Thoracic Veins and Sustained Atrial Fibrillation

超出所提供的空间。本研究项目的广泛和长期目标是验证胸静脉内的重复快速活动（RRA）是持续性房颤（AF）机制的基础这一假设。最近的研究表明，阵发性AF发作通常由来自胸静脉的RRA引发和维持，包括肺静脉、马歇尔静脉和上级腔静脉。持续性AF包括持续性AF和永久性AF。虽然胸静脉中的RRA是阵发性AF机制的基础，但RRA与持续性AF机制之间的关系尚不清楚。本资助提案的目的是在人类和犬模型中进行研究，以测试持续性AF的胸静脉假设。具体目的：（1）我们将在持续性房颤患者中进行术中标测研究和射频（RF）消融研究，以证明人体胸静脉中存在RRA，比较胸静脉与左心房和右心房的激动率。(2)交感神经刺激、β受体阻滞剂和抗心律失常药物对快速起搏胸静脉诱发持续性房颤犬模型的影响。我们将对犬胸静脉的心包外部分进行慢性快速起搏，以诱导持续性房颤。将使用高密度计算机标测来确定所有胸静脉是否存在RRA。然后，我们将确定RRA是否可以通过药物或电生理干预来抑制或增强。(3)犬的胸静脉可以在不与心房相连的情况下扩张。使用射频消融技术，其中一条胸静脉将在其与其余心房的连接处电隔离。将从该静脉进行慢性快速起搏，以确定在不与心房电连接的情况下是否可以在静脉内诱导持续RRA。(4)通过胸静脉隔离终止持续性房颤。我们将通过胸部静脉慢性快速起搏诱导房颤。在第二次手术中，我们将进行心外膜射频导管消融，以将所有胸静脉与心房电隔离。(5)胸静脉的免疫细胞化学研究。我们将使用免疫细胞化学染色技术来确定胸静脉中是否有起搏细胞，以及起搏细胞的位置是否与RRA的部位相关。 性能现场=

EXCEED THE SPACE PROVIDED. The broad and long-term objective of this research project is to test the hypothesis that repetitive rapid activities (RRAs) within the thoracic veins underlie the mechanisms of sustained atrial fibrillation (AF). Recent studies show that paroxysmal AF episodes are often initiated and maintained by RRAs from the thoracic veins, including pulmonary veins, the vein of Marshall, and the superior vena cava. Sustained AF includes both persistent AF and permanent AF. While RRAs in the thoracic veins underlie the mechanisms of paroxysmal AF, the relation between RRAs and the mechanisms of sustained AF is less clear. The purpose of the present grant proposal is to perform studies in humans and in a canine model to test the Thoracic Vein Hypothesis of sustained AF. Specific Aims: (1) We will perform intraoperative mapping studies and radiofrequency (RF) ablation studies in human patients with sustained AF to demonstrate the presence of RRAs in human thoracic veins, and to compare the activation rate within the thoracic veins and those in the LA and RA. (2) Effects of sympathetic stimulation, beta blockade and antiarrhythmic drugs on a canine model of sustained AF induced by rapid pacing of the thoracic veins. We will perform chronic rapid pacing of the extrapericardial portion of a canine thoracic vein to induce sustained AF. High density computerized mapping will be used to determine whether or not there are RRAs from all thoracic veins. We will then determine if the RRAs can be suppressed or enhanced by pharmacological or electrophysiological intervention. (3) Thoracic veins in dogs can fibrillate without being connected to the atria. Using RF ablation technique, one of the thoracic veins will be electrically isolated at its junction from the remainder of the atria. Chronic rapid pacing will be performed from that vein to determine if sustained RRAs can be induced within the vein without being electrically connected to the atria. (4) Termination of sustained AF by thoracic vein isolation. We will induce AF by chronic rapid pacing in a thoracic vein. During second surgery, we will perform epicardial RF catheter ablation to electrically isolate all thoracic veins from the atria. (5) Immunocytochemical studies of the thoracic veins. We will use immunocytochemical staining techniques to determine if there are pacemaking cells in the thoracic veins, and whether or not the location of the pacemakina cells correlate with the sites of RRAs. PERFORMANCE SITE ========================================Section End===========================================