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 weeks post implantation. Capture threshold was stable. Baseline AERP values (38.1±2.3 and 39.5±2.0 using 70ms and 120ms 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 non-physiological. 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.

中文翻译：

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一种新的可植入工具，用于反复评估自由活动大鼠的室上电生理和心房颤动敏感性

心房颤动（AF）的复杂病理生理学仍受多种危险因素的控制，目前仍难以捉摸。基本的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对AF敏感性的主要因素。尽管在该研究领域中非常需要可负担的动物模型，但体内啮齿类动物研究受到技术挑战的限制。最近，我们推出了一种可植入系统，用于对非卧床大鼠的房颤敏感性进行长期评估。然而，技术上的考虑不允许我们进行伴随的室上电生理测量。在这里，我们设计了一种新颖的四极电极，专门用于门诊大鼠的综合心房研究。电极由医用级硅树脂，四个铂铱电极和不锈钢固定销制成。体外进行初始质量验证，然后在成年大鼠中植入，并在植入后第1、4和8周进行重复的电生理研究。捕获阈值稳定。基线AERP值（分别使用70ms和120ms S1-S1周期长度的38.1±2.3和39.5±2.0）证实了在麻醉状态下预期没有速率适应，并验证了我们的预测：麻醉下报道的明显更高的值是非生理性的。AF基底与电生理参数的并行评估验证了我们最近发现的AF敏感性随时间的逐渐增加，并证明此现象与以AERP缩短为特征的电重构过程有关。我们的发现表明，微型四极电极是一种有力的新工具，为在AF研究中更好地利用大鼠打开了机会之窗。