Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles

Liang Tang, Boyoung Joung, Masahiro Ogawa, Peng-Sheng Chen, Shien-Fong Lin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50% (DCaT50) and 90% (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.

Original languageEnglish
Pages (from-to)1364-1371
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume23
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Action Potentials
Ventricular Fibrillation
Rabbits
Calcium
KATP Channels
Myocardial Ischemia
Voltage-Sensitive Dye Imaging
Pinacidil
Endocardium
Microelectrodes

Keywords

  • APD shortening
  • calcium
  • early afterdepolarization
  • triggered activity
  • ventricular fibrillation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles",
abstract = "Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50{\%} (DCaT50) and 90{\%} (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5{\%} of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.",
keywords = "APD shortening, calcium, early afterdepolarization, triggered activity, ventricular fibrillation",
author = "Liang Tang and Boyoung Joung and Masahiro Ogawa and Peng-Sheng Chen and Shien-Fong Lin",
year = "2012",
month = "12",
doi = "10.1111/j.1540-8167.2012.02400.x",
language = "English",
volume = "23",
pages = "1364--1371",
journal = "Journal of Cardiovascular Electrophysiology",
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number = "12",

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TY - JOUR

T1 - Intracellular calcium dynamics, shortened action potential duration, and late-phase 3 early afterdepolarization in Langendorff-perfused rabbit ventricles

AU - Tang, Liang

AU - Joung, Boyoung

AU - Ogawa, Masahiro

AU - Chen, Peng-Sheng

AU - Lin, Shien-Fong

PY - 2012/12

Y1 - 2012/12

N2 - Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50% (DCaT50) and 90% (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.

AB - Introduction: To elucidate the mechanism of late-phase 3 early after depolarization (EAD) in ventricular arrhythmogenesis, we hypothesized that intracellular calcium (Cai) overloading and action potential duration (APD) shortening may promote late-phase 3 EAD and triggered activity, leading to development of ventricular fibrillation (VF). Methods and Results: In isolated rabbit hearts, we performed microelectrode recording and simultaneous dual optical mapping of transmembrane potential (Vm) and Ca i transient on left ventricular endocardium. An IKATP channel opener, pinacidil, was used to abbreviate APD. Rapid pacing was then performed. Upon abrupt cessation of rapid pacing with cycle lengths of 60-200 milliseconds, there were APD90 prolongation and the corresponding Cai overloading in the first postpacing beats. The duration of Cai transient recovered to 50% (DCaT50) and 90% (DCaT 90) in the first postpacing beats was significantly longer than baseline. Abnormal Cai elevation coupled with shortened APD produced late-phase 3 EAD induced triggered activity and VF. In additional 6 preparations, the heart tissues were treated with BAPTA-AM, a calcium chelator. BAPTA-AM significantly reduced the maximal Cai amplitude (26.4 ± 3.5% of the control; P < 0.001) and the duration of Cai transients in the mapped region, preventing the development of EAD and triggered activity that initiated VF. Conclusions: I KATP channel activation along with Cai overloading are associated with the development of late-phase 3 EAD and VF. Because acute myocardial ischemia activates the I KATP channel, late-phase 3 EADs may be a mechanism for VF initiation during acute myocardial ischemia.

KW - APD shortening

KW - calcium

KW - early afterdepolarization

KW - triggered activity

KW - ventricular fibrillation

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U2 - 10.1111/j.1540-8167.2012.02400.x

DO - 10.1111/j.1540-8167.2012.02400.x

M3 - Article

VL - 23

SP - 1364

EP - 1371

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 12

ER -