title: Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart.
abstract: OBJECTIVE
  We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic beta-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF.
  
  
  METHODS
  Eight patients (aged 67 +/- 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 +/- 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [(11)C]meta-hydroxy-ephedrine (HED) volume of distribution (V (d)) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 +/- 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 +/- 6 years, p < 0.01 vs patients) data.
  
  
  RESULTS
  MGU in patients was reduced in both normal remote (0.44 +/- 0.14 micromol.min(-1).g(-1)) and dysfunctional (0.49 +/- 0.14 micromol.min(-1).g(-1)) segments compared with controls (0.61 +/- 0.7 micromol.min(-1).g(-1); p < 0.001 vs both). HED V (d) was reduced in dysfunctional segments of patients (38.9 +/- 21.2 ml.g(-1)) compared with normal segments (52.2 +/- 19.6 ml.g(-1)) and compared with controls (62.7 +/- 11.3 ml.g(-1)). In patients, regional MGU was correlated with HED V (d).
  
  
  CONCLUSIONS
  The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Mongillo
authors.forename: Anna S
authors.initials: AS
authors.lastname: John
authors.forename: Lucia
authors.initials: L
authors.lastname: Leccisotti
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D000368:Aged; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000175:diagnosis; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D006321:Heart; D006333:Heart Failure / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D007333:Insulin Resistance; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D012680:Sensitivity and Specificity; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis
chemical_list: D019788:Fluorodeoxyglucose F18; D005947:Glucose; D009638:Norepinephrine