部分支持NHLBI资助HL039707 P01 - P01 - HL087226和Leducq基金会（JJ和OB），由西班牙社会的心脏病奖学金基金会，佩德罗巴里DE LA的Maza和基金会阿方马丁Escudero（DFR）联邦法国， Cardiologie（RPM），心脏节律协会奖学金奖，日本心脏基金会的奖学金/电学（我的）日本社会。

1。摘取心脏Langendorff灌流羊重达35-40公斤，用4-6毫克/公斤异丙酚和60-100毫克/公斤戊巴比妥钠麻醉。心被删除通过开胸手术和循环含氧（95％O2，5％CO2）台氏在一个恒定流速为240-270毫升/分钟，pH值7.4和35.5-37.5 ° C。的解决方案连接到的Langendorff灌注系统台氏（毫米）的组成是：氯化钠，4.0氯化钾，氯化镁，氯化钙1.8，碳酸氢钠24，磷酸二氢钠1.2，葡萄糖5.6 130，和白蛋白0.04 g / L时Blebbistatin 10微米（恩佐生命科学国际公司普利茅斯会议，PA，美国）是用来降低收缩力。 2。拉伸诱发房颤的Langendorff灌注羊心隔离，冠状动脉灌注心脏经历了一个心房跨室间隔穿刺，使均衡的两个心房腔内压力。所有静脉窍，然后密封，除下腔静脉，这是空心连接数字传感器（BIOPAC系统的传感器TSD104A; BIOPAC系统公司，Goleta，CA，USA）和流出导管，其不限成员名额心房以上的高度控制内部心房压力。压力增加至12厘米H 2 O，从而导致一个〜30％心房量相对增加，在6厘米H 2 O的体积整个实验过程中，压力是保持稳定。密封静脉之前tetrapolar电极导管（TORQ，美敦力公司/明尼阿波利斯/ MN /美国）被放置在每个肺静脉从远端的两个电极使用BIOPAC系统放大器（采样率，1.0千赫）的双极性信号记录（DA100C; BIOPAC系统公司，Goleta，加利福尼亚，美国）。两个额外的custum双极电极置于左心耳（LAA）和右心耳顶部的屋顶上。 3。光的映射成立<ol><li>心外膜标测左心耳。一个推注5至10毫升的迪4 ANEPPS（10毫克/毫升）（Sigma - Aldrich公司，圣路易斯，密苏里州，美国）和一个10分钟的装载时间，需要获得电压敏感的激光激发后的荧光（532纳米）的外膜表面。发出荧光，然后通过600纳米传输，长通滤波器和投射到LittleJoe CCD摄像机（80x80像素，SciMeasure分析系统，公司迪凯特，GA，美国）和后天在每秒800帧的速度（见示意图图1A）。五秒钟的电影，在2分钟的间隔期间自动对焦。映射的外膜表面的面积是 2〜14厘米。 </li><li>解放军完整的心内膜光映射。第二个LittleJoe CCD相机（80x80像素）与外膜相机同步。一个10毫米直径的双通道刚性内窥镜（珠穆朗玛峰VIT公司弗兰德，新泽西州，美国）与90度领域的观点是通过左心室前壁介绍，跨二尖瓣专注于心内膜表面解放军。解放军光映射区域〜4厘米，这使得可视化的四个肺静脉和心房septo肺包（图1A，B） 。内窥镜是安装在C - CCD摄像头，通过一个特制的目镜适配器。激光532纳米的光，然后传递到内窥镜的激励渠道，通过液体光导（0.2核心）。 </li></ol> 4。心房颤动协议在连续心房舒展，AF是通过爆裂（12赫兹，5毫秒脉冲，2X舒张阈值）由位于左心耳顶部起搏电极起搏诱导。 AF是允许继续为50分钟，5秒光学电影，在两分钟的间隔收购。不断收集双极录音。光电影的收购触发双极录音5秒段的同步采集。 5。频率分析频率分析，可以在AF识别活化率高的地区，沿左，右心房之间的频率梯度。主频（DF）的地图是从每个光电影获得应用快速傅立叶变换算法（FFT）后的时间序列的荧光信号记录在每个像素。FFT也适用于5秒的双极性信号（高通滤波在3 Hz和低通在35赫兹过滤）与光的电影同步。 6。心房颤动动态<ol><li>相图的生成。自动对焦的动态分析，通过Hilbert变换产生的阶段电影的优势。14简言之，在每个像素中记录的动作电位的瞬时相位是由改造等，每一个频谱分量是其相应的季度周期转向原始时间序列信号15 AfterwarDS，瞬时相位信号是从逆转换的信号，原始信号的比例切线。相位角值之间的π和π弧度，表示为一个连续的配色方案，以构建一个阶段的地图，其中连续的空间相变反映了激励，复极和恢复的过程。14 </li><li>表征的激活模式。各阶层的激活模式可以识别使用阶段的电影（图2），包括下列内容： <ul><li>转子是确定存在一个奇点，持续一个以上的旋转（图2A）趋同的所有阶段。 </li><li>突破定义为波前出现在视野和向外传播在目标模式（图2B）。 </li><li>被定义为至少四个连续周期波，从视野相同的位置，与类似的方向和波间的时间间隔（图2C），新兴Spatiotemporally组织定期波。 </li></ul></li></ol>进一步量化允许从特定地区所取得的最常见的激活模式的空间相关性最高的频域。后者突出了解放军测绘内膜表面的至关重要的作用，因为它通常代表该地区最高的频域位于在急性房颤。 7。代表性的成果： 主频（DF）的梯度从解放军左心耳和RAA的急性拉伸诱导AF。东风最高的区域是本地化的肺静脉或在解放军某一个或接近 11代表AF情节是在图3所示，其中最高的DF是解放军本地化（右下肺静脉）。研究结果支持在解放军驾驶AF高频率源的存在与左右的DF在阵发性房颤的烧蚀程序观察梯度一致16。 激活使用相图电影模式的定量分析显示，人数最多的转子是在解放军全军和左心耳之间的交界处发现，8偶尔有可能，以确定长期转子的旋转中心（奇异点）定位最高的频域。由于心房组织代表一个三维结构，确定转子上的映射解放军内膜表面表明，这些转子的旋转中心（长丝），最终垂直于表面的映射区域。图4显示了这样一个从解放军的心内膜同时对左心耳，这也与相关性之间的解放军和左心耳（分别为9和6.4赫兹）的频率梯度fibrillatory传导记录转子。转子的数量一直在解放军高于左心耳，这表明解放军折返重要作用，以保持在这个模型中的心律失常。 总的来说，结果支持这一理论，在左心房的稳定和快速的转子驱动急性牵拉诱导的自动对焦和所产生的波，经过他们的头朝着右心房复杂，空间分布的传导阻滞模式，表现为fibrillatory传导，逐级递减的主导频率。 <img src="/files/ftp_upload/3103/3103fig1.jpg" alt="图1" /> 图1的实验图解成立。答：刚性内窥镜介绍，通过左心室和二尖瓣口的前壁，并专注于内膜表面后的左心房（解放军）。耦合的内窥镜CCD相机和激光照射是通过连接内窥镜下激光液体指导。心外膜标测是对左心耳。双极电极置于右心房和左心房的屋顶上。从肺静脉获得额外的双极性信号。乙：左心房开放用于说明目的侧壁以下侧视图。内窥镜的一角，照亮了解放军的心内膜表面。双极电极位于左心房的屋顶上。左心耳，左心耳。 LV：左心室。 RA：右心房。 RV：右心室。 <img src="/files/ftp_upload/3103/3103fig2.jpg" alt="图2" /> 图2不同的图案，确定后一代相电影激活。答：左心耳（LAA）连续快照显示了一个围绕其旋转中心（奇异点）的转子旋转。从左至右，完成一个完整的旋转。乙：一个样本突破LAA，激活模式。波向上每右上角的观点和向外传播领域。 C：四个spatiotemporally举办周期波（0，182，352和512毫秒，分别）来自解放军走向LAA，地区。等时线绘制在10毫秒的间隔。底部，动作电位的不同阶段的关键是颜色编码。 <img src="/files/ftp_upload/3103/3103fig3.jpg" alt="图3" /> 图3：确定急性牵拉诱导AF频率最高的一个孤立的羊心的Langendorff灌注活动的地区。答：解剖视图，左心耳（LAA），右心耳（RAA），左心房后壁（解放军）。解放军的形象是一个四个肺静脉（PV）的映射区域内镜下查看。乙：光映射获得左心耳和解放军的东风地图。在RAA的频率值是由双极电图。频率最高的地区是位于解放军。 C：代表的功率谱，其中最大的DF对应到12.4赫兹在解放军权的PV地区。 LSPV：左上肺静脉。 LIPV：左下肺静脉。 RSPV：右上肺静脉。 RIPV：右下肺静脉。转载自参考11（Filgueiras拉玛大卫何塞Jalife心房颤动的内在机制，在基础科学，临床Electrophysiologist，第3（主编查尔斯Antzelevitch）141-156（桑德斯，2011年）。 <img src="/files/ftp_upload/3103/3103fig4.jpg" alt="图4" /> 图4。Simultaneousphase地图（A，B）和主频地图（三）从后左心房（解放军）和左心耳（LAA）。答：从解放军的连续快照，显示其奇异点的转子和漂流。 B：阶段从LAA，同时快照。激活模式显示兼容fibrillatory传导的传播波。奇异点也是在目前fibrillatory传导地区wavebreaks的相关。 （见视频4）：从解放军和左心耳的同时主频地图。最快的地区是位于解放军（10赫兹），这与转子相图分析存在关联。在左心耳的频率最高的是6赫兹，fibrillatory传导相关。在C组的右侧，从解放军和左心耳的单个像素光学激活所示。

