CANINE MYOCARDIAL BETA-ADRENERGIC, MUSCARINIC RECEPTOR DENSITIES AFTER DENERVATION - A PET STUDY

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.