Electrophysiology of the pulmonary vein myocardium in AF

描述（由申请人提供）：房颤是最常见的心律失常，并导致显著的发病率和死亡率。最近，有证据表明，心房颤动可能是肺静脉心房肌局灶性活动的结果。然而，这种形式的房颤的机制尚不清楚，也不清楚为什么这些病灶在肺静脉中占优势。本申请的长期目标是研究肺静脉心房心肌的电生理特性，并确定致炎基质的结构/功能关系。特别是，我们将在心房扩张和心房颤动的犬模型中利用心脏激动的高分辨率光学标测来确定局灶性心房颤动的确切机制。在第一个特定目的中，我们将确定肺静脉心肌中心律失常的潜在底物，并确定触发剂（如钙通道激动剂和α-肾上腺素能激动剂）的作用。在第二个具体目标中，我们将研究急性肺静脉扩张对局灶性房颤的基质和触发的作用。在第三个具体目标中，我们将研究慢性肺静脉扩张对局灶性房颤的基础和机制的影响。在最后一个具体目标中，我们将研究肺静脉心肌的局灶性放电如何与心房其余部分的易损基质相互作用，以产生持续性房颤。

DESCRIPTION (provided by applicant): Atrial fibrillation is the most common arrhythmia and accounts for significant morbidity and mortality. Recently, evidence has suggested that atrial fibrillation may be a result of focal activity from the atrial myocardium of the pulmonary veins. However, the mechanism of this form of atrial fibrillation is not known nor is the reason why there is a predominance of these foci in the pulmonary veins. It is the long-term goal of this application to study the electrophysiologic properties of the atrial myocardium of the pulmonary veins and define structure/function relationships of the arrhythmogenic substrate. In particular, we will utilize high resolution optical mapping of cardiac activation in a canine model of atrial dilatation and atrial fibrillation to identify the precise mechanism of focal atrial fibrillation. In the first Specific Aim, we will identify the potential substrate for arrhythmias in the myocardium of the pulmonary vein and identify the role of triggers such as calcium channel agonists and a-adrenergic agonists. In the second Specific Aim, we will study the role of acute pulmonary vein dilatation on the substrate and triggering of focal atrial fibrillation. In the third Specific Aim, we will study the effect chronic pulmonary vein dilatation on the substrate and mechanism of focal atrial fibrillation. In the last Specific Aim, we will study how focal discharges from the pulmonary vein myocardium interact with the vulnerable substrate of the remainder of the atrium to produce sustained atrial fibrillation.