Clarithromycin attenuates myocardial ischemia-reperfusion injury.
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.
Nakajima
Takuya
T
Tokyo Medical and Dental University, Department of Cardiovascular Medicine, Japan.
Hishikari
Keiichi
K
Ogawa
Masahito
M
Watanabe
Ryo
R
Suzuki
Jun-ichi
J
Nagashima
Ayako
A
Masumura
Mayumi
M
Takayama
Kiyoshi
K
Hirata
Yasunobu
Y
Nagai
Ryozo
R
Isobe
Mitsuaki
M
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
D061965:Matrix Metalloproteinase Inhibitors; D011500:Protein Synthesis Inhibitors; D017291:Clarithromycin