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Cardiovascular Research 2007 76(1):110-118; doi:10.1016/j.cardiores.2007.05.027
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Copyright © 2007, European Society of Cardiology

Infusion of adrenomedullin improves acute myocarditis via attenuation of myocardial inflammation and edema

Bobby Yanagawaa,1, Masaharu Kataokaa,1, Shunsuke Ohnishia,*,1, Makoto Kodamab, Koichi Tanakaa, Yoshinori Miyaharaa, Hatsue Ishibashi-Uedac, Yoshifusa Aizawab, Kenji Kangawad and Noritoshi Nagayaa,*

aDepartment of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan
bDivision of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
cDepartment of Pathology, National Cardiovascular Center, Osaka, Japan
dDepartment of Biochemistry, National Cardiovascular Center Research Institute, Osaka, Japan

*Corresponding authors. Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. Tel.: +81 6 6833 5012; fax: +81 6 6835 5496. sonishi{at}ri.ncvc.go.jp nnagaya{at}ri.ncvc.go.jp

Objective Our aim was to assess whether adrenomedullin (AM), a potent vasodilator peptide with a variety of cardioprotective effects, has a therapeutic potential for the treatment of acute myocarditis in a rat model.

Methods One week after myosin injection, rats received a continuous infusion of AM or vehicle for 2 weeks, and pathological and physiological investigations were performed.

Results AM treatment significantly reduced the infiltration of inflammatory cells in myocarditic hearts, and decreased the expressions of macrophage chemoattractant protein-1, matrix metalloproteinase-2 and transforming growth factor-β. Myocardial edema indicated by increased heart weight to body weight ratio and wall thickness was attenuated by AM infusion (5.7±0.5 vs. 6.5±0.4 g/kg, and 1.9±0.3 vs. 2.8±0.5 mm, respectively). Infusion of AM significantly improved left ventricular maximum dP/dt and fractional shortening of myocarditic hearts (4203±640 vs. 3450±607 mm Hg/s, and 21.3±4.1 vs. 14.7±5.1%, respectively).

Conclusion Infusion of AM improved cardiac function and pathological findings in a rat model of acute myocarditis. Thus, infusion of AM may be a potent therapeutic strategy for acute myocarditis.

KEYWORDS Autoimmune myocarditis; Adrenomedullin; Angiogenesis; Inflammation

1 These authors contributed equally to this work.


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