Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse

Abstract

The prevalence of urinary symptoms increases with age and is a significant source of distress, morbidity, and expense in the elderly. Recent evidence suggests that symptoms in the aged may result from sensory dysfunction, rather than abnormalities of detrusor performance. Therefore, we employed a pressure/flow multichannel urethane-anesthetized mouse cystometry model to test the hypothesis that in vivo detrusor performance does not degrade with aging. Secondarily, we sought to evaluate sensory responsiveness to volume using pressure-volume data generated during bladder filling. Cystometric data from 2-, 12-, 22-, and 26-mo-old female C57BL6 mice were compared. All 2- and 12-mo-old mice, 66% of 22-mo-old mice, and 50% of 26-mo-old mice responded to continuous bladder filling with periodic reflex voiding. Abdominal wall contraction with voiding had a minimal contribution to expulsive pressure, whereas compliance pressure was a significant contributor. Maximum bladder pressure, estimated detrusor pressure, detrusor impulse (pressure-time integral), as well as indices of detrusor power and work, did not decrease with aging. Bladder precontraction pressures decreased, compliance increased, and nonvoiding contraction counts did not change with increasing age. Intervoid intervals, per-void volumes, and voiding flow rates increased with age. Calculations approximating wall stress during filling suggested loss of bladder volume sensitivity with increasing age. We conclude that aging is associated with an impaired ability to respond to the challenge of continuous bladder filling with cyclic voiding, yet among responsive animals, voiding detrusor contraction strength does not degrade with aging in this murine model. Furthermore, indirect measures suggest that bladder volume sensitivity is diminished. Thus, changes in homeostatic reserve and peripheral and/or central sensory mechanisms may be important contributors to aging-associated changes in bladder function.

Evidence of increased centrally enhanced bladder compliance with ageing in a mouse model

“…These ages correspond to young, mature, old and oldest old, and are representative of maturation and ageing over the lifespan of colony mice [23]. Sample sizes were chosen based on prior ageing mouse cystometry results [1]. In all, 23 mice underwent cystometric preparation to obtain five successful cystometric filling/voiding studies in each age group.…”

“…Mice were prepared for constant-infusion cystometry following published methods [1]. Anaesthesia was established with i.p.…”

“…The bladder was constantly filled at 0.025 mL/min using room-temperature normal saline delivered by a calibrated syringe pump with in-line pressure transducer. This rate has been used in prior ageing reports in the mouse model [1,24]. The impact of ageing on urine production has not been directly reported; however, standard diet colony mouse urine production (0.35-0.7 μL/min [25]) is very small compared with this filling rate.…”

“…Ageing is associated with increases in bladder compliance, especially early in filling, in the mouse cystometric model [1]. In the absence of outlet obstruction or urinary symptoms, data from other animal models and in humans either confirm or do not refute this finding [2][3][4][5].…”

“…By contrast, mice and other animal cystometric models show repetitive non-voiding contractions (NVCs) of greater amplitude and frequency as the voiding threshold is approached. NVCs may vary in both frequency and intensity depending upon the degree of bladder distension and age, showing a decline from 0.4 to <0.1 Hz over the lifespan in the mouse [1,18]. NVCs have been interpreted as pre-voiding activity [19] or as the result of bladder pathology [20].…”