基于特征化定量心电图策略分析小鼠心脏电生理固有稳态制式

doi:10.12122/j.issn.1673-4254.2024.10.17

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (10): 1985-1994.doi: 10.12122/j.issn.1673-4254.2024.10.17

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基于特征化定量心电图策略分析小鼠心脏电生理固有稳态制式

成思怡¹^,²^,³^,⁴(), 陈泽锐¹^,²^,³^,⁴, 于长江¹^,²^,³^,⁴, 孙图成¹^,²^,³^,⁴, 朱烁基¹^,²^,³^,⁴(), 刘南波¹^,²^,³^,⁴(), 朱平¹^,²^,³^,⁴()

^1.华南理工大学医学院，广东广州 510006
^2.南方医科大学附属广东省人民医院//广东省医学科学院，广东广州 510180
^3.广东省心脏病发病机制与精准防治重点实验室，广东广州 510180
^4.广州市心脏病发病机制与防治重点实验室，广东广州 510180

收稿日期:2024-04-25 出版日期:2024-10-20 发布日期:2024-10-31
通讯作者: 朱烁基,刘南波,朱平 E-mail:debarah17@foxmail.com;zhushuoji@gmail.com;liu.nanbo@163.com;tanganqier@163.com
作者简介:成思怡，在读硕士研究生，E-mail: debarah17@foxmail.com
基金资助:
国家自然科学基金青年科学基金(82100275);广东省基础与应用基础研究重大项目(2023B0303000005);广州市科技计划项目(202201000006)

Intrinsic steady-state pattern of mouse cardiac electrophysiology: analysis using a characterized quantitative electrocardiogram strategy

Siyi CHENG¹^,²^,³^,⁴(), Zerui CHEN¹^,²^,³^,⁴, Changjiang YU¹^,²^,³^,⁴, Tucheng SUN¹^,²^,³^,⁴, Shuoji ZHU¹^,²^,³^,⁴(), Nanbo LIU¹^,²^,³^,⁴(), Ping ZHU¹^,²^,³^,⁴()

^1.School of Medicine, South China University of Technology, Guangzhou 510006, China
^2.Guangdong Provincial People's Hospital Affiliated to Southern Medical University, Guangzhou 510180, China
^3.Guangdong Provincial Key Laboratory of Pathogenesis, Targeted Prevention and Treatment of Heart Disease, Guangzhou 510180, China
^4.Guangzhou Key Laboratory of Cardiac Pathogenesis and Prevention, Guangzhou 510180, China

Received:2024-04-25 Online:2024-10-20 Published:2024-10-31
Contact: Shuoji ZHU, Nanbo LIU, Ping ZHU E-mail:debarah17@foxmail.com;zhushuoji@gmail.com;liu.nanbo@163.com;tanganqier@163.com
Supported by:
National Natural Science Foundation of China Youth Science Foundation(82100275)

摘要/Abstract

摘要：

目的高分辨定量剖析生理状态下小鼠心脏电生理本底稳态属性。方法随机选取成年C57BL/6小鼠22只（雌雄1∶1），采用无麻醉法固定小鼠四肢，自主呼吸下通过灵敏十二导联电生理采集器（ECG_sqa）记录心电波形，包括小鼠特征性P波、R波及ST波，应用LabScribe软件读取与量化心前区V3导联上单一心动周期内高分辨时程参数与振幅参数，使用独立样本t检验比较组间差异，联合皮尔逊相关检验与简单线性回归绘制雌雄心电参数拟合散点图，按相关性强弱区分共享与独特关联对参数，从而揭示定量关联网络概貌。结果 ECG_sqa分析共识别与量化14个特征型心电参数，28.6%的组间差异具有统计学意义。与雄组相比，雌组R波与ST波的振幅与速率均更高（P<0.05）。在初级关联分析所鉴定的51个关联对中，关联阳性群占比为47.1%，其中涵盖雌雄共有（29.2%）、雄特有（29.2%）与雌特有（41.7%）三大关联组。关联对二阶聚类分析发现，雌雄心脏各波形电压的振幅-速率关联对处于普遍稳定强相关水平（P<0.01），而雄组心电特征展现出房-室互联模式，以及雌组心电特征展现独特心房电导系统质量依赖模式。关联群组分布网络特征显示，雌雄各自特有关联参数与共有关联参数之间具有一定程度串联模式。结论本研究聚焦雌雄小鼠天然心脏电信号的可被精确识别的数理特征，发现心电波重要特征参数的内在关联网络，揭示心房与心室电传导系统内部联结特征及其性别差异性，可为心血管生理与病理的纵深机制探索提供潜在适用的电稳态制式参照。

关键词: 心脏电生理, 定量心电策略, P波, R波, ST波

Abstract:

