SPONTANEOUS ATRIAL TACHYCARDIA RELATED TO VAGAL TONE

心房扑动和纤颤是常见的房性心律失常， 由一种可再入机制支撑。然而，启动再入大气层 需要一个过早的冲动，它与一个区域相互作用 单向闭塞。这项拟议的研究旨在了解 早搏是在正常完整的犬房产生的。在……里面 具体地说，该提案侧重于迷走神经机制及其如何 自相矛盾地引发了快速性心律失常。在分离组织中的初步结果 已经证明乙酰胆碱(ACH)可以自发地启动 纤颤。在ACH诱导的一段时间的停滞、激活之后 序列图显示，最初的两到三个紧密耦合 Beats集中来自不同的站点，然后过渡到 折返型。提出的初始震源机制 去极化是多个心房起搏器的非同步放电 随之而来的是后来的可变入口闭塞，抑制了 重置这些潜在的起搏器。另一项建议是， 入口阻塞是由于ACH引起的起搏器超极化。 膜。这项提案将调查这些相同的机制是否 正常生理状态下犬完整心房的功能 条件。最初，不同浓度的ACH将被注入 不同细胞外固定浓度的窦房结动脉 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，将在剂量依赖的情况下产生过早的Beta和纤颤 举止。此外，降低细胞外钾水平将 增加ACH诱发纤颤的概率。使用250个栅格 单极电极、心电图会同时记录和高值 密度激活序列图将由任何自发的 早搏或纤颤。初步研究表明，ACH- 在β受体阻滞剂存在的情况下会发生诱导纤颤。然而， 其他研究人员的研究表明，肾上腺素能音调对 重要的角色。我们认为肾上腺素能音调不是必需的，但 增加自发性胆碱能纤颤的可能性。 肾上腺素能-胆碱能相互作用将通过添加 ACH输注过程中去甲肾上腺素的本底水平。因为ACH- 调制钾通道被认为在血管紧张素转换过程中起着重要的作用。 入口阻断后，该通道也会受到腺苷的调制，腺苷起作用 在同一通道上独立于ACH受体。最后，直接迷走 将进行神经刺激以确定是否正常模式的 神经活动也会导致过早的去极化。首先，对 迷走神经分支将被持续刺激以确定哪条神经 会引发纤颤。然后是阶段性刺激，定时为自发刺激 将进行心房除极，以确定临界时间 在这个周期中。

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.