title: Clarithromycin attenuates myocardial ischemia-reperfusion injury.
abstract: BACKGROUND
  MMP activity is upregulated in the heart after myocardial ischemia reperfusion, and its activation contributes to the changes in left ventricular (LV) dysfunction. A major macrolide antibiotic, clarithromycin has many biological functions including MMP regulation. However, little is known about the effect of clarithromycin in myocardial reperfusion injury via MMPs. Our objective was to clarify the role of MMPs regulated by clarithromycin in the progression of myocardial reperfusion injury.
  
  
  METHODS
  We administered clarithromycin to rats with ischemia-reperfusion injury twice a day for 7 days before and 14 days after reperfusion.
  
  
  RESULTS
  Clarithromycin resulted in a significant reduction of the infarction area:area at risk ratio and preserved fractional shortening ratio after 14 days of reperfusion. Immunohistochemical analysis revealed that macrophages were the primary cellular source of MMPs. Fewer macrophages were detected in the ischemic area of the hearts following ischemia reperfusion in the clarithromycin-treated group compared with the vehicle-treated group. Although ischemia-reperfusion injury resulted in LV fibrosis with increasing MMP activities, clarithromycin significantly reduced these changes.
  
  
  CONCLUSIONS
  Clarithromycin is effective for attenuating myocardial ischemia-reperfusion injury by suppressing MMPs.
authors.affiliation: Tokyo Medical and Dental University, Department of Cardiovascular Medicine, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakajima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hishikari
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Ayako
authors.initials: A
authors.lastname: Nagashima
authors.forename: Mayumi
authors.initials: M
authors.lastname: Masumura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takayama
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D017291:Clarithromycin / Q000494:pharmacology*; D005355:Fibrosis / Q000503:physiopathology / Q000517:prevention & control; D008264:Macrophages / Q000201:enzymology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D009203:Myocardial Infarction / Q000201:enzymology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D011500:Protein Synthesis Inhibitors; D017291:Clarithromycin