Evaluation of Formation of Granulation Tissue Caused by Metallic Stent Placement in a Rat Urethral Model

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Journal of vascular and interventional radiology: JVIR (Impact Factor: 2.41). 10/2010; 21(12):1884-90. DOI: 10.1016/j.jvir.2010.07.026
Source: PubMed


To evaluate the feasibility of metallic stent placement and the formation of granulation tissue caused by stent placement in a rat urethral model.
A bare self-expanding metallic stent was inserted in the urethra under fluoroscopic guidance in 20 male Sprague-Dawley rats. Ten rats were euthanized at 4 weeks (group A), and the other 10 were euthanized at 8 weeks after stent placement (group B). Stenosis diameter, number of epithelial layers, degree of inflammatory cell infiltration, thickness of submucosal fibrosis, and percentage of granulation tissue area were assessed.
Stent placement was technically successful in all rats. Urethrograms showed perforation in three rats, partial migration in three, and stone formation in four. Granulation tissue formation was observed in all rats at the stent-implanted urethra, and the average percentage of granulation tissue area accounted for 41% and 45% of the original urethral lumen area in groups A and B, respectively. Urethrograms and urethral specimens showed significantly less stenosis diameter, less thickness of submucosal fibrosis, and lower percentage of granulation tissue area in the proximal urethra than in the distal urethra in both groups (P < .05). Histologic results demonstrated significantly fewer epithelial layers in group B compared with group A (P = .028).
Placement of a self-expandable metallic stent proved to be feasible in the rat urethra and an efficient approach to stimulate granulation tissue formation as a potential model for reproducing the mechanisms of restenosis.

Download full-text


Available from: Jin Hyoung Kim, Jun 19, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To develop an experimental model of infravesical urinary obstruction in female rats. After median caudal laparotomy, the urethra of 14 female rats was delicately separated from the vagina and loosely wrapped with cellophane tape measuring 0.4 x 1.0 cm. The animals were evaluated 4 (n=7) and 8 (n=7) weeks later. Five additional control animals were only subjected to separation of the urethra and vagina and monitored for 12 weeks. After four weeks, three rats presented vesical dilation associated with discrete ureteral ectasis in 2 animals, with the third presenting discrete hydronephrosis in one kidney. After eight weeks, five rats (71.4%) presented vesical distension with bilateral ureterohydronephrosis. No significant changes (p>0.05) in serum urea or creatinine occurred in any group compared to preoperative values. We present here an inexpensive and simple method for the slow induction of urethral obstruction in adult female rats, with the development of progressive vesical hypertrophy and ureterohydronephrosis, which may be used as an experimental model for the study of different aspects of obstructive nephropathy.
    Full-text · Article · Jan 2011 · Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia
  • [Show abstract] [Hide abstract]
    ABSTRACT: Case description: An 8-month-old castrated male mixed-breed dog was evaluated because of hematuria, stranguria, and dysuria of approximately 2 weeks' duration that developed immediately following elective castration. Clinical findings: Results of physical examination, ultrasonography, retrograde double-contrast cystourethrography, and urethroscopy were consistent with a traumatic urethral stricture immediately proximal to the os penis resulting in a partial obstruction of urine outflow. Results of ultrasonographic examination of abdominal organs were considered normal. Digital radiography revealed no evidence of calculi. Treatment and outcome: Balloon dilation of the urethral stricture was performed and was followed by 2 bougienage procedures during the subsequent 2 weeks when clinical signs returned. The owners declined scrotal urethrostomy, and a self-expanding, covered nitinol stent was placed approximately 3 weeks after the initial evaluation, resulting in amelioration of clinical signs. Results of follow-up urethroscopy and contrast cystourethrography 1 year after stent placement revealed a statically positioned, patent urethral stent, although a small number of polypoid mucosal structures were identified distal to the stent and 1 small structure consistent with tissue ingrowth into the stent was identified. Clinical relevance: Placement of a covered nitinol stent resulted in long-term resolution of clinical signs associated with traumatic stricture of the penile urethra in this young dog. Because the os penis in dogs limits radial expansion of the urethra, its presence may limit the use of stents in this location.
    No preview · Article · Apr 2013 · Journal of the American Veterinary Medical Association
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To evaluate the effectiveness of small interfering RNA (siRNA) targeting matrix metalloproteinase 9 (MMP-9) in suppressing granulation tissue formation caused by bare metallic stent placement in a rat urethral model. Materials and methods: All experiments were approved by the committee of animal research. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra with fluoroscopic guidance. One group of 10 rats (group A) was treated with MMP-9 siRNA/bioreducible branched polyethylenimine-disulfide cross-linked-indocyanine green (bioreducible BPEI-SS-ICG), while the other group of 10 rats (group B) received control siRNA/bioreducible BPEI-SS-ICG treatment. All rats were sacrificed at 4 weeks. The therapeutic effectiveness of the MMP-9 siRNA/bioreducible BPEI-SS-ICG complex was assessed by comparing the two results of retrograde urethrography, histologic examination, and quantification of MMP-9 by using zymography and Western blot analysis between the two groups. The Mann-Whitney U test was used to evaluate differences. Results: Stent placement was successful in all rats without a single case of migration at follow-up. Retrograde urethrography performed 4 weeks after stent placement demonstrated significantly larger luminal diameters of the urethra within the stents in group A compared with those in group B (P = .011). Histologic analysis revealed that the mean percentage of granulation tissue area (P < .001), mean number of epithelial layers (P < .001), and mean thickness of submucosal fibrosis (P < .001) were significantly decreased in group A compared with group B. Meanwhile, the mean density of inflammatory cell infiltration did not significantly differ between the two groups (P = .184). Quantitative analysis disclosed MMP-9 levels to be lower in group A relative to group B, indicating positive inhibition of MMP-9 by MMP-9 siRNA/bioreducible BPEI-SS-ICG. Conclusion: MMP-9 siRNA/bioreducible BPEI-SS-ICG is effective for inhibiting granulation tissue formation after bare metallic stent placement in a rat urethral model.
    Full-text · Article · Nov 2013 · Radiology