Shutaro Manabe

Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney?

BACKGROUND In our fetal lamb model of lower urinary tract obstruction, a valved shunt preserves bladder function. This study investigates the effects on renal histology. METHODS We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared renal histology in 4 groups: group A-OU without shunt, group B-low-pressure shunt (15-54mmH2O), group C-high-pressure shunt (95-150mmH2O). Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS We delivered 32 fetuses from 23 ewes: 13 fetuses in group A (9 survived), 6 fetuses in group B (5 survived), 7 fetuses in group C (5 survived), and 6 fetuses in group D. Histologically, we found renal tubular distention, vacuolated degeneration of tubular epithelial cells in 7 lambs, and cyst formation in 4 lambs in group A. There was renal tubular distention in two lambs, and cyst formation in one lamb in both groups B and C, with vacuolated degeneration of tubular epithelial cells observed in all but 1 lamb in each group. CONCLUSIONS V-A shunting prevents multicystic dysplastic kidney (MCDK). Some lambs have renal tubular distention and vacuolated degeneration of renal tubular epithelial cells.

Pressure limited vesico-amniotic shunt allows normal lung growth in a fetal lamb model of obstructive uropathy.

BACKGROUND In our fetal lamb model of lower urinary tract obstruction, a pressure limited shunt preserves bladder function and renal development. This study investigates the effects on pulmonary histology. METHODS We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared pulmonary histology in 4 groups: group A, OU without shunt; group B, pressure limited shunt; group C, non-valved shunt. Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS We compared 27 fetuses: 7 fetuses in group A, 4 fetuses in group B, 2 fetuses in group C, and 14 fetuses in group D. There was no significant difference in lung volume in any group. In group A, there were some areas of atelectasis and incomplete alveolar formation histologically. The alveoli in group A lambs lungs had a predominance of type II cells, whereas group B lambs lungs were lined by type I epithelial cells and were essentially indistinguishable from controls. CONCLUSIONS This study suggests that using a pressure-limited vesico-amniotic shunt in OU may preserve the renal tract and the lungs.

Does a large abdominal wall defect affect lung growth

BACKGROUND/PURPOSE Respiratory distress in babies with large abdominal wall defects suggests a relationship to decreased diaphragmatic movement. We evaluated pulmonary development in a fetal lamb gastroschisis model. METHODS We created gastroschisis in 25 fetal lambs at 60days gestation (group A). Controls were 14 nonoperated lambs. (Group B) were all delivered at term. Lung volume, histology, and type 1 (AT1)/type 2 (AT2) cell ratios (AT1 ratio) were determined. We subdivided group A, comparing lambs with a large defect and scoliosis [group A (S)] with the remainder [group A (NS)]. RESULTS Twenty-five lambs survived (11 fetuses in group A and 14 fetuses in group B). Lung volume in group A (S) was less than in group A (NS) (p<0.05). The AT1 ratio in group A was lower than in group B (p<0.01), without any difference in radial alveolar counts (RACs) or alveolar growth, and no association between scoliosis and alveolar differentiation. CONCLUSION Gastroschisis in a sheep model reduces the AT1 ratio but not the RAC. Severe scoliosis affects lung volume but not the AT1 ratio, suggesting reduced diaphragmatic movement in fetuses with large abdominal defects.