Atrial Fibrillation Begets Atrial Fibrillation in Small Animals: Characterization of New Rat Model of Spontaneous Atrial Fibrillation.

Background/Objectives: We previously described a rat model of AF induced by long-term transesophageal atrial burst pacing. Here, we further characterize this model by exploring arrhythmia inducibility, spontaneous AF occurrence, and related autonomic and molecular changes. Methods: Twelve adult male Wistar rats were randomized into two groups: control (n = 5) and AF (n = 7). The rats in the AF group underwent 10 days of transesophageal atrial pacing. In the control rats, the same protocol was mimicked. Spontaneous AF occurrence and heart rate variability (HRV) were evaluated before, during, and after stimulation. Left atrial RNA levels of Hcn1, Hcn2, Hcn4, and Pitx2 were evaluated. Results: In AF, no animal presented spontaneous AF before stimulation. After stimulation initiation, all AF rats presented spontaneous AF (p = 0.08). In the AF rats, HRV analysis revealed a progressive increase in the standard deviation of the RR intervals after atrial stimulation initiation (p < 0.01). The left atrial RNA levels of Hcn4 were higher (p = 0.03) and Pitx2 levels were lower (p = 0.02) in the AF rats compared to the control group. Conclusions: This study validates our previous data and confirms the occurrence of spontaneous AF following long-term atrial pacing in rats. Relatively increased parasympathetic modulation and changes in the atrial expression of Hcn4, encoding for I_f, and Pitx2 likely play critical mechanistic roles in this model.