Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia

Yen Bin Liu, Yuan Teh Lee, Hui Nam Pak, Shien-Fong Lin, Michael C. Fishbein, Lan S. Chen, C. Noel Bairey Merz, Peng Sheng Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Background: Significant cardiac neural and electrophysiologic remodeling occurs with hypercholesterolemia (HC). Whether simvastatin can reverse HC-induced remodeling is unclear. Objective: The purpose of this study was to determine the mechanisms underlying the antiarrhythmic effects of statins. Methods: Rabbits (N = 38) were fed HC chow (HC), standard chow (Control), HC chow followed by standard chow (Withdrawal), or HC chow and simvastatin (Statin) for 8 weeks. The hearts then were Langendorff-perfused for electrophysiologic studies. Nerves were identified by immunostaining of growth-associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Action potential duration (APD) restitution in normal hearts with (N = 5) and without (N = 5) simvastatin therapy also was studied. Results: Serum cholesterol levels (mg/dL) were 1,855 ± 533 in HC, 50 ± 21 in Control, 570 ± 115 in Withdrawal, and 873 ± 112 in Statin groups (P <.001). Compared with HC (16,700 ± 5,342; 12,200 ± 3,878 μm2/mm2), the Statin group had significantly reduced GAP43-positive (10,289 ± 3,393 μm2/mm2, P = .03) and TH-positive (7,685 ± 2,959 μm2/mm2, P = .04) nerve density, respectively. APD was longer in HC rabbits than in controls (192 ± 20 ms vs 174 ± 17 ms; P <.03). Withdrawal and Statin groups had less APD prolongation than HC group. Statin group has less repolarization heterogeneity than HC group (P <.01). Statin therapy flattened the slope of APD restitution in normal hearts. Ventricular fibrillation was either induced or occurred spontaneously in 79% of hearts in HC, 20% in Control, and 66% in Withdrawal groups. However, there was no VF in hearts of Statin group (P <.001). Conclusion: Simvastatin significantly reduced vulnerability to ventricular fibrillation via the mechanism of reduction of HC-induced neural and electrophysiologic remodeling.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalHeart Rhythm
Volume6
Issue number1
DOIs
StatePublished - 1 Jan 2009

Keywords

  • Arrhythmia
  • Lipids
  • Nervous system
  • Pathology
  • Statin

Fingerprint Dive into the research topics of 'Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia'. Together they form a unique fingerprint.

  • Cite this

    Liu, Y. B., Lee, Y. T., Pak, H. N., Lin, S-F., Fishbein, M. C., Chen, L. S., Merz, C. N. B., & Chen, P. S. (2009). Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia. Heart Rhythm, 6(1), 69-75. https://doi.org/10.1016/j.hrthm.2008.10.004