Document Detail


Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction.
MedLine Citation:
PMID:  12732605     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. METHODS AND RESULTS: To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non-MRA (n=69) groups after revascularization. All patients were administered angiotensin-converting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0+/-0.6% to 53.2+/-0.8% versus 46.5+/-0.8% to 51.0+/-0.8%, Pinteraction=0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5+/-1.0 to 90.6+/-2.4 versus 87.5+/-1.3 to 106.8+/-3.5 mL/m2, Pinteraction=0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (Pinteraction=0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (Pinteraction=0.002). CONCLUSIONS: These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis.
Authors:
Masaru Hayashi; Takayoshi Tsutamoto; Atsuyuki Wada; Takashi Tsutsui; Chitose Ishii; Keijin Ohno; Masanori Fujii; Atsushi Taniguchi; Tomokazu Hamatani; Yoshitaka Nozato; Ken Kataoka; Naoki Morigami; Masato Ohnishi; Masahiko Kinoshita; Minoru Horie
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial     Date:  2003-05-05
Journal Detail:
Title:  Circulation     Volume:  107     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-06-02     Completed Date:  2003-06-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2559-65     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardivascular Medicine, Nagahama City Hospital, Nagahama, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Biological Markers / analysis
Collagen / biosynthesis*
Drug Therapy, Combination
Female
Hemodynamics / drug effects
Humans
Male
Middle Aged
Multivariate Analysis
Myocardial Infarction / drug therapy*,  physiopathology
Myocardium / metabolism*
Peptide Fragments / blood
Procollagen / blood
Prospective Studies
Receptors, Mineralocorticoid / antagonists & inhibitors*
Spironolactone / therapeutic use*
Stroke Volume / drug effects
Ventricular Remodeling / drug effects*
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Biological Markers; 0/Peptide Fragments; 0/Procollagen; 0/Receptors, Mineralocorticoid; 0/procollagen Type III-N-terminal peptide; 52-01-7/Spironolactone; 9007-34-5/Collagen
Comments/Corrections
Comment In:
Circulation. 2003 May 27;107(20):2525-7   [PMID:  12777314 ]

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


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