Objective To explore the intrinsic steady-state electrophysiological properties of mouse heart under physiological conditions by high-resolution quantitative analysis. Methods Twenty-two young adult C57BL/6 mice with a 1:1 male-to-female ratio were used. The limbs of the mice were fixed without anesthesia, and electrocardiographic waveforms, including characteristic P-waves, R-waves, and ST-waves, were recorded using a sensitive 12-lead electrophysiological recorder (ECG_sqa) under spontaneous breathing. LabScribe software was used to extract and quantify high-resolution time course and amplitude parameters within a single cardiac cycle from the V3 precordial lead. Pearson correlation test combined with simple linear regression was used to generate a scatter plot of ECG parameter fitting. The common and unique correlation parameters were separately identified by joint associations for profiling the quantitative association network. Results ECG_sqa analysis identified and quantified 14 characteristic ECG parameters, 28.6% of which showed statistical differences between the groups. Compared to male mice, female mice exhibited higher amplitudes and velocities of R and ST waves. Among the 51 association pairs identified in primary association analysis, 47.1% were positively correlated, including shared (29.2%), male-specific (29.2%), and female-specific (41.7%) association groups. Second-order clustering of the association pairs revealed that the amplitude-rate association pairs of each waveform voltage in both male and female mouse hearts were strongly correlated. The male mice showed an atrioventricular interconnection pattern, while the female mice showed a unique atrial conduction system quality dependence. The distribution network characteristics of the association groups showed that sex-specific and common correlation sets formed a certain series pattern. Conclusion We discovered a novel intrinsic correlation network of cardiac electrophysiological traits in male and female mice, which reveals the key internal quantitative characteristics and gender difference of both atrial and ventricular conduction systems.

Key words: cardiac electrophysiology, quantitative ECG strategy, P wave, R wave, ST wave

成思怡, 陈泽锐, 于长江, 孙图成, 朱烁基, 刘南波, 朱平. 基于特征化定量心电图策略分析小鼠心脏电生理固有稳态制式[J]. 南方医科大学学报, 2024, 44(10): 1985-1994.

Siyi CHENG, Zerui CHEN, Changjiang YU, Tucheng SUN, Shuoji ZHU, Nanbo LIU, Ping ZHU. Intrinsic steady-state pattern of mouse cardiac electrophysiology: analysis using a characterized quantitative electrocardiogram strategy[J]. Journal of Southern Medical University, 2024, 44(10): 1985-1994.

图/表 10

图1 单个心动周期内电生理波段的特征参数与ECGsqa分析路径

Fig.1 Characteristic parameters and mathematical application pathway of ECGsqa parameters within one single cardiac cycle.

图2 小鼠主要心电时程ECGsqa量化参数具有性别间保守性

Fig. 2 The main quantified ECGsqa time course parameters in mice are conserved between genders. A: Heart rate. B: P wave rising segment duration. C: R wave rising segment duration. D: ST rising segment duration. E: PP interval. F: PR interval. G: P interval. H: QT interval.

图3 小鼠房室心电波幅与导速的ECGsqa量化值具有性别差异特征

Fig.3 Quantitative values of atrioventricular ECGsqa amplitude and velocity in mice harbor mathematical characteristics of gender differences. A: P wave amplitude. B: R wave amplitude. C: ST segment amplitude. D: P wave velocity. E: R wave velocity. F: ST segment velocity.

图4 雌雄小鼠心电最显著线性关联参数识别组

Fig.4 Identification group of the most significant linear correlation parameters in ECGsqa of both male and female mice. A: P wave amplitude is positively correlated with atrial depolarization rate (ADV). B: R wave amplitude is positively correlated with ventricular depolarization rate (VDV). C: ST segment amplitude is positively correlated with ventricular ST segment velocity.

图5 雌雄小鼠心电次显著线性关联参数识别组

Fig.5 Identification group of secondary significant linear correlation parameters in ECGsqa of both male and female mice. A: PP interval is positively correlated with TP interval. B: PR/PP ratio is negatively correlated with TP/PP ratio. C: PP interval is positively correlated with TP/PP ratio. D: QT/PP ratio is negatively correlated with TP/ PP ratio.

图6 雄鼠最显著独特心电线性相关参数识别组

Fig.6 The most significant unique identification group of ECG linear parameters related to male mice. A: Male PP interval is negatively correlated with male PR/PP ratio. B: Male P wave amplitude is positively correlated with male R wave amplitude. C: Male ADV is positively correlated with male VDV.

图7 雄鼠次显著独特心电线性相关参数识别组

Fig.7 Identification group of unique cardiac electrical linearity-related parameters in male mice. A: Male R wave amplitude is positively correlated with male ST segment amplitude. B: Male VDV is positively correlated with male ST segment velocity. C: Male P wave amplitude is positively correlated with male ST segment amplitude. D: Male ADV is positively correlated with male ST segment velocity.

图8 雌鼠最显著独特心电线性相关参数识别组

Fig.8 The most significant unique identification group of ECG linearity-related parameters in female mice. A: Female heart rate is negatively correlated with female PP interval. B: Female heart rate is negatively correlated with female PR interval. C: Female PP interval is positively correlated with female PR interval. D: Female PP interval is negatively correlated with female QT/PP ratio.

图9 雌鼠次显著独特心电线性相关参数识别组

Fig.9 Secondary significant unique identification group of ECG linearity-related parameters in female mice. A: Female heart rate is negatively correlated with female QT interval. B: Female heart rate is positively correlated with female QT/PP ratio. C: Female heart rate is negatively correlated with female TP ratio. D: Female heart rate is negatively correlated with female TP/PP ratio. E: Heart rate is negatively correlated the peak time of rising P wave in female. F: Female PR interval is positively correlated with female QT interval.

图10 定量心电关联参数网探识小鼠心脏电传导系统固有生理稳态模式

Fig.10 Quantitative ECG correlation parameter network characterizes the intrinsic physiological homeostasis pattern of the mouse cardiac electrical conduction system.

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基于特征化定量心电图策略分析小鼠心脏电生理固有稳态制式

Intrinsic steady-state pattern of mouse cardiac electrophysiology: analysis using a characterized quantitative electrocardiogram strategy

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