Canine myocardial beta-adrenergic, muscarinic receptor densities after denervation: a PET study.
In an effort to better understand cardiac neurotransmission, PET was serially used in dogs to assess changes in ventricular muscarinic (MR) and beta-adrenergic receptor (beta-AR) densities following chemical or surgical denervation.


METHODS
Beta-adrenergic and MR receptor concentrations were studied in beagle dogs nine days after chemical sympathectomy (using the neurotoxin 6-hydroxydopamine) or 3-7 wk and 23-28 wk after surgical intrapericardial denervation.


RESULTS
In control dogs (n = 13), global beta-AR and MR concentrations were 32 +/- 4 and 62.2 +/- 10.4 pmole/ml tissue, respectively. Nine days after 6-hydroxytk; 1opamine (n = 8), hemodynamic tests and MIBG scintigraphy demonstrated the destruction of cardiac sympathetic innervation. Beta-adrenergic density increased by 190% (p < 0.001) while MR density remained unchanged. Three to 7 wk after surgery (n = 5), hemodynamic tests and MIBG scintigraphy demonstrated both parasympathetic and sympathetic denervations. Beta-adrenergic density was increased by 219% while MR concentration remained unchanged. Twenty-three to 28 wk after surgery, atrial innervation was restored (hemodynamic tests) while ventricular sympathetic innervation was not (MIBG scintigraphy). Beta-adrenergic density remained high.


CONCLUSIONS
The present study demonstrates the ability of PET to serially assess myocardial receptor concentrations. The absence of change in MR density and the prolonged up-regulation of beta-AR following heart denervation are the main findings of the present study.
Valette
H
H
Service Hospitalier Frédéric Joliot, DRIPP-CEA, Orsay, France.
Deleuze
P
P
Syrota
A
A
Delforge
J
J
Crouzel
C
C
Fuseau
C
C
Loisance
D
D
D019797:3-Iodobenzylguanidine; D000818:Animals; D003714:Denervation; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation; D006439:Hemodynamics; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D009206:Myocardium / Q000737:chemistry*; D016627:Oxidopamine; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D011976:Receptors, Muscarinic / Q000032:analysis*; D013563:Sympathectomy, Chemical; D014055:Tomography, Emission-Computed
D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D019797:3-Iodobenzylguanidine; D016627:Oxidopamine