© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Beneficial effects of adrenomedullin on left ventricular remodeling after myocardial infarction in rats
aFirst Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
bFirst Department of Pathology, Miyazaki Medical College, Kihara, Kiyotake, Miyazaki 889-1692, Japan
cDepartment of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan
* Corresponding author. Tel.: +81-985-850-872; fax: +81-985-856-596. keto{at}post.miyazaki-med.ac.jp
Objective: We previously reported that plasma adrenomedullin (AM) levels increase in patients with acute myocardial infarction (MI) and AM inhibits growth of rat cardiac myocytes and fibroblasts. The aim of this study was to examine the effects of long-term administration of AM on left ventricular (LV) remodeling, hemodynamic and hormonal parameters in a rat model of MI. Methods: Rats with MI induced by left coronary ligation were intravenously infused with 1.0 µg/h of recombinant human AM or saline by osmotic mini-pump. After infusion for 4 weeks, hemodynamic and hormonal studies were performed, and the myocyte size and collagen volume in non-infarct LV area were quantified morphometrically. Results: When compared with the MI rats infused with saline, continuous infusion of AM reduced the heart weight/body weight (4.4±0.2 vs. 3.6±0.1 g/kg, P<0.01), myocyte size (922±23 vs. 868±10 µm2, P<0.05) and collagen volume fraction of non-infarct LV area (7.6±0.8 vs. 4.8±0.5%, P<0.05), without affecting the infarct size. The AM infusion had no significant effect on the arterial pressure, but decreased the LV end-diastolic pressure (8.8±1.8 vs. 4.4±0.5 mmHg, P<0.05) in the MI rats. The plasma level of endogenous rat AM in the MI rats infused with human AM was reduced by 27% (P<0.05), with a slight reduction of plasma atrial natriuretic peptide, compared with the control. Conclusions: Continuous administration of AM had beneficial effects on LV remodeling and hemodynamics in MI rats, suggesting the possibility that this peptide could be a useful therapeutic tool for acute MI.
KEYWORDS Fibrosis; Heart failure; Infarction; Remodeling; Vasoactive agents
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