Amiodarone Attenuates the Upregulated Matrix Metalloproteinase-2 Activity in a Rat Myocardial Infarction Model

概要

論文の詳細を見る
Structural remodeling occurs in diverse heart diseases and affects their clinical courses. We reportedthat amiodarone suppresses both electrical and structural remodeling in a canine persistent atrial fi brillation model.As a mechanism for amiodarone’s effect on structural remodeling, we suggested its inhibitory effect on matrixmetalloproteinase（ MMP） activity. To elucidate it, we investigated the eff ect of amiodarone on MMP activity in a ratmyocardial infarction model created by left coronary artery（ LCA） ligation. Adult Sprague-Dawley rats were dividedinto sham-operated （Sham）, sham-operated with amiodarone （Sham+AMD）, LCA-ligated without amiodarone （MI）and LCA-ligated with amiodarone rats （MI+AMD）. Amiodarone （20 mg/kg/day） was administered for 2 weeksbefore and for 4 weeks after operation. The hearts were excised at 4 weeks after operation. MMP-2 activity wasmeasured by gelatin zymography. At 4 weeks after surgery, left ventricular fractional shortening was decreased inMI but not in MI+AMD rats. There was no diff erence in the infarct size between MI and MI+AMD rats （P=NS）.As compared with Sham, MMP-2 activity was increased in MI （P<0.01）, but not in MI+AMD （P=NS versus Sham;P<0.05 versus MI）. MMP-2 activity was not increased in Sham+AMD（ P=NS）. Thus, amiodarone exerts an inhibitoryeff ect on MMP activity. This may be related to the improvement left ventricular function in MI rats.