Atrionodal Bundles:Histologic and Physiologic Validation

描述（由申请人提供）：射频（RF）导管消融“慢”或“快”房室结通路可以治疗房室结再入性心动过速（AVNRT），也可以改变心室对心房扑动和颤动的反应。然而，这些心律失常的组织和机制都不为人所知。最近，我们证明了两个独立的心房回路在房室交界区重叠：“肌瓣器”的组成部分，“环和垂直板”，它们也形成下内侧心房壁；并且，胶原蛋白包裹着AVN的“多肢输入”：“心房结束（ABs）和近端房室束（PAVB）”，后者位于心房壁内侧心外膜外。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；来自心房组织和特化组织的eap在心房组织和特化组织重叠部位的痕迹中并排出现；心房eap和收缩随着高钾暴露而停止。假设：在人类和狗的心脏中存在一个特殊的多肢AVN输入，具有独特的组织学和传导特性。具体目的是确定：1)抗体和PAVB在人心脏中的位置；2)路西法黄（Lucifer Yellow， LY）离子导入后引起AB电位的肌细胞及其电通路；3)通过对SAN- ab间隔的评估，对ABs和SAN进行程序刺激时，ABs的传输特性；4)由于ly -纤维的选择性消融或AB/PAVB连接的横断，导致SAN-AVN间隔的改变，每种抗体在AVN激活中的作用。方法：电势记录将同时使用(a)固定导管电极在SAN， 3ABs， PAVB和AVN监测电耦合，(b)导线电极定位注射和记录部位，光消融反应，(c)多电极阵列斑块，(d) 1% LY或3M KCI微移液管电极记录和使用电流脉冲注射染料。消融将使用蓝光和手术刀刀片。解剖，LY途径和光分解的影响将通过三维分析和重建进行评估。电位形态的改变和传导间隔将通过SAN迹线的时序和eap和tap的相关性得到证实。这些研究有望在组织水平上为评估传播、心律失常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.