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Title: Short-term fetal bladder outflow obstruction in the ovine model : bladder morphology, physiology and in-utero urodynamics
Author: Farrugia, Marie-Klaire
ISNI:       0000 0004 2673 1936
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2008
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Aim: Previous work carried out at the Institute of Child Health revealed that in the fetal sheep, combined urethral and urachal occlusion initiated at 75 days gestation (full term = 145 days) and maintained for 30 days resulted in dilated, hypocontractile and hypercompliant bladders, associated with uniformly disrupted kidney development. The aim of this project was to create a less severe model of fetal bladder outlet obstruction, and to define the role of the urachus. This model would then be utilised to investigate the prenatal onset of obstructive bladder dysfunction by means of in-utero radiotelemetered urodynamics. We hypothesised that short-term obstruction would result in a thick-walled bladder with preserved contractility and compliance, and that urachal ligation alone would result in similar features.;Methods: Male fetal lambs were assigned to urachal ligation and partial urethral occlusion, urachal ligation only, or sham, groups. Histological analyses, filling cystometry and contractility studies were performed following nine days of obstruction. Natural-fill radiotelemetered urodynamics were performed on the urachal and urethral occlusion group.;Results: Nine days urachal and urethral occlusion from mid-gestation caused hydronephrosis and increased bladder weight, protein and DNA content. Detrusor smooth muscle architecture was maintained but urothelia were thickened and showed basal apoptosis. Bladder compliance, wall stress and contractility were not significantly deranged. The thickest, most compliant bladders were found to be associated with kidneys exhibiting glomerular cysts. Urachal obstruction alone also resulted in similar changes, suggesting that the male fetal lamb urethra is a high-resistance conduit at this gestation. Radiotelemetered urodynamics were only feasible in the obstructed group from 94 days gestation, and revealed the presence of early-onset hypercontractility. Fetal voids became increasingly frequent and prolonged, occurring at higher voiding pressures baseline filling pressures did not vary significantly over the nine-day period of observation.;Conclusion: Short-term fetal bladder outflow obstruction from mid-gestation generated thick-walled bladders without evidence of contractile failure these were associated with cystic kidneys. Detrusor hypercontractility and raised voiding pressures were observed within hours of obstruction, although filling pressures remained stable. Future work will investigate the effect of vesico-amniotic shunting on bladder function.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available