Document Detail


Differential effects of statins (pravastatin or simvastatin) on ventricular ectopic complexes: Galpha(i2), a possible molecular marker for ventricular irritability.
MedLine Citation:
PMID:  20381662     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retrospective studies suggest that statins might exert an antiarrhythmic effect on the heart. The mechanism of this effect is unclear. Parasympathetic stimulation of the heart has been shown to protect against ventricular arrhythmias. The goal of this study was to determine the effect of statins on ventricular arrhythmias and its correlation with changes in parasympathetic responsiveness and Galpha(i2) expression. Patients were randomized to pravastatin and simvastatin in a double-blind crossover design. Ventricular arrhythmias were determined by analysis of 24-hour Holter recordings. Spectral RR interval analysis of Holter studies determined peak high-frequency power fraction, which reflects parasympathetic modulation of heart rate. Expression of Galpha(i2), a molecular component of the parasympathetic response pathway, was determined by Western blots of patients' lymphocytes. Pravastatin treatment decreased the incidence of ventricular premature complexes by 22.5 + or - 3.4% (n = 20, p <0.05), couplets, and runs of 3 to 6 beats of nonsustained ventricular tachycardia from 9.8 + or - 2.67 to 3.9 + or - 1.25 events/patient/24 hours (n = 12, p <0.05). Pravastatin increased peak high-frequency fraction by 29.8 + or - 4.3% (n = 33, p <0.001), while Galpha(i2) expression increased by 51.3 + or - 22.5% (n = 21, p <0.05). Effects of simvastatin on ventricular premature complexes and nonsustained ventricular tachycardia were not significant. Relative changes in couplets and nonsustained ventricular tachycardia in pravastatin-treated patients correlated negatively with changes in Galpha(i2) and high-frequency fraction (rho = -0.588 and rho = -0.763, respectively, n = 12, p <0.05). In conclusion, these data suggest that pravastatin might decrease cardiac irritability via an increase in parasympathetic responsiveness and that changes in Galpha(i2) expression might serve as a molecular marker for this effect, which might play a role in the molecular mechanism of the antiarrhythmic effect of statins.
Authors:
C Michael Welzig; Ho-Jin Park; Jack Naggar; Deborah Confalone; Joanne Rhofiry; Julie Shea; Richard H Karas; N A Mark Estes; Jonas B Galper
Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-02-20
Journal Detail:
Title:  The American journal of cardiology     Volume:  105     ISSN:  1879-1913     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-12     Completed Date:  2010-06-15     Revised Date:  2012-05-09    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1112-7     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Biological Markers / blood*
Blotting, Western
Cross-Over Studies
Densitometry
Dose-Response Relationship, Drug
Double-Blind Method
Electrocardiography, Ambulatory
Female
Follow-Up Studies
GTP-Binding Protein alpha Subunit, Gi2 / biosynthesis*,  blood
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*,  therapeutic use
Male
Middle Aged
Pravastatin / administration & dosage*,  therapeutic use
Prognosis
Retrospective Studies
Simvastatin / administration & dosage*,  therapeutic use
Treatment Outcome
Ventricular Premature Complexes / blood,  drug therapy*,  physiopathology
Grant Support
ID/Acronym/Agency:
R01 HL074876/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 79902-63-9/Simvastatin; 81093-37-0/Pravastatin; EC 3.6.5.1/GTP-Binding Protein alpha Subunit, Gi2

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