REENTRANT WAVEFRONTS IN VENTRICULAR FIBRILLATION

由于心室颤动（VF）引起的心脏性猝死是一种重要的 公共卫生问题。 然而，我们对VF的了解是有限的。 的 这个研究项目的一个广泛的，长期的目标是阐明 重入波前的产生和维持机制 在VF。 申请人此前曾报告， 波前负责犬模型中VF的产生。 在这份资助申请中，申请人提出研究重入 在体内和体外的VF中的波前。 计算机绘图研究 将在人类患者和犬中进行，以记录 在Wiggers的阶段IIVF中存在折返波前。 计算机化 标测技术和标准跨膜微电极记录 技术将用于研究一种新的体外模型， 再入 将检验以下假设：（1）多个 在人类的Wiggers II期VF期间存在折返波前， 在正常健康狗和急性缺血狗中。 (2)的 折返波前在功能性传导区域周围循环 由经历分级反应的细胞形成的块（折返的“核心”） 但不是完整的动作电位。 没有解剖学上的障碍， 返回的核心 (3)在正常组织中， 波前的波长比凹入波前的波长长。 因此，存在可激发间隙。 (4)核心的大小， 可激发间隙的持续时间在确定 再入大气层的产生和维持。 (5)减少的扰动 芯的尺寸减小了组织的体积 支持再入波阵面。 因此， 核心，更容易诱导多重入波前和VF。 （六） 减小可激发能隙的扰动可以保护重入 通过竞争波阵面将波阵面从终端分离。 因此 可激发能隙越小，可重入体的寿命越长 波阵面，VF更容易维持自己。 (7)的大小 重入波前的核心和可激发间隙都是 因缺血而减少，使心脏易于发生心室颤动 在这种情况下。 这些研究将进一步加深我们对 人类VF产生和维持的基本机制，以及 对突发性心脏病的预防和治疗有了新的认识 死亡

Sudden cardiac death due to ventricular fibrillation (VF) is an important public health problem. However, our understanding of VF is limited. The broad, long-term objective of this research project is to elucidate the mechanisms of the generation and the maintenance of reentrant wavefronts in VF. The applicant has previously reported that the reentrant wavefronts are responsible for the generation VF in the canine model. In this grant application, the applicant proposes to study the reentrant wavefronts in VF both in vivo and in vitro. Computerized mapping studies will be performed in human patients and in dogs to document that reentrant wavefronts are present in Wiggers' stage II VF. Computerized mapping techniques and standard transmembrane microelectrode recording techniques will be used to study a novel in vitro model of sustained reentry. The following hypotheses will be tested: (1) Multiple reentrant wavefronts are present during Wiggers' stage II VF in humans, in normal healthy dogs, and in acutely ischemic dogs. (2) The reentrant wavefront circulates around an area of functional conduction block (the 'core' of reentry) formed by cells undergoing graded responses but not full action potentials. There is no anatomical barrier at the core of reentry. (3) In normal tissue, the cycle length of the reentrant wavefront is longer than the wavelength of the reentrant wavefront. Therefore, an excitable gap is present. (4) The size of the core and the duration of the excitable gap are both important in determining the generation and maintenance of reentry. (5) Perturbations that decrease the size of the core decrease the volume of tissue that is needed to support a reentrant wavefront. Therefore, the smaller the size of the core, the easier to induce multiple reentrant wavefronts and VF. (6) Perturbations that decrease the excitable gap can protect the reentrant wavefronts from termination by competing wavefronts. Therefore, the smaller the excitable gap, the longer the life-span of the reentrant wavefronts, and the easier for VF to sustain itself. (7) The size of the core and the excitable gap of the reentrant wavefronts are both decreased by ischemia, predisposing the heart to ventricular fibrillation in this setting. These studies will further our understanding of the basic mechanisms of the generation and maintenance of VF in humans, and lead to new insights into prevention and treatment of sudden cardiac death.