title: Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial.
abstract: BACKGROUND
  Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery.
  
  
  RESULTS
  Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked β-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands.
  
  
  CONCLUSIONS
  Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Howell
authors.forename: Houman
authors.initials: H
authors.lastname: Ashrafian
authors.forename: Nigel E
authors.initials: NE
authors.lastname: Drury
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Ranasinghe
authors.forename: Hussain
authors.initials: H
authors.lastname: Contractor
authors.forename: Henrik
authors.initials: H
authors.lastname: Isackson
authors.forename: Melanie
authors.initials: M
authors.lastname: Calvert
authors.forename: Lynne K
authors.initials: LK
authors.lastname: Williams
authors.forename: Nick
authors.initials: N
authors.lastname: Freemantle
authors.forename: David W
authors.initials: DW
authors.lastname: Quinn
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: Michael
authors.initials: M
authors.lastname: Frenneaux
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bonser
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Mascaro
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Graham
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rooney
authors.forename: Ian C
authors.initials: IC
authors.lastname: Wilson
authors.forename: Domenico
authors.initials: D
authors.lastname: Pagano
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000117:Acetylglucosamine / Q000378:metabolism; D000368:Aged; D001021:Aortic Valve / Q000601:surgery*; D001024:Aortic Valve Stenosis / Q000601:surgery*; D002303:Cardiac Output, Low / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000627:therapeutic use; D006350:Heart Valve Prosthesis; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D015994:Incidence; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011188:Potassium / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D011188:Potassium; D000117:Acetylglucosamine