Long-term functional change of cryoinjury-induced detrusor underactivity and effects of extracorporeal shock wave therapy in a rat model

Abstract

Purpose: To investigate the long-term functional change of cryoinjury-induced detrusor underactivity (DU) and the therapeutic potential of repeated low-energy shock wave therapy (LESW).

Methods: Fifty-six female Sprague-Dawley rats were assigned into sham and cryoinjury of bladder with or without LESW (0.05 or 0.12 mJ/mm²; 200 pulses; twice a week for 2 weeks after cryoinjury). Under halothane anesthesia, an incision was made in lower abdomen, and cryoinjury was provoked by bilateral placement of a chilled aluminum rod on the bladder filled with 1 ml saline. Measurement of contractile responses to KCl and carbachol in vitro, conscious voiding, and histological and protein changes were performed on week 1, 2, and 4 after cryoinjury.

Results: Cryoinjury of bladder induced a significant decrease in the detrusor contraction amplitude at week 1 (55.0%) and week 2 (57.2%), but the decrease in the contractile response to KCl and carbachol was only noted at week 1. At week 1, significantly increased COX-2 and TGF-β1 expression accompanied a decrease of VEGF and CGRP expression. At week 4, there was a partial recovery of voiding function and a significant increase in the Ki-67 staining. LESW treatment at higher energy level further amplified the Ki-67 staining and improved the recovery of contraction amplitude and the expression of TGF-β1 and VEGF.

Conclusions: Cryoinjury of detrusor induces DU/UAB with functional impairment lasting for up to 4 weeks, but the associated molecular changes are restored by 2 weeks. LESW improved bladder wall composition, and hastened functional recovery from cryoinjury.

Keywords: Cryoinjury; Detrusor underactivity; Shock wave.