Thoracic Veins and Sustained Atrial Fibrillation

超出提供的空间。这项研究项目的广泛和长期目标是检验胸静脉内的重复快速活动(RRA)是持续性房颤(AF)机制的基础这一假说。最近的研究表明，阵发性房颤发作通常是由来自胸腔静脉的RRAS发起和维持的，包括肺静脉、马歇尔静脉和上腔静脉。持续性房颤包括持续性房颤和永久性房颤。虽然胸静脉中的RRAS是阵发性房颤的基础，但RRAS与持续性房颤的机制之间的关系尚不清楚。目前拨款提案的目的是在人类和犬类模型中进行研究，以检验持续性房颤的胸腔静脉假说。具体目标：(1)我们将在人类持续性房颤患者中进行术中标测研究和射频消融研究，以证实RRAS在人类胸腔静脉中的存在，并比较胸腔静脉与LA和RA中RRAS的激活率。(2)交感神经刺激、β受体阻滞剂和抗心律失常药物对犬胸静脉快速起搏持续性房颤模型的影响。我们将对犬胸静脉心包外部分进行慢性快速起搏，以诱发持续性房颤。将使用高密度计算机标测来确定是否存在来自所有胸腔静脉的RRAS。然后，我们将确定是否可以通过药物或电生理干预来抑制或增强RRAS。(3)犬胸静脉可在不与心房相连的情况下发生纤颤。使用射频消融技术，其中一条胸腔静脉将在其交界处与心房的其余部分电隔离。将从该静脉进行慢性快速起搏，以确定是否可以在不与心房电连接的情况下在静脉内诱导持续的RRAS。(4)胸静脉隔离术终止持续性房颤。我们将通过胸腔静脉慢性快速起搏来诱发房颤。在第二次手术中，我们将进行心外膜射频导管消融术，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腔静脉中是否有起搏细胞，以及起搏细胞的位置是否与RRAS的位置相关。表演网站========================================Section End===========================================

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===========================================