A new fetal rat model of gastroschisis: Development and early characterization

Background/Purpose: The perinatal management and pathophysiology of gastros chisis remain controversial. Large animal experimental models of gastroschi sis are inherently limited by expense and length of gestation, making multi ple studies and statistical analysis difficult. To address these limitation s the authors have developed a model of gastroschisis in the fetal rat. Methods: Twenty-one time-dated pregnant rats underwent laparotomy at 18 1/2 day's gestational age. The exposed uterus was bathed in ritodrine for toco lysis. The right posterior leg was exteriorized through a hysterotomy, and under a dissecting microscope (16x) the fetal small bowel was exteriorized through a small incision performed on the right lower abdominal quadrant. T he amniotic fluid was restored with saline solution and the hysterotomy clo sed with a purse-string suture. Control fetuses underwent hysterotomy and l eg manipulation only. The surgical time was uniformly less than 60 minutes. Fetuses were harvested by cesarean section at 21 1/2 days' gestational age . Fetal intestine was assessed by microscopic examination, and fetal weight , intestinal length, and intestinal weight per unit length were evaluated. Results: There was a significant surgical and anesthetic learning curve, wh ich is not included in this report. After this, the authors achieved a mate rnal survival of 100% (n = 21). We created gastroschisis in 64 fetuses (58 survivors, 90.6%), and 33 fetuses were only manipulated (30 survivors, 90.9 %). The number of induced gastroschisis per pregnant rat varied between 2 a nd 5 with median of 3. On gross examination, eviscerated intestine appeared dilated, edematous, and covered by peel when compared with control intesti ne. Fetuses with gastroschisis had significantly reduced body weight (4.1 /- 0.5 v 5.6 g +/- 0.5 g) and intestinal length (102 +/- 19 V 210 +/- 17 mm ) relative to controls, whereas the intestinal weight per unit length (1.75 +/- 0.29 v 0.71 +/- 0.1 mg/mm) was markedly increased (P < .001). Conclusions: The pathophysiology observed in this experimental model appear s to resemble human gastroschisis. In comparison with large animal models, the rat model offers the advantages of low expense, short gestation, litter mate controls, and high maternal and fetal survival rates. In addition, the re are specific probes and reagents available for application of molecular methodology to clarify the mechanisms responsible for the intestinal damage . This model appears appropriate for future experimental studies on gastros chisis. J Pediatr Surg 36:273-216. Copyright (C) 2001 by W.B. Saunders Comp any.