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

Marco Mongillo, Anna S. John, Lucia Leccisotti, Dudley J. Pennell, Paolo G. Camici

Research output: Contribution to journalArticle

Abstract

Purpose: We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-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 18F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [11C]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 μmol·min-1·g-1) and dysfunctional (0.49 ± 0.14 μmol·min-1·g -1) segments compared with controls (0.61 ± 0.7 μmol·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. 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.

Original languageEnglish
Pages (from-to)1172-1177
Number of pages6
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume34
Issue number8
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Cardiac imaging
  • Congestive heart failure
  • Insulin resistance
  • Positron emission tomography
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

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