Atrial Fibrillation-Promoting Effect of Altered Left Atrial Calcium-Handling Proteins in Heart Failure

Abstract

Background and Objectives: The incidence of atrial fibrillation (AF) is increased in heart failure (HF). Two major mechanisms of ventricular arrhythmia in HF are reentry mechanism due to tissue fibrosis and triggered activity due to an altered calcium-handling process. Unlike studies on ventricular arrhythmogenesis, only few studies investigated the relationship between changes in the calcium-handling process in atrial tissue and their relationship with atrial arrhythmogenesis in HF. Materials and Methods: HF was induced by myocardial infarction, and the rats were fed a normal sodium diet for 10 weeks and administered isoproterenol (30 μg/[kg∙h]) for the last 2 weeks of the experiment. Echocardiography and AF induction studies were conducted. In addition, mRNA and protein expressions of sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), phospholamban (PLB), ryanodine receptor 2 (RyR2), and sodium calcium exchanger (NCX) were studied. Results: In the HF group, the ejection fractions were significantly decreased. AF duration (12.4±7.9 sec sham and 441.7±12.4 sec HF) and inducibility (8.0%±3.3% sham and 48.5%±10.6% HF) were significantly increased relative to the sham group. Atrial fibrosis tissue amounts were significantly increased in HF (0.20%±0.02% sham and 3.41%±0.45% HF). Atrial SERCA, PLB, RyR2 protein, and mRNA expressions were significantly decreased in HF, while the NCX protein expression was significantly increased in the HF group. The protein PLB/SERCA ratio was significantly increased by about 33% in the HF group. Conclusion: Changes in the protein and mRNA levels of calciumhandling proteins and increase in the degree of atrial fibrosis are important contributing factors of AF in severe HF.