Document Detail

Bladder outlet obstruction: progression from inflammation to fibrosis.
MedLine Citation:
PMID:  20590549     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO.
MATERIALS AND METHODS: Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham-operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription-polymerase chain reaction for collagen, transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), hypoxia inducible factor 1α (HIF-1α), and platelet-derived growth factor (PDGF-A) was performed on all samples, as well as immunohistochemistry (IHC) for α-smooth muscle actin (α-SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis.
RESULTS: After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high-pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF-β, CTGF, HIF-1α, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for α-SMA showed a progressive increase associated with the elevated bladder pressures. Masson's trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks.
CONCLUSION: With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation.
Peter D Metcalfe; JianFei Wang; Haiyan Jiao; Yue Huang; Keijiro Hori; Ronald B Moore; Edward E Tredget
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  BJU international     Volume:  106     ISSN:  1464-410X     ISO Abbreviation:  BJU Int.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-16     Completed Date:  2011-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100886721     Medline TA:  BJU Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  1686-94     Citation Subset:  IM    
Copyright Information:
Division of Paediatric Surgery, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
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MeSH Terms
Collagen / metabolism
Connective Tissue Growth Factor / metabolism
Cystitis / pathology
Disease Models, Animal
Disease Progression
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Muscle, Smooth / pathology*
Platelet-Derived Growth Factor / metabolism
Rats, Inbred F344
Reverse Transcriptase Polymerase Chain Reaction
Transforming Growth Factor beta / metabolism
Urinary Bladder / pathology*
Urinary Bladder Neck Obstruction / pathology*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Platelet-Derived Growth Factor; 0/Transforming Growth Factor beta; 0/platelet-derived growth factor A; 139568-91-5/Connective Tissue Growth Factor; 9007-34-5/Collagen

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