Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
University Heart and Vascular Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Europace. 2021 Jun 7;23(6):958-969. doi: 10.1093/europace/euaa369.
Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized.
We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (-7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (-20% vs. average) and atrial ERP (-25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age.
This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.
基因改造小鼠是研究心房性心律失常机制的强大模型，但鼠类心房电生理学的正常范围尚未得到充分描述。
我们分析了来自 221 项离体 Langendorff 灌流心脏电生理（EP）研究的结果，这些研究涉及来自不同遗传背景（C57BL/6、FVB/N、MF1、129/Sv、瑞士白化鼠）的 2.5 至 17.7 个月（平均 7 个月）的野生型小鼠（女性 114 只，男性 107 只）。总结了不同起搏周期长度（PCL）下左房单相动作电位时程（LA-APD）、房间隔激活时间（IA-AT）和心房有效不应期（ERP）。确定了影响心房电生理学的因素，包括遗传背景、性别和年龄。在 100ms PCL 时，LA-APD70 为 18±0.5ms，心房 ERP 为 27±0.8ms，IA-AT 为 17±0.5ms。LA-APD 随 PCL 延长而延长（APD70 从 80 至 120ms PCL 延长 17%），而 IA-AT 则缩短（80 至 120ms PCL 缩短 7%）。雌性性别与较长的 ERP 相关（女性比男性长 14%）。遗传背景影响心房电生理学：与其他遗传背景相比，瑞士白化鼠背景下的 LA-APD70（短 20%）和心房 ERP（短 25%）更短。129/Sv 小鼠的 LA-APD70（长 25%）和 IA-AT（长 44%）更长。FVB/N（长 34%）和 6 个月以下的年轻实验组的心房 ERP 更长。
本研究确定了鼠类心房电生理参数的正常范围。遗传背景对这些参数有深远的影响，至少与性别和年龄的影响相当。这些结果可以为鼠类心房电生理学的实验设计和解释提供信息。
