A new implantable tool for repeated assessment of supraventricular electrophysiology and atrial fibrillation susceptibility in freely moving rats

Michael Murninkas, Roni Gillis, Danielle I. Lee, Sigal Elyagon, Nikhil S. Bhandarkar, Or Levi, Rotem Polak, Hadar Klapper-Goldstein, Wesam Mulla, Yoram Etzion

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. NEW & NOTEWORTHY 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.

Original languageEnglish
Pages (from-to)H713-H724
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume320
Issue number2
DOIs
StatePublished - 1 Feb 2021

Keywords

  • Atrial arrhythmia
  • Atrial effective refractory period
  • Atrial fibrillation substrate
  • Electrical remodeling
  • Sinus node recovery time

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