Cardiac Arrhythmia Research Laboratory, Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Am J Physiol Heart Circ Physiol. 2021 Feb 1;320(2):H713-H724. doi: 10.1152/ajpheart.00676.2020. Epub 2020 Dec 18.
The complex pathophysiology of atrial fibrillation (AF) is governed by multiple risk factors in ways that are still elusive. Basic electrophysiological properties, including atrial effective refractory period (AERP) and conduction velocity, are major factors determining the susceptibility of the atrial myocardium to AF. Although there is a great need for affordable animal models in this field of research, in vivo rodent studies are limited by technical challenges. Recently, we introduced an implantable system for long-term assessment of AF susceptibility in ambulatory rats. However, technical considerations did not allow us to perform concomitant supraventricular electrophysiology measurements. Here, we designed a novel quadripolar electrode specifically adapted for comprehensive atrial studies in ambulatory rats. Electrodes were fabricated from medical-grade silicone, four platinum-iridium poles, and stainless-steel fixating pins. Initial quality validation was performed ex vivo, followed by implantation in adult rats and repeated electrophysiological studies 1, 4, and 8 wk postimplantation. Capture threshold was stable. Baseline AERP values (38.1 ± 2.3 and 39.5 ± 2.0 using 70-ms and 120-ms S1-S1 cycle lengths, respectively) confirmed the expected absence of rate adaptation in the unanesthetized state and validated our prediction that markedly higher values reported under anesthesia are nonphysiological. Evaluation of AF substrate in parallel with electrophysiological parameters validated our recent finding of a gradual increase in AF susceptibility over time and demonstrated that this phenomenon is associated with an electrical remodeling process characterized by AERP shortening. Our findings indicate that the miniature quadripolar electrode is a potent new tool, which opens a window of opportunities for better utilization of rats in AF research. Rodents are increasingly used in AF research. However, technical challenges restrict long-term supraventricular electrophysiology studies in these species. Here, we developed an implantable electrode adapted for such studies in the rat. Our findings indicate that this new tool is effective for long-term follow-up of critical parameters such as atrial refractoriness. Obtained data shed light on the normal electrophysiology and on the increased AF susceptibility that develops in rats with implanted atrial electrodes over time.
心房颤动(AF)的复杂病理生理学受多种风险因素的影响,但这些因素的作用方式仍难以捉摸。基本电生理特性,包括心房有效不应期(AERP)和传导速度,是决定心房心肌易感性的主要因素。尽管在该研究领域非常需要负担得起的动物模型,但体内啮齿动物研究受到技术挑战的限制。最近,我们引入了一种可用于长期评估活动大鼠 AF 易感性的植入式系统。然而,技术考虑因素不允许我们同时进行超室性电生理测量。在这里,我们设计了一种新型四极电极,专门用于活动大鼠的全面心房研究。电极由医用级硅酮、四个铂铱极和不锈钢固定销制成。最初的质量验证是在离体进行的,然后将其植入成年大鼠体内,并在植入后 1、4 和 8 周重复进行电生理研究。捕获阈值稳定。基础 AERP 值(分别使用 70-ms 和 120-ms S1-S1 周期长度时为 38.1±2.3 和 39.5±2.0)证实了未麻醉状态下预期不存在频率适应,并且验证了我们的预测,即在麻醉下报告的明显更高值是非生理的。与电生理参数并行评估 AF 底物,验证了我们最近的发现,即在时间上 AF 易感性逐渐增加,并表明这种现象与以 AERP 缩短为特征的电重塑过程有关。我们的研究结果表明,微型四极电极是一种强大的新工具,为更好地利用大鼠进行 AF 研究开辟了机会。啮齿动物越来越多地用于 AF 研究。然而,技术挑战限制了这些物种的长期超室性电生理研究。在这里,我们开发了一种适用于大鼠此类研究的可植入电极。我们的研究结果表明,这种新工具对于长期跟踪关键参数(如心房不应期)非常有效。获得的数据揭示了正常电生理以及随着时间的推移在植入心房电极的大鼠中发展的增加的 AF 易感性。