title: Tight glycemic control protects the myocardium and reduces inflammation in neonatal heart surgery.
abstract: BACKGROUND
  Neonatal cardiac surgery evokes hyperglycemia and a systemic inflammatory response. Hyperglycemia is associated with intensified inflammation and adverse outcome in critically ill children and in pediatric cardiac surgery. Recently we demonstrated that tight glycemic control (TGC) reduced morbidity and mortality of critically ill children. Experimental data suggest that insulin protects the myocardium in the setting of ischemia-reperfusion injury, but this benefit could be blunted by coinciding hyperglycemia. We hypothesized that insulin-titrated TGC, initiated prior to myocardial ischemia and reperfusion, protects the myocardium and attenuates the inflammatory response after neonatal cardiac surgery.
  
  
  METHODS
  This is a prospective randomized study at a university hospital. Fourteen neonates were randomized to intraoperative and postoperative conventional insulin therapy or TGC. Study endpoints were effects on myocardial damage and function; inflammation, endothelial activation, and clinical outcome parameters.
  
  
  RESULTS
  Tight glycemic control significantly reduced circulating levels of cardiac troponin-I (p = 0.009), heart fatty acid-binding protein (p = 0.01), B-type natriuretic peptide (p = 0.002), and the need for vasoactive support (p = 0.008). The TGC suppressed the rise of the proinflammatory cytokines interleukin-6 (p = 0.02) and interleukin-8 (p = 0.05), and reduced the postoperative increase in C-reactive protein (p = 0.04). Myocardial concentrations of Akt, endothelial nitric-oxide synthase, and their phosphorylated forms were not different between groups.
  
  
  CONCLUSIONS
  In neonates undergoing cardiac surgery, intraoperative and postoperative TGC protects the myocardium and reduces the inflammatory response. This appears not to be mediated by an early, direct insulin signaling effect, but may rather be due to independent effects of preventing hyperglycemia during reperfusion.
authors.affiliation: Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Belgium. dirk.vlasselaers@uzleuven.be
authors.forename: Dirk
authors.initials: D
authors.lastname: Vlasselaers
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
authors.forename: Lies
authors.initials: L
authors.lastname: Langouche
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van den Heuvel
authors.forename: Ilse
authors.initials: I
authors.lastname: Milants
authors.forename: Pieter
authors.initials: P
authors.lastname: Wouters
authors.forename: Patrick
authors.initials: P
authors.lastname: Wouters
authors.forename: Bart
authors.initials: B
authors.lastname: Meyns
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Troels Krarup
authors.initials: TK
authors.lastname: Hansen
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016638:Critical Illness / Q000628:therapy; D006330:Heart Defects, Congenital / Q000097:blood / Q000601:surgery; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin