title: Multiparametric molecular imaging provides mechanistic insights into sympathetic innervation impairment in the viable infarct border zone.
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 (11)C-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 (13)N-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 (11)C-hydroxyephedrine was smaller than epinephrine (41 ± 8 vs. 47% ± 6% of left ventricle, P = 0.004), whereas defect of a third catecholamine, (11)C-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).
  
  
  CONCLUSIONS
  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.
authors: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland.
authors: Riikka
authors: R
authors: Lautamaki
authors: Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors: Tetsuo
authors: T
authors: Sasano
authors: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland.
authors: Takahiro
authors: T
authors: Higuchi
authors: Nuklearmedizinische Klinik, Technische University of Munich, Munich, Germany; and.
authors: Stephan G
authors: SG
authors: Nekolla
authors: Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors: Albert C
authors: AC
authors: Lardo
authors: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland.
authors: Daniel P
authors: DP
authors: Holt
authors: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland.
authors: Robert F
authors: RF
authors: Dannals
authors: Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors: M Roselle
authors: MR
authors: Abraham
authors: Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany bengel.frank@mh-hannover.de.
authors: Frank M
authors: FM
authors: Bengel
mesh_terms: D000641:Ammonia / Q000737:chemistry; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes / Q000737:chemistry; D002395:Catecholamines / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004809:Ephedrine / Q000031:analogs & derivatives / Q000737:chemistry; D004837:Epinephrine / Q000737:chemistry; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D057054:Molecular Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging; D009474:Neurons / Q000473:pathology; D010477:Perfusion; D010656:Phenylephrine / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry; D013552:Swine; D013564:Sympathetic Nervous System; D013610:Tachycardia / Q000503:physiopathology; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D002395:Catecholamines; D019275:Radiopharmaceuticals; D010656:Phenylephrine; D000641:Ammonia; D004809:Ephedrine; D004837:Epinephrine
keywords: magnetic resonance imaging; myocardial infarction; positron emission tomography; sympathetic innervation