Effect of diabetes mellitus on sympathetic neuronal regeneration studied in the model of transplant reinnervation.
The transplanted heart is initially denervated but undergoes subsequent sympathetic reinnervation. It thus provides a unique model for studying regeneration as a specific component of autonomic nerve biology. The aim of this study was to determine the effect of diabetes mellitus on the regenerational capacity of sympathetic neurons using molecule-targeted PET.


METHODS
Twenty-two nonrejecting, otherwise healthy cardiac transplant recipients underwent PET with the (11)C-labeled physiologic neurotransmitter epinephrine at 4.0 +/- 3.3 y after surgery. Sympathetic reinnervation was defined as regional restoration of epinephrine retention to values within normal limits.


RESULTS
Reinnervation was observed in 8 of 12 patients with no evidence of diabetes and in 6 of 10 patients with a long-term history of diabetes mellitus. The regional extent of reinnervation (4.7% +/- 5.3% of left ventricle vs. 19.1% +/- 20.6% for nondiabetic recipients, P = 0.04) and the regeneration rate (0.8% +/- 1.0% of left ventricle per year vs. 8.0% +/- 10.1% for nondiabetic recipients, P = 0.04) were significantly reduced in diabetic subjects. In a multivariate model, diabetes mellitus was an independent determinant of allograft reinnervation. Finally, the reappearance of innervation was found to correlate with an improved chronotropic and inotropic response to stress in a standardized, symptom-limited exercise test including radionuclide angiography.


CONCLUSIONS
The regenerational capacity of the sympathetic nervous system of the heart is reduced, but not abolished, by diabetes mellitus. This study on cardiac transplant recipients further supports a general link between impaired glucose handling and cardiac autonomic nerve function.
Bengel
Frank M
FM
Nuklearmedizinische Klinik und Poliklinik, Technischen Universität München, Munich, Germany. fbengel1@jhmi.edu
Ueberfuhr
Peter
P
Schäfer
Dominik
D
Nekolla
Stephan G
SG
Reichart
Bruno
B
Schwaiger
Markus
M
D002395:Catecholamines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation* / Q000503:physiopathology*; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D011877:Radionuclide Imaging; D020127:Recovery of Function / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D002395:Catecholamines