Persistent detrusor overactivity in rats after relief of partial urethral obstruction

Abstract

Detrusor overactivity (DO) persists after prostatectomy in 20% to 25% of patients with benign disease. Assuming that nonvoiding contractions (NVCs) can be used as a surrogate for DO in humans, the rat model of obstruction/ deobstruction may allow us to study the pathophysiology of persistent DO after deobstruction. We investigated bladder function, with a special focus on NVCs, in rats by use of a new, modified method of obstruction and deobstruction and compared these results with those obtained by use of the conventional method. Seventy female SpragueDawley rats underwent 1) sham operation (n ϭ 10), 2) obstruction by a modified method (Modif-Obs; n ϭ 12), 3) obstruction/deobstruction by the conventional method (Conv-Obs/Deobs; n ϭ 13), or 4) obstruction/deobstruction by the modified method (Modif-Obs/ Deobs; n ϭ 35). The Modif-Obs/Deobs animals were divided into subgroups with (DOϩ) and without (DOϪ) NVCs. Two weeks after partial urethral obstruction, the animals were deobstructed, and 1 wk later cystometry was performed with recording of intravesical and intra-abdominal pressures. NVCs were shown in all groups: ModifObs (80%), Conv-Obs/Deobs (100%), and Modif-Obs/Deobs (40%). In the Modif-Obs/Deobs group, bladder weight and the muscle-tocollagen ratio were higher in DOϩ than in DOϪ rats. The ModifObs/Deobs group showed no mortality compared with 25% mortality in the Conv-Obs/Deobs group. The modified method may be more adequate for studying persistent DO after deobstruction, because it resulted in pressure/volume-and DO-related parameters similar to those found in the clinical situation. The persistence of DO after deobstruction may partly be due to irreversible changes in the bladder caused during the period of obstruction. urinary bladder; cystometry BENIGN PROSTATIC HYPERPLASIA occurs as part of the aging process in men and affects Ͼ 50% of the male population over 60 yr of age (11). The clinical symptoms of benign prostatic hyperplasia are caused not only by the mass-related increase in urethral resistance but also by pathologic processes in the bladder wall secondary to the bladder outlet obstruction (BOO) (18,26,35,40). In many studies on patients with BOO undergoing surgery for benign prostatic hyperplasia, a significant percentage of patients report persistence of storage (irritative) symptoms, associated with detrusor overactivity (DO) on urodynamic investigation, even if the obstruction was successfully relieved. In fact, DO has been shown to persist after prostatectomy in 20% to 25% of patients treated for benign disease (2,19,29,33).Rats subjected to BOO will develop hyperactive voiding, characterized by increased frequency and nonvoiding contractions (NVCs), which persists after deobstruction in a proportion of the animals (6,20,23,24,27,30). The relations between symptoms, BOO, and bladder function can, for obvious reasons, not be studied in animal models. However, assuming that NVCs can be used as a surrogate parameter for DO in humans, the rat model of obstruction/deobstruction may offer an op...

Flow Starting Point and Voiding Mechanisms Measured by Simultaneous Registrations of Intravesical, Intra-abdominal, and Intraurethral Pressures in Awake Rats

“…Based on the fact that, without the IPHFOs, the bladder contains significant amounts of residual urine [10,19,25,26], IPHFOs are presumed to be responsible for efficient voiding in male [6,25] and female [7] rats. However, their exact role in voiding remains controversial.…”

“…This was followed by IPHFOs showing pulsatile fluctuation of the IVP curve (phase 2) [4]. After that, the curve increased again (phase 3) [6,7], and the initial point of this increase was defined as TmP3. The top of this increase was defined as TmP4, and there was a rapid pressure decline to the low level seen prior to micturition contraction (phase 4).…”

“…In rat cystometry, understanding these reciprocal actions that result in bladder emptying requires careful interpretation of the unpredictable intravesical pressure (IVP) curve based on simultaneous urethral activity [3], which is primarily caused by intra-abdominal pressure (IAP) changes during the awake condition [4,5]. In anesthetized rats, the dynamic nature of voiding has been well proven and documented based on observations of the simultaneous activities of the bladder and urethra [6,7,8]. However, controversy persists concerning interpretations of the IVP curve of awake animals during the voiding phase due to unpredictable IAP changes and the lack of a reliable method for measuring urethral activity in the awake condition [9].…”

“…On transvesical cystometry in anesthetized rats, the IVP curve shape during micturition can be divided into four distinct phases [6,7,10]. It has been well proven that urinary flow starts at the initial point of the second phase, followed by intraluminal pressure high-frequency oscillations (IPHFOs), and that the conventional concept of micturition pressure (MP) exists between the third and fourth phases [4,5,6,7].…”

“…It has been well proven that urinary flow starts at the initial point of the second phase, followed by intraluminal pressure high-frequency oscillations (IPHFOs), and that the conventional concept of micturition pressure (MP) exists between the third and fourth phases [4,5,6,7]. However, this has never been described in awake rats due to the lack of an adequate method for assessing intraurethral pressure (IUP) in this condition.…”