emergentes do mesmo local no campo de visão, com sentido semelhantes e inter-onda intervalo (Figura 2C). </li></ul></li></ol> Quantificação ainda permite a correlação espacial dos domínios com maior freqüência o padrão mais comum de ativação obtida por aquela região em particular. Este último destaca o papel crucial do mapeamento da superfície endocárdica do PLA, uma vez que geralmente representa a região onde os domínios maior freqüência estão localizados durante AF aguda. 7. Resultados representativos: Dominante freqüência (DF) gradientes de PLA para LAA e RAA estão presentes durante aguda induzida por estiramento AF. A região mais alta DF está localizada tanto em ou perto de uma das veias pulmonares ou em algum lugar do PLA. 11 Um representante AF episódio é mostrado na Figura 3, no qual a maior DF está localizada no PLA (direito inferior da veia pulmonar). Os resultados apóiam a presença de fontes de alta freqüência na condução PLA AF consistente com a da esquerda para a direita gradientes DF observado durante procedimentos de ablação na fibrilação atrial paroxística humana. 16 Quantificação dos padrões de ativação usando filmes mapa de fase mostra que o maior número de rotores é encontrado no PLA e na junção entre o PLA eo LAA. 8 Ocasionalmente, é possível identificar de longa duração rotores, cujo centro de rotação (ponto de singularidade) localiza com o domínio de freqüência mais alta. 10 Como o tecido atrial representa uma estrutura tridimensional, identificando os rotores na superfície mapeada endocárdica do PLA sugere que o centro de rotação dos rotores (filamento) é eventualmente perpendicular à superfície da área de mapeamento . A Figura 4 mostra como um rotor gravado a partir do endocárdio do PLA com condução fibrilatório simultânea para o LAA, que também se correlaciona com um gradiente de freqüência entre o PLA eo LAA (9 e 6,4 Hz, respectivamente). O número de rotores é consistentemente maior no PLA que o LAA, o que sugere um papel essencial de reentrada sobre o PLA para manter a arritmia neste modelo. Globalmente, os resultados suportam a teoria de que os rotores estável e rápido no átrio esquerdo pode conduzir aguda induzida por estiramento AF e as ondas que emanam submeter complexos, padrões bloco espacialmente distribuídos de condução, como eles cabeça em direção ao átrio direito, manifestando-se como condução fibrilatório e diminuindo progressivamente dominante freqüência. <img src="/files/ftp_upload/3103/3103fig1.jpg" alt="Figura 1" /> Figura 1. Representação esquemática do conjunto experimental. A: A borescope rígida é introduzido através da parede anterior do ventrículo esquerdo e do orifício da válvula mitral e incidiu sobre a superfície do endocárdio do átrio esquerdo posterior (PLA). Uma câmera CCD é acoplado ao borescope e iluminação a laser é fornecida através de um guia a laser líquido conectado à parte inferior do borescope. Mapeamento epicárdico é executada no LAA. Eletrodos bipolares são colocados no átrio direito e teto do átrio esquerdo. Sinais adicionais bipolar são obtidos a partir das veias pulmonares. B: Vista lateral