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没有利益冲突的声明。

中分离出来的羊心的拉伸引起的急性房颤的特点类似于人类的阵发性房颤的一些属性。 1中的左到右的DF梯度的存在在急性羊心内心房压力的增加使维护长期的时间，观察患者心房扩张的风险较高的AF自动对焦。羊心房也有类似的人体电生理研究注册的 16因此，了解的机制，维持在此急性模型的自动对焦，可改善目前在人类的阵发性房颤的治疗策略。一些当前方法的局限性是：第一...

<table border="1"><tbody><tr><td> 材料名称 </td><td> 公司 </td><td> 目录编号 </td></tr><tr><td> 安乐死 </td><td></td><td></td></tr><tr><td>肝素</td><td>西格玛</td><td> H3393 </td></tr><tr><td>异丙酚</td><td>雅培</td><td> 5206-04-03 </td></tr><tr><td>戊巴比妥</td><td> Lundbeck公司公司</td><td> NDC 67386-501-55 </td></tr><tr><td>介绍人18号</td><td> Terumo公司</td><td> SS * FF1832 </td></tr><tr><td>翻边气管导管（9毫米） </td><td>肛门指诊兽医</td><td> ＃9440 </td></tr><tr><td>光纤喉镜案例</td><td>肛门指诊兽医</td><td> ＃991 </td></tr><tr><td>光纤刀片</td><td>肛门指诊兽医</td><td> ＃984 </td></tr><tr><td>操作剪刀</td><td>肛门指诊兽医</td><td> ＃9702＃1944 </td></tr><tr><td>手术刀手柄＃3固体4“ </td><td> Roboz外科仪器有限责任公司</td><td> RS - 9843 </td></tr><tr><td>无菌手术刀片</td><td> Roboz外科仪器有限责任公司</td><td> RS - 9801 - 10 </td></tr><tr><td>通风袋</td><td> Westmed </td><td> 562013 </td></tr><tr><td>模拟人生剪刀弯夏普/钝</td><td> Roboz外科仪器有限责任公司</td><td> RS - 7035 </td></tr><tr><td>组织钳（× 2） </td><td>肛门指诊兽医</td><td> ＃1895年</td></tr><tr><td>坎特罗威茨胸钳，11“ </td><td>生物医学研究仪器公司</td><td> 34-1980 </td></tr><tr><td> Finochietto大胸部吊具</td><td>卡普外科仪器公司</td><td> KS - 7301 </td></tr><tr><td>开胸手术剪</td><td> Rostfrei索林根</td><td></td></tr><tr><td>塑料托盘</td><td> NALGENE </td><td>菲舍尔</td></tr><tr><td> 光的映射 </td><td></td><td></td></tr><tr><td>波恩剪刀（× 2） </td><td> Roboz手术器械有限责任公司</td><td> RS - 5840SC </td></tr><tr><td>手术丝</td><td>菲舍尔</td><td> 50-900-04214 </td></tr><tr><td>微解剖钳</td><td> Roboz手术器械有限责任公司</td><td> RS - 5130 </td></tr><tr><td> Tetrapolar电极导管（TORQ）（× 4） </td><td>美敦力公司</td><td> 05580SP </td></tr><tr><td>数字传感器。 BIOPAC系统传感器</td><td> BIOPAC系统，公司</td><td> RX104A </td></tr><tr><td> BIOPAC系统放大器</td><td> BIOPAC系统，公司</td><td> DA - 100C </td></tr><tr><td> DI - 4 - ANEPPS </td><td> Sigma - Aldrich公司，圣</td><td> D8604 - 5毫克</td></tr><tr><td> Blebbistatin </td><td>恩佐生命科学国际公司</td><td> BML - E1315 - 0025 </td></tr><tr><td> LittleJoe CCD摄像机（× 2） </td><td> SciMeasure分析系统，公司</td><td></td></tr><tr><td>双通道刚性内窥镜</td><td>珠峰VIT公司</td><td> R10 - 25 - 0 - 90 </td></tr><tr><td>灌注泵（× 2） </td><td>科尔帕默</td><td> GK - 77920 - 30 </td></tr><tr><td>温度探头</td><td>科尔帕默</td><td> R - 08491 - 02 </td></tr><tr><td>酸度计</td><td>菲舍尔</td><td> 01-913-806 </td></tr><tr><td>数字温度测量仪</td><td>科尔帕默</td><td> GK89000 - 10 </td></tr><tr><td>充氧过滤器</td><td>索林</td><td> 05318 </td></tr><tr><td>硅灌注管（L / S 15） </td><td> MASTERFLEX </td><td> 96410-15 </td></tr><tr><td>激光导光（× 6） </td><td>奥丽尔公司</td><td> 77536 </td></tr><tr><td>液体光导（0.2核心） </td><td> Newport公司</td><td> 77556 </td></tr><tr><td>激光发生器（1瓦）（× 1） </td><td>上海梦Lsaer Tecchnology </td><td> SDL - 532 - 1000T </td></tr><tr><td>激光发生器（5瓦）（× 1） </td><td>光谱物理激光器</td><td>轧机5sJ </td></tr></tbody></table>

