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*

*Corresponding author for this work

Research output: Contribution to journalArticle

106 Scopus citations

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 (I Ca ) 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 (R 2 = 0.94; P < 0.001) and TH (R 2 = 0.91; P < 0.001). We conclude that HC resulted in nerve sprouting, sympathetic hyperinnervation, and increased I Ca . 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
StatePublished - 30 May 2003

Keywords

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

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