Multiparametric molecular imaging provides mechanistic insights into sympathetic innervation impairment in the viable infarct border zone

Riikka Lautamaki, Tetsuo Sasano, Takahiro Higuchi, Stephan G. Nekolla, Albert C. Lardo, Daniel P. Holt, Robert F. Dannals, M. Roselle Abraham, Frank M. Bengel

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Impaired catecholamine handling in the viable infarct border zone may play an important role in ventricular remodeling and lethal arrhythmia. We sought to get further biologic insights into cardiac sympathetic neuronal pathology after myocardial infarction, using multiple tomographic imaging techniques. Methods: In a porcine model of myocardial infarction (n = 13), PET and MR imaging were performed after 4-6 wk and integrated with electrophysiologic testing and postmortem histology. Results: PET with the physiologic neurotransmitter 11C-epinephrine, which is sensitive to metabolic degradation unless it is stored and protected in neuronal vesicles, identified a defect exceeding the perfusion defect (defined by 13N-ammonia; defect size in all animals, 42 ± 12 vs. 35% ± 12% of left ventricle, P < 0.001). In a subgroup of 7 animals, defect of the metabolically resistant catecholamine 11C-hydroxyephedrine was smaller than epinephrine (41 ± 8 vs. 47% ± 6% of left ventricle, P = 0.004), whereas defect of a third catecholamine, 11C-phenylephrine, which is sensitive to metabolic degradation, was similar to epinephrine (48 ± 6 vs. 47% ± 6%, P = 0.011 vs. perfusion defect). Histology confirmed the presence of nerve fibers in the infarct border zone. Tagged MR imaging identified impaired peak circumferential wall strain and wall thickening in myocardial segments with epinephrine/perfusion mismatch (n = 6). Confirmatory of prior work, inducible ventricular tachycardia was associated with a larger epinephrine/perfusion mismatch (n = 11). Conclusion: In the viable infarct border zone, neuronal vesicular catecholamine storage and protection from metabolic degradation are more severely altered than catecholamine uptake. This alteration may reflect an intermediate state between normal innervation and complete denervation in advanced disease.

Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number3
DOIs
Publication statusPublished - Mar 1 2015
Externally publishedYes

Keywords

  • Magnetic resonance imaging
  • Myocardial infarction
  • Positron emission tomography
  • Sympathetic innervation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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