Non-electrophysiological mechanisms, such as fibrosis, have been shown to be important substrates predisposing to electrical instability. Preceding the development of fibrosis is inflammation, in which inflammatory mediators such as interleukin-6 and tissue necrosis factor alpha play important roles.
The impact of inflammation in arrhythmogenesis is poorly understood. While fibrosis may play a role in later onset of arrhythmias, a significant number of arrhythmias occur early in the disease process, such as in the early post-myocardial infarction period or in the early postoperative state, when acute inflammation, rather than fibrosis, is predominant. In addition, the relationship between chronic inflammation and predisposition to arrhythmias also warrants further study.
Recent studies have found an association between inflammatory cytokines, such as interleukin-6 (IL6), and certain arrhythmias, including atrial fibrillation and ventricular arrhythmias. The cause-and-effect relationship of this association is unknown. Using transgenic models of human diseases including myocardial infarction and congestive heart failure; optical mapping studies of arrhythmias; and various molecular and histologic studies, my research will focus on establishing the role of inflammatory markers such as IL-6 in arrhythmogenesis and on characterizing the precise molecular mechanisms of this relationship.