RT Journal Article
SR Electronic
T1 Characterizing the biology of sympathetic nerve terminal regeneration in the human heart - A multi-tracer PET-CT study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 431
OP 431
VO 51
IS supplement 2
A1 Bravo, Paco
A1 Lautamäki, Riikka
A1 Merrill, Jennifer
A1 Carter, Debra
A1 Holt, Daniel
A1 Hilton, John
A1 Nekolla, Stephan
A1 Dannals, Robert
A1 Russell, Stuart
A1 Bengel, Frank
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/431.abstract
AB 431 Objectives Sympathetic innervation partially recovers in the initially denervated, transplanted heart. Catecholamine transport, vesicular storage, and metabolic degradation, important subcellular components for sympathetic nerve terminal function, have been previously assessed by the PET tracers C-11 hydroxyephedrine (HED), C-11 epinephrine (EPI), and C-11 phenylephrine (PHEN) respectively. Nevertheless, whether all these mechanisms recover simultaneously remains unclear. Methods We employed a multi-tracer PET-CT protocol in 10 nonrejecting, otherwise healthy transplant recipients (TR) and in 7 healthy volunteers (HV). On day 1, dynamic imaging was performed with N-13 ammonia and EPI. On day 2, HED and PHEN were employed. Results All HV had regionally homogeneous left ventricular (LV) blood flow and retention of EPI, HED and PHEN. Washout was only observed for PHEN (T½46±5min). In TR, blood flow was homogenous, but regional catecholamine uptake of varying degrees was observed in the anteroseptal LV. The reinnervated area (area within 2SD of the mean of normals) comprised 24±19% of the LV for HED, but only 7±7% for EPI, suggesting the presence of an area of incompletely restored innervation. In this area, PHEN washout was enhanced when compared to the area with completely restored HED and EPI retention (T½36±6 vs 40±5min;P<0.05), and when compared to normals (P<0.01). Conclusions While regional catecholamine uptake-1 is more extensively restored after transplantation, only a fraction of this area also shows efficient vesicular storage. Accelerated turnover of PHEN in the remaining area with restored uptake-1 suggests inefficient vesicular storage and enhanced metabolic degradation. Our study provides further insights into subcellular components of sympathetic innervation, which regenerate at different rates and different degrees. This may have implications for other diseases involving cardiac autonomic dysfunction. Research Support W.W. Smith Charitable Trus