Ionic Currents and Calcium Homeostasis in Atrial Arrhythmogenesis of Chronic Obstructive Pulmonary Disease Animal Model

Project: A - Government Institutionb - Ministry of Science and Technology

Project Details

Description

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. And the therapeutic agents for COPD may also potential the occurrence of 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 past year, we had successfully create a COPD animal model through intra-tracheal infusion of porcine pancreatic elastase in rabbit with confirmation by pulmonary function test, and examine the conduction property and study the electrophysiological properties of PV and SAN or RA and LA 1 month after COPD creation. And we found COPD inceeased the PV arrhythmogenesis. For the future study, in the 1st year, we will use whole cell patch clamp to study the ionic currents modulation of SAN, LA, RA and PVs of COPD animal in order to understand the effects of COPD on ionic currents in AF trigger and substrates, which may potentially contribute to the COPD related atrial arrhythmogenesis. In the 2nd year, we will use the Fluo-3 fluorescence to learn the calcium transient and calcium spark and Western blot to investigate the calcium regulatory protein, in order to study the relationship between Ca2+ homeostasis and COPD related atrial arrhythmogenesis. In the 3rd year, we will use conventional electrophysiological with drug superfusion of atria and PVs and whole cell patch clamp with drug incubation of atrial and PVs myocytes to study the relationship of therapeutic drug (Salbutamol) for COPD and the occurrence of AF.
StatusFinished
Effective start/end date8/1/177/31/18

Keywords

  • Atria
  • Atrial Fibrillation
  • Chronic Obstructive Pulmonary Disease
  • Pulmonary vein