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(Circulation. 2004;110:426-431.)
© 2004 American Heart Association, Inc.

Original Articles

Adrenomedullin Administration Immediately After Myocardial Infarction Ameliorates Progression of Heart Failure in Rats

Ryosai Nakamura, MD; Johji Kato, MD, PhD; Kazuo Kitamura, MD, PhD; Hisamitsu Onitsuka, MD, PhD; Takuroh Imamura, MD, PhD; Yuanning Cao, MD; Kousuke Marutsuka, MD, PhD; Yujiro Asada, MD, PhD; Kenji Kangawa, PhD; Tanenao Eto, MD, PhD

From the First Department of Internal Medicine (R.N., J.K., K. Kitamura, H.O., T.I., Y.C., T.E.) and First Department of Pathology (K.M., Y.A.), Miyazaki Medical College, University of Miyazaki, Miyazaki, and Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka (K. Kangawa), Japan.

Correspondence to Tanenao Eto, MD, PhD, First Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan. E-mail keto{at}med.miyazaki-u.ac.jp

Received November 18, 2003; de novo received January 14, 2004; revision received March 23, 2004; accepted March 26, 2004.

Background— Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats.

Methods and Results— Rats were infused with 1.0 µg/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P<0.05) and body weight gain (32%; P<0.01) and reduced heart weight (–28%; P<0.01), lung weight (–26%; P<0.01), left ventricular (LV) end-diastolic pressure (11.4±2.0 versus 4.0±0.6 mm Hg, mean± SEM; P<0.01), collagen volume fraction of noninfarcted LV (–39%; P<0.05), and plasma levels of endogenous rat AM (–38%; P<0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI but significantly reduced urinary excretion of isoprostane (–61%; P<0.01) and noninfarcted LV mRNA levels of ACE (–31%; P<0.05) and p22-phox (–30%; P<0.05).

Conclusions— AM administration during the early period of MI improved the survival and ameliorated progression of LV remodeling and heart failure. This beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA expression in noninfarcted LV in the AM infusion period.

Key Words: adrenomedullin • heart failure • myocardial infarction • remodeling

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