REENTRANT WAVEFRONTS IN VENTRICULAR FIBRILLATION

室颤(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的理解是有限的。这个 这项研究项目的广泛、长期目标是阐明 折返波前的产生和维持机制 在VF中。申请人之前曾报告说，重入者 在犬模型中，波前是产生室颤的主要原因。 在这份助学金申请中，申请者提议研究重入者 体内和体外VF中的波前。计算机化测绘研究 将在人类病人和狗身上进行，以记录 在威格斯的第二阶段VF中出现了折返波前。计算机化 标测技术与标准跨膜微电极记录 这些技术将被用于研究一种新的体外模型。 重返大气层。将检验以下假设：(1)多个 在人类Wigger的II期VF期间，出现了折返波前， 在正常健康的狗身上，在急性脑缺血的狗身上。(2) 折返波阵面围绕功能传导区域循环 由经历分级反应的细胞形成的阻挡(再入的“核心”) 但不是全部的动作电位。没有解剖学上的障碍 再入核心。(3)在正常组织中，折返者的周期长度 波前比折射式波前的波长长。 因此，存在一个可兴奋的缺口。(4)核心的大小和 可激发间隙的持续时间对于确定 再入大气层的产生和维持。(5)减少的扰动 核心的大小减少了需要的组织体积 支持一个可再入的波前。因此，对象的大小越小 磁芯越易诱发多个折返波前和室颤。(6) 减小可激发间隙的微扰可以保护折返者 由竞争波阵面终止的波阵面。因此， 可激性间隙越小，折返者的寿命越长 波前，VF更容易维持自身。(7)大小 折射型波前的核心和可激发带隙都是 因缺血而减少，使心脏容易发生室颤 在这种情况下。这些研究将进一步加深我们对 人类室性心动过速发生和维持的基本机制 为预防和治疗突发心脏病提供新的见解 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.