BACKGROUND: Heart failure increases autonomic nerve activities and changes intracellular calcium (Ca(i)) dynamics. OBJECTIVE: The purpose of this study was to investigate the hypothesis that abnormal Ca(i) dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure. METHODS: Simultaneous optical mapping of Ca(i) and membrane potential was performed in isolated Langendorff-perfused PV-left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 micromol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6). RESULTS: Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Ca(i), late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 +/- 0.6 beats/s (N = 4) to 6.5 +/- 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV-LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid-Schiff (PAS)-positive cells were present at the focal discharge sites. CONCLUSION: Ca(i) dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves.
BACKGROUND:Heart failure increases autonomic nerve activities and changes intracellular calcium (Ca(i)) dynamics. OBJECTIVE: The purpose of this study was to investigate the hypothesis that abnormal Ca(i) dynamics are responsible for triggered activity in the pulmonary veins (PVs) during acetylcholine infusion in a canine model of heart failure. METHODS: Simultaneous optical mapping of Ca(i) and membrane potential was performed in isolated Langendorff-perfused PV-left atrial (LA) preparations from nine dogs with ventricular pacing-induced heart failure. Mapping was performed at baseline, during acetylcholine (1 micromol/L) infusion (N = 9), and during thapsigargin and ryanodine infusion (N = 6). RESULTS:Acetylcholine abbreviated the action potential. In four tissues, long pauses were followed by elevated diastolic Ca(i), late phase 3 early afterdepolarizations, and atrial fibrillation (AF). The incidence of PV focal discharges during AF was increased by acetylcholine from 2.4 +/- 0.6 beats/s (N = 4) to 6.5 +/- 2.2 beats/s (N = 8; P = .003). PV focal discharge and PV-LA microreentry coexisted in 6 of 9 preparations. The spatial distribution of dominant frequency demonstrated a focal source pattern, with the highest dominant frequency areas colocalized with PV focal discharge sites in 35 (95%) of 37 cholinergic AF episodes (N = 8). Thapsigargin and ryanodine infusion eliminated focal discharges in 6 of 6 preparations and suppressed the inducibility of AF in 4 of 6 preparations. PVs with focal discharge have higher densities of parasympathetic nerves than do PVs without focal discharges (P = .01), and periodic acid-Schiff (PAS)-positive cells were present at the focal discharge sites. CONCLUSION:Ca(i) dynamics are important in promoting triggered activity during acetylcholine infusion in PVs from pacing-induced heart failure. PV focal discharge sites have PAS-positive cells and high densities of parasympathetic nerves.
Authors: J M Cao; M C Fishbein; J B Han; W W Lai; A C Lai; T J Wu; L Czer; P L Wolf; T A Denton; I P Shintaku; P S Chen; L S Chen Journal: Circulation Date: 2000-04-25 Impact factor: 29.690
Authors: James Kneller; Renqiang Zou; Edward J Vigmond; Zhiguo Wang; L Joshua Leon; Stanley Nattel Journal: Circ Res Date: 2002-05-17 Impact factor: 17.367
Authors: Joachim R Ehrlich; Tae-Joon Cha; Liming Zhang; Denis Chartier; Peter Melnyk; Stefan H Hohnloser; Stanley Nattel Journal: J Physiol Date: 2003-07-07 Impact factor: 5.182
Authors: Eugene Patterson; Ralph Lazzara; Bela Szabo; Hong Liu; David Tang; Yu-Hua Li; Benjamin J Scherlag; Sunny S Po Journal: J Am Coll Cardiol Date: 2006-02-23 Impact factor: 24.094
Authors: Masahiro Ogawa; Shengmei Zhou; Alex Y Tan; Juan Song; Ghassan Gholmieh; Michael C Fishbein; Huai Luo; Robert J Siegel; Hrayr S Karagueuzian; Lan S Chen; Shien-Fong Lin; Peng-Sheng Chen Journal: J Am Coll Cardiol Date: 2007-07-10 Impact factor: 24.094
Authors: Jérôme Kalifa; José Jalife; Alexey V Zaitsev; Suveer Bagwe; Mark Warren; Javier Moreno; Omer Berenfeld; Stanley Nattel Journal: Circulation Date: 2003-08-04 Impact factor: 29.690
Authors: Jason Ng; Roger Villuendas; Ivan Cokic; Jorge E Schliamser; David Gordon; Hemanth Koduri; Brandon Benefield; Julia Simon; S N Prasanna Murthy; Jon W Lomasney; J Andrew Wasserstrom; Jeffrey J Goldberger; Gary L Aistrup; Rishi Arora Journal: Circ Arrhythm Electrophysiol Date: 2011-03-18
Authors: Andrea Uradu; Juyi Wan; Anisiia Doytchinova; Keith C Wright; Andrew Y T Lin; Lan S Chen; Changyu Shen; Shien-Fong Lin; Thomas H Everett; Peng-Sheng Chen Journal: Heart Rhythm Date: 2017-03-24 Impact factor: 6.343