Based on the lack of efficacy of current therapies and similarities between risk factors for atherosclerosis (hardening of the arteries) and AF, we began to investigate whether oxidative stress, a mechanism similar to inflammation thought to be responsible for atherosclerosis, might be playing a role in causing AF. We studied this in pigs first and found that when we put pigs into AF, they had a large increase in oxidative stress markers. Then, we made a mouse that had too much oxidative stress in the heart, and this mouse developed AF. Based on this and other data in humans, we hypothesized that oxidative stress can cause AF.