A new fetal rat model of gastroschisis: Development and early characterization (original) (raw)
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Fetal gastrointestinal motility in a rabbit model of gastroschisis
Journal of Pediatric Surgery, 2004
Purpose: Gastrointestinal (GI) dysmotility occurs frequently in full-term infants with gastroschisis (GS). Although controversial, preterm delivery of infants with GS has been advocated to prevent the development of GI dysmotility, and understanding the etiology of gestational-related bowel injury may lead to prenatal therapies. Using a fetal rabbit model, the authors assessed in vivo and in vitro GI motility in preterm GS fetuses. Methods: On gestation day 24 (term, 31), surgery was performed in maternal rabbits and GS induced in fetuses, whereas control fetuses underwent sham procedures. On gestation day 29, both groups of fetuses received ultrasound-guided intragastric injection of fluorescein and colored microspheres. Two hours after injection, fetuses were delivered by cesarean section and stomach and small intestine harvested intact. "GI motility" was calculated as the distance traveled by fluorescein divided by total length. In vitro studies of fetal gastric muscle strips contractility responses to bethanechol, a cholinergic agonist, were assessed in an organ bath system. Data were analyzed as paired and unpaired t tests and expressed as means Ϯ SEM. Results: GS reduced fetal body weight and intestinal length compared with controls (28.4 Ϯ 1.4 v. 33.5 Ϯ 1.5 g, 36.9 Ϯ 1.8 v. 25.9 Ϯ 1.2 cm; P Ͻ .05, respectively). Fetuses with GS showed markedly reduced in vivo GI motility (51.4 Ϯ 2.9 v 24.8 Ϯ 2.7%; P Ͻ .05) and in vitro gastric contractile tension (769 Ϯ 53 v 396 Ϯ 26 mNcm 2 ; P Ͻ .05). Conclusions: GI exposure to amniotic fluid reduces intestinal motility and gastric contractility functions in the preterm rabbit fetus. The results suggest that GS-associated impairment of GI neuromuscular functions occurs in utero, before term, and may be responsive to manipulation of amniotic fluid content or other therapeutic interventions.
Gastroschisis in the partially extraamniotic fetus: Experimental study
Journal of Pediatric Surgery, 1993
l The short, thick, matted bowel, often found in gastroschisis, has been attributed to a variety of factors. We designed an original animal model in order to isolate the effect of amniotic fluid on the fetal bowel. We created experimental gastroschisis in fetal rabbits. Extruded bowel was kept out of the amniotic sac in half of the operated fetuses. At term, 7 days after surgery, 21 surviving fetuses (12 intraamniotic gastroschisis BAG] and 9 extraamniotic gastroschisis [EAG]) and 16 control littermates were collected for study. Five parameters were measured in each animal: body weight, intestinal weight, intestinal length, bowel diameter, and bowel wall thickness. Fetal mortality due to the extraamniotic fixation technique was 25%. We found no statistically significant difference in body weight, intestinal weight, or bowel wall thickness. An enormous difference was found in intestinal length (P c .OOOl among the three groups). Bowel diameter was significantly different (P = .02) in the extreme groups (IAG and controls), with the intestine being more dilated in IAG than in EAG and controls. Gastroschisis in the absence of amniotic fluid was not as damaging to the fetal intestine as "natural" intraamniotic gastroschisis.
Archives of Gynecology and Obstetrics, 2012
Purpose In order to further define the challenges, minimally invasive fetal surgery will have to overcome human fetuses with gastroschisis. The purpose of this study was to compare macroscopic and histopathologic characteristics of experimental laparoschisis in sheep fetuses with actual cases of gastroschisis from a postmortem series of human fetuses. Methods Employing fetoscopy, we created a laparoschisis model in eight fetal sheep between 74 and 92 days of gestation (median 86.5 days). Twenty to 31 days after fetoscopic creation of fetal laparoschisis, six surviving fetuses were harvested for macroscopic and histopathologic assessments of the experimental lesion. These findings were compared to those of ten human fetuses with gastroschisis after termination of pregnancy. Results In the six sheep fetuses, both macroscopic and histopathologic intestinal changes achieved by this animal model resembled those of the human fetuses with gastroschisis. The surface of the intestine, liver and stomach exposed to the amniotic fluid was covered by a thick pseudocapsule made up of reactive fibroblasts and a dense capillary network. Parts of the capsule showed a foreign body-type reaction.
