Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application

Abstract

Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.