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


RESULTS
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.


CONCLUSIONS
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.
Chou
Chung-Chuan
CC
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA.
Nihei
Motoki
M
Zhou
Shengmei
S
Tan
Alex
A
Kawase
Ayaka
A
Macias
Edgar S
ES
Fishbein
Michael C
MC
Lin
Shien-Fong
SF
Chen
Peng-Sheng
PS
D000200:Action Potentials; D000818:Animals; D016880:Anisotropy; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000503:physiopathology; D006325:Heart Atria / Q000503:physiopathology*; D006652:Histological Techniques; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology; D010477:Perfusion; D011667:Pulmonary Veins / Q000378:metabolism / Q000503:physiopathology*
D002118:Calcium