title: Infusion of adrenomedullin improves acute myocarditis via attenuation of myocardial inflammation and edema.
abstract: 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.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Bobby
authors.initials: B
authors.lastname: Yanagawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
mesh_terms: 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
chemical_list: 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