Current methods o f studying fetal bladder physiology are human fetal ultrasound and physiological measurements made in whole organ preparations, muscle strip studies and in vivo fetal bladders.
2.7.1 Ultrasound studies of the developing bladder
As early as 20 weeks o f gestation, the human fetal bladder is able to store and empty urine; with increasing gestation, these functions mature as bladder capacity and
every 60 minutes by 40 weeks gestation (Hata and Deter, 1992). The maximum fetal bladder volume increases from 1 ml at 20 weeks gestation to 36 - 54 ml by 40 weeks gestation (Rabinowitz et al, 1989) with average voiding lasting approximately 9.5 seconds; complete bladder emptying is achieved by 40 weeks gestation.
2.7.2 Ontogeny of animal fetal bladder physiology
Whole bladder studies from the fetal calf reveal that with increasing gestation, the fetal bladder demonstrates increased compliance (the bladder is able to accommodate increased urinary volume without an increase in intravesical pressure) (Coplen et al, 1994; Koo et al, 1995). This was confirmed in a study using circularly clamped fetal bladder strips (Baskin et al, 1994a). It has since been postulated that the change in compliance during gestation is associated with the documented transformation in collagen subtype expression (Kim et al, 1991a; Koo et al, 1997). Furthermore, muscle tone has also been implicated; compliance increases through gestation because the immature fetal bladder has high active smooth muscle tone that decreases with
maturation allowing for this greater urine accommodation (Coplen et al, 1994; Dean et al, 1997).
Active contractile fimction also develops during gestation. Early gestation whole bladder preparations from the fetal calf emptied by 50 % when stimulated with the muscarinic agonist, bethanechol, whilst mid and late gestation preparations emptied to almost completion (Koo et al, 1995). These age-related differences in contractility may only relate to the upper half o f the fetal bladder (Lee et al, 1994).
By documenting pressure changes within the fetal bladder using indwelling catheters,
ovine fetal bladder contractions were discernable at 1 2 0 days gestation and could be
pharmacologically manipulated (Kogan and Iwamoto, 1989); contractile function appeared to be under cholinergic and P-adrenergic control. By using a similar method at the same gestation, nitric oxide also appeared to be active in lower urinary tract function (Mevorach et al, 1994). Finally, during this period, ovine fetal voiding appeared to coincide with periods o f electrocortical activity in the fetal brain (Wlodek et al, 1989) suggesting that descending control o f bladder activity was developed.
Pressure recordings within the fetal pig also show maturation o f bladder function (Olsen et al, 2001). During the second trimester, fetuses showed no sign o f active storage and voiding with continuous urine flow with apparent flow increases synchronous with bladder contractions; this suggests that at this gestation in the fetal pig, the bladder acts simply as a conduit. By the third trimester, distinct periods o f voiding were observed with urethral urine flow, bladder contractions (that were o f higher pressure than earlier in gestation) and the development o f urethral sphincter bursting activity.
2.7.3 Physiology of the obstructed fetal bladder
reported hypocontractile obstructed bladder strips. In contrast, by different methodology, Peters et al (1992b) reported reduced compliance in the obstructed ovine fetus. Levin et al (2 0 0 1) also described hypocontractile responses in ovine fetal bladders after short-term
bladder outflow obstruction.
2.7.4 In vivo fetal cystometry
Currently, only three studies have documented pressure characteristics in the fetal
bladder, in the fetal sheep and fetal pig, using externalised catheters. Kogan and Iwamoto (1989) used intravesical catheters, connected to pressure recorders, in the fetal sheep. With the ewes ambulatory, fetal bladder pressures were documented following intravenous ftirosemide administration or by artificially filling the bladder. Similarly, Mevorach et al (1994) documented bladder contractions in the ovine fetus by artificially filling the bladder with warm saline and pressures recorded with intravesical catheters. Finally, under maternal sedation, Olsen et al (2001) reported fetal bladder pressures in the porcine fetus using intravesical catheters but without any artificial means o f bladder filling by instillation or forced diuresis. These studies, however, are not without problems: animals will try to remove catheters on their flanks, animals have imposed immobility and are stressed, there is an increased risk o f infection and fetal mortality and studies tend to be o f a short duration. Furthermore, ambulatory urodynamics in humans suggest that artificial filling and a stressful environment may result in nonphysiological detrusor activity; compliance remains high, unstable detrusor activity is more fi-equently observed, voided volumes are lower and maximum voided pressures higher (Robertson et al, 1994; Robertson et al, 1996; Vereecken and Van Nuland, 1998; Webb et al, 1990). To
overcome these difficulties, investigators have used radiotelemetry devices to monitor bladder pressure. These have a number o f advantages (Mills et al, 2000): reduced stress to animals (no handling, restraining or tethering to recording machines, no anaesthesia and no invasive monitoring), monitoring can be over a prolonged period o f time
providing meaningful physiological data, and computer-based monitoring allows accurate mathematical analysis. Radiotelemetered cystometry had been used successfully to describe ambulatory pressure recordings in the bladder, by natural filling, in the adult pig (Mills et al, 2000) and adult monkey (El Ghoneimi et al, 1999) and the obstructed adult pig (Speakman et al, 1987); such technology has not been evaluated in the fetal bladder.