Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany.
Cardiovascular Research Institute Duesseldorf (CARID), University Duesseldorf, Medical Faculty, Duesseldorf, Germany.
PLoS One. 2018 Aug 22;13(8):e0201910. doi: 10.1371/journal.pone.0201910. eCollection 2018.
Electrophysiological studies in mice, the prevailing model organism in the field of basic cardiovascular research, are impeded by the low yield of programmed electrical stimulation (PES).
To investigate a modified approach for ventricular arrhythmia (VA) induction and a novel scoring system in mice.
A systematic review of literature on current methods for PES in mice searching the PubMed database revealed that VA inducibility was low and ranged widely (4.6 ± 10.7%). Based on this literature review, a modified PES protocol with 3 to 10 extrastimuli was developed and tested in comparison to the conventional PES protocol using up to 3 extrastimuli in anesthetized wildtype mice (C57BL/6J, n = 12). Induced VA, classified according to the Lambeth Convention, were assessed by established arrhythmia scores as well as a novel arrhythmia score based on VA duration.
PES with the modified approach raised both the occurrence and the duration of VA compared to conventional PES (0% vs 50%; novel VA score p = 0.0002). Particularly, coupling of >6 extrastimuli raised the induction of VA. Predominantly, premature ventricular complexes (n = 6) and ventricular tachycardia <1s (n = 4) were observed. Repeated PES after adrenergic stimulation using isoprenaline resulted in enhanced induction of ventricular tachycardia <1s in both protocols.
Our findings suggest that the presented approach of modified PES enables effective induction and quantification of VA in wildtype mice and may well be suited to document and evaluate detailed VA characteristics in mice.
在基础心血管研究领域，作为主要模式生物的小鼠的电生理研究受到程控电刺激（PES）成功率低的阻碍。
研究一种改良的心室性心律失常（VA）诱导方法和一种新的评分系统在小鼠中的应用。
通过对 PubMed 数据库中有关当前小鼠 PES 方法的文献进行系统回顾，发现 VA 的可诱导性较低且范围广泛（4.6 ± 10.7%）。基于该文献回顾，我们开发了一种改良的 PES 方案，使用 3 至 10 个额外刺激，与使用多达 3 个额外刺激的传统 PES 方案在麻醉的野生型小鼠（C57BL/6J，n = 12）中进行了比较。根据兰贝斯公约进行分类的诱导性 VA 通过已建立的心律失常评分以及基于 VA 持续时间的新型心律失常评分进行评估。
与传统 PES 相比，改良方案的 PES 不仅提高了 VA 的发生频率，还延长了 VA 的持续时间（0%比 50%；新型 VA 评分 p = 0.0002）。特别是，超过 6 个额外刺激的偶联增加了 VA 的诱导。主要观察到过早的心室搏动（n = 6）和 <1 秒的室性心动过速（n = 4）。在使用异丙肾上腺素进行肾上腺素刺激后重复 PES 可增强两种方案中 <1 秒的室性心动过速的诱导。
我们的研究结果表明，所提出的改良 PES 方法能够有效诱导和量化野生型小鼠的 VA，并且可能非常适合记录和评估小鼠中详细的 VA 特征。
