Intracellular Calcium Dynamics and Anisotropic Reentry in Isolated Canine Pulmonary Veins and Left Atrium

Abstract

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. Methods and Results-We studied 7 isolated, Langendorff-perfused canine left atrial (LA) and PV preparations and used 2 cameras to map membrane potential alone (Vm, nϭ3) or Vm and intracellular calcium simultaneously (Ca i , nϭ4). Rapid atrial pacing induced 26 episodes of focal discharge from the proximal PVs in 5 dogs. The cycle lengths were 223Ϯ52 ms during ryanodine infusion (nϭ13) and 133Ϯ59 ms during ryanodine plus isoproterenol infusion (nϭ13). 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

Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure

“…6 These manipulations did not cause significant APD shortening to induce late phase 3 early afterdepolarizations. Rather, they facilitate the development of delayed afterdepolarizations.…”

“…The overall incidence of focal discharge was calculated by the average of the total number of focal discharges in 4 seconds. APD 80 was the interval between phase 0 and the time of 80% repolarization, measured at a pacing cycle length of 500 ms. Monoexponential fit was used to compute the time constant of the decline of Ca i transient (τ) at a pacing cycle length of 1,000 ms. APD 80 and τ values in four nonpaced PV-LA preparations from normal dogs used in a previously published study 6 were measured for control. Fast Fourier transform was used to determine the frequency at each pixel during 4 seconds of AF.…”

“…Periodic acid-Schiff (PAS) method (Accustain Schiff's reagent, SigmaAldrich, Inc, MO, USA) was used to stain for cellular glycogen content. 6 …”

“…4 Heart failure is associated with abnormal Ca i handling and increased NCX activity. 5 The purpose of this study was to perform high-density simultaneous membrane potential (Vm) and Ca i mapping 6 to determine if Ca i dynamics are directly responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of pacing-induced heart failure. A second aim of the study was to perform immunohistochemical studies to test the hypothesis that autonomic innervation and specialized conducting cells are juxtaposed to the PV focal discharge sites.…”

Expression of tyrosine hydroxylase and growth-associated protein 43 in aging atrial fibrillation patients of Xinjiang Uygur and Han nationality

“…Patterson et al (2006) found that the continuous increase in relaxing period tension was an important cause of EAD, in which the increasing intracellular calcium concentration of the relaxing period was the cause of inducing AF. By using an optical mapping technique, Chou et al (2005) detected that when dogs' atrial muscle cell membrane and pulmonary vein regeneration or nerve automatic activity decreased, the rate of forming cardiac intracellular calcium overload and EAD decreased significantly, which would promote the recovery of AF.…”