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.
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.


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.
Department of Cardivascular Medicine, Nagahama City Hospital, Nagahama, Japan.
Masaru
M
Hayashi
Takayoshi
T
Tsutamoto
Atsuyuki
A
Wada
Takashi
T
Tsutsui
Chitose
C
Ishii
Keijin
K
Ohno
Masanori
M
Fujii
Atsushi
A
Taniguchi
Tomokazu
T
Hamatani
Yoshitaka
Y
Nozato
Ken
K
Kataoka
Naoki
N
Morigami
Masato
M
Ohnishi
Masahiko
M
Kinoshita
Minoru
M
Horie
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000096:biosynthesis*; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D013148:Spironolactone; D003094:Collagen