Document Detail

Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice: role of oxidative stress.
MedLine Citation:
PMID:  10969037     Owner:  NLM     Status:  MEDLINE    
Oxidative stress might play an important role in the progression of left ventricular (LV) remodeling and failure that occur after myocardial infarction (MI). We determined whether reactive oxygen species (ROS) are increased in the LV remodeling and failure in experimental MI with the use of electron spin resonance spectroscopy and whether the long-term administration of dimethylthiourea (DMTU), hydroxyl radical (.OH) scavenger, could attenuate these changes. We studied 3 groups of mice: sham-operated (sham), MI, and MI animals that received DMTU (MI+DMTU). Drugs were administered to the animals daily via intraperitoneal injection for 4 weeks.OH was increased in the noninfarcted myocardium from MI animals, which was abolished in MI+DMTU. Fractional shortening was depressed by 65%, LV chamber diameter was increased by 53%, and the thickness of noninfarcted myocardium was increased by 37% in MI. MI+DMTU animals had significantly better LV contractile function and smaller increases in LV chamber size and hypertrophy than MI animals. Changes in myocyte cross-sectional area determined with LV mid-free wall specimens were concordant with the wall thickness data. Collagen volume fraction of the noninfarcted myocardium showed significant increases in the MI, which were also attenuated with DMTU. Myocardial matrix metalloproteinase-2 activity, measured with gelatin zymography, was increased with MI after 7 and 28 days, which was attenuated in MI+DMTU. Thus, the attenuation of increased myocardial ROS and metalloproteinase activity with DMTU may contribute, at least in part, to its beneficial effects on LV remodeling and failure. Therapies designed to interfere with oxidative stress might be beneficial to prevent myocardial failure.
S Kinugawa; H Tsutsui; S Hayashidani; T Ide; N Suematsu; S Satoh; H Utsumi; A Takeshita
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation research     Volume:  87     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-09-27     Completed Date:  2000-09-27     Revised Date:  2008-01-22    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  392-8     Citation Subset:  IM    
Cardiovascular Medicine, Graduate School of Medical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Body Weight
Cyclic N-Oxides / chemistry
Electron Spin Resonance Spectroscopy
Free Radical Scavengers / therapeutic use*
Matrix Metalloproteinases / metabolism
Myocardial Infarction / drug therapy*,  physiopathology
Myocardium / enzymology,  pathology
Organ Size
Oxidative Stress*
Reactive Oxygen Species / metabolism
Spin Labels
Thiourea / analogs & derivatives*,  therapeutic use*
Ventricular Dysfunction, Left / physiopathology,  prevention & control*
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Reactive Oxygen Species; 0/Spin Labels; 2226-96-2/tempol; 61805-96-7/1,3-dimethylthiourea; 62-56-6/Thiourea; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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