| Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia. | |
| | |
MedLine Citation:
|
PMID: 19121803 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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 |
Related Documents
:
|
2816903 - Determinants of high density lipoprotein cholesterol in middle-aged seventh-day adventi... 12864743 - Fate of fatty acids at rest and during exercise: regulatory mechanisms. 3330443 - Exercise-induced renal dysfunction studied by 99mtc-dtpa in hypertensives and normotens... |
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: 2011-05-09 |
Medline Journal Info:
|
Nlm Unique ID: 101200317 Medline TA: Heart Rhythm Country: United States |
Other Details:
|
Languages: eng Pagination: 69-75 Citation Subset: IM |
Affiliation:
|
Department of Internal Medicine, Division of Cardiology, National Taiwan University Hospital and National Taiwan University School of Medicine, UCLA, Los Angeles, California, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cholesterol / blood* Electrophysiologic Techniques, Cardiac Female 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 Immunohistochemistry Rabbits Simvastatin / therapeutic use* Treatment Outcome Ventricular Fibrillation / physiopathology, prevention & control Ventricular Remodeling / drug effects*, physiology |
| Grant Support | |
ID/Acronym/Agency:
|
HL66389/HL/NHLBI NIH HHS; HL71140/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 HL071140-05A1/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 HL078932-01/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 |
| Chemical | |
Reg. No./Substance:
|
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 57-88-5/Cholesterol; 79902-63-9/Simvastatin |
| Comments/Corrections | |
Comment In:
|
Heart Rhythm. 2009 Jan;6(1):76-7
[PMID:
19121804
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Do abandoned leads pose risk to implantable cardioverter-defibrillator patients?
Next Document: Diacylglycerol kinase zeta inhibits G(alpha)q-induced atrial remodeling in transgenic mice.