Solifenacin/Mirabegron Induces an Acute Compliance Increase in the Filling Phase of the Capacity-Reduced Urinary Bladder: A Pressure-Volume Analysis in Rats

Abstract

Aims: Pressure in the bladder, which is a high compliance organ, is only slightly elevated to a considerable filling volume during storage. Although cystometry off-line offers mean compliance, no protocol is available for real-time assays of the dynamics of bladder compliance, and the potential impact of solifenacin and mirabegron on dynamic bladder compliance has not been established.Methods: Along with constantly infused cystometry, a pressure-volume analysis (PVA) was performed by plotting intra-vesical volume against pressure in Sprague-Dawley rats. The instant compliance was assayed as the slope of the trajectory, and the mean compliance (Cm) was determined by the slope of the line produced by regression of the data points at the end of the first, second, and third quarters of the filling phase.Results: Under a steady-state, the PVA trajectory moved clockwise which shaped coincident enclosed loops with stable compliance. Though administering to naïve animals solifenacin, but not mirabegron (both 1 × 10−5−1 × 10−1 mg/kg, i.a.) decreased the peak pressure, both of these reagents exhibited acute increments in the trajectory slope and Cm of the filling phase in a dose-dependent manner (ED50 = 1.4 × 10−4 and 2.2 × 10−5 mg/kg, respectively). Resembling urine frequency/urgency in OAB patients, the voiding frequency of a capacity-reduced bladder was increased in association with decreased compliance which was ameliorated by both acute solifenacin and mirabegron injections (both 1 × 10−1 mg/kg).Conclusion: In addition to their well-known anti-inotropic/relaxative effects, solifenacin, and mirabegron induce an acute increase in bladder compliance to ameliorate OAB-like syndromes. Together with time-domain cystometry, PVA offers a platform for investigating the physiology/pathophysiology/pharmacology of bladder compliance which is crucial for urine storage.

Bladder compliance dynamics of pelvic organ prolapse patients subjected to robotic-assisted sacrocolpopexy

“…Whereas, with advancements in computer technology, simultaneously displaying cystometry with PVA is no longer a challenge nowadays. Notably, a recent pre-clinical study demonstrates on-line PVA provides real-time and continuous monitoring of compliance that is automatically calculated by the computer with minimal processing performed by clinicians/scientists [5]. Furthermore, as the pressure increment during bladder lling in the time-domain cystometry is trivial that results in a miserable resolution requiring careful data acquisition/analysis by experts.…”

“…Thereby, to speci cally investigate compliance in stages of interesting, e.g., at a critical pressure triggering a voiding or the minimal volume immediately after a voiding, is still a challenge. Notably, a preclinical study has recently demonstrated the pressure-volume analysis (PVA) is able to assay the dynamics of bladder compliance in rodents [5]; and a very recent study has analyzed voiding work of human bladder using PVA [6]. Yet, if PVA can be used also in clinical practices to measure compliance dynamics of human subject/patients is unclear.…”

Trans-vaginal mesh repair improves bladder compliance in pelvic organ prolapse patients with voiding dysfunctions: A retrospective cohort study

“…Derived from the cystometry, the pressure-volume analysis (PVA) of voiding cycles was established by plotting Vive against Pdet (Figure 1A and B) 15,16,18 . The mean compliance (Cm) during the filling stage was calculated by dividing the infused volume by the threshold pressure (i.e., change in Vive/change in Pdet;…”

“…For this purpose, history of POP patients with voiding difficulties were reviewed; and their data of urodynamic investigations measured before and after the procedure were analyzed by focusing on changes in bladder compliance and associated parameters. Moreover, as a preclinical study has demonstrated pressurevolume analysis (PVA) as a tool that graphically and conceptually assesses the bladder compliance 15 ; and a retrograde cohort analysis has very recently established PVA in stress urinary incontinence patients 16 , we established PVA of POP patients and assayed the bladder compliance as the slope of the regression line of the trajectory during the filling stage.…”

Modification of bladder thermodynamics in stress urinary incontinence patients submitted to trans-obturator tape: A retrospective study based on urodynamic assessment

“…The vesical pressure (Figure 1A Pves), abdominal pressure (Pabd), detrusor pressure (Pdet), urethral flow (Flow), voided volume (Vvod), infused volume (Vinf), and intravesical volume (Vive) were recorded online, and the mean voiding pressure (Figure 1B Pv, the mean Pdet during fluid emission), the voided volume (Vv, the volume evacuated by the bladder), the voiding time (Tv, the time of fluid emission), and the mean voiding resistance (Rv, calculated by Pv/(Vv/Tv)) were analyzed off-line. Derived from the cystometry (Figure 2A), the PVA of voiding cycles was established by plotting Pdet versus Vive (Figure 2B) (Peng et al, 2020;Peng et al, 2021). Comparable to cystometry, orthogonal projection of the top trajectory onto the abscissa represented the voided volume (Vv) of a voiding cycle, and the trajectory-enclosed area (Apv) was analyzed using an imageprocessing program (ImageJ, LOCI, Madison, WI, United States).…”