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Bladder outlet obstruction: progression from inflammation to fibrosis
Author(s) -
Metcalfe Peter D.,
Wang JianFei,
Jiao Haiyan,
Huang Yue,
Hori Keijiro,
Moore Ronald B.,
Tredget Edward E.
Publication year - 2010
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2010.09445.x
Subject(s) - ctgf , masson's trichrome stain , fibrosis , growth factor , medicine , pathology , connective tissue , bladder outlet obstruction , platelet derived growth factor , immunohistochemistry , elastin , platelet derived growth factor receptor , muscle hypertrophy , inflammation , urology , prostate , receptor , cancer
Study Type – Aetiology (case control)
Level of Evidence 3b 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.