Abstract

Ageing is designated among the main risk factors of atrial fibrillation (AF), the most common cardiac arrhythmia. It is estimated that 70% of AF patients are aged 65 and over. A particular Wistar-derived rat model of successful aging, the LOU/c/jall (LOU) rats, can live more than 35 months, equivalent to 100 years in humans, while the maximal lifespan of Wistar rats is around 22 months. Previous studies have shown that elderly Wistar rats are more vulnerable to AF than young congeners. In another hand, LOU rats have shown exceptional resistance to age-related diseases including neurodegenerative disorders, obesity, and hypertension. Very few data are available about the susceptibility of LOU rats to AF. Understand whether LOU rats' healthy aging is associated with resistance to AF. Male and female rats will be divided into five groups: LOU and Wistar rats of 5 months (young), 20 months (old), and 32 months (very old: LOU rats only). AF vulnerability and cardiac structure/function were evaluated in vivo by transesophageal electrophysiological study and echocardiography. Atrial conduction velocity was analyzed by ex vivo optical mapping. Immunohistochemistry, immunoblot analysis, and qPCR were used to investigate the levels of biomarkers involved in atrial inflammation and fibrosis. We observed increased atrial fibrosis in old Wistar rats compared to their younger counterparts. Old Wistar rats demonstrated a significantly higher incidence of AF compared to other groups. Echocardiography highlighted a more pronounced age-related atrial remodelling in 20-month-old Wistar rats compared to the other groups. Very old LOU rats exhibited normalized atrial fibrous content, maintained cardiac functions, and similar resistance to AF than young rats. Although these results were obtained from male animals, ongoing analyses are currently performed in females to determine whether differences related to biological sex are elucidated. Very old male LOU rats show significant resistance to AF compared to old Wistar rats. Our study suggests that LOU rats may carry innate cardioprotective properties probably limiting atrial fibrosis and inflammation to promote resistance to age-associated cardiac arrhythmias.