Micro-recanalization in a biodegradable graft for reconstruction of the vas deferens is enhanced by sildenafil citrate
Department of Urology, University of Iowa, Iowa City, IA 52242, USA.Asian Journal of Andrology (Impact Factor: 2.6). 11/2010; 12(6):814-8. DOI: 10.1038/aja.2010.55
This study investigated the effect of sildenafil citrate on micro-recanalization and neovascularization, which were previously demonstrated in a rat model using biodegradable grafts (BGs) for vas deferens reconstruction. A total of 24 male rats underwent bilateral vasectomy with removal of a 0.5-cm vasal segment and were randomly assigned to four groups. Groups 1 and 2 underwent immediate vasovasostomy. Groups 3 and 4 underwent interposition of a 0.5-cm BG in the vasal gap. Groups 1 and 3 were given 5 mg kg(-1) day(-1) oral sildenafil. Other groups were given placebo. Rats were housed with females 12 weeks postoperatively. Reconstructed vasal segments were harvested 16 weeks postoperatively and analyzed histologically. Fluid from the distal vasal stump was analyzed for motile sperm. Urine samples obtained 16 weeks postoperatively were analyzed for cGMP levels. cGMP levels in rats treated with sildenafil were significantly higher than in control rats. No pregnancies were sired by grafted groups. In all, 5/6 rats in group 1 and 3/6 rats in group 2 sired litters. No motile sperm were noted in the vasal fluid of the grafted groups. Motile sperm were noted in all rats in group 1 and in 5/6 rats in group 2. In addition, 29 and 4 microcanals were detected in the sildenafil and placebo groups, respectively (P = 0.023). No microcanal exceeded 3 mm in length. An average of 12 and 28 blood vessels per graft were noted in the placebo and sildenafil groups, respectively (P < 0.0001). In conclusion, sildenafil enhances micro-recanalization and neovascularization in BG used for vas deferens reconstruction, but does not increase the microcanal length after 16 weeks.
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ABSTRACT: To investigate the effect of the combination of locally delivered growth factors and oral sildenafil citrate on cross-conduit microrecanalization. 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. 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). 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.
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ABSTRACT: Phosphodiesterase (PDE) enzymes are widely distributed throughout the body, having numerous effects and functions. The use of on-demand PDE5 inhibitors for the treatment of erectile dysfunction (ED) has recently obtained approval for chronic daily dosing for the same indication. There are published data supporting the use of PDE5 inhibitors for the treatment of lower urinary tract symptoms (LUTS) caused by BPH. Additional reports suggest befeit by these agents in patients with chronic heart failure, pulmonary hypertension, essential hypertension, and for the treatment of ischemia. Various central nervous system disorders have been described as targets by for PDE5 inhibitors. Sildenafil may have a potential therapeutic indication as a cognitive enhancer in age-related cerebral conditions. There is preclinical evidence for further investigation of the use of PDE5A inhibitors to improve recovery of cerebral function in humans after stroke by enhancing angiogenesis, neurogenesis and improving neurologic function. Sildenafil delays intestinal ulceration by an increase in the secretion of mucus/fluid and a decrease in hypermotility, and has a protective effect in reducing gastric damage. Larger scale, well designed clinical trials are needed to ascertain the safety, efficacy and cost-effectiveness of PDE5 inhibitors in the future treatment of both urologic and non-urologic diseases. In this review, potential applications of PDE5 inhibitors on urologic, cardiovascular, gastrointestinal, and central nervous system disorders will be updated.
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ABSTRACT: Purpose: Vasectomy is one of the most common urological operations performed, and provides permanent contraception. Many vasectomized men ultimately seek vasectomy reversal because of unforeseen changes in lifestyle. Vasovasostomy has varying rates of success. In this study, we utilize vas deferens (VD), artery, and vein grafts to reconstruct 30% and 50%defects of the total vas deferens length. Materials and methods: Forty two male Wistar rats were divided into three groups as VD graft, carotid artery and external jugular vein transplantations. Each group was equally divided into 2 different subgroups according to the length of transplant material as 1.0 cm (n = 7) and 1.5 cm (n = 7). To evaluate whether these materials may be used for long segment vas deferens reconstruction, the patency rate, partial or total graft occlusion, and histologic examination of all specimens were examined. Results: No patency was found in any of the grafts and many of them suffered destructive changes in anatomic structure. Sperm granulomas were determined around the testicular side anastomosis due to accumulated semen fluid which was in our belief, a result of aperistaltic zone caused by the grafts. Conclusion: When the poor results obtained in our study are put into perspective, vasoepididymostomy is the only treatment method to date for reconstruction of large segment vas deferens defects.