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Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1α on left ventricular function and perfusion in a porcine model of myocardial infarction

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Abstract

Background

Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1α (SDF-1α) has been shown to be critical for stem cell homing to injured tissue.

Methods

Myocardial infarction was induced in pigs via microembolization of the distal left anterior descending artery. Two weeks after myocardial infarction animals underwent catheter-based transendocardial injection of SDF-1α into the periinfarct myocardium (18 injections, 5 ìg per injection) (n = 12) or sham-intervention (n = 8). Tc99m sestamibi single-photon emission computed tomography (SPECT) and electromechanical mapping (EMM) of the left ventricle were performed two and seven weeks after myocardial infarction.

Results

Infarct size by tetrazolium staining was similar in both groups (8.9 ±1.2% of left ventricle vs. 8.9 ± 2.6%). Vessel density in the periinfarct area was significantly higher in SDF-1α treated animals than in controls (349 ± 17/mm2 vs. 276 ± 21/mm2, p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1α animals and increased in controls (difference between groups p = 0.05 for ejection fraction and p < 0.05 for stroke volume). Linear local shortening (EMM) did not change in controls (11.4 ± 1.3% to 11.5 ± 0.5%) but decreased significantly in SDF-1α treated animals (12.1 ± 0.9% to 8.4 ± 0.9%, p < 0.05, p < 0.05 for difference between groups). SDF-1 delivery was associated with a substantial loss of collagen in the periinfarct area (32±5% vs. 61±6% in control animals, p < 0.005).

Conclusion

A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1α in experimental myocardial infarction increases periinfarct vessel density, fails to improve myocardial perfusion, is associated with loss of collagen in the periinfarct area and impairs left ventricular function.

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Authors and Affiliations

  1. Department of Cardiology, RWTH Aachen University, Pauwelstraße 30, 52074, Aachen, Germany

    Karl-Christian Koch M.D., Elisa A. Liehn M.D., Christos Rammos cand.med., Dominik Mueller cand.med., Joerg Schroeder M.D., Tarek Dimassi M.D. & Christian Weber M.D.

  2. Department of Nuclear Medicine, RWTH Aachen University, Aachen, Germany

    Wolfgang M. Schaefer M.D., PhD

  3. Cardiovascular Molecular Biology, RWTH Aachen University, Aachen, Germany

    Elisa A. Liehn M.D. & Christian Weber M.D.

  4. Department of Animal Research, RWTH Aachen University, Aachen, Germany

    Thaddaeus Stopinski

Authors
  1. Karl-Christian Koch M.D.
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  2. Wolfgang M. Schaefer M.D., PhD
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  3. Elisa A. Liehn M.D.
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  4. Christos Rammos cand.med.
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  5. Dominik Mueller cand.med.
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  6. Joerg Schroeder M.D.
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  7. Tarek Dimassi M.D.
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  8. Thaddaeus Stopinski
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  9. Christian Weber M.D.
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Corresponding author

Correspondence to Karl-Christian Koch M.D..

Additional information

Drs. Koch and Schaefer contributed equally to this study.

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Koch, KC., Schaefer, W.M., Liehn, E.A. et al. Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1α on left ventricular function and perfusion in a porcine model of myocardial infarction. Basic Res Cardiol 101, 69–77 (2006). https://doi.org/10.1007/s00395-005-0570-3

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  • DOI: https://doi.org/10.1007/s00395-005-0570-3

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