do átrio esquerdo após a abertura da parede lateral para fins de ilustração. A ponta do borescope ilumina a superfície endocárdica do PLA. Um eletrodo bipolar está localizado no teto do átrio esquerdo. LAA: left apêndice atrial. LV: ventrículo esquerdo. RA: átrio direito. VD: ventrículo direito. <img src="/files/ftp_upload/3103/3103fig2.jpg" alt="Figura 2" /> Figura 2. Diferentes padrões de ativação identificados após a geração de filmes de fase. A: tiros snap seqüencial do apêndice atrial esquerdo (AAE) mostram o giro de um rotor em torno do seu centro de rotação (ponto de singularidade). Da esquerda para a direita, uma rotação completa seja concluída. B: Uma amostra padrão de ativação avanço sobre o LAA. A onda aparece na uppor canto direito do campo de visão e se propaga para fora. C: Quatro espaço-temporalmente organizada ondas periódicas (A 0, 182, 352 e 512 ms, respectivamente) proveniente da região PLA para o LAA. Isócronas são plotadas em intervalos de 10 ms. Fundo, a chave para as diferentes fases do potencial de ação é um código de cores. <img src="/files/ftp_upload/3103/3103fig3.jpg" alt="Figura 3" /> Figura 3. Identificação das regiões com maior freqüência a atividade durante o estiramento aguda induzida por AF em um coração de ovelha Langendorff-perfundidos isolados. A: vista anatômico do apêndice atrial esquerdo (AAE), aurícula direita (RAA) e do átrio esquerdo posterior (PLA). PLA imagem é uma visão endoscópica da região mapeada com as quatro veias pulmonares (VPs). B: DF mapas obtidos pelo mapeamento óptico na LAA e PLA. Valor da freqüência na RAA foi obtida a partir eletrogramas bipolares. A região de maior freqüência está localizado no PLA. C: Representante espectros de potência, em que o DF máximo corresponde a 12,4 Hz na região PLA dos PVs direita. VPSE: veia pulmonar superior esquerda. VPIE: veia pulmonar inferior esquerda. VPSD: veia pulmonar superior direita. VPID: veia pulmonar direita inferior. Reproduzido da referência 11 (David Filgueiras Rama e José Jalife. Mecanismos subjacentes Fibrilação Atrial. Em Ciência Básica para Electrophysiologist Clínica, vol. 3 (ed. Charles Antzelevitch) 141-156 (SAUNDERS, 2011). <img src="/files/ftp_upload/3103/3103fig4.jpg" alt="Figura 4" /> Figura 4. Simultaneousphase mapas (A, B) e mapas de freqüência dominante (C) a partir do átrio esquerdo posterior (PLA) e apêndice atrial esquerdo (AAE). A: tiros snap seqüencial a partir do PLA mostrando um rotor ea deriva do seu ponto de singularidade. B: tiros fase simultânea pressão da LAA. Padrões de ativação mostram ondas de propagação compatível com a condução fibrilatório. Pontos de singularidade também estão presentes em correlação com wavebreaks na região de condução fibrilatório. (Veja também o vídeo 4) C: simultânea mapas freqüência dominante do PLA e do LAA. O mais rápido região está localizada no PLA (9 Hz), que se correlaciona com a presença de um rotor na análise mapa de fase. A maior freqüência na LAA é de 6 Hz, que se correlaciona com condução fibrilatório. No lado direito do painel C, único pixel de ativações óptica de PLA e LAA são mostrados.

