title: Effect of combined locally delivered growth factors and systemic sildenafil citrate on microrecanalization in biodegradable conduit for vas deferens reconstruction.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, University of Iowa, Iowa City, Iowa 52242-1089, USA.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Rosevear
authors.forename: Yogita
authors.initials: Y
authors.lastname: Krishnamachari
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Ariza
authors.forename: Surya K
authors.initials: SK
authors.lastname: Mallapragada
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
authors.forename: Barry R
authors.initials: BR
authors.lastname: De Young
authors.forename: Moshe
authors.initials: M
authors.lastname: Wald
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D053758:Nanoparticles; D010879:Piperazines / Q000008:administration & dosage*; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014649:Vas Deferens / Q000601:surgery; D014669:Vasovasostomy / Q000379:methods*
chemical_list: D010879:Piperazines; D020574:Proto-Oncogene Proteins c-sis; D011687:Purines; D013450:Sulfones; D016212:Transforming Growth Factor beta; D000068677:Sildenafil Citrate