Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies
Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies
复制标题
DOI：
10.1152/physiolgenomics.00034.2003
复制
发表时间：
2003-09-29
影响因子：
4.6
通讯作者：
Berul, CI
中科院分区：
文献类型：
--
作者：
Maguire, CT;Wakimoto, H;Berul, CI
在基因工程小鼠中，程序化的室性刺激被用于激发室性心律失常。尽管人们对这一领域的翻译研究很感兴趣，但很少有人注意区分表型正常小鼠诱导性室性心动过速(VT)的选择性和特异性。我们的目的是评估可能增强野生型(WT)小鼠VT诱导性的因素。对4个品系230只WT小鼠进行了在体心脏电生理研究。将八极电极导管插入颈静脉，并向右心房和右心室推进。使用程序性电刺激(PES)和突发起搏评估基线的心室传导、不应期和心律失常的诱发性。我们发现，在68/230(30%)小鼠中可诱发非持续性室速(大于或等于4次)。室速持续时间为1.6+/-2.4 S，最长发作时间为2 4 S，诱发VT的能力因品系和年龄不同而异。诱导性室速小鼠的心室有效不应期(VERP)(44+/-12ms)明显短于非诱导性室速小鼠(61+/-16ms，P<；0.001)。VERP随年龄增长而增加(P<；0.001)，尽管存在与应变相关的变异。我们的结论是，WT小鼠的非持续性室速是可重复诱导的和常见的。遗传背景的可变性可能使某些菌株更容易发生心律失常。EPS方法影响诱导性室速的患病率和特异性。随着耦合间期的缩短和紧耦合外刺激技术的应用，室速的诱发率增加。在分析小鼠模型中的PES和猝发起搏数据时，应仔细考虑这些因素，以最大限度地减少假阳性并优化准确性。
Programmed ventricular stimulation is being performed for the provocation of ventricular arrhythmias in genetically engineered mice. Despite the high level of interest in this area of translational research, little attention has been given to differentiating between selectivity and specificity of induced ventricular tachycardia (VT) in phenotypically normal mice. We aimed to assess factors that may enhance inducibility of VT in wild-type (WT) mice. In vivo intracardiac electrophysiological studies (EPS) were performed in 230 WT mice of 4 strains. An octapolar electrode catheter was inserted into a jugular vein and advanced to the right atrium and ventricle. Baseline ventricular conduction, refractoriness, and arrhythmia inducibility were assessed using programmed electrical stimulation ( PES) and burst pacing. We found that nonsustained VT ( greater than or equal to 4 beats) was inducible in 68/230 (30%) mice. Duration of VT was 1.6 +/- 2.4 s, and the longest episode lasted 24 s. VT inducibility differed by strain and age. Ventricular effective refractory period ( VERP) was shorter in mice with inducible VT ( 44 +/- 12 ms) compared with noninducible mice ( 61 +/- 16 ms, P < 0.001). VERP increased with age ( P < 0.001), albeit with strain-related variability. We conclude that nonsustained VT in WT mice is reproducibly inducible and common. Genetic background variability may predispose certain strains to a higher incidence of arrhythmia induction. EPS methods impact prevalence and specificity of inducible VT. Increased VT inducibility was seen with shorter coupling intervals and application of tightly coupled extrastimuli techniques. These factors should be carefully considered when analyzing PES and burst pacing data in murine models to minimize false positives and optimize accuracy.