Intracellular calcium dynamics and anisotropic reentry in isolated canine pulmonary veins and left atrium

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-06, Vol.111 (22), p.2889-2897
• Main Authors: CHOU, Chung-Chuan, NIHEI, Motoki, SHENGMEI ZHOU, TAN, Alex, KAWASE, Ayaka, MACIAS, Edgar S, FISHBEIN, Michael C, LIN, Shien-Fong, CHEN, Peng-Sheng
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Anisotropy; Atrial Fibrillation - etiology; Atrial Fibrillation - metabolism; Atrial Fibrillation - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Calcium - metabolism; Cardiology. Vascular system; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dogs; Heart - physiopathology; Heart Atria - physiopathology; Histological Techniques; In Vitro Techniques; Medical sciences; Myocardium - cytology; Perfusion; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Pulmonary Veins - metabolism; Pulmonary Veins - physiopathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.104.498758

Rapid activations due to either focal discharge or reentry are often present during atrial fibrillation (AF) in the pulmonary veins (PVs). The mechanisms of these rapid activations are unclear. We studied 7 isolated, Langendorff-perfused canine left atrial (LA) and PV preparations and used 2 cameras to map membrane potential alone (Vm, n=3) or Vm and intracellular calcium simultaneously (Ca(i), n=4). Rapid atrial pacing induced 26 episodes of focal discharge from the proximal PVs in 5 dogs. The cycle lengths were 223+/-52 ms during ryanodine infusion (n=13) and 133+/-59 ms during ryanodine plus isoproterenol infusion (n=13). The rise of Ca(i) preceded Vm activation at the sites of focal discharge in 6 episodes of 2 preparations, compatible with voltage-independent spontaneous Ca(i) release. Phase singularities during pacing-induced reentry clustered specifically at the PV-LA junction. Periodic acid-Schiff (PAS) stain identified large cells with pale cytoplasm along the endocardium of PV muscle sleeves. There were abrupt changes in myocardial fiber orientation and increased interstitial fibrosis in the PV and at the PV-LA junction. PV muscle sleeves may develop voltage-independent Ca(i) release, resulting in focal discharge. Focal discharge may also be facilitated by the presence of PAS-positive cells that are compatible with node-like cells. During reentry, phase singularities clustered preferentially at sites of increased anisotropy such as the PV-LA junction. These findings suggest that focal discharge caused by spontaneous calcium release and anisotropic reentry both contribute to rapid activations in the PVs during AF.