Kushiyama Yasunori, Honjo Haruo, Niwa Ryoko, Takanari Hiroki, Yamazaki Masatoshi, Takemoto Yoshio, Sakuma Ichiro, Kodama Itsuo, Kamiya Kaichiro
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and
Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H750-8. doi: 10.1152/ajpheart.00228.2016. Epub 2016 Jul 15.
It has been reported that blockade of the inward rectifier K(+) current (IK1) facilitates termination of ventricular fibrillation. We hypothesized that partial IK1 blockade destabilizes spiral wave (SW) re-entry, leading to its termination. Optical action potential (AP) signals were recorded from left ventricles of Langendorff-perfused rabbit hearts with endocardial cryoablation. The dynamics of SW re-entry were analyzed during ventricular tachycardia (VT), induced by cross-field stimulation. Intercellular electrical coupling in the myocardial tissue was evaluated by the space constant. In separate experiments, AP recordings were made using the microelectrode technique from right ventricular papillary muscles of rabbit hearts. Ba(2+) (10-50 μM) caused a dose-dependent prolongation of VT cycle length and facilitated termination of VT in perfused hearts. Baseline VT was maintained by a stable rotor, where an SW rotated around an I-shaped functional block line (FBL). Ba(2+) at 10 μM prolonged I-shaped FBL and phase-singularity trajectory, whereas Ba(2+) at 50 μM transformed the SW rotation dynamics from a stable linear pattern to unstable circular/cycloidal meandering. The SW destabilization was not accompanied by SW breakup. Under constant pacing, Ba(2+) caused a dose-dependent prolongation of APs, and Ba(2+) at 50 μM decreased conduction velocity. In papillary muscles, Ba(2+) at 50 μM depolarized the resting membrane potential. The space constant was increased by 50 μM Ba(2+) Partial IK1 blockade destabilizes SW rotation dynamics through a combination of prolongation of the wave length, reduction of excitability, and enhancement of electrotonic interactions, which facilitates termination of ventricular tachyarrhythmias.
据报道，内向整流钾电流（IK1）的阻断有助于终止室颤。我们假设部分IK1阻断会使螺旋波（SW）折返不稳定，从而导致其终止。使用心内膜冷冻消融技术，从Langendorff灌注兔心脏的左心室记录光学动作电位（AP）信号。在交叉场刺激诱发的室性心动过速（VT）期间，分析SW折返的动力学。通过空间常数评估心肌组织中的细胞间电耦合。在单独的实验中，使用微电极技术从兔心脏的右心室乳头肌进行AP记录。Ba(2+)（10 - 50 μM）导致灌注心脏中VT周期长度呈剂量依赖性延长，并促进VT的终止。基线VT由一个稳定的转子维持，其中一个SW围绕一条I形功能阻滞线（FBL）旋转。10 μM的Ba(2+)延长了I形FBL和相奇点轨迹，而50 μM的Ba(2+)将SW旋转动力学从稳定的线性模式转变为不稳定的圆形/摆线蜿蜒。SW的不稳定并未伴随着SW的破裂。在恒定起搏下，Ba(2+)导致AP呈剂量依赖性延长，50 μM的Ba(2+)降低传导速度。在乳头肌中，50 μM的Ba(2+)使静息膜电位去极化。50 μM的Ba(2+)使空间常数增加。部分IK1阻断通过波长延长、兴奋性降低和电紧张相互作用增强的组合，使SW旋转动力学不稳定，这有助于终止室性快速心律失常。
