Infusion of adrenomedullin improves acute myocarditis via attenuation of myocardial inflammation and edema.
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-beta. 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).


CONCLUSIONS
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.
Yanagawa
Bobby
B
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan.
Kataoka
Masaharu
M
Ohnishi
Shunsuke
S
Kodama
Makoto
M
Tanaka
Koichi
K
Miyahara
Yoshinori
Y
Ishibashi-Ueda
Hatsue
H
Aizawa
Yoshifusa
Y
Kangawa
Kenji
K
Nagaya
Noritoshi
N
D000208:Acute Disease; D053607:Adrenomedullin; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood; D004452:Echocardiography; D004487:Edema / Q000188:drug therapy / Q000276:immunology; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D009218:Myosins; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics
C507862:ADM protein, human; D015415:Biomarkers; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016212:Transforming Growth Factor beta; D053607:Adrenomedullin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009218:Myosins