The validation of a functional, isolated pig bladder model for physiological experimentation

Brian Parsons

doi:10.3389/fphar.2012.00052

Abstract

Characterizing the integrative physiology of the bladder requires whole organ preparations. The purpose of this study was to validate an isolated large animal (pig) bladder preparation, through arterial and intravesical drug administration, intravesical pressure recording, and filming of surface micromotions. Female pig bladders were obtained from the local abattoir and arterially perfused in vitro. Arterial and intravesical pressures were recorded at varying volumes. Bladder viability was assessed histologically and by monitoring inflow and outflow pH. Arterial drug administration employed boluses introduced into the perfusate. Intravesical administration involved slow instillation and a prolonged dwell-time. Surface micromotions were recorded by filming the separation of surface markers concurrently with intravesical pressure measurement. Adequate perfusion to all bladder layers was achieved for up to 8 h; there was no structural deterioration nor alteration in inflow and effluent perfusate pH. Arterial drug administration (carbachol and potassium chloride) showed consistent dose-dependent responses. Localized movements (micromotions) occurred over the bladder surface, with variable correlation with fluctuations of intravesical pressure. The isolated pig bladder is a valid approach to study integrative bladder physiology. It remains viable when perfused in vitro, responds to different routes of drug administration and provides a model to correlate movements of the bladder wall directly to variation of intravesical pressure.

Highlights

The primary physiological functions of the urinary bladder are the storage of urine at relatively low intravesical pressure and its expulsion at appropriate times
The contractile properties of the bladder are controlled by descending central inhibition and activation which overlay a complex autonomous activity. The latter is most readily characterized when the bladder is freed from central control (Van Duyl, 1985; Coolsaet et al, 1993; Sugaya and de Groat, 2000; Drake et al, 2003a,b; Gevaert et al, 2009). It is manifest as localized contractions and stretches of the bladder wall which can be enhanced by increases in intravesical volume or by applying a muscarinic receptor agonist at low concentrations (Gillespie et al, 2003; Lagou et al, 2004)
In early experiments as the whole bladder apparatus was being developed, we found that perfusion rates of 30 ml/min or above led to excessive edema

Summary

Introduction

The primary physiological functions of the urinary bladder are the storage of urine at relatively low intravesical pressure and its expulsion (voiding) at appropriate times. The contractile properties of the bladder are controlled by descending central inhibition and activation which overlay a complex autonomous (spontaneous) activity The latter is most readily characterized when the bladder is freed from central control (Van Duyl, 1985; Coolsaet et al, 1993; Sugaya and de Groat, 2000; Drake et al, 2003a,b; Gevaert et al, 2009). It is manifest as localized contractions and stretches of the bladder wall which can be enhanced by increases in intravesical volume or by applying a muscarinic receptor agonist at low concentrations (Gillespie et al, 2003; Lagou et al, 2004). Spontaneous contractions contribute to the overall contractile properties of the bladder under physiological and pathological conditions such as the overactive bladder (Kinder and Mundy, 1987)

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