Modulation of ventricular spiral-wave reentry by cardiac ion channel blockade

功能性折返在室性心动过速/室颤（VT/VF）的发生和维持中起着重要作用。人们提出了“引导圆”、各向异性折返和螺旋型兴奋等概念来解释心脏的功能折返，但其确切机制仍有待阐明。我们通过高分辨率光学成像研究了VT的动力学和药理学调制。用冷冻消融法在Langendorff灌流的兔心脏左心室内膜侧制作了厚约1 mm的二维心外膜下室壁心肌片。心脏用di-4-ANEPPS（2 μM）染色，通过高速摄像机（时间和空间分辨率分别为± 1.3ms和± 0.1mm）获得心室肌荧光图像。交叉场刺激诱发的室性心动过速常为单次折返“Z”形阻滞功能线的结果。岑 ...更多信息 与心肌纤维方向无关的阻滞线中段与动作电位的突然相移有关。在阻滞中心线处获得了小幅度的双电位，但没有电通道，表明存在“前导环”型电紧张性相互作用。这两个终末节段是由旋转支点周围的局部传导延迟引起的，这些线总是平行于心肌纤维方向。由波前曲率结合组织各向异性产生的源-汇不平衡可能是枢轴点周围局部传导延迟的原因。吡西卡尼、丙吡胺和西苯唑啉对Na^+通道的阻断通过增强局部传导延迟延长了末端阻断线，并在回路中（除了枢轴点周围）引起了明显的电活动（可兴奋间隙）。这些结果表明，在二维心室肌功能折返是由波前的曲率和组织各向异性引起的波前-尾相互作用和源-库的不平衡。少

It is widely accepted that functional reentry plays an important role in the initiation and maintenance of ventricular tachycardia/fibrillation (VT/VF). Various concepts including "leading circle", anisotropic reentry and spiral-type excitation have been proposed to explain the functional reentry in the heart but its precise mechanisms remain to be elucidated. We investigated dynamics and pharmacological modulation cf VT by high-resolution optical mapping. Two-dimensional subepicardial ventricular myocardial sheet (〜1 mm in thickness) of the Langendorff-perfused rabbit heart was made by cryoablation of the endocardial side of the left ventricle. The heart was stained with di-4-ANEPPS (2 μM), and fluorescence images of theventricular myocardium were obtained via a high-speed video camera (temporal and spatial resolutions of〜1.3 ms and 〜0.1 mm, respectively). VT induced by cross-field stimulation was often the result of single reentry around a "Z"-shaped functional line of block. The cen … More tral segment of the block line, which was independent of the myocardial fiber direction, was associated with an abrupt phase-shift of the action potential. Small amplitude double potentials without electrical diastole were obtained at the central block line suggesting "leading circle"-type electrotonic interaction. The two terminal segments were caused by localized conduction delay around pivot points of the rotation and these lines were always parallel to the myocardial fiber direction. Source-to-sink imbalance created by wavefront curvature combined with tissue anisotropy may be responsible for the localized conduction delay around the pivot paints. Blockade of Na^+ channels by pilsicainide, disopyramide and cibenzoline extended the terminal block lines through the enhancement of the localized local conduction delay and caused appreciable electrical diastole (excitable gap) in the circuit except around pivot points. These results suggest that functional reentry in the two-dimensional ventricular myocardium is determined by wavefront-tail interaction and source-sink imbalance caused by wavefront curvature and tissue anisotropy. Less