Vascular therapy for radiation cystitis

Purpose The underlying pathology of radiation cystitis is cellular and vascular damage followed by increased fibrosis and inflammation. This study was to determine if neovascular‐promoting therapy could reduce the pathological changes in the bladder wall associated with pelvic irradiation. Methods Adult female Lewis inbred rats were irradiated with a single dose of 20 Gy directed at their bladder. Four weeks later, 30 rats were divided equally into one of three treatment groups for bladder wall injection of: (1) PBS (Control); (2) PBS containing 50 ng vascular endothelial growth factor (VEGF 165 ); or (3) PBS containing 1 × 10 6 rat endothelial cells (EC). Age‐matched non‐irradiated rats (n = 10) served as untreated controls. At either 1.5 or 3 months following radiation, bladders were analyzed for collagen deposition using Masson's Trichrome staining of collagen and muscle and vascularization using Von Willebrand factor staining of ECs. Quantitative‐PCR was used to examine markers of angiogenesis, hypoxia, and fibrosis. Results The collagen/muscle ratio was doubled in the control group 3 months post‐irradiation ( P  < 0.05 vs. non‐irradiated bladders). Both ECs and VEGF inhibited increases in collagen content ( P  < 0.05 vs. control). Similarly, irradiation reduced bladder wall vessel counts compared to non‐irradiated controls ( P  < 0.05) and both ECs and VEGF maintained vessel counts similar to that of non‐irradiated controls ( P  < 0.05). PCR analysis showed a higher expression of neovascular markers (CD31, KDR) in the EC and VEGF groups compared to non‐irradiated controls ( P  < 0.05). Conclusions Angiogenesis therapy may be useful in the prevention and/or treatment of the underlying pathology of radiation cystitis. Neurourol. Urodynam. 30:428–434, 2011. © 2010 Wiley‐Liss, Inc.