Effects of Endurance Exercise and Progesterone Levels on Atrial Fibrillation Inducibility in a Transgenic Goat Model Exhibiting Atrial Fibrosis

The normal functioning of the heart involves a series of events that result in a coordinated muscle contraction, enabling blood circulation throughout the body. Atrial fibrillation (AF) is a prevalent cardiac arrhythmia characterized by irregular contractions of the atria, the smaller upper chambers of the heart. While the exact mechanisms behind AF are not fully understood, multiple factors contribute to its development, including fibrosis. Fibrosis, the development of fibrous connective tissue in the heart, disrupts normal electrical activity, thereby perpetuating the arrhythmia. In our research, we have created a transgenic (TG) goat model that exhibits atrial fibrosis and experiences sustained episodes of AF. With this model, we conducted several studies to better understand the baseline characteristics of the model and explore the effects of specific environmental triggers. Initially, we compared the AF burden in the TG model to a control group consisting of wild-type (WT) animals. Additionally, we examined inflammatory markers and levels of selected target genes at the cellular and tissue level in these animals to identify any potential contributors to AF development. Subsequently, we designed an exercise study to investigate the impact of endurance exercise on animals with AF. Interestingly, we observed an increase in inducible AF episodes in both TG and WT goats during the study, with a return to near-baseline levels by the third month. Furthermore, we explored the influence of pregnancy on AF inducibility in TG and WT goats. We noted a decrease in an inducible AF in all animals during pregnancy, followed by a significant increase immediately after parturition. Upon concluding the pregnancy study, we developed additional experiments to examine the role of progesterone (P4) in AF development. Throughout our studies, we observed a potential protective effect of P4 on arrhythmia, as withdrawal of the hormone increased levels of AF. Through our investigations using a large animal TG model of atrial fibrosis, we have identified several physiological stressors and their impact on the development of AF. These findings contribute to a better understanding of AF pathologies and may guide future research and potential therapeutic interventions