DOES VT BEGET VT? REMODELING IN HEALED INFARCTION

迁延性心房颤动(房颤)通过电刺激调节心房。 重建使房颤永久化(房颤产生房颤)。对于插曲来说是否如此 由陈旧性心肌梗死(MI)引起的室性心动过速(VT)不是 已知如此，这项提议询问VT是否会产生VT。一个相关的问题是VT如何 通过电信号重塑梗塞的脑室。实验和临床 有证据表明，NG后VT是折返性的。在VT维护期间 机制存在争议，难治性在室性心动过速的启动中的作用是 通常是没有争议的。因此，我们建议研究发作性室性心动过速 影响室性心动过速的诱导性并重塑不应期。研究假设是 基于梗塞(1Z)、边缘(13Z)和 与心肌梗死相关的正常(新西兰)区组织和心肌梗死现象 因心脏记忆、衰竭或肥大而导致的复极重构。 假设一是室性心动过速甚至已经在心脏中重塑了不稳定。 由MI重塑。假设2是IZ、BZ的不稳定重塑 新西兰对室上性心动过速的影响有不同反应 起源。假设3是VT依赖的诱导性变化是由 BZ的耐火性重构与IZ或IZ的差异 去新西兰。假设4是BZ和NZ平台的变化和 复极电流是这些区域不稳定重构的原因。 纸巾。为了验证这些假设，我们将使用治愈了心肌梗塞的猪 通过珠粒栓塞术。来自1/3试验的快或慢的室性起搏(VP) 网站将模拟发作性室速。室速诱导性与梗死区心内膜 难治性；将使用Carto电子解剖导管进行活体评估 MI前后和MI后VP的映射。终末体外研究 将使用全电池电压钳位来关联改装的BZ和NZ 平台离子流变化时的耐火性。我们会稳扎稳打 Ik和Ial的状态、峰活化和动力学性质 Ik1和InaCa的电流-电压关系。Indo-1和Fluo-3录制的 钙瞬变将被用来确定方向和相对 InaCa流量的大小。因INA重新激活而导致的不稳定将 通过电压和向上冲程速度随时间变化的恢复来检测。如果 研究假设是正确的，那么不稳定和不均匀的重建 心肌梗死后心脏的特性可能导致阵发性室速 对室性心动过速诱导性有正面或负面影响。如果出现后一种情况， 基于起搏的新疗法可能成为可能。如果前者是真的，那么 可以针对这种重塑进行预防性治疗。

Protracted atrial fibrillation (AF) conditions the atrium through electrical remodeling to perpetuate AF (AF begets AF). Whether this is true for episodic ventricular tachycardia (VT) due to healed myocardial infarction (MI) is not known so this proposal asks whether VT begets VT. A related issue is how VT electrically remodels the infarcted ventricle. Experimental and clinical evidence indicates that post-NG VT is reentrant. While VT maintenance mechanisms are controversial, the role of refractoriness in VT initiation is usually not disputed. We therefore propose to study whether episodic VT affects VT inducibility and remodels refractoriness. Study hypotheses were based on the distinct properties of the infarcted (1Z), border (13Z), and normal (NZ) zone tissues associated with MI and on the phenomena of repolarization remodeling due to cardiac memory, failure or hypertrophy. Hypothesis 1 is that VT remodels refractoriness even in hearts already remodeled by MI. Hypothesis 2 is that refractoriness remodeling in the IZ, BZ and NZ differentially responds to the influence of VT rate versus site of origin. Hypothesis 3 is that VT-dependent changes in inducibility result from differences in refractoriness remodeling of the BZ with respect to the IZ or to the NZ. Hypothesis 4 is that changes in BZ and NZ plateau and repolarization currents are responsible for refractoriness remodeling in these tissues. To test these hypotheses we will use swine having healed MI caused by bead embolization. Fast or slow ventricular pacing (VP) from 1 of 3 test sites will simulate episodic VT. VT inducibility and peri-infarct endocardial refractoriness; will be assessed in vivo using CARTO electro-anatomic catheter mapping before and after MI and after VP of MI. Terminal in vitro studies will use whole cell voltage clamp to correlate remodeled BZ and NZ refractoriness with changes in plateau ion currents. We will measure steady state, peak activated and kinetic properties of Ik and ICaL and the current-voltage relations of Ik1 and InaCa. Indo-1 and fluo-3 recordings of the calcium transient will be used to determine the direction and relative magnitude of InaCa flux. Refractoriness due to INa reactivation will be detected via voltage and time-dependent recovery of upstroke velocity. If the study hypotheses are true then the labile and inhomogeneous remodeling properties of the post-MI heart may cause episodic VT to have either a positive or negative effect on VT inducibility. If the latter occurs then novel therapy based on pacing may be possible. If the former is true then preventive therapy could be directed against such remodeling.