SPONTANEOUS ATRIAL TACHYCARDIA RELATED TO VAGAL TONE

心房扑动和颤动是常见的房性心律失常， 由可重入机制维持。 然而，启动重返大气层 需要一个过早的冲动，与一个区域的相互作用， 单向阻断 这项研究旨在了解 在正常完好的犬心房中产生过早冲动。 在 特别是，该提案侧重于迷走神经机制以及它们如何能够 反而会引发心律失常 分离组织的初步结果 已经证明乙酰胆碱（ACH）可以自发地启动 纤维性颤动 在一段时间的ACH诱导的停滞后，激活 序列图显示，最初的两到三个紧密耦合的 心搏起源于不同部位的局灶性搏动，随后过渡到 重入模式 初步协调机制的拟议机制 去极化是多个心房起搏器的异步放电 伴随着后来部位的可变入口阻滞， 重置这些潜在的起搏器 还提议 传入阻滞是由于乙酰胆碱诱发的起搏器超极化所致 膜。 该提案将调查这些相同的机制是否 在正常生理条件下， 条件 最初，将不同浓度的ACH输注至 窦房结动脉在不同浓度的细胞外 钾 根据初步研究，预计 在正常生理条件下产生心率的ACH浓度 范围内，将以剂量依赖性方式产生过早的β和纤颤 方式 此外，降低细胞外钾水平将 增加ACH诱发纤颤的可能性。 使用250的网格 单极电极，将同时记录电描记图， 密度激活序列图将构建任何自发的 早搏或纤颤。 初步研究表明，ACH- 诱导的纤维性颤动在β受体阻滞剂存在下发生。 然而，在这方面， 其他研究者的研究表明，肾上腺素能紧张在 重要的作用 我们认为肾上腺素能紧张不是必需的， 增加自发性胆碱能纤维性颤动的可能性。 肾上腺素能-胆碱能相互作用将通过添加以下物质进行研究： ACH输注期间去甲肾上腺素的背景水平。 因为ACH- 调节的钾通道被认为在 入口阻滞时，通道也将被腺苷调制， 在同一通道上独立于ACH受体。 最后，直接迷走神经 将进行神经刺激，以确定是否正常模式的 神经活动也可产生过早的去极化。 第一对 迷走神经分支将被持续刺激，以确定 引发纤维化。 然后进行阶段性刺激，定时到自发的 将进行心房去极化，以确定临界时间 在周期中。

Atrial flutter and fibrillation are common atrial arrhythmias that are sustained by a reentrant mechanism. However, initiation of reentry requires a premature impulse which interacts with a region of unidirectional block. The proposed research is designed to understand how premature impulses are generated in the normal intact canine atria. In particular, the proposal focuses on vagal mechanisms and how they can paradoxically start tachyarrhythmias. Initial results in isolated tissue have demonstrated that acetylcholine (ACH) can spontaneously initiate fibrillation. Following a period of ACH-induced arrest, activation sequence maps demonstrated that the initial two to three closely coupled beats originated focally from separate sites followed by a transition to a reentrant pattern. the proposed mechanism of the initial focal depolarizations is the asynchronous firing of multiple atrial pacemakers accompanied by variable entrance block at later sites, inhibiting the resetting of these latent pacemakers. It is further proposed that the entrance block is due to the ACH-induced hyperpolarization of the pacemaker membranes. this proposal will investigate whether these same mechanisms function in the intact canine atrium under more normal physiologic conditions. Initially, variable concentrations of ACH will be infused into the sinus node artery at different fixed concentrations of extracellular potassium. It is anticipated, based on preliminary studies, that concentration of ACH that produce heart rates in the normal physiologic range, will generate premature betas and fibrillation in a dose-dependent manner. Furthermore, lowering the extracellular potassium level will increase the probability of ACH-induced fibrillation. Using a grid of 250 unipolar electrodes, electrograms will be simultaneously recorded and high density activation sequence maps will be constructed of any spontaneous premature beats or fibrillation. Preliminary studies have shown that ACH- induced fibrillation occurs in the presence of beta blockade. However, studies by other investigators have suggested that adrenergic tone plays an important role. We propose that the adrenergic tone is not necessary but enhances the probability of spontaneous cholinergic fibrillation. Adrenergic-cholinergic interactions will be studied by the addition of background levels of norepinephrine during ACH infusion. Because the ACH- modulated potassium channel is thought to play an important role in the entrance block, the channel will also be modulated by adenosine, which acts on the same channel independently of ACH receptors. Finally, direct vagal nerve stimulation will be performed to determine if normal patterns of neural activity can also generate premature depolarizations. First, right vagal branches will be stimulated continuously to determine which nerve initiates fibrillations. Then phasic stimulation, timed to the spontaneous atrial depolarizations, will be performed to determine the critical time during the cycle.