2009 Volume 60 Issue 1-4 Pages 45-53
Structural remodeling occurs in diverse heart diseases and affects their clinical courses. We reported that amiodarone suppresses both electrical and structural remodeling in a canine persistent atrial fibrillation model. As a mechanism for amiodarone's effect on structural remodeling, we suggested its inhibitory effect on matrix metalloproteinase (MMP) activity. To elucidate it, we investigated the effect of amiodarone on MMP activity in a rat myocardial infarction model created by left coronary artery (LCA) ligation. Adult Sprague-Dawley rats were divided into 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 weeks before and for 4 weeks after operation. The hearts were excised at 4 weeks after operation. MMP-2 activity was measured by gelatin zymography. At 4 weeks after surgery, left ventricular fractional shortening was decreased in MI but not in MI+AMD rats. There was no difference 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 inhibitory effect on MMP activity. This may be related to the improvement left ventricular function in MI rats.
