Abstract
The Adriamycin rat model (ARM) has been used to produce visceral malformations in fetuses to explain the mechanisms of foregut division. The models vary in the dosage of Adriamycin (ADR) and in the number of applications. Our study of a modified ARM using 2.2 mg/kg of ADR for 2 days only, intraperitonealy in pregnant rats, is presented. A total of 81 fetuses were obtained with this model from the ADR group, 74 (91%) alive. Uretero-hydronephrosis (UHN) was observed in 70 fetuses (95%), esophageal atresia (EA) in 68 (92%), duodenal atresia (DA) in 68 (92%), bladder hypoplasia (BH) in 67 (90%), plus other malformations. In evaluating amniotic fluid (AF) volume of the fetuses with EA with tracheo-esophageal fistula (TEF) (group I) and EA without TEF (group II), both associated with bilateral UHN when compared with the control group (group III), groups I and II showed higher AF volume in groups I and II than the control group (group III) did (p=0.0001). In conclusion, ARM was adequate to produce EA and other visceral malformations. The use of ADR in a higher dosage for a shorter period of time produced better results than those presented in previous literature. The increase of AF volume obtained in fetuses presenting EA plus bilateral UHN strongly suggests, despite ureteral dilatation (urinary obstruction), that a malformed communication may exist between the urinary system and the amniotic cavity, permitting the existence of polyhydramnios that is due to digestive obstruction such as EA and DA.
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References
Myers NA (1974) Oesophageal atresia: the epitome of modern surgery. Ann R Coll Surg Engl 54:227
Holder TM (1986) Esophageal atresia and tracheoesophageal fistula. In: Ashcraft KW, Holder TM (eds) Pediatric esophageal surgery. Grune & Stratton Inc, Orlando, pp 29–52
Chittmittrapap S, Spitzs L, Kiely EM, Brereton RJ (1989) Oesophageal atresia and associated anomalies. Arch Dis Child 64:364–368
Harmon CM, Coran AG (1998) Congenital anomalies of the esophagus. In: O’Neill JA Jr, Rowe MI, Grosfeld JL, Fonkalsrud EW, Coran AG (eds). Pediatric surgery, 5th edn. Mosby-Year Book, Missouri, pp 941–967
Martín C, Darnell A, Durán C, Bermúdez P, Mellado F, Rigol S (2004) Magnetic resonance imaging of the intrauterine fetal genitourinary tract. Abdom Imaging 28:1–34
McKenna MK, Goldstein RB, Stringer MD (1995) Small or absent fetal stomach prognostic signicance. Radiology 197:729–733
Gutierrez GR, Paramo HF, Alfaro EM, Huerta MV (1996) Diagnóstico ultrasonográfico de polidramnios y su asociación con malformaciones congénitas. Ginecol Obstet Mex 64:1
Kimble RM, Harding JE, Kolbe A (1998) Does gut atresia cause polyhydramnios? Pediatr Surg Int 13:115–117
Bastide A, Manning F, Harman C, Lange I, Morrison I (1986) Ultrasound evaluation of amniotic fluid: outcome of pregnancies with severe oligohydramnios. Am J Obstet Gynecol 154:895–900
Barss VA, Benacerraf BR, Frigoletto FDJR (1984) Second trimester oligohydramnionios, a predictor of poor fetal outcome. Obstet Gynecol 64:608
Xia H, Otten C, Migliazza L, Diez-Pardo JA, Tovar JA (1999) Tracheal malformations in experimental esophageal atresia. J Pediatr Surg 34(4):536–539
Beasley SW, Diez-Pardo J, Qi BQ, Tovar JA, Xia HM (2000) The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis. Pediatr Surg Int 16:465–472
Thompson DJ, Modello JA, Strenbing RJ (1978) Teratogenicity of Adriamycin and Daunomycin in the rat end rabbit. Teratology 17:151–158
Orford JE, Cass DT (1999) Dose response relationship between Adriamycin and birth defects in rat model of VATER association. J Pediatr Surg 34(3):392–398
Qi BQ, Merei J, Farmer P, Hasthorpe S, Myers NA, Beasley SW, Hutson JM (1997) Cardiovascular malformations in rat fetuses with oesophageal atresia and tracheo-oesophageal fistula induced by adriamycin. Pediatr Surg Int 12:556–564
Xia H, Migliazza L, Montedonico S, Rodrigues JI, Diez-Pardo JA, Tovar JA (1999) Skeletal malformations associated with esophageal atresia: clinical and experimental studies. J Pediatr Surg 34(9):1385–1392
Liu MI, Hutson JM, Zhou B (1999) Critical timing embryogenesis in a adriamycin-exposed rat model: a clue to the origin of the bladder. J Pediatr Surg 34(11):1647–1651
Liu MI, Huston JM (2000) Cloacal and urogenital malformations in adriamycin-exposed rat fetuses. BJU 86(1):107–112
Merei J, Batiha A, Hani BI, El-Qudah M (2001) Renal anomalies in the VATER animal model. J Pediatr Surg 36(11):1693–1697
Williams AK, Qi BQ, Beasley SW (2001) Demonstration of abnormal notochord development by three-dimensional reconstructive imaging in the rat model of esophageal atresia. Pediatr Surg Int 17:21–24
Diez-Pardo JA, Qi BQ, Navarro C, Tovar JA (1996) A new rodent experimental model of esophageal atresia and tracheoesophageal fistula: preliminary report. J Pediatr Surg 31(4):498–502
Crisera CA, Maldonado TS, Kadison AS, Li M, Longaker MT, Gittes GK (1999) Patterning of “Distal Esophagus” in esophageal atresia with tracheo-esophageal fistula: is thyroid transcription factor 1 a player? J Surg Res 92:245–249
Crisera CA, Grau JB, Maldonado TS, Kadison AS, Longaker MT, Gittes GK (2000) Defective epithelial-mesenchymal interactions dictate the organogenesis of tacheoesophageal fistula. Pediatr Surg Int 16:256–261
Gross RE (1953) The surgery of infancy and childhood. W.B. Saunders, Philadelphia
Qi BQ, Diez-Pardo JA, Navarro C, Tovar JA (1996) Narrowing the embryologic window of the adriamycin-induced rat model of esophageal atresia and tracheoesophageal fistula. Pediatr Surg Int 11:444–447
Merei J, Hasthorpe S, Farmer P, Hutson JM (1999) Visceral anomalies in prenatally adriamycin-exposed rat fetuses: a model for the VATER association. Pediatr Surg Int 15:11–16
Brace RA (1997) Physiology of amniotic fluid volume regulation. Clin Obstet Gynecol 40(2):280–289
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França, W.M.G., Gonçalves, A., Moraes, S.G. et al. Esophageal atresia and other visceral anomalies in a modified Adriamycin rat model and their correlations with amniotic fluid volume variations. Ped Surgery Int 20, 602–608 (2004). https://doi.org/10.1007/s00383-004-1240-5
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DOI: https://doi.org/10.1007/s00383-004-1240-5