Abstract 3891: Insulin-titrated Maintenance of Normoglycemia and Glycemia-independent cardioprotection in Ischemic/Reperfused Dogs
Objective This study was designed to identify the role of glycemia-independent action of insulin in myocardial ischemia/reperfusion (MI/R) and investigate the relative contribution of blood glucose control versus glycemia-independent effects in insulin-elicited cardioprotection.
Methods Anesthetized dogs were subjected to left anterior descending coronary artery occlusion for 30 min followed by 4 h of reperfusion, and randomized into four groups (n=8/group ): two normoglycemic (3.9 – 6.1 mmol/l) groups and two hyperglycemic (10.0 –16.7mmol/l) groups with either normal (10 – 40 mU/l) or elevated (100 –200 mU/l) insulin levels. Target glucose and insulin levels were achieved by peripancreatic vessels ligation, GIK application and 50% glucose infusion.
Results High insulin benefited cardiac output and ventricular contractility independently of blood glucose levels whereas the improved diastolic function required both elevated insulin and concomitant high blood glucose (n=8, P<0.05). Reduced infarct size and MI/R-induced cardiomyocyte apoptosis (Caspase 3 activation and TUNEL staining) were attributable to insulin application only when blood glucose was maintained normal, while coronary endothelial apoptosis were rescued in a glycemia-independent manner, comparing both high insulin groups with their corresponding normal insulin groups (n=8, P<0.01). Furthermore, myocardial injury could be partially alleviated by insulin with either glucose levels as evidenced by decreased plasma contents of CK-MB, while cTnT declined only when normoglycemia was maintained and Myoglobin showed no statistical difference between groups with different insulin levels (n=8, P<0.05). Besides, myocardial infiltrated leukocytes and myeloperoxidase content were consistently decreased by insulin under normoglycemia but increased in the presence of hyperglycemia (n=8, P<0.05).
Conclusion In addition to glycemia control, insulin exerts direct glycemia-independent actions on promoting post-ischemic functional recovery, alleviating myocardial injury and coronary endothelial apoptosis, and interfering in MI/R-associated inflammation, all of which may contribute to insulin-elicited protection for the I/R heart.