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

心房颤动（AF）是一个复杂的的心律失常，发病率和死亡率高 。1,2它是最常见的持续心脏节律紊乱在临床实践中，其患病率在未来几年内预计将增加3内心房压力增加和扩张早就认识到导致自动对焦，其中强调利用动物模型的相关性和拉伸研究自动对焦动态的1,4。了解底层自动对焦的机制，需要可视化的高时空分辨率的心脏电波。虽然高时空分辨率，可以实现由传统的用于人体电生理研究的常规电气映射，内心房电极的少数，可以同时使用，限制了空间分辨率和排除任何详细的追踪期间心律失常的电波。引进的光映射在90年代初启用宽领域fibrillatory活动的表征与亚毫米级的空间分辨率在动物模型5,6和快速旋转的电波模式（转子）fibrillatory来源识别活动中可能发生的心室或心房。7-9使用相结合的时间和频域的分析，光映射，它是可能的，证明在AF高频率的定期活动的离散网站，沿左，右心房之间的频率梯度。与最快转子的地区，出现频率最高的激活和驱动器整体的心律失常。10,11波这样的转子所产生的交互功能性或解剖上的障碍，在他们的道路fibrillatory传导现象。12测绘内膜表面后左心房（解放军），允许与转子频率最高的自动对焦波在该地区的动态跟踪。重要的是，解放军是腔内导管为基础的烧蚀程序是最成功的终止AF患者中，13，其中强调了学习的左心房室内的自动对焦动态的相关性的地区。在这里，我们描述了一个羊急性牵张诱导AF，它类似于人类阵发性房颤的一些特征模型。补充左心房心外膜标测与心内膜解放军测绘使用的是双通道刚性内窥镜C -安装一个CCD摄像头，它代表了最直接的方法，可视化最相关的区域的激活模式，自动对焦维护。

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

这份报告提供了并发心内膜和心外膜完整的Langendorff灌注期间拉伸诱发房颤羊心左心房的电激发光的映射的方法和结果的详细说明。

高分辨率的心内膜和心外膜光学在拉伸诱发心房颤动的羊模型的映射

 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 次观看.  University of Michigan. 这份报告提供了并发心内膜和心外膜完整的Langendorff灌注期间拉伸诱发房颤羊心左心房的电激发光的映射的方法和结果的详细说明。

视频: 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.

守望的左心耳封闭装置心房颤动

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

科研

医学

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.

结合消融房颤左心耳封堵

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.

室颤由传统的封闭胸技术大鼠模型和复苏

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.

房颤消融机器人

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.

高分辨率光学制图对小鼠心房电生理的评价

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.

使用电子地图的光映射数据的高通量分析

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.

在心房颤动治疗中，为食道冷却或加热，以减少左心房消融期间的食管损伤

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.

Aachener Minipigs的无菌性心包炎作为心房肌病和心房颤动的模型

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.

小鼠后肢坏死模型中脚垫脉管系统的高分辨率三维成像

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.

经食管心房爆破起搏在大鼠心房颤动诱导中的应用

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