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As características do trecho aguda induzida por AF no coração ovelhas isoladas lembram algumas das propriedades dos recursos humanos fibrilação atrial paroxística. Um aumento agudo na pressão intra-atrial no coração de ovelha permite a manutenção da AF por longos períodos de tempo, semelhante a um maior risco de AF observada em pacientes com dilatação atrial. A presença de um gradiente da esquerda para a direita no DF ovelhas átrios também é semelhante aos registrados em humanos estudos elet...

<table border="1"><tbody><tr><td> Nome do material </td><td> Companhia </td><td> Número Catálogo </td></tr><tr><td> Eutanásia </td><td></td><td></td></tr><tr><td> Heparina </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> Introdutor de calibre 18 </td><td> Terumo </td><td> SS * FF1832 </td></tr><tr><td> Tubo endotraqueal com cuff (9 mm) </td><td> DRE Veterinária </td><td> # 9440 </td></tr><tr><td> Caso Laringoscópio de Fibra Óptica </td><td> DRE Veterinária </td><td> # 991 </td></tr><tr><td> Lâmina de fibra óptica </td><td> DRE Veterinária </td><td> # 984 </td></tr><tr><td> Tesoura operacional </td><td> DRE Veterinária </td><td> # 9702 # 1944 </td></tr><tr><td> Handle bisturi # 3 Solid 4 &quot; </td><td> Roboz Surgical Instrument Co., Inc. </td><td> RS-9843 </td></tr><tr><td> Estéril lâminas de bisturi </td><td> Roboz Surgical Instrument Co., Inc. </td><td> RS-9801-10 </td></tr><tr><td> Saco de ventilação </td><td> Westmed </td><td> 562013 </td></tr><tr><td> Sims tesoura curva Sharp / Blunt </td><td> Roboz Surgical Instrument Co., Inc. </td><td> RS-7035 </td></tr><tr><td> Pinça (× 2) </td><td> DRE Veterinária </td><td> # 1895 </td></tr><tr><td> Pinça Kantrowitz Torácica, 11 &quot; </td><td> Biomedical Research Instruments, Inc. </td><td> 34-1980 </td></tr><tr><td> Finochietto Spreader Peito Grande </td><td> Kapp Surgical Instrument Inc. </td><td> KS-7301 </td></tr><tr><td> Toracotomia tesouras </td><td> Rostfrei Solingen </td><td></td></tr><tr><td> Bandeja de plástico </td><td> Nalgene </td><td> Fischer </td></tr><tr><td> Mapeamento óptico </td><td></td><td></td></tr><tr><td> Bonn Tesoura (× 2) </td><td> Roboz Surgical Instrument Co., Inc </td><td> RS-5840SC </td></tr><tr><td> Cirúrgico de seda </td><td> Fischer </td><td> 50-900-04214 </td></tr><tr><td> Micro Pinça Dissecting </td><td> Roboz Surgical Instrument Co., Inc </td><td> RS-5130 </td></tr><tr><td> Tetrapolar cateteres-eletrodos (Torq) (× 4) </td><td> Medtronic Inc. </td><td> 05580SP </td></tr><tr><td> Sensor digital. Biopac transdutor Sistemas </td><td> Biopac Systems, Inc. </td><td> RX104A </td></tr><tr><td> Biopac amplificador de Sistemas </td><td> Biopac Systems, Inc. </td><td> DA-100C </td></tr><tr><td> Di-4-ANEPPS </td><td> Sigma-Aldrich, St. </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 da câmera de vídeo (× 2) </td><td> SciMeasure Analytical Systems, Inc. </td><td></td></tr><tr><td> Dual-channel borescope rígida </td><td> Everest VIT, Inc. </td><td> R10-25-0-90 </td></tr><tr><td> Bombas de perfusão (× 2) </td><td> Cole Parmer </td><td> GK-77920-30 </td></tr><tr><td> Sonda de temperatura </td><td> Cole Parmer </td><td> R-08491-02 </td></tr><tr><td> medidor de pH </td><td> Fischer </td><td> 01-913-806 </td></tr><tr><td> Indicador de temperatura digitais </td><td> Cole Parmer </td><td> GK89000-10 </td></tr><tr><td> Filtros oxigenador </td><td> Sorin </td><td> 05318 </td></tr><tr><td> Tubos de perfusão de silício (L / S 15) </td><td> Masterflex </td><td> 96410-15 </td></tr><tr><td> Guias de luz laser (x 6) </td><td> Oriel Corporação </td><td> 77536 </td></tr><tr><td> Líquido luz-guia (0,2 no core) </td><td> Newport Corporation </td><td> 77556 </td></tr><tr><td> Laser gerador (1 watt) (× 1) </td><td> Sonho Xangai Lsaer Tecchnology </td><td> SDL-532-1000T </td></tr><tr><td> Laser gerador (5 watts) (× 1) </td><td> Spectra Physics Lasers </td><td> MILL 5sJ </td></tr></tbody></table>

