Effect of combined locally delivered growth factors and systemic sildenafil citrate on microrecanalization in biodegradable conduit for vas deferens reconstruction

Urology. 2012 Apr;79(4):967.e1-4. doi: 10.1016/j.urology.2011.11.030. Epub 2012 Jan 27.

Abstract

Objective: To investigate the effect of the combination of locally delivered growth factors and oral sildenafil citrate on cross-conduit microrecanalization.

Methods: A total of 42 rats were divided into 7 groups. Of the 42 rats, 6 underwent bilateral vasectomy and bilateral end-to-end vasovasostomy and 12 underwent bilateral vasectomy. Of the latter 12, 6 received sildenafil citrate orally (10 mg/kg/d) for 24 weeks and 6 received placebo. A total of 24 rats underwent bilateral vasectomy and bilateral reconstruction with implantation of a 5-mm biodegradable conduit that bridged the 2 vasal ends. Of the 24 rats with conduits, 12 also had 250 pg of transforming growth factor-β and 12.5 pg of platelet-derived growth factor-β sustained release nanoparticles placed in immediate proximity to the conduit. The remaining 12 rats with conduits (6 without growth factors and 6 with growth factors) also received sildenafil citrate orally (10 mg/kg/d) for 24 weeks; the others received placebo. The reconstructed segments were harvested for histologic examination at 24 weeks.

Results: Five of 6 primary vasovasostomy and no vasectomy-only rats sired litters. Significantly more microcanals per conduit were observed in rats receiving sildenafil citrate: without growth factors, 3.9 vs. 0 canals/conduit (P < 0.001); with growth factors, 5.5 vs. 0.25 canals/conduit (P < 0.001). The rats receiving sildenafil citrate with growth factors showed a trend toward more microcanals per conduit than the rats receiving sildenafil citrate without growth factors (5.5 vs 3.9; P = .10). Rats receiving growth factors but no sildenafil citrate did not produce more canals than the rats receiving neither growth factor nor sildenafil citrate (0.25 vs 0; P = NS).

Conclusion: Orally administered sildenafil citrate enhances formation of microcanalization after postvasectomy reconstruction using a biodegradable conduit in a rat model. Locally delivered growth factors appear to increase the number of microcanals.

MeSH terms

  • Absorbable Implants
  • Animals
  • Male
  • Microcirculation / drug effects
  • Nanoparticles
  • Piperazines / administration & dosage*
  • Proto-Oncogene Proteins c-sis / administration & dosage*
  • Purines / administration & dosage
  • Rats
  • Sildenafil Citrate
  • Sulfones / administration & dosage*
  • Transforming Growth Factor beta / administration & dosage*
  • Vas Deferens / surgery
  • Vasovasostomy / methods*

Substances

  • Piperazines
  • Proto-Oncogene Proteins c-sis
  • Purines
  • Sulfones
  • Transforming Growth Factor beta
  • Sildenafil Citrate