Pediatric Surgery International, 2008
Amniotic fluid exchange is a method for prevention of intestinal damage in gastroschisis, but its techniques are different in studies. We investigated the effects of amnioinfusion exchange on histological changes of intestine and feasibility and safety of amniotic fluid exchange through central vein catheter (CVC) placed in pregnant rabbit uterus. A total of 15 pregnant New Zealand white rabbits were selected. Fetuses were randomly divided into three groups (case, control, sham). On gestational day 25, under general anesthesia with midline laparotomy, the graved bicornuate uterus was exposed. In controls, fetus abdomen was opened by a transverse incision in right lower quadrant region and intestines were eviscerated. In cases, after intestine evisceration, a central venous catheter was passed from mother skin and uterus and fixed to uterus wall. In shams, fetus was delivered on gestational day 32 and its abdomen was opened. In case group, after operation, 1-2 cc of warm saline solution was replaced through catheter every 6 h. On gestational day 32, fetuses of case and control groups were delivered. Mucosal and serosal thickness, muscle thickness, fibrin deposition, serosal collagen and ganglia were compared. Ten fetuses as shams, 7 fetuses as controls and 7 fetuses as case group were studied. Serosal thickness was 4.5 ± 3.6 lm in shams, 64.2 ± 28.7 lm in controls and 6 ± 4.1 lm in cases. Serosal thickness in control group was higher than sham (P \ 0.001) and case (P \ 0.002) groups. In case group, infiltration of inflammatory cells with mild edema without fibroblast infiltration was seen. Application of the CVC technique was found to be a simple procedure that effectively decreased serosal inflammatory response of intestine in gastroschisis.
Surgical Endoscopy, 2020
Introduction This is the cumulative technical report on the operative procedures and limitations of fetoscopic bag insertion, intestinal bag placement, and bag fixation to the fetus in a series of pilot studies in an ovine model for prenatal treatment of gastroschisis. Material and methods In 24 German blackhead sheep, a surgically created gastroschisis was managed by fetoscopic placement of the extruded intestines into a bag. The bag was then fastened onto the fetal abdominal wall. Different materials (sterile gloves, latex condoms, laparosopic retrieval bags) and different fixation techniques (laparoscopic staplers, interrupted and continuous sutures) have been examined. The fetuses were retrieved and evaluated at the end of gestation. Results Uterine bag insertion was successful in 15 of 24 (62.5%) and intestinal bag placement in 10 of 15 available fetuses (66.6%). The main factor limiting fetoscopic procedures was chorioamniotic separation (CAS). Sterilized condoms provided the most appropriate type of bags and the V-Loc™ running suture, the most expedient type of fixation, which was achieved in 9 of the 10 fetuses (complete = 2, partially = 7) by using a three port access (5 mm and 2 × 3 mm). All bags were encountered completely or partially dislocated from the fetus at the end of gestation. Conclusions Fetoscopic intestinal bag placement and fixation in gastroschisis technically demanding. None of the evaluated techniques led to permanent anchorage of the bag to the fetus. The development of specially designed instruments, bags and fixation methods is required to optimize this approach.
Bowel dilation as a predictor of adverse outcome in isolated fetal gastroschisis
Prenatal Diagnosis, 2010
This study was designed to evaluate bowel diameter as a predictor of adverse outcome in isolated fetal gastroschisis. Retrospective study involving 94 singleton pregnancies. Ultrasound measurements of herniated bowel transverse diameter (BTD) were performed up to 3 weeks before delivery. Adverse outcome was intrauterine/neonatal death and/or bowel complications. Last BTD was recorded at 35.6 ± 1.6 weeks and mean interval to delivery was 6.2 ± 5.0 days. Intrauterine/neonatal death occurred in 10 (10.6%) cases; bowel complications were observed in 8 (8.5%). BTD ≥ 15, ≥ 20, ≥ 25, and ≥ 30 mm were found in 87, 46, 13, and 4% of pregnancies with a favorable outcome, respectively. BTD ≥ 25 mm sensitivity was 38%, and positive and negative predictive values were 38 and 87%. For BTD ≥ 30 mm, the values were 19, 50, and 85%. Observed/expected BTD ROC curve showed an area of 0.67, best cut-off value at 1.39; prediction values were similar to those for BTD ≥ 25 mm. Bowel dilatation was also significantly associated with lower rate of primary surgical closure, longer period to full oral feeding, and prolonged hospital stay. Bowel dilatation demonstrated up to 3 weeks before delivery is a predictor of intestinal complications and is associated with lower rate of primary surgical closure, longer period to achieve full oral feeding, and hospital stay.
