Aims
The Sprague–Dawley (SD) rat, an out-bred, all-purpose strain, has served well for lower urinary tract research. However, to test new cellular therapies for conditions such as stress urinary incontinence, an in-bred rat strain with immune tolerance, such as the Lewis rat, may be more useful. The objective of this study was to reveal any differences in lower urinary tract continence mechanisms between the Lewis and SD rat.
Methods
The contribution of (1) the striated and smooth muscle to the mechanical and functional properties of the urethra in vitro, and (2) the striated sphincter to leak point pressure (LPP) and reflex continence mechanisms in vivo were assessed in normal (control) Lewis and SD rats and in a model of stress urinary incontinence produced by bilateral pudendal nerve transection.
Results
Control, Lewis rats had significantly lower LPP, significantly less fast-twitch skeletal muscle and relied less on the striated sphincter for continence than control, SD rats, as indicated by the failure of neuromuscular blockade with alpha-bungarotoxin to reduce LPP. Nerve transection significantly decreased LPP in the SD rat, but not in the Lewis rat. Although the Lewis urethra contained more smooth muscle than the SD rat, it was less active in vitro as indicated by a low urethral baseline pressure and lack of response to phenylephrine.
Conclusions
We have observed distinct differences in functional and mechanical properties of the SD and Lewis urethra and have shown that the Lewis rat may not be suitable as a chronic model of SUI via nerve transection.
Urethral dysfunction is a common complication of diabetes mellitus, spinal cord injury, vaginal childbirth, and pelvic trauma. Stress urinary incontinence (SUI) is the involuntary loss of urine due to the inability of the urethral sphincter to maintain a tight seal during the storage phase, and is a disease that physically and emotionally affects 25 million American women annually [1]. There are currently several treatments for SUI including surgery, Kegel exercises, and electrical stimulation, each accompanied by limited effectiveness and/or complications [2–3]. We believe that regenerative medicine techniques applied to the native urethra may aid in improving the function and support of the diseased urethra. Thus, we have begun the development of a tissue engineered urethral wrap (TEUW) for placement as a cuff around the native urethra and integration with the host tissue. The goal of this work was to determine optimized culture conditions for TEUWs and to determine if their use in vivo improves urethral function.
Urethral dysfunction is a common complication of diabetes mellitus, spinal cord injury, vaginal childbirth, and pelvic trauma. Stress urinary incontinence (SUI) is the involuntary loss of urine due to the inability of the urethral sphincter to maintain a tight seal during the storage phase and is a condition that physically and emotionally affects 25 million American women annually [1]. There are currently several treatments for SUI including surgery, Kegel exercises, and electrical stimulation, each accompanied by limited effectiveness and/or complications [2–3]. We believe that regenerative medicine techniques, applied to the native urethra, may aid in improving the function and support of the diseased urethra. Thus, we have begun the development of a tissue engineered urethral wrap (TEUW) for placement as a cuff around the native urethra and integration with the host tissue. The goal of this work was to explore structural and mechanical effects following implantation of a TEUW.
Millions of people worldwide suffer from an involuntary leakage of urine, a condition known as urinary incontinence. In the US alone, the estimated cost of managing this is more than $16 billion [1]. Stress urinary incontinence (SUI), the most common form, is characterized by involuntary leakage of urine from effort or exertion during actions such as laughing, coughing, or sneezing. SUI largely occurs as a result of weak or damaged pelvic muscles that support the bladder and urethra, which makes the urethra unable to maintain its seal and allows urine to leak. Current SUI treatments such as pelvic floor muscle training, vaginal inserts, pharmacologic therapeutics, and surgical procedures are limited by ineffectiveness and/or subsequent complications [2, 3].
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.