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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

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.

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Compliance with ethical standards

ᅟ

Funding

This work was supported by the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and the German Research Council (DFG grant HI 1789/2-1).

Conflicts of interest

None.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not describe any studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany

    Rudolf A. Werner, Yoshifumi Maya, Constantin Lapa, Ken Herrmann & Takahiro Higuchi

  2. Comprehensive Heart Failure Center, University of Würzburg, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany

    Rudolf A. Werner & Takahiro Higuchi

  3. Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan

    Yoshifumi Maya

  4. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, München, Germany

    Christoph Rischpler

  5. Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, MD, USA

    Mehrbod S. Javadi

  6. Department of Radiology, Hyogo College of Medicine, Hyogo, Japan

    Kazuhito Fukushima

  7. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Ken Herrmann

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  1. Rudolf A. Werner
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  2. Yoshifumi Maya
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  8. Takahiro Higuchi
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Correspondence to Takahiro Higuchi.

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Werner, R.A., Maya, Y., Rischpler, C. et al. Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by 11C-hydroxyephedrine. Eur J Nucl Med Mol Imaging 43, 312–318 (2016). https://doi.org/10.1007/s00259-015-3171-x

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  • DOI: https://doi.org/10.1007/s00259-015-3171-x

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