Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by 11C-hydroxyephedrine

Rudolf A. Werner, Yoshifumi Maya, Christoph Rischpler, Mehrbod S. Javadi, Kazuhito Fukushima, Constantin Lapa, Ken Herrmann, Takahiro Higuchi

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Purpose: An altered state of the cardiac sympathetic nerves is an important prognostic factor in patients with coronary artery disease. The aim of this study was to investigate regional sympathetic nerve damage and restoration utilizing a rat model of myocardial transient ischemia and a catecholamine analog PET tracer, 11C-hydroxyephedrine (11C-HED). Methods: Transient myocardial ischemia was induced by coronary occlusion for 20 min and reperfusion in male Wistar rats. Dual-tracer autoradiography was performed subacutely (7 days) and chronically (2 months) after ischemia, and in control rats without ischemia using 11C-HED as a marker of sympathetic innervation and 201TI for perfusion. Additional serial in vivo cardiac 11C-HED and 18F-FDG PET scans were performed in the subacute and chronic phases after ischemia. Results: After transient ischemia, the 11C-HED uptake defect areas in both the subacute and chronic phases were clearly larger than the perfusion defect areas in the midventricular wall. The subacute 11C-HED uptake defect showed a transmural pattern, whereas uptake recovered in the subepicardial portion in the chronic phase. Tyrosine hydroxylase antibody nerve staining confirmed regional denervation corresponding to areas of decreased 11C-HED uptake. Serial in vivo PET imaging visualized reductions in the area of the 11C-HED uptake defects in the chronic phase consistent with autoradiography and histology. Conclusion: Higher susceptibility of sympathetic neurons compared to myocytes was confirmed by a larger 11C-HED defect with a corresponding histologically identified region of denervation. Furthermore, partial reinnervation was observed in the chronic phase as shown by recovery of subepicardial 11C-HED uptake.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number2
Publication statusPublished - Feb 1 2016
Externally publishedYes


  • C-Hydroxyephedrine
  • Ischemia
  • Nerve sprout
  • Rat
  • Sympathetic nerve

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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