DOES VT BEGET VT? REMODELING IN HEALED INFARCTION

心房颤动（AF）是通过电生理信号传导到心房， 重塑以延续AF（AF引发AF）。 这是否适用于偶发事件 心肌梗死（MI）治愈后引起的室性心动过速（VT） 因此，该提议询问VT是否产生VT。 一个相关的问题是， 电重塑梗塞的心室 实验和临床 有证据表明NG后VT是折返性的。 VT维护期间 机制是有争议的，不应性在VT启动中的作用是 通常没有争议。 因此，我们建议研究发作性VT是否 影响VT诱导和重塑不应性。 研究假设为 基于梗死区（1Z）、边界（13Z）和 与MI相关的正常（NZ）区组织和 由于心脏记忆、衰竭或肥大导致的复极重塑。 假设1是室性心动过速重塑不应性，即使在心脏已经 由MI改造。 假设2是IZ、BZ中的不应性重塑 和NZ对VT率与部位的影响有不同的反应。 起源 假设3是VT依赖性的诱导性变化是由以下因素引起的： BZ相对于IZ的不应性重塑差异，或 到NZ 假设4是BZ和NZ平台的变化， 复极电流负责这些不应性重塑 组织中 为了验证这些假设，我们将使用已治愈的MI引起的猪 通过微珠栓塞。 3项测试中的1项测试的快速或慢速心室起搏（VP） 临床试验机构将模拟阵发性室性心动过速。 室性心动过速诱导和梗死周围内皮细胞 不应性;将使用CARTO电解剖导管在体内进行评估 MI前后和MI VP后的标测。 终末体外研究 将使用全细胞电压钳来关联重构的BZ和NZ 不应期与平台离子电流的变化。 我们将稳步地 Ik和ICaL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记录 钙瞬变将用于确定方向和相对 InaCa通量的大小。 由于INa再活化导致的不应性将 通过电压和上行程速度的时间依赖性恢复来检测。 如果 研究假设成立，则不稳定和不均匀的重塑 心肌梗死后心脏的性质可能导致阵发性室性心动过速， 对VT诱导的积极或消极影响。 如果发生后者， 基于起搏的新疗法是可能的。 如果前者是真的， 预防性治疗可以针对这种重塑。

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.