Pre- and post-synaptic sympathetic function in human hibernating myocardium.
OBJECTIVE
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 ([(11)C]meta-hydroxy-ephedrine; HED) and beta-adrenoceptor (beta-AR) density ([(11)C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls.


RESULTS
The volume of distribution (V(d)) 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 V(d) 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 beta-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).


CONCLUSIONS
Noradrenaline uptake-1 mechanism and beta-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.
John
Anna S
AS
National Heart and Lung Institute, Imperial College, Hammersmith Hospital, Du Cane Road, London, UK.
Mongillo
Marco
M
Depre
Christophe
C
Khan
Muhammad T
MT
Rimoldi
Ornella E
OE
Pepper
John R
JR
Dreyfus
Gilles D
GD
Pennell
Dudley J
DJ
Camici
Paolo G
PG
D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017682:Myocardial Stunning / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011877:Radionuclide Imaging; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013569:Synapses / Q000000981:diagnostic imaging / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine