Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart.
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.
Mongillo
Marco
M
Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London, UK.
John
Anna S
AS
Leccisotti
Lucia
L
Pennell
Dudley J
DJ
Camici
Paolo G
PG
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
D019788:Fluorodeoxyglucose F18; D005947:Glucose; D009638:Norepinephrine