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Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography

Abstract

Purpose

Positron emission tomography (PET) studies in patients with diabetic autonomic neuropathy (DAN) have demonstrated the impact of this disease on cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate the effects of selective partial sympathetic denervation of the left ventricle (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic catecholamine re-uptake (uptake-1), β-adrenoceptor (β-AR) density and MBF non-invasively by means of PET in a canine model of regional sympathetic denervation.

Methods

In 11 anaesthetised dogs, the sympathetic nerves of the free wall and septum of the LV were removed by means of dissection and phenol painting. Three weeks later, the animals were studied with PET. MBF was measured at baseline and following i.v. adenosine (140 μg kg−1 min−1) and dobutamine (20 μg kg−1 min−1) using15O-labelled water. Sympathetic denervation was confirmed by an 80±12% decrease in the volume of distribution (Vd) of [11C]hydroxyephedrine (HED) compared with innervated regions. Myocardial β-AR density was measured using [11C]CGP12177.

Results

Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [11C]HED Vdwas inversely correlated with MBF in both regions at baseline, and the correlation was lost during hyperaemia in denervated regions. However, for any given value of MBF, [11C]HED Vdwas significantly lower in the denervated regions. β-AR density was comparable in denervated and innervated regions (17.9±4.2 vs 18.4±3.3 pmol g−1;p=NS).

Conclusion

In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [11C]HED Vd, did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [11C]HED Vdand MBF in both denervated and innervated regions.

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Acknowledgements

The authors would like to acknowledge the assistance of the staff of the MRC Clinical Sciences Centre and Hammersmith Imanet. We wish to thank Andrew Blyth and Hope McDevitt for their invaluable help in carrying out PET scans. We would also like to thank Mr. J. Hynd and Dr. M. Mansaray for their help in the denervation procedure.

This study was funded through the Project Grant No. PG/97034 from the British Heart Foundation.

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Correspondence to Ornella E. Rimoldi.

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Rimoldi, O.E., Drake-Holland, A.J., Noble, M.I.M. et al. Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography. Eur J Nucl Med Mol Imaging 34, 197–205 (2007). https://doi.org/10.1007/s00259-006-0233-0

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  • DOI: https://doi.org/10.1007/s00259-006-0233-0

Keywords

  • Coronary circulation
  • Autonomic neuropathy
  • Myocardial blood flow
  • Positron emission tomography