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

Chung Chuan Chou; Bich Lien Nguyen; Alex Y. Tan; Po Cheng Chang; Hui Ling Lee; Fun Chung Lin; San Jou Yeh; Michael C. Fishbein; Shien Fong Lin; Delon Wu; Ming Shien Wen; Peng Sheng Chen

doi:10.1016/j.hrthm.2008.04.009

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

Chung Chuan Chou, Bich Lien Nguyen, Alex Y. Tan, Po Cheng Chang, Hui Ling Lee, Fun Chung Lin, San Jou Yeh, Michael C. Fishbein, Shien Fong Lin, Delon Wu, Ming Shien Wen, Peng Sheng Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

40 Scopus citations

Abstract

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 μmol/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.

Original language	English
Pages (from-to)	1170-1177
Number of pages	8
Journal	Heart Rhythm
Volume	5
Issue number	8
DOIs	https://doi.org/10.1016/j.hrthm.2008.04.009
State	Published - 08 2008
Externally published	Yes

Keywords

Acetylcholine
Atrium
Calcium
Fibrillation
Heart failure
Mapping

Access to Document

10.1016/j.hrthm.2008.04.009

Cite this

Chou, C. C., Nguyen, B. L., Tan, A. Y., Chang, P. C., Lee, H. L., Lin, F. C., Yeh, S. J., Fishbein, M. C., Lin, S. F., Wu, D., Wen, M. S., & Chen, P. S. (2008). Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure. Heart Rhythm, 5(8), 1170-1177. https://doi.org/10.1016/j.hrthm.2008.04.009

@article{eb2405dae85240349fbddd4f5df37dea,

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

abstract = "Background: Heart failure increases autonomic nerve activities and changes intracellular calcium (Cai) dynamics. Objective: The purpose of this study was to investigate the hypothesis that abnormal Cai 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 Cai 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 μmol/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 Cai, 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: Cai 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.",

keywords = "Acetylcholine, Atrium, Calcium, Fibrillation, Heart failure, Mapping",

author = "Chou, {Chung Chuan} and Nguyen, {Bich Lien} and Tan, {Alex Y.} and Chang, {Po Cheng} and Lee, {Hui Ling} and Lin, {Fun Chung} and Yeh, {San Jou} and Fishbein, {Michael C.} and Lin, {Shien Fong} and Delon Wu and Wen, {Ming Shien} and Chen, {Peng Sheng}",

year = "2008",

month = aug,

doi = "10.1016/j.hrthm.2008.04.009",

language = "英语",

volume = "5",

pages = "1170--1177",

journal = "Heart Rhythm",

issn = "1547-5271",

publisher = "Elsevier B.V.",

number = "8",

}

TY - JOUR

T1 - Intracellular calcium dynamics and acetylcholine-induced triggered activity in the pulmonary veins of dogs with pacing-induced heart failure

AU - Chou, Chung Chuan

AU - Nguyen, Bich Lien

AU - Tan, Alex Y.

AU - Chang, Po Cheng

AU - Lee, Hui Ling

AU - Lin, Fun Chung

AU - Yeh, San Jou

AU - Fishbein, Michael C.

AU - Lin, Shien Fong

AU - Wu, Delon

AU - Wen, Ming Shien

AU - Chen, Peng Sheng

PY - 2008/8

Y1 - 2008/8

N2 - Background: Heart failure increases autonomic nerve activities and changes intracellular calcium (Cai) dynamics. Objective: The purpose of this study was to investigate the hypothesis that abnormal Cai 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 Cai 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 μmol/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 Cai, 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: Cai 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.

AB - Background: Heart failure increases autonomic nerve activities and changes intracellular calcium (Cai) dynamics. Objective: The purpose of this study was to investigate the hypothesis that abnormal Cai 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 Cai 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 μmol/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 Cai, 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: Cai 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.

KW - Acetylcholine

KW - Atrium

KW - Calcium

KW - Fibrillation

KW - Heart failure

KW - Mapping

UR - http://www.scopus.com/inward/record.url?scp=48049086994&partnerID=8YFLogxK

U2 - 10.1016/j.hrthm.2008.04.009

DO - 10.1016/j.hrthm.2008.04.009

M3 - 文章

C2 - 18554987

AN - SCOPUS:48049086994

SN - 1547-5271

VL - 5

SP - 1170

EP - 1177

JO - Heart Rhythm

JF - Heart Rhythm

IS - 8

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this