Transurethral versus suprapubic catheterization to test urethral function in rats

Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization. There was no significant difference in peak bladder pressure during LPP testing whether measured with a transurethral or suprapubic catheter. There was no significant difference in peak bladder pressure between the first and second catheter insertions. However, peak EMG firing rate, as well as peak EMG amplitude and EMG amplitude difference between peak and baseline were significantly higher after the first catheter insertion compared to the second insertion, regardless of the catheter method. Our results suggest that route of catheterization does not alter urethral function, e.g. create a functional partial outlet obstruction. Either catheterization method could be used for LPP and/or EUS EMG testing in rats.

High-density spinal cord stimulation selectively activates lower urinary tract afferents

Epidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.

Secretomes of human pluripotent stem cell-derived smooth muscle cell progenitors upregulate extracellular matrix metabolism in the lower urinary tract and vagina

Background: Adult mesenchymal stem cells (MSCs) have been studied extensively for regenerative medicine, however, they have limited proliferation in vitro, and the long culture time induces cell senescence. MSCs also contribute to tissue repair through their paracrine function. In this study, we sought to examine the paracrine effects of smooth muscle cell progenitors (pSMC) on the urethra and adjacent vagina of stress urinary incontinence rodents. We use human pluripotent stem cell (PSC) lines to derive pSMCs to overcome the issue of decreased proliferation and to obtain a homogenous cell population. This novel approach for treatment of urinary incontinence can also be expanded into treatments for other pelvic floor disorders. Method: Three human PSC lines were differentiated into pSMCs. The conditioned medium (CM) from pSMC culture, which contain pSMC secretomes, was harvested. To examine the effect of the CM on the extracellular matrix of the lower urinary tract, human bladder smooth muscle cells (bSMCs) and vaginal fibroblasts were treated with pSMC-CM in vitro. Stress urinary incontinence (SUI) was induced in rats by surgical injury of the urethra and adjacent vagina. SUI rats were treated with pSMC-CM and monitored for 5 weeks. Urethral pressure testing was performed prior to euthanasia, and tissues were harvested for PCR, Western Blot and histological staining. Kruskal-Wallis one-way ANOVA test and Student t-test were used for statistical comparisons. Results: pSMC-CM upregulated MMP-2, TIMP-2, collagen, and elastin gene expression, and MMP-9 activity in human bladder and vaginal cells consistent with elastin metabolism modulation. pSMC-CM treatment restored in vivo urethral function (increase in leak point pressure compared to intact controls, p<0.05) and increased collagen and elastin expression in the urethra and the adjacent vagina. pSMC-CM also restored the smooth muscle cell layer in the adjacent vagina. Conclusion: Conditioned media from smooth muscle cell progenitors derived from pluripotent stem cells restored urethral function and vaginal smooth muscle cell and elastin content. These findings support a novel therapeutic potential for PSC-based treatments for SUI and pelvic floor disorders where tissues are affected by elastin and smooth muscle loss.

Assessment of the urinary tract

This chapter covers assessment techniques for examining the urinary tract. It begins with symptoms and definitions that indicate assessment would be necessary and a procedure for general initial assessment, and baseline investigations. It then explains cystoscopy and relevant findings, urodynamic tests, uroflowmetry, cystometry, and filling cystometry, as well as additional urodynamic tests (e.g. ambulatory urodynamics and videourodynamics). Finally, urethral pressure profilometry for testing urethral function are described. Guidelines to the correct terminology used to describe symptoms and diagnoses are laid out as well as definitions of compliance and contractility, along with illustrative figures to show the assessment process of the urinary tract.