Experimental Studies Of Chronic Atrial Fibrillation The Left Atrium And Pulmonary Vein Reconstruction Mechanism

BackgroundAtrial fibrillation (AF) is the most common and persistent arrhythmia in clinical practice. However, the underlying mechanism of AF remains unclear. Recently, the progression in treating AF with radiofrequency ablation has promoted the study on mechanism of AF. In fact, this procedure aims directly at the substrate of AF, and structural remodeling of atrium is the substrate of AF. Structural remodeling during AF includes: (1) changes at the ultranstructural level in cardiomyocytes; (2) fibrosis of extracellular matrix; (3) atrial dilatation. Previous studies showed that electrical remodeling was reversible within 7 to 14 days after cardioversion, but structural remodeling did not reverse, and inducibility of AF had not changed. The atrial structural remodeling contributed to contractile dysfunction, and prolonged the recovery of contractile function after cardioversion. So the atrial structural remodeling is an important substrate for occurrence and maintenance of AF, but its molecular mechanism and influential factor were unclear. Many studies showed that matrix metalloproteinase (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) system, renin-angiotensin system (RAS) contributed to AF. Some recent studies have shown that ischemia-reperfusion injury is mediated by increased levels of cytosolic calcium, which causes activation of the calcium-dependent proteases calpain I and calpain II . Calpains may cause degradation of contractile proteins and myofilaments, so the normal sarcomere structure was disturbed. The calpain is a Ca²⁺ -dependent neutral proteinase. The calpain system comprised three molecules: two Ca²⁺ -dependent proteases, μ-calpain and m-calpain(also called calpain I and II respectively), and a third polypeptide, calpastatin. Calpain I and...