Abstract
Atrial fibrillation (AF) is a progressive arrhythmia with underlying mechanisms that are not fully elucidated, partially due to lack of reliable and affordable animal models. Here, we introduce a system for long-term assessment of AF susceptibility (substrate) in ambulatory rats implanted with miniature electrodes on the atrium. Rats 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 and atrial fibrosis. In the MI group only, AF duration was correlated with the level of atrial 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 the shams. In addition, we excluded anxiety\\depression due to social-isolation as an AF promoting factor. Finally, enhanced biocompatibility of the atrial electrode did not inhibit the gradual development of AF substrate over a testing period of up to 8 weeks. Overall, we successfully validated the first system for long-term AF substrate testing in ambulatory rats.
Highlights
Atrial fibrillation (AF) is a progressive arrhythmia with underlying mechanisms that are not fully elucidated, partially due to lack of reliable and affordable animal models
As a first step in the characterization of our new system, we evaluated the AF substrate of healthy rats implanted with the Miniature-Bipolar Hook Electrode (MBHE) system and subjected to 1 W recovery period from the initial surgery (Fig. 2A,B, Base group)
These findings suggest that the implantation surgery per-se does not promote AF substrate formation
Summary
Atrial fibrillation (AF) is a progressive arrhythmia with underlying mechanisms that are not fully elucidated, partially due to lack of reliable and affordable animal models. Hulsmans et al.[19] reported the development of a miniaturized pacemaker for long-term pacing studies in rodents This technically-advanced system may open remarkable new opportunities, the currently introduced pacer could not be used for the electrophysiological (EP) testing, which was done conventionally under deep anesthesia as a single terminal procedure. Our laboratory has developed the Miniature-Bipolar Hook Electrode (MBHE), which is adapted for cardiac pacing and EP of rodents This tool enabled efficient EP studies in anesthetized rodents[20,21,22] as well as important, previously technically-challenging EP studies in unanesthetized rats and mice[20,23,24]. In the present study, based on the MBHE system for unanesthetized rodents[23,24,25], we aimed to leverage our implantable device for long-term testing of AF substrate development in fully ambulatory rats over a period of four weeks. The obtained experimental findings expose some important properties of the system itself as well as the underlying pathological factors that were selected for testing
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