Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

Chung Chuan Chou, Shengmei Zhou, Hideki Hayashi, Motoki Nihei, Yen Bin Liu, Ming Shien Wen, San Jou Yeh, Michael C. Fishbein, James N. Weiss, Shien-Fong Lin, Delon Wu, Peng-Sheng Chen

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.

Original languageEnglish
Pages (from-to)895-906
Number of pages12
JournalJournal of Physiology
Volume580
Issue number3
DOIs
StatePublished - May 1 2007

Fingerprint

Action Potentials
Cardiac Arrhythmias
Ventricular Fibrillation
Myocardial Infarction
Rabbits
Calcium
Ventricular Premature Complexes
Excitation Contraction Coupling
Ventricular Tachycardia
Isolated Heart Preparation
Propranolol
Membrane Potentials
Infarction
Heart Ventricles
Maintenance
Incidence

ASJC Scopus subject areas

  • Physiology

Cite this

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts. / Chou, Chung Chuan; Zhou, Shengmei; Hayashi, Hideki; Nihei, Motoki; Liu, Yen Bin; Wen, Ming Shien; Yeh, San Jou; Fishbein, Michael C.; Weiss, James N.; Lin, Shien-Fong; Wu, Delon; Chen, Peng-Sheng.

In: Journal of Physiology, Vol. 580, No. 3, 01.05.2007, p. 895-906.

Research output: Contribution to journalArticle

Chou, Chung Chuan ; Zhou, Shengmei ; Hayashi, Hideki ; Nihei, Motoki ; Liu, Yen Bin ; Wen, Ming Shien ; Yeh, San Jou ; Fishbein, Michael C. ; Weiss, James N. ; Lin, Shien-Fong ; Wu, Delon ; Chen, Peng-Sheng. / Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts. In: Journal of Physiology. 2007 ; Vol. 580, No. 3. pp. 895-906.
@article{7a5ae782c4f9414fa1f6519f5afd3e7e,
title = "Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts",
abstract = "We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37{\%} showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.",
author = "Chou, {Chung Chuan} and Shengmei Zhou and Hideki Hayashi and Motoki Nihei and Liu, {Yen Bin} and Wen, {Ming Shien} and Yeh, {San Jou} and Fishbein, {Michael C.} and Weiss, {James N.} and Shien-Fong Lin and Delon Wu and Peng-Sheng Chen",
year = "2007",
month = "5",
day = "1",
doi = "10.1113/jphysiol.2006.120659",
language = "English",
volume = "580",
pages = "895--906",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

AU - Chou, Chung Chuan

AU - Zhou, Shengmei

AU - Hayashi, Hideki

AU - Nihei, Motoki

AU - Liu, Yen Bin

AU - Wen, Ming Shien

AU - Yeh, San Jou

AU - Fishbein, Michael C.

AU - Weiss, James N.

AU - Lin, Shien-Fong

AU - Wu, Delon

AU - Chen, Peng-Sheng

PY - 2007/5/1

Y1 - 2007/5/1

N2 - We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.

AB - We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.

UR - http://www.scopus.com/inward/record.url?scp=34249844194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249844194&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2006.120659

DO - 10.1113/jphysiol.2006.120659

M3 - Article

VL - 580

SP - 895

EP - 906

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 3

ER -