Assessment of atrial fibrillation substrate in freely moving rats exposed to underlying pathological conditions

Background: Atrial fibrillation (AF) is a progressive and difficult to treat arrhythmia. Various factors promote AF by mechanisms that are not fully elucidated and require reliable and affordable animal models. In the present work we introduce a system for long-term assessment of AF susceptibility (substrate) in ambulatory rats.

Methods and Results: Rats implanted with miniature electrodes on the right atrium were subjected to excessive aldosterone (ALDO) or solvent only (Sham). An additional group was exposed to myocardial infarction (MI). AF substrate was tested two- and four-weeks post implantation and was also compared with implanted rats early post-implantation (Base). ALDO and MI increased the AF substrate compared to Base. LA fibrosis was increased as well. In the MI group only, AF duration was correlated with the level of LA fibrosis and was inversely correlated with systolic function. Unexpectedly, Shams also developed progressive AF-substrate relative to Base individuals. Further studies indicated that serum inflammatory markers (IL-6, TNF-alpha) were not elevated in these rats. In addition, an experiment in which rats could interact through a barrier, excluded social-isolation as a contributing factor. Finally, improved biocompatibility of the atrial electrode could not inhibit the gradual development of intrinsic AF substrate over a testing period of up to 8 weeks.

Conclusions: We validated a system for long-term AF substrate evaluation in ambulatory rats. The description of intrinsic AF substrate as well as the new gained insights on the effects of ALDO and MI should facilitate utility of this system for preclinical research and drug testing.