The Journal of Thoracic and Cardiovascular Surgery
Volume 137, Issue 6 , Pages 1508-1514 , June 2009

Selective phosphodiesterase-5 inhibition reduces neointimal hyperplasia in rat carotid arteries after surgical endarterectomy

  • Kristóf Hirschberg, MD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
    • Corresponding Author InformationAddress for reprints: Kristóf Hirschberg, MD, Experimental Laboratory of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 326, OG 2, 69120 Heidelberg, Germany.
    • ,
  • Tamás Radovits, MD, PhD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
    • ,
  • Sivakkanan Loganathan

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • ,
  • László Entz, MD, PhD

      Affiliations

    • Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
    • ,
  • Carsten J. Beller, MD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • ,
  • Marie–Luise Gross, MD

      Affiliations

    • Department of Pathology, University of Heidelberg, Heidelberg, Germany
    • ,
  • Peter Sandner, PhD

      Affiliations

    • Bayer HealthCare, Wuppertal, Germany
    • ,
  • Matthias Karck, MD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • ,
  • Gábor Szabó, MD, PhD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany

Received 23 July 2008 ,Revised 16 September 2008 ,Accepted 13 October 2008.

  • Image Result

    Morphometric results and representative histologic cross-sections from the different groups (hematoxylin and eosin staining). A, Percentage of stenosis (neointimal/original luminal area ratio). B, Neo

    Morphometric results and representative histologic cross-sections from the different groups (hematoxylin and eosin staining). A, Percentage of stenosis (neointimal/original luminal area ratio). B, Neointimal/medial area ratio. C, Sham group. D, Control endarterectomy group with massive neointima proliferation. E, Significantly less neointima formation after treatment with vardenafil. ∗P < .05 vs sham operation; †P < .05 vs control endarterectomy.

  • Image Result
    Representative photomicrographs (B–C, E–F, and H–I) and semiquantitative scoring (A, D, and G) of immunohistochemical staining for transforming growth factor β1 (TGF-β1; red stain, A–C) and α-smooth m

    Representative photomicrographs (B–C, E–F, and H–I) and semiquantitative scoring (A, D, and G) of immunohistochemical staining for transforming growth factor β1 (TGF-β1; red stain, A–C) and α-smooth muscle actin (Alpha-sm actin; brown stain, D–F) and for cyclic guanosine monophosphate (cGMP; red stain) in the neointima (G–I) are shown in the control endarterectomy group (B, E, and H) and the vardenafil treatment group (C, F, and I). m, media; ni, neointima. ∗P < .05 vs control endarterectomy.

  • Image Result
    Cyclic guanosine monophosphate (cGMP) plasma concentrations (in picomoles per milliliter) measured by means of competitive enzyme immunoassay in the different groups. ∗P < .05 vs unoperated control an

    Cyclic guanosine monophosphate (cGMP) plasma concentrations (in picomoles per milliliter) measured by means of competitive enzyme immunoassay in the different groups. ∗P < .05 vs unoperated control and control endarterectomy.

  • Image Result
    Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling (TUNEL)–positive cell count in 1000 μm2 of neointima in the control endarterectomy and vardenafil groups.

    Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling (TUNEL)–positive cell count in 1000 μm2 of neointima in the control endarterectomy and vardenafil groups.

 This work was partially supported by Bayer HealthCare, Wuppertal, Germany. Peter Sandner, PhD, is an employee of Bayer HealthCare, Wuppertal, Germany.

PII: S0022-5223(08)01723-6

doi: 10.1016/j.jtcvs.2008.10.016

The Journal of Thoracic and Cardiovascular Surgery
Volume 137, Issue 6 , Pages 1508-1514 , June 2009

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