title: Cardioprotective effects of glucose and insulin administration while maintaining normoglycemia (GIN therapy) in patients undergoing coronary artery bypass grafting.
abstract: BACKGROUND
  Coronary artery bypass grafting (CABG) is complicated by ischemia-reperfusion injury jeopardizing myocyte survival.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  We conducted a randomized controlled trial at a tertiary care university teaching hospital.
  
  
  METHODS
  We studied 99 patients undergoing elective CABG.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  GIN therapy protects the myocardium and inhibits ischemia-induced AMPK activation.
authors.affiliation: Department of Anesthesia, McGill University, Montreal, Canada H3A 1A1.
authors.forename: George
authors.initials: G
authors.lastname: Carvalho
authors.forename: Patricia
authors.initials: P
authors.lastname: Pelletier
authors.forename: Turki
authors.initials: T
authors.lastname: Albacker
authors.forename: Kevin
authors.initials: K
authors.lastname: Lachapelle
authors.forename: Denis R
authors.initials: DR
authors.lastname: Joanisse
authors.forename: Roupen
authors.initials: R
authors.lastname: Hatzakorzian
authors.forename: Ralph
authors.initials: R
authors.lastname: Lattermann
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: André
authors.initials: A
authors.lastname: Marette
authors.forename: Thomas
authors.initials: T
authors.lastname: Schricker
mesh_terms: D000368:Aged; D000758:Anesthesia; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism*; D002316:Cardiotonic Agents; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004452:Echocardiography; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009204:Myocardial Revascularization; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control; D016896:Treatment Outcome; D019209:Troponin C / Q000097:blood
chemical_list: D001786:Blood Glucose; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D019209:Troponin C; D006003:Glycogen; D006006:Glycogen Synthase; D051058:Oncogene Protein v-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose