Atrionodal Bundles:Histologic and Physiologic Validation

描述（由申请人提供）：“慢”或“快”房室结通路的射频（RF）导管消融可治愈房室结折返性心动过速（AVNRT），还可改变心房扑动和颤动的心室反应。 然而，这些心律失常的组织和机制都不清楚。 最近，我们证明了两个独立的心房回路在AV交界区重叠：“肌肉瓣膜装置”的组成部分，“周向和垂直层”，也形成了下内侧心房壁;和，胶原包裹的“多肢输入”到AVN：“房室结束（AB）和近端AV束（PAVB）”，这是内侧心房壁心外膜的外部。 我们发现，每个组织都具有独特的细胞外（EAP）和跨膜动作电位（TAP）和传输特性;来自心房和专门组织的EAP并排出现在心房和专门组织重叠的部位;心房EAP和收缩随着暴露于高钾而停止。 假设：在人和狗的心脏中存在具有独特组织学和传导特性的专门的多肢AVN输入。 具体目的是确定：（1）ABs和PAVB在人心脏中的位置;（2）荧光黄（LY）离子导入后引起AB电位的心肌细胞及其电通路;（3）程序刺激ABs和SAN时ABs的传输特性，通过评估SAN-AB间期; 4）每种AB通过选择性消融LY-灌注的肌纤维或切断AB/PAVB连接而改变SAN-AVN间期，从而在AVN激活中发挥作用。 方法：将同时使用（a）SAN、3AB、PAVB和AVN处的固定导管电极记录电位，以监测电耦合，（B）线电极定位注射和记录部位，对光消融的反应，（c）多电极阵列斑块，（d）1% LY或3 M KCl微移液器电极记录，并使用电流脉冲注射染料。 将使用蓝光和手术刀片进行消融。 将通过3D分析和重建评价解剖结构、LY通路和光解效应。 电位形态和传导间期的改变将通过SAN迹线中的计时以及EAP和TAP的相关性来确认。 这些研究有望为评价组织水平的传播、肿瘤发生和药物相互作用提供基础。

DESCRIPTION (provided by applicant): Radiofrequency (RF) catheter ablation of either the "slow" or "fast" AV nodal pathways can cure AV node reentrant tachycardia (AVNRT) and also modify ventricular response to atrial flutter and fibrillation. However, neither the tissues nor mechanisms underlying these arrhythmias are known. Recently, we demonstrated that two separate atrial circuits overlap in the AV junction region: components of the "muscular valvular apparatus", the "circumferential and the perpendicular laminae," which also form the inferior medial atrial wall; and, the collagen encased "multilimb input" to the AVN: the "atrionodal bundles (ABs) and the proximal AV bundle (PAVB)," which is outside of the medial atrial wall epicardium. We showed that each tissue possess unique extracellular (EAP) and transmembrane action potentials (TAP) and transmission properties; EAPs from the atrial and specialized tissues appear side-by-side in traces made at sites where the atrial and specialized tissues overlap; and atrial EAPs and contractions ceased with exposure to high potassium. HYPOTHESIS: A specialized multilimb AVN input with unique histologic and conduction properties is present in human and dog heart. SPECIFIC AIMS are to determine: 1) the position of the ABs and the PAVB in human heart; 2) the myocyte evoking the AB potential and its electrical pathway after iontophoresis of Lucifer Yellow (LY); 3) transmission properties of the ABs during program stimulation of the ABs and SAN by evalulation of the SAN-AB intervals; 4) each ABs role in AVN activation by alterations in the SAN-AVN interval due either to selective ablation of LY-fiUed myofibers or to transection of the AB/PAVB junctions. METHODS: Electrical potentials will be recorded using simultaneous (a) stationary catheter electrodes at the SAN, 3ABs, PAVB, and AVN to monitor electrical coupling, (b) wire electrodes to localize injection and recording sites, responses to photoablation, (c) multielctrode array plaque, (d) 1 percent LY or 3M KCI miropipet electrodes for recording and dye injection using current pulses. Ablations will be made using blue light and scalpel blades. The anatomy, LY pathways, and effects of photoloysis will be evaluated by 3D analysis and reconstructions. Alterations in morphology of electrical potentials, and conduction intervals will be confirmed via timing in the SAN trace and correlation of EAPs and TAPs. These studies are expected to provide a basis for evaluating transmission, arrhythmogenesis, and drug interactions at the tissue level.