Gastroschisis: Prenatal Diagnosis and Outcome
Congenital Anomalies - From the Embryo to the Neonate, 2018
The purpose of this retrospective cohort study was to investigate and identify prenatal predictors of perinatal outcomes of gastroschisis. Antenatal data included extra-abdominal bowel dilatation (EABD) and intra-abdominal bowel dilatation (IABD). Perinatal data included gestational age, sex, and birth weight. Surgical data included presence of intestinal atresia, necrosis, perforation, strictures, and method of closure. Outcome data included duration of mechanical ventilation and total parenteral nutrition, pseudoobstruction, sepsis, reoperations, length of hospital stay, and mortality rates. Results were analyzed in 65 patients. EABD was documented in 55 patients with no significant difference between simple and complex gastroschisis group. In 27 patients (in 32% of simple and 73% of complex cases), IABD persisted until the last ultrasound scan. Simple gastroschisis group had a shorter hospital stay, shorter ventilation support duration, less bowel pseudoobstruction, less need for reoperation, and received less parenteral nutrition. The most frequent extraintestinal complication was sepsis. The only factor that has been shown to predict poorer outcomes of gastroschisis is the presence of complex gastroschisis. Current available evidence suggests that antenatal bowel dilatation is not associated with increased risk of adverse perinatal outcome in infants with gastroschisis. Also, the absence of bowel dilatation cannot fully exclude complex patients.
The effect of gestational age at birth on morbidity in patients with gastroschisis
Journal of Pediatric Surgery, 1996
• Infants born with gastroschisis frequently present with an eviscerated intestinal segment that is inflamed and thickened. The damaged segment of intestine displays absorption and motility disturbances for a variable period of time after gastroschisis repair. Clinical and animal research suggests that the damage to the eviscerated intestine is caused by prolonged exposure to amniotic fluid and/or progressive constriction on the intestine and its blood supply by the umbilical ring. Some obstetricians and pediatric surgeons have advocated early elective delivery to decrease the exposure of the bowel to these potentially damaging influences. Fifty-five patients underwent gastroschisis repair at the authors' institution during the last 6 years. Many of these patients had early elective delivery after their pulmonary maturity was judged adequate based on their amniotic lecithin/sphingomyelin ratios, The patients were divided into three groups according to gestational age at the time of delivery. Elective early delivery did not lessen the need for silo closure or hasten the time until enteral feeding could be tolerated. The hospital stay was not shortened for the early delivery group. This retrospective review supports the concept that patients with sonographicaliy identified antenatal gastroschisis are best managed by delivery at full term.
Journal of Pediatric Surgery, 1989
To investigate roles of short peptides in gastroschisis (GS), we comprehensively analyzed peptides in amniotic fluid (AF), creating a fetal lamb model of GS. We created GS in 4 fetal lambs at 60 days of gestation. Three GS and 4 normal fetuses were delivered at term (145 days) by cesarean section, when AF samples were collected. Short peptides in the AF samples were detected and identified by mass spectrometry. One of the identified peptides was synthesized and it's functions were investigated. In total, 77 peptide peaks were detected in the AF samples. Of these, 12 peptides showed significantly different intensity between the GS and control groups. Three of the 12 peptides were identified. One of the identified peptides with high intensity in the GS group was amino acids (AA) 135-185 of lamb annexin 7 (ANX7). A synthesized peptide for AA168-211 of human ANX7, which corresponded to AA135-185 of lamb ANX7, decreased anti-inflammatory cytokine secretion from mesothelial cells by an cytokine array study. We report a unique AF peptide profile in a GS model. One of the peptides increased in GS was suggested to possess pro-inflammatory potential. These peptides would be related to the pathophysiology of GS.