Atrial fibrillation (AF), associated with electrical remodeling and high arrhythmogenesis in PVs and atrial substrates, is the most common cardiac arrhythmia and can induce cardiac dysfunction and stroke. Chronic obstructive pulmonary disease (COPD) is associated with increased likelihood of atrial fibrillation/atrial flutter. Reduced forced expiratory volume in 1 second (FEV1), higher PaCO2 values and a higher value of pulmonary artery systolic pressure (PASP) all contribute to higher risk of AF. Chamber dilatation or hypertrophy secondary to COPD could partially account for AF occurrence. Anatomical and potential electrophysiological remodeling such as elevated atrial pressure and altering the electrophysiological properties of atrial tissues, fibrosis of PVs and stretching of PVs secondary to airflow obstruction and/or pulmonary hypertension may also play a role in COPD initiated AF. Other potential mechanisms include chronic systemic inflammation and oxidative stress, both play important roles in AF as well as in COPD, also might underlying the pathogenesis of COPD related AF. However, the mechanisms underlying the arrhythmogenesis of COPD are not clear despite several potential mechanisms proposed. Abnormal ionic channel and calcium dysregulation may lead to PV or atrial arrhythmogenesis and lead to atrial fibrillation. Therefore, the purposes of this study will to investigate the arrhythmogenic effects of COPD in AF triggers and substrate through in vivo and in vitro experiments. In the first year study, we will create a COPD animal model, and examine the histopathological changes and inflammatory cytokines from SAN, RA, LA and PVs. Also we will study the conduction property of both atria, and study the electrophysiological properties to see whether PV and SAN or RA and LA may response differently to COPD. In the 2nd year, we will study the effects of COPD on ionic currents in AF trigger and substrates, which may potentially contribute to the COPD related atrial arrhythmogenesis. In the 3rd year, we will study the relationship between Ca2+ homeostasis and COPD related atrial arrhythmogenesis.
|Effective start/end date||8/1/15 → 7/31/16|
- atrial fibrillation
- B-type natriuretic peptide
- heart failure
- pulmonary vein