Animal models in pediatric surgery.
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Abnormalities, Drug-Induced↗
Biomedical subjects
S Montedonico
Publications and source records attributed to S Montedonico.
Regional differences in nitrergic neuronal density in the developing porcine urinary bladder.
Nitric oxide (NO) is involved in normal bladder physiology by regulating local arteriolar tone and smooth muscle relaxation and modulating the production of extracellular matrix proteins in vitro. Little information is available regarding the nitrergic innervation of the bladder during development. In this study we investigated the changes in density and morphology of the intramural nitrergic neurons of the porcine urinary bladder during development using whole-mount preparation. Bladder specimens were obtained from porcine foetuses of gestational age 60 days (n=5) and 90 days (n=5) and from newborn piglets (n=5) after perfusion fixation. Bladders were divided into base, body, and dome. Whole-mount preparation using NADPH-diaphorase (NADPH-d) histochemistry was used to visualize nitrergic innervation of the urinary bladders and to measure density of NADPH-positive ganglia (including single neurons), number of NADPH-d positive neurons per ganglion, and size of individual neurons. One-way ANOVA and chi-square tests were used for statistical analysis with a p-value <0.05 considered statistically significant. NADPH-d positive ganglia were numerous in the muscular layer of all three age groups. At E60, ganglion density was significantly higher in the body (mean 880/cm(2)) than in the dome (397/cm(2)) or the base (676/cm(2)). The ganglion density significantly decreased with age. The number of NADPH-d positive neurons per ganglion increased significantly between E90 and birth (p<0.01). A marked increase in the size of individual neurons over time was also seen (p<0.001), predominantly due to an increase in cytoplasm. Our data on whole-mount preparations demonstrate that significant maturation in nitrergic neuronal density and morphology occurs in the porcine urinary bladder, at least until birth.
Aging↗
Skeletal malformations associated with esophageal atresia: clinical and experimental studies.
BACKGROUND/PURPOSE: Patients with esophageal atresia (EA) often have skeletal malformations. The purpose of this study is to examine if similar defects occur in rat fetuses prenatally exposed to Adriamycin, a chemical capable of causing EA in these animals. METHODS: The charts of 443 babies with EA were reviewed to assess the incidence and nature of these defects in them. Time-mated female rats were given either 2 mg/kg intraperitoneal Adriamycin (experimental group, n = 16) or no treatment (control group, n = 4) on gestational days 8 and 9, and the fetuses were removed near term. Skeletal anatomy was studied after alcian blue and alizarin red staining. RESULTS: A total of 528 skeletal malformations, mainly abnormal segmentation and vertebral identity (extra or defective bodies or ribs), mishaped vertebral bodies, and limb malformations like radial aplasia or hypoplasia were found in 245 babies (55%). Costal fusion and sternal anomalies were present in 17 and 4 babies, respectively. In the animal study, all control fetuses were normal, whereas 83 of 134 experimental fetuses (62%) had EA accompanied by other malformations. No segmentation or vertebral identity anomalies were seen, but butterfly, wedged, and asymmetric vertebral bodies were found at various levels in all animals with EA and in about half of those without it. Three fetuses had rib anomalies, and 3 more had sternal malformations. Ossification of limbs was delayed in treated fetuses and short, thick, and crooked bones were seen in 4 of 31 fetuses with EA and in none of the Adriamycin-exposed ones without EA. CONCLUSIONS: Adriamycin exposure induces in fetal rats, in addition to esophageal, duodenal, and anorectal atresias, high proportions of vertebral malformations and some limb defects of nature not identical but quite similar to that of babies with EA. This further validates this model for investigating the nature of the processes leading to EA and its associated malformations.
Animals↗
Effects of esophageal shortening on the gastroesophageal barrier: an experimental study on the causes of reflux in esophageal atresia.
