The effects of microenergy acoustic pulses on an animal model of obesity‐associated stress urinary incontinence. Part 1: Functional and histologic studies

Abstract

Aim Obesity is a strong independent risk factor for urinary incontinence. Effective therapeutic approaches for obesity‐associated stress urinary incontinence (OA‐SUI) are lacking as the mechanisms remain unclear. The aim of our study is to explore the impacts of microenergy acoustic pulse (MAP) therapy on urethral and pelvic floor muscle structure and function in female lean and fatty rats. Methods A total 24 Zucker fatty (ZF) and 24 Zucker lean (ZL) female 24‐week‐old rats were grouped into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. For MAP treatment, 500 pulses were delivered at an energy level of 0.033 mJ/mm 2 and a frequency of 3 Hz and were applied twice a week for 4 weeks. After a 1‐week washout, all rats underwent conscious cystometry and leak‐point pressure (LPP) measurements followed by ex vivo organ‐bath assay and histological study. Results ZF rats had lower LPP as compared to ZL rats, and MAP treatment significantly improved LPP in ZF rats (P < .05). Impaired muscle contractile activity (MCA) in organ‐bath study was noted in ZF rats. MAP treatment significantly increased MCA in ZF rats (P < .05) and also increased the thickness of the striated muscle layer and the number of neuromuscular junctions (NMJs). In situ, MAP activated muscle satellite cells significantly (P < .05). Conclusions Obesity impairs the function of both the urethral sphincter and the pelvic floor and leads to atrophy and distortion of the striated muscle in obese female rats. These issues contribute to OA‐SUI. MAP improves continence by stimulating muscle regeneration and nerve innervation as well as by activating satellite cells.

Regenerating Urethral Striated Muscle by CRISPRi/dCas9-KRAB-Mediated Myostatin Silencing for Obesity-Associated Stress Urinary Incontinence

“…24,32 In addition, our previous work shows that muscle stem/progenitor cells can be activated (using microenergy acoustic pulses [MAP]) for urethral stM regeneration, thus improving urinary function. 35,36 StMs were found throughout the main portion of the…”

“…Very recently, we reported that MAP treatment restored micturition function in ZF rats via activation of muscle stem/progenitor cells to regenerate the urethral sphincter muscle. 35,36 With the goal of finding alternative, potentially more effective, efficient ways to accomplish this task, we applied CRISPRi/MSTN system in the OA-SUI animal model in vivo. Strikingly, 4 weeks after the delivery of CRISPRi/MSTN system in the urethral tissue, the LPP significantly improved by twofold in the ZF rats.…”

Microenergy acoustic pulses promotes muscle regeneration through in situ activation of muscle stem cells

“…The application of MAP treatment was performed on the same hindlimb at 1 week after the initial injury by using a compact electromagnetic unit with an unfocused acoustic pulse source (LiteMed Inc.). 9 Animals were under general anesthesia and the shock wave probe was applied directly to the shaved tibialis anterior (TA) muscles and was coupled to the skin using ultrasound gel (Aquasonic, Parker Laboratories Inc.). The MAP had an energy flux density at 0.059 mJ/mm 2 , and 500 pulses were delivered at 3 Hz.…”

“…7 Recently, an improved technology of Li-ESWT named microenergy acoustic pulses (MAP) has been developed. 8,9 Compared to the traditional Li-ESWT and other shock wave-based therapies, the beam of the acoustic pulses of MAP is defocused to allow more even energy distribution to the treated tissue and eliminates the potential damage to issue at focal point. 10 We discovered that MAP ameliorated stress urinary incontinence (SUI) by enhancing regeneration of striated muscles in the external urinary sphincter and pelvic floor in rats.…”

“…10 We discovered that MAP ameliorated stress urinary incontinence (SUI) by enhancing regeneration of striated muscles in the external urinary sphincter and pelvic floor in rats. 9 Currently, MAP is under Phase III clinical trial for treating SUI and expected to receive Food and Drug Administration approval for clinical use soon.…”