Abstract 4741: Inhibiting Apoptosis Delays Postischemic Cardiac Dysfunction
Early Cardioprotection by Insulin Alleviates Chronic Adverse Remodeling and Improves Cardiac Function in Post-Ischemic Rat Hearts
Objectives: Insulin exerts significant anti-apoptotic effects in acute myocardial ischemia/reperfusion (MI/R). However, the contribution of insulin to the prolonged cardiac remodeling and function in the ischemic heart remains unclear. This study attempted to determine whether early insulin treatment influences prolonged post-ischemic cardiac structural and functional changes.
Methods: Adult male rats were subjected to left anterior descending coronary artery occlusion and were randomized to receive one of the following treatments: saline (4 ml/kg/h i.v. infusion beginning 10 min before ischemia and continuing for 2 h), insulin (60 U/L, i.v. followed by hypodermic injection of insulin (0.5 U/ml, 1ml/kg/d, daily) for 3 d after myocardial ischemia) or insulin plus wortmannin (15 μg/kg i.v. injection 15 min before insulin treatment).
Results: Insulin treatment significantly reduced infarct size (n=6, P<0.01), decreased plasma creatine kinase and lactate dehydro-genase activities, and decreased apoptosis index and caspase-3 activity (P<0.01) 24 h after ischemia. At the end of 4 wks after the ischemia surgery, MI rats receiving insulin treatment showed a smaller LV cavity and thicker systolic interventricular septum compared with those in the saline-treated animals (0.32±0.03 and 0.25±0.02 cm vs. 0.46±0.04 and 0.17±0.02 cm, respectively, n=12, P<0.05), and increased cardiac ejection fraction and LV fractional shortening (78.1%±3.9% and 42.6%±3.4% vs. 61.4%±5.1% and 29.6%±3.2%, respectively, P<0.05). Inhibition of insulin signaling with wortmannin not only blocked insulin’s anti-apoptotic effect, but also abolished the effects of insulin on cardiac structure and function.
Conclusion: These data indicate that early treatment with insulin not only exerts acute protection for ischemic heart but also retards the subsequent development of ischemic heart failure.