Department of Human and Animal Physiology, Biological Faculty, Lomonosov Moscow State University, Leninskie gory 1, building 12, Moscow, 119991, Russia.
Pirogov Russian National Research Medical University (RNRMU), Ostrovitjanova 1, Moscow, 117997, Russia.
J Physiol. 2021 Jun;599(11):2803-2821. doi: 10.1113/JP280485. Epub 2021 May 1.
The developmental changes of the caval (SVC) and pulmonary vein (PV) myocardium electrophysiology are traced throughout postnatal ontogenesis. The myocardium in SVC as well as in PV demonstrate age-dependent differences in the ability to maintain resting membrane potential, to manifest automaticity in a form of ectopic action potentials in basal condition and in responses to the adrenergic stimulation. Electrophysiological characteristics of two distinct types of thoracic vein myocardium change in an opposite manner during early postnatal ontogenesis with increased proarrhythmicity of pulmonary and decreased automaticity in caval veins. Predisposition of PV cardiac tissue to proarrhythmycity develops during ontogenesis in time correlation with the establishment of sympathetic innervation of the tissue. The electrophysiological properties of caval vein cardiac tissue shift from a pacemaker-like phenotype to atrial phenotype in accompaniment with sympathetic nerve growth and adrenergic receptor expression changes.
The thoracic vein myocardium is considered as a main source for atrial fibrillation initiation due to its high susceptibility to ectopic activity. The mechanism by which and when pulmonary (PV) and superior vena cava (SVC) became proarrhythmic during postnatal ontogenesis is still unknown. In this study, we traced postnatal changes of electrophysiology in a correlation with the sympathetic innervation and adrenergic receptor distribution to reveal developmental differences in proarrhythmicity occurrence in PV and SVC myocardium. A standard microelectrode technique was used to assess the changes in ability to maintain resting membrane potential (RMP), generate spontaneous action potentials (SAP) and adrenergically induced ectopy in multicellular SVC and PV preparations of rats of different postnatal ages. Immunofluorescence imaging was used to trace postnatal changes in sympathetic innervation, β1- and α1A-adrenergic receptor (AR) distribution. We revealed that the ability to generate SAP and susceptibility to adrenergic stimulation changes during postnatal ontogenesis in an opposite manner in PV and SVC myocardium. While SAP occurrence decreases with age in SVC myocardium, it significantly increases in PV cardiac tissue. PV myocardium starts to demonstrate RMP instability and proarrhythmic activity from the 14th day of postnatal life which correlates with the appearance of the sympathetic innervation of the thoracic veins. In addition, postnatal attenuation of SVC myocardium automaticity occurs concomitantly with sympathetic innervation establishment and increase in β1-ARs, but not α1A-AR levels. Our results support the contention that SVC and PV myocardium electrophysiology change during postnatal development, resulting in higher PV proarrhythmicity in adults.
腔静脉（SVC）和肺静脉（PV）心肌电生理学的发育变化在整个出生后发育过程中都有迹可循。SVC 和 PV 中的心肌在维持静息膜电位的能力、在基础条件下以异位动作电位的形式表现出自发性以及对肾上腺素刺激的反应方面表现出年龄依赖性差异。两种不同类型的胸静脉心肌的电生理特征在出生后早期发育过程中以相反的方式发生变化，肺静脉的致心律失常性增加，腔静脉的自动性降低。PV 心脏组织对致心律失常性的易感性在发育过程中随着组织交感神经支配的建立而发展。SVC 心脏组织的电生理特性从起搏样表型转变为伴交感神经生长和肾上腺素能受体表达变化的心房表型。
胸静脉心肌由于其对外源活动的高度敏感性而被认为是引发房颤的主要来源。PV 和 SVC 在出生后发育过程中变得致心律失常的机制和时间仍不清楚。在这项研究中，我们跟踪了电生理学的出生后变化，与交感神经支配和肾上腺素能受体分布相关联，以揭示 PV 和 SVC 心肌致心律失常性发生的发育差异。我们使用标准的微电极技术评估了不同出生后年龄大鼠的多细胞 SVC 和 PV 标本中维持静息膜电位（RMP）、产生自发性动作电位（SAP）和肾上腺素诱导的异位的能力的变化。免疫荧光成像用于追踪出生后交感神经支配和β1-和α1A-肾上腺素能受体（AR）分布的变化。我们发现，在出生后发育过程中，PV 和 SVC 心肌的 SAP 发生和对肾上腺素刺激的敏感性以相反的方式发生变化。虽然 SVC 心肌的 SAP 发生随着年龄的增长而减少，但在 PV 心脏组织中却显著增加。从出生后第 14 天开始，PV 心肌开始表现出 RMP 不稳定和致心律失常活动，这与胸静脉的交感神经支配的出现有关。此外，SVC 心肌自动性的出生后衰减与交感神经支配的建立以及β1-AR的增加同时发生，但与α1A-AR 水平无关。我们的研究结果支持这样一种观点，即 SVC 和 PV 心肌电生理学在出生后发育过程中发生变化，导致成年 PV 的致心律失常性增加。
