De Groot Joris R, Coronel Ruben
Experimental and Molecular Cardiology Group, Department of Clinical and Experimental Cardiology, Academic Medical Center, PO Box 22700, Amsterdam 1100 DE, The Netherlands.
Cardiovasc Res. 2004 May 1;62(2):323-34. doi: 10.1016/j.cardiores.2004.01.033.
Sudden cardiac death forms a major cause of mortality. Myocardial ischemia-induced ventricular fibrillation (VF) is frequently the underlying mechanism. Ventricular arrhythmias arise in two distinct phases during the first hour of ischemia. The first, the 1A phase, has been extensively studied, and few studies relate to the 1B phase. The latter is associated with intercellular electrical uncoupling, mediated by decreased conductance of gap junction channels. Although the relation between gap junctional uncoupling and decreased conduction velocity appears clear under normoxic conditions, additional factors contribute to conduction slowing during ischemia, and VF occurs preferentially at moderate levels of uncoupling. A potential mechanism of arrhythmias depends on temporary electrotonic depression of intrinsically viable tissue by the large bulk of the ischemic zone. This causes conduction slowing and conduction block in the surviving layers, leading to arrhythmias. These arrhythmias then resolve with progression of uncoupling. It is unknown whether either accelerated uncoupling or maintenance of gap junctional communication is antiarrhythmic. Ischemic preconditioning postpones both gap junctional uncoupling and occurrence of VF. Given the burden of sudden death and the large number of casualties in the low-risk population, there is, even in the era of implantable cardiac defibrillators, need for further understanding the mechanism of ischemia-induced VF.
心脏性猝死是主要的死亡原因。心肌缺血诱发的心室颤动（VF）常常是其潜在机制。在缺血的第一个小时内，室性心律失常出现在两个不同阶段。第一个阶段即1A期，已得到广泛研究，而与1B期相关的研究较少。后者与细胞间电脱耦联有关，由缝隙连接通道电导降低介导。尽管在常氧条件下缝隙连接脱耦联与传导速度降低之间的关系似乎很明显，但在缺血期间还有其他因素导致传导减慢，且心室颤动优先发生在中等程度的脱耦联水平。心律失常的一个潜在机制取决于大量缺血区域对内在存活组织的暂时电紧张性抑制。这会导致存活层的传导减慢和传导阻滞，从而引发心律失常。随着脱耦联的进展，这些心律失常随后会得到缓解。目前尚不清楚加速脱耦联或维持缝隙连接通讯是否具有抗心律失常作用。缺血预处理可推迟缝隙连接脱耦联和心室颤动的发生。鉴于猝死的负担以及低风险人群中的大量伤亡情况，即使在植入式心脏除颤器时代，仍需要进一步了解缺血诱发心室颤动的机制。