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

Fibrilação atrial (FA) é uma arritmia cardíaca complexa, com alta morbidade e mortalidade 1,2. É o mais comum distúrbio do ritmo cardíaco mantido visto na prática clínica e sua prevalência é esperado um aumento nos próximos anos. 3 Aumento da pressão intra-atrial e dilatação ter sido reconhecido por muito tempo para levar a AF, 1,4 o que evidencia a relevância da utilização de modelos animais para estudar e esticar AF dinâmica. Compreender os mecanismos subjacentes AF requer visualização das ondas elétrica cardíaca com resolução espacial e temporal. Enquanto a alta resolução temporal pode ser obtida através do mapeamento elétrica convencional, tradicionalmente usado em humanos estudos eletrofisiológicos, o pequeno número de eletrodos intra-atrial que podem ser usados ​​simultaneamente limita a resolução espacial e impede qualquer acompanhamento detalhado das ondas elétricas durante a arritmia. A introdução de mapeamento óptico no início dos anos 90 a caracterização de campo amplo de atividade fibrilatório habilitado, juntamente com sub-milímetro resolução espacial em modelos animais 5,6 e levou à identificação de padrões de ondas girando rapidamente elétrica (rotores) como as fontes do fibrilatório atividade que pode ocorrer nos ventrículos ou aurículas. 7-9 Usando o tempo e combinada no domínio da freqüência análises de mapeamento óptico, é possível demonstrar locais discretos de atividade de alta frequência periódica durante AF, juntamente com gradientes de frequência entre átrio esquerdo e direito . A região com a mais rápida rotores ativa na maior frequência e unidades da arritmia em geral. 10,11 As ondas que emanam rotor como interagir com os obstáculos ou anatômica ou funcional em seu caminho, resultando no fenômeno da condução fibrilatório. 12 Mapeamento da superfície endocárdica do o átrio esquerdo posterior (PLA), permite o rastreamento de AF onda dinâmica na região com a maior freqüência de rotor. Importante, o PLA é a região onde intracavitária cateter procedimentos baseados ablativos são mais bem sucedidos AF terminando em pacientes, 13, que ressalta a relevância do estudo AF dinâmica do interior do átrio esquerdo. Descrevemos aqui um modelo de ovelhas de estiramento agudo induzido por AF, que se assemelha a algumas das características do ser humano fibrilação atrial paroxística. Mapeamento epicárdico no átrio esquerdo é complementada com mapeamento endocárdico do PLA usando um canal dual-borescope rígida c-montado em uma câmera CCD, que representa a abordagem mais direta de visualizar os padrões de ativação na região mais relevantes para a manutenção da FA.

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

Este relatório fornece uma descrição detalhada da metodologia e os resultados do mapeamento endocárdico e epicárdico simultâneos óptico de excitação elétrica no átrio esquerdo intacto de um coração de ovelha Langendorff-perfundidos durante o alongamento induzida por fibrilação atrial.

Alta Resolução Mapeamento endocárdico e epicárdico óptico em um modelo de Ovinos de Stretch Induzida por Fibrilação Atrial

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

high-resolution-endocardial-epicardial-optical-mapping-sheep-model

Research

JoVE Journal

Medicine

14.7K visualizações.  University of Michigan. Este relatório fornece uma descrição detalhada da metodologia e os resultados do mapeamento endocárdico e epicárdico simultâneos óptico de excitação elétrica no átrio esquerdo intacto de um coração de ovelha Langendorff-perfundidos durante o alongamento induzida por fibrilação atrial.

Vídeo: 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.

O WATCHMAN Esquerda dispositivo de fechamento atrial Appendage para Fibrilação Atrial

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

Medicina

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.

Ablação por cateter em combinação com o fechamento do apêndice atrial esquerdo para Fibrilação Atrial

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.

Um modelo de rato de Fibrilação Ventricular e Reanimação por Técnica de tórax fechado convencional

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 Ablação de Fibrilação Atrial

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.

Avaliação eletrofisiológica de murino átrios com mapeamento óptico de alta resolução

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.

Análise de alto throughput de dados de mapeamento óptico usando o 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.

Resfriamento ou Aquecimento do Esôfago para reduzir a lesão esofágica durante a ablação atrial esquerda no tratamento da fibrilação atrial

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 estéril em Miniporcos Aachener como modelo para miopatia atrial e fibrilação atrial

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.

Imagem tridimensional de alta resolução da Vasculatura do Footpad em um Modelo de Gangrena Hindlimb Murine

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.

Transesofágico Atrial Burst Pacing para Indução de Fibrilação Atrial em Ratos

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