Therapeutic Efficacy of Alpha-Lipoic Acid against Acute Myocardial Infarction and Chronic Left Ventricular Remodeling in Mice

Abstract

Background. We hypothesized that daily administration of a potent antioxidant (α-lipoic acid: ALA) would protect the heart against both acute myocardial infarction (AMI) and left ventricular remodeling (LVR) post-AMI. Methods and Results. Two separate studies were conducted. In the AMI study, C57Bl/6 mice were fed ALA daily for 7 d prior to a 45-minute occlusion of the left coronary artery (LCA). Mean infarct size in control mice (fed water) was 60 ± 2%. Mean infarct size in ALA-treated mice was 42 ± 3% in the 15 mg/kg·d group and 39 ± 3% in the 75 mg/kg·d group (both P<0.05 vs. control). In the LVR study, AMI increased LV end-systolic volume (LVESV) and reduced LV ejection fraction (LVEF) to a similar extent in both groups when assessed by cardiac MRI 1 day after a 2-hour LCA occlusion. Treatment with ALA (75 mg/kg·d) or H2O was initiated 1 day post-AMI and continued until study’s end. Both LVESV and LVEF in ALA-treated mice were significantly improved over control when assessed 28 or 56 days post-AMI. Furthermore, the survival rate in ALA-treated mice was 63% better than in control mice by 56 days post-AMI. Conclusions. Daily oral ingestion of ALA not only protects mice against AMI but also attenuates LVR and preserves contractile function in the months that follow.