BACKGROUND/PURPOSE: Gastroesophageal reflux (GER) is frequently recognized after surgical repair of esophageal atresia. The aim of this study was to test the hypothesis that one or more components of the gastroesophageal pressure barrier are weakened by esophageal anastomosis under tension. METHODS: Lower esophageal sphincter pressure (LESP), crural sling pressure (CSP), and the length of the intraabdominal segment of the esophagus (LIAE) were measured by pull-through perfusion manometry in 20 rats before and after resection of 15 mm of the cervical esophagus, and in eight rats before and after esophageal transection (control group). RESULTS: This manouver decreased the LESP from 44.9+/-17.4 to 30.9+/-12.3 mm Hg and the LIAE from 17.9+/-2.8 to 15.8+/-2.4 mm (P < .05) in experimental animals, whereas they did not significantly change in controls. CSP did not change significantly. CONCLUSIONS: Anastomosis of the esophagus under tension in this model decreases significantly the lower esophageal sphincter tone and length of the intraabdominal esophagus, but it does not change the crural sling pressure. Postoperative reflux in patients operated on for esophageal atresia might be in part, caused by this mechanism.
Anastomosis, Surgical↗
Gastroesophageal reflux after combined lower esophageal sphincter and diaphragmatic crural sling inactivation in the rat.
This study tests the hypothesis that either selective or combined destruction of the lower esophageal sphincter and the diaphragmatic crural sling should induce reflux in the rat. Pull-through perfusion manometry was performed before and after lower esophageal myectomy, crural myotomy, or both. pH monitoring was used to detect reflux. Unmanipulated rats served as controls. Paired t tests were used for comparison of pre- and postoperative pressure values and contingency tables with Fisher's tests for examining the association between the interventions and the appearance of reflux. Esophageal myectomy decreased only sphincteric pressure from 25.9+/-15.5 to 9+/-6 mm Hg (P < 0.01), whereas crural myotomy decreased only sling pressure from 26.2+/-13.3 to 7.3+/-3.9 mm Hg (P < 0.01). Simultaneous performance of both procedures decreased sphincteric and crural pressures from 20.4+/-7.5 to 7.6+/-4.3 mm Hg (P < 0.01) and from 45.9+/-20.6 to 18.2+/-7.4 mm Hg (P < 0.01), respectively. None of the control, myectomy, or myotomy animals showed reflux upon pH-metry but 5/8 rats in which both procedures were performed had prolonged acid exposure. No esophagitis was seen. In conclusion, normal rats do not have reflux. Selective destruction of either the sphincter or the crural sling does not induce reflux, despite causing flattening of their respective manometric profiles. Conversely, combined inactivation of both components is significantly associated with reflux.
Animals↗
Muscular architecture and manometric image of gastroesophageal barrier in the rat.
The two components of the gastroesophageal barrier, the sphincter and the crural sling, closely overlap in humans, whereas they are widely separated in the rat. This investigation correlates the anatomical components of the barrier and their manometric counterparts in this animal. Sphincteric and crural sling pressures were measured in four quadrants in 23 rats. Muscle thickness was measured at nine levels of the gastroesophageal junction in the same quadrants in 12 rats and the muscular architecture of the region was studied in 10 fresh specimens. The manometric sphincteric component is stronger on the right side where the thickest muscle fibers anchor to the anterior and posterior borders of a mucosal ridge that almost surround the cardia. Conversely, the sling pressure is highest towards the left where the muscular bundles straddle the esophagus. In conclusion, there is a close correspondence between the manometric image and the muscular architecture of the components of the gastroesophageal barrier in the rat. The anatomical arrangement of U-shaped muscular bundles oriented in opposite directions creates a particularly powerful antireflux mechanism.
Animals↗
[Respiratory malformations associated with esophageal atresia].
AIMS: Since trachea, lungs and esophagus develop from foregut and esophageal atresia is a defect of its normal division, we examined the occurrence of respiratory malformations in a large clinical series of esophageal atresia. MATERIALS AND METHODS: The records of 415 patients born with esophageal atresia between 1965 and 1996 and 129 autopsies of the same patients were retrospectively reviewed. The presence of other associated anomalies was carefully studied and noted. RESULTS: Of 415 patients with esophageal atresia, 25 (6%) had one or more associated respiratory malformations. Only 8 patients (2.8%) having bronchopulmonary malformations were diagnosed clinically (8/286) while 17 (13.2%) were diagnosed at autopsy (17/129). The most frequent malformations were: lung segmentation defects (n = 14), pulmonary hypoplasia (n = 9) and tracheomalacia (n = 4). Eighty percent of esophageal atresia patients had another associated malformations specially of the cardiovascular system. CONCLUSIONS: Esophageal atresia patients have a high incidence of