Document Detail

Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia.
MedLine Citation:
PMID:  19121803     Owner:  NLM     Status:  MEDLINE    
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 microm(2)/mm(2)), the Statin group had significantly reduced GAP43-positive (10,289 +/- 3,393 microm(2)/mm(2), P = .03) and TH-positive (7,685 +/- 2,959 microm(2)/mm(2), 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.
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
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-10-07
Journal Detail:
Title:  Heart rhythm : the official journal of the Heart Rhythm Society     Volume:  6     ISSN:  1556-3871     ISO Abbreviation:  Heart Rhythm     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-04-21     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101200317     Medline TA:  Heart Rhythm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  69-75     Citation Subset:  IM    
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MeSH Terms
Cholesterol / blood*
Electrophysiologic Techniques, Cardiac
Follow-Up Studies
Heart Conduction System / drug effects,  pathology*,  physiopathology
Heart Ventricles / drug effects,  innervation*,  physiopathology
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Hypercholesterolemia / blood,  drug therapy*,  physiopathology
Simvastatin / therapeutic use*
Treatment Outcome
Ventricular Fibrillation / physiopathology,  prevention & control
Ventricular Remodeling / drug effects*,  physiology
Grant Support
HL66389/HL/NHLBI NIH HHS; HL71140/HL/NHLBI NIH HHS; P01 HL078931/HL/NHLBI NIH HHS; P01 HL078931-01A10003/HL/NHLBI NIH HHS; P01 HL078931-020003/HL/NHLBI NIH HHS; P01 HL078931-030003/HL/NHLBI NIH HHS; P01 HL078931-040003/HL/NHLBI NIH HHS; P01 HL078931-050003/HL/NHLBI NIH HHS; P50 HL52319/HL/NHLBI NIH HHS; R01 HL071140/HL/NHLBI NIH HHS; R01 HL071140-05A1/HL/NHLBI NIH HHS; R01 HL071140-06/HL/NHLBI NIH HHS; R01 HL071140-06S1/HL/NHLBI NIH HHS; R01 HL071140-07/HL/NHLBI NIH HHS; R01 HL071140-07S1/HL/NHLBI NIH HHS; R01 HL078932/HL/NHLBI NIH HHS; R01 HL078932-01/HL/NHLBI NIH HHS; R01 HL078932-02/HL/NHLBI NIH HHS; R01 HL078932-03/HL/NHLBI NIH HHS; R01 HL078932-04/HL/NHLBI NIH HHS; R01 HL078932-05A1/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 97C5T2UQ7J/Cholesterol; AGG2FN16EV/Simvastatin
Comment In:
Heart Rhythm. 2009 Jan;6(1):76-7   [PMID:  19121804 ]

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