Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: Role of purkinje fibers and triggered activity

Mitsunori Maruyama, Boyoung Joung, Liang Tang, Tetsuji Shinohara, Young Keun On, Seongwook Han, Eue Keun Choi, Dae Hyeok Kim, Mark J. Shen, James N. Weiss, Shien Fong Lin, Peng Sheng Chen

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Rationale: Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome. Objective: We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (Vm) to elevated intracellular calcium (Cai) (high diastolic Cai-voltage coupling gains). Methods and Results: We simultaneously mapped Cai and Vm on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca i elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 μmol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 μmol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Cai-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). IK1 suppression with CsCl (5 mmol/L, n=3), BaCl2 (3 μmol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca i-voltage coupling gain and enabled epicardium to also generate TAs. Conclusions: Higher diastolic Cai-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. IK1 is a major factor that determines the diastolic Ca i-voltage coupling gain.

Original languageEnglish
Pages (from-to)399-408
Number of pages10
JournalCirculation Research
Volume106
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

Fingerprint

Purkinje Fibers
Intracellular Membranes
Cardiac Arrhythmias
Calcium
Isoproterenol
Ryanodine
Pericardium
Sarcoplasmic Reticulum
Ventricular Fibrillation
Ventricular Tachycardia
Potassium
Rabbits
Membranes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Maruyama, Mitsunori ; Joung, Boyoung ; Tang, Liang ; Shinohara, Tetsuji ; On, Young Keun ; Han, Seongwook ; Choi, Eue Keun ; Kim, Dae Hyeok ; Shen, Mark J. ; Weiss, James N. ; Lin, Shien Fong ; Chen, Peng Sheng. / Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias : Role of purkinje fibers and triggered activity. In: Circulation Research. 2010 ; Vol. 106, No. 2. pp. 399-408.
@article{a326fbbbb43f41d19e5fd04e4e9de17c,
title = "Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: Role of purkinje fibers and triggered activity",
abstract = "Rationale: Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome. Objective: We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (Vm) to elevated intracellular calcium (Cai) (high diastolic Cai-voltage coupling gains). Methods and Results: We simultaneously mapped Cai and Vm on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca i elevation (SCaE) was noted after defibrillation in 32{\%} of ventricular tachycardia/ventricular fibrillation at baseline and in 81{\%} during isoproterenol infusion (0.01 to 1 μmol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 μmol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Cai-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). IK1 suppression with CsCl (5 mmol/L, n=3), BaCl2 (3 μmol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca i-voltage coupling gain and enabled epicardium to also generate TAs. Conclusions: Higher diastolic Cai-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. IK1 is a major factor that determines the diastolic Ca i-voltage coupling gain.",
author = "Mitsunori Maruyama and Boyoung Joung and Liang Tang and Tetsuji Shinohara and On, {Young Keun} and Seongwook Han and Choi, {Eue Keun} and Kim, {Dae Hyeok} and Shen, {Mark J.} and Weiss, {James N.} and Lin, {Shien Fong} and Chen, {Peng Sheng}",
year = "2010",
month = "2",
day = "1",
doi = "10.1161/CIRCRESAHA.109.211292",
language = "English",
volume = "106",
pages = "399--408",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

Maruyama, M, Joung, B, Tang, L, Shinohara, T, On, YK, Han, S, Choi, EK, Kim, DH, Shen, MJ, Weiss, JN, Lin, SF & Chen, PS 2010, 'Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: Role of purkinje fibers and triggered activity', Circulation Research, vol. 106, no. 2, pp. 399-408. https://doi.org/10.1161/CIRCRESAHA.109.211292

Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias : Role of purkinje fibers and triggered activity. / Maruyama, Mitsunori; Joung, Boyoung; Tang, Liang; Shinohara, Tetsuji; On, Young Keun; Han, Seongwook; Choi, Eue Keun; Kim, Dae Hyeok; Shen, Mark J.; Weiss, James N.; Lin, Shien Fong; Chen, Peng Sheng.

In: Circulation Research, Vol. 106, No. 2, 01.02.2010, p. 399-408.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias

T2 - Role of purkinje fibers and triggered activity

AU - Maruyama, Mitsunori

AU - Joung, Boyoung

AU - Tang, Liang

AU - Shinohara, Tetsuji

AU - On, Young Keun

AU - Han, Seongwook

AU - Choi, Eue Keun

AU - Kim, Dae Hyeok

AU - Shen, Mark J.

AU - Weiss, James N.

AU - Lin, Shien Fong

AU - Chen, Peng Sheng

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Rationale: Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome. Objective: We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (Vm) to elevated intracellular calcium (Cai) (high diastolic Cai-voltage coupling gains). Methods and Results: We simultaneously mapped Cai and Vm on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca i elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 μmol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 μmol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Cai-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). IK1 suppression with CsCl (5 mmol/L, n=3), BaCl2 (3 μmol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca i-voltage coupling gain and enabled epicardium to also generate TAs. Conclusions: Higher diastolic Cai-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. IK1 is a major factor that determines the diastolic Ca i-voltage coupling gain.

AB - Rationale: Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome. Objective: We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (Vm) to elevated intracellular calcium (Cai) (high diastolic Cai-voltage coupling gains). Methods and Results: We simultaneously mapped Cai and Vm on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca i elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 μmol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 μmol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Cai-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). IK1 suppression with CsCl (5 mmol/L, n=3), BaCl2 (3 μmol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca i-voltage coupling gain and enabled epicardium to also generate TAs. Conclusions: Higher diastolic Cai-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. IK1 is a major factor that determines the diastolic Ca i-voltage coupling gain.

UR - http://www.scopus.com/inward/record.url?scp=76349122416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76349122416&partnerID=8YFLogxK

U2 - 10.1161/CIRCRESAHA.109.211292

DO - 10.1161/CIRCRESAHA.109.211292

M3 - Article

C2 - 19926871

AN - SCOPUS:76349122416

VL - 106

SP - 399

EP - 408

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 2

ER -