Cardioprotective effects of glucose and insulin administration while maintaining normoglycemia (GIN therapy) in patients undergoing coronary artery bypass grafting.

Abstract

Coronary artery bypass grafting (CABG) is complicated by ischemia-reperfusion injury jeopardizing myocyte survival. The aim of the study was to investigate whether glucose and insulin administration, while maintaining normoglycemia (GIN therapy) using a hyperinsulinemic-normoglycemic clamp technique, is cardioprotective in patients undergoing CABG. We conducted a randomized controlled trial at a tertiary care university teaching hospital. We studied 99 patients undergoing elective CABG. Patients were randomly assigned to receive either GIN from the beginning of surgery until 24 h after CABG (GIN, n = 49) or standard metabolic care (control, n = 50). We measured plasma concentrations of cardiac troponin I and free fatty acids, cardiac function as assessed by transesophageal echocardiography, glycogen content, glycogen synthase activity, and the expression of AMP-activated protein kinase (AMPK) and protein kinase B (AKT) in cardiomyocytes. Patients receiving GIN therapy showed an attenuated release of cardiac troponin I (P < 0.05) and improved myocardial function (P < 0.05). Systemic free fatty acid concentrations were suppressed (P < 0.05), whereas intracellular glycogen content and glycogen synthase activity were not altered. The AMPK activity remained unchanged during ischemia in the GIN group, whereas it increased in the control group (P < 0.05). Enhanced AKT phosphorylation before ischemia was observed (P < 0.05) in the presence of GIN. However, there was no evidence for AKT-dependent AMPK inhibition. GIN therapy protects the myocardium and inhibits ischemia-induced AMPK activation.