H. Valette et al., CANINE MYOCARDIAL BETA-ADRENERGIC, MUSCARINIC RECEPTOR DENSITIES AFTER DENERVATION - A PET STUDY, The Journal of nuclear medicine, 36(1), 1995, pp. 140-146
In an effort to better understand cardiac neurotransmission, PET was s
erially 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 concen
trations were studied in beagle dogs nine days after chemical sympathe
ctomy (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; 1
opamine (n = 8), hemodynamic tests and MIBG scintigraphy demonstrated
the destruction of cardiac sympathetic innervation. Beta-adrenergic d
ensity increased by 190% (p < 0.001) while MR density remained unchang
ed. Three to 7 wk after surgery (n = 5), hemodynamic tests and MIBG sc
intigraphy demonstrated both parasympathetic and sympathetic denervati
ons. Beta-adrenergic density was increased by 219% while MR concentrat
ion remained unchanged. Twenty-three to 28 wk after surgery, atrial in
nervation was restored (hemodynamic tests) while ventricular sympathet
ic innervation was not (MIBG scintigraphy). Beta-adrenergic density re
mained high. Conclusion: The present study demonstrates the ability of
PET to serially assess myocardial receptor concentrations. The absenc
e of change in MR density and the prolonged up-regulation of beta-AR f
ollowing heart denervation are the main findings of the present study.