Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits

Yen Bin Liu, Chau Chung Wu, Long Sheng Lu, Ming Jai Su, Chii Wann Lin, Shien Fong Lin, Lan S. Chen, Michael C. Fishbein, Peng Sheng Chen, Yuan Teh Lee

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n = 10) or standard (S, n = 10) chows for 12 weeks (protocol 1), and with HC (n = 12) or S (n = 10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097 ± 288 mg/dL in HC group and 59 ± 9 mg/dL in S group for protocol 1 and were 1889 ± 577 mg/dL in HC group and 50 ± 21 mg/dL in S group for protocol 2. Density of growth-associated protein 43- (GAP43) and tyrosine hydroxylase- (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0 ± 3.1 versus 9.1 ± 3.4 pA/pF; P <0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2 = 0.94; P <0.001) and TH (R2 = 0.91; P <0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.

Original languageEnglish
Pages (from-to)1145-1152
Number of pages8
JournalCirculation Research
Volume92
Issue number10
DOIs
Publication statusPublished - May 30 2003
Externally publishedYes

Fingerprint

Atrial Remodeling
Ventricular Fibrillation
Hypercholesterolemia
Rabbits
Cholesterol
GAP-43 Protein
Tyrosine 3-Monooxygenase
Action Potentials
Serum
Calcium

Keywords

  • Arrhythmia
  • Ion channels
  • Lipids
  • Nervous system
  • Pathology

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits. / Liu, Yen Bin; Wu, Chau Chung; Lu, Long Sheng; Su, Ming Jai; Lin, Chii Wann; Lin, Shien Fong; Chen, Lan S.; Fishbein, Michael C.; Chen, Peng Sheng; Lee, Yuan Teh.

In: Circulation Research, Vol. 92, No. 10, 30.05.2003, p. 1145-1152.

Research output: Contribution to journalArticle

Liu, Yen Bin ; Wu, Chau Chung ; Lu, Long Sheng ; Su, Ming Jai ; Lin, Chii Wann ; Lin, Shien Fong ; Chen, Lan S. ; Fishbein, Michael C. ; Chen, Peng Sheng ; Lee, Yuan Teh. / Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits. In: Circulation Research. 2003 ; Vol. 92, No. 10. pp. 1145-1152.
@article{493c548b93ed441ea58e3bcc243658d8,
title = "Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits",
abstract = "Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n = 10) or standard (S, n = 10) chows for 12 weeks (protocol 1), and with HC (n = 12) or S (n = 10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097 ± 288 mg/dL in HC group and 59 ± 9 mg/dL in S group for protocol 1 and were 1889 ± 577 mg/dL in HC group and 50 ± 21 mg/dL in S group for protocol 2. Density of growth-associated protein 43- (GAP43) and tyrosine hydroxylase- (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0 ± 3.1 versus 9.1 ± 3.4 pA/pF; P <0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2 = 0.94; P <0.001) and TH (R2 = 0.91; P <0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.",
keywords = "Arrhythmia, Ion channels, Lipids, Nervous system, Pathology",
author = "Liu, {Yen Bin} and Wu, {Chau Chung} and Lu, {Long Sheng} and Su, {Ming Jai} and Lin, {Chii Wann} and Lin, {Shien Fong} and Chen, {Lan S.} and Fishbein, {Michael C.} and Chen, {Peng Sheng} and Lee, {Yuan Teh}",
year = "2003",
month = "5",
day = "30",
doi = "10.1161/01.RES.0000072999.51484.92",
language = "English",
volume = "92",
pages = "1145--1152",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits

AU - Liu, Yen Bin

AU - Wu, Chau Chung

AU - Lu, Long Sheng

AU - Su, Ming Jai

AU - Lin, Chii Wann

AU - Lin, Shien Fong

AU - Chen, Lan S.

AU - Fishbein, Michael C.

AU - Chen, Peng Sheng

AU - Lee, Yuan Teh

PY - 2003/5/30

Y1 - 2003/5/30

N2 - Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n = 10) or standard (S, n = 10) chows for 12 weeks (protocol 1), and with HC (n = 12) or S (n = 10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097 ± 288 mg/dL in HC group and 59 ± 9 mg/dL in S group for protocol 1 and were 1889 ± 577 mg/dL in HC group and 50 ± 21 mg/dL in S group for protocol 2. Density of growth-associated protein 43- (GAP43) and tyrosine hydroxylase- (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0 ± 3.1 versus 9.1 ± 3.4 pA/pF; P <0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2 = 0.94; P <0.001) and TH (R2 = 0.91; P <0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.

AB - Whether hypercholesterolemia (HC) can induce proarrhythmic neural and electrophysiological remodeling is unclear. We fed rabbits with either high cholesterol (HC, n = 10) or standard (S, n = 10) chows for 12 weeks (protocol 1), and with HC (n = 12) or S (n = 10) chows for 8 weeks (protocol 2). In protocol 3, 10 rabbits were fed with various protocols to observe the effects of different serum cholesterol levels. Results showed that the serum cholesterol levels were 2097 ± 288 mg/dL in HC group and 59 ± 9 mg/dL in S group for protocol 1 and were 1889 ± 577 mg/dL in HC group and 50 ± 21 mg/dL in S group for protocol 2. Density of growth-associated protein 43- (GAP43) and tyrosine hydroxylase- (TH) positive nerves in the heart was significantly higher in HC than S in protocol 1. Compared with S, HC rabbits had longer QTc intervals, more QTc dispersion, longer action potential duration, increased heterogeneity of repolarization and higher peak calcium current (ICa) density (14.0 ± 3.1 versus 9.1 ± 3.4 pA/pF; P <0.01) in protocol 1 and 2. Ventricular fibrillation was either induced or occurred spontaneously in 9/12 of hearts of HC group and 2/10 of hearts in S group in protocol 2. Protocol 3 showed a strong correlation between serum cholesterol level and nerve density for GAP43 (R2 = 0.94; P <0.001) and TH (R2 = 0.91; P <0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased ICa. The neural and electrophysiological remodeling was associated with prolonged action potential duration, longer QTc intervals, increased repolarization dispersion, and increased ventricular vulnerability to fibrillation.

KW - Arrhythmia

KW - Ion channels

KW - Lipids

KW - Nervous system

KW - Pathology

UR - http://www.scopus.com/inward/record.url?scp=0038285658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038285658&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000072999.51484.92

DO - 10.1161/01.RES.0000072999.51484.92

M3 - Article

VL - 92

SP - 1145

EP - 1152

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 10

ER -