Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

Purpose 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 F-18- fluorodeoxyglucose ( FDG). Pre- synaptic noradrenaline re- uptake was measured by calculating [ C-11] 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 mu mol.min(-1) . g(-1)) and dysfunctional ( 0.49 +/- 0.14 mu mol . min(-1) .g(-1)) segments compared with controls ( 0.61 +/- 0.7 mu mol . 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 Vd. Conclusion 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.