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Pre- and post-synaptic sympathetic function in human hibernating myocardium

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function.

Methods

Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([11C]meta-hydroxy-ephedrine; HED) and β-adrenoceptor (β-AR) density ([11C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls.

Results

The volume of distribution (Vd) of HED in HM (47.95±28.05 ml/g) and infarcted myocardium (42.69±25.76 ml/g) was significantly reduced compared with controls (66.09±14.48 ml/g). The Vd of HED in normal myocardium (49.93±20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial β-AR density was significantly lower in HM (5.49±2.35 pmol/g), infarcted (4.82±2.61 pmol/g) and normal (5.86±1.81 pmol/g) segments of patients compared with healthy controls (8.61±1.32 pmol/g).

Conclusion

Noradrenaline uptake-1 mechanism and β-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM.

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Authors and Affiliations

  1. National Heart and Lung Institute, Imperial College, Hammersmith Hospital, London, UK

    Anna S. John, Ornella E. Rimoldi, John R. Pepper, Gilles D. Dreyfus, Dudley J. Pennell & Paolo G. Camici

  2. Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Marco Mongillo, Muhammad T. Khan, Ornella E. Rimoldi & Paolo G. Camici

  3. Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry New Jersey, New Jersey, NJ, USA

    Christophe Depre

  4. Cardiovascular Research Institute, Department of Medicine, University of Medicine and Dentistry New Jersey, New Jersey, NJ, USA

    Christophe Depre

  5. Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY, USA

    Ornella E. Rimoldi

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  1. Anna S. John
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Correspondence to Paolo G. Camici.

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John, A.S., Mongillo, M., Depre, C. et al. Pre- and post-synaptic sympathetic function in human hibernating myocardium. Eur J Nucl Med Mol Imaging 34, 1973–1980 (2007). https://doi.org/10.1007/s00259-007-0507-1

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  • DOI: https://doi.org/10.1007/s00259-007-0507-1

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