Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography.
OBJECTIVE
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), beta-adrenoceptor (beta-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 microg kg(-1) min(-1)) and dobutamine (20 microg kg(-1) min(-1)) using(15)O-labelled water. Sympathetic denervation was confirmed by an 80+/-12% decrease in the volume of distribution (V(d)) of [(11)C]hydroxyephedrine (HED) compared with innervated regions. Myocardial beta-AR density was measured using [(11)C]CGP12177.


RESULTS
Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [(11)C]HED V(d)was 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, [(11)C]HED V(d)was significantly lower in the denervated regions. beta-AR density was comparable in denervated and innervated regions (17.9+/-4.2 vs 18.4+/-3.3 pmol g(-1); p=NS).


CONCLUSIONS
In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [(11)C]HED V(d), did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [(11)C]HED V(d)and MBF in both denervated and innervated regions.
Rimoldi
Ornella E
OE
MRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Drake-Holland
Angela J
AJ
Noble
Mark I M
MI
Camici
Paolo G
PG
D000818:Animals; D017763:Autonomic Denervation; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D001783:Blood Flow Velocity; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation; D006940:Hyperemia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D011877:Radionuclide Imaging