Abstract WP263: Increased Cardiac Inflammation and Atrial Fibrillation Inducibility in Aged Females: The Niche for Cardio-Embolic Strokes?

Abstract

Background: Elderly women have higher morbidity, mortality and disability after stroke compared to age-matched men. Cardio embolism from atrial fibrillation (AF) remains the primary cause of severe strokes in elderly women. Why females have higher rates of atrial arrhythmias and embolism as they age is unknown. Studying differences in atrial substrate inflammation and arrhythmogenesis may help us understand these sex differences. Methods: Aged male and female C57BL6 wild type mice (18-20 months old) were injected with carbachol 50μg/kg for AF induction and ambulatory telemetry monitors were implanted. AF events were analyzed using Ponemah software and LabChart software for one day. Another cohort of naïve aged wild type mice were sacrificed and intracardiac perfusion was performed. Hearts were collected and prepared into a single cell suspension using series of mechanical and enzymatic digestion steps. The cells were stained with antibodies for F4/80, Ly6C, CD11b, CD11c, and Gr1 antibodies. Sample data was acquired on a Cytoflex and analyzed using FlowJo software. Results: Aged females had significantly higher AF events, (110.7± 22.6, n=6), as compared to aged males (13.7±10.8 events, n=4), p=0.05. Flow cytometry showed that aged females have significantly more macrophages (CD11b + /F480 + ) (102.6±18.5) as compared to aged males, 26.6±3.4, p=.01, n=3/group. There were also significantly more monocytes (CD11b + /Ly6c + ) in aged wild type females (176.6±50.8) vs. aged males (44.3±13.2), p=0.05, n=3/group. No significant difference was seen in dendritic cell numbers (CD11c + ), p=0.3, n=3/ group. Conclusion: Our study shows that aged females have higher rates of AF after chemical induction as compared to males. They also have higher monocyte and macrophage populations in cardiac tissue as compared to aged males. This suggests that there is increased baseline cardiac inflammation in aged females, which may be the niche for arrhythmia generation in females. This in itself may lead to increased stroke risk. Anti-inflammatory therapies that control atrial substrate inflammation may be an important potential target for stroke prevention in women. Quantification of brain embolic events using MRI and Fluoro-jade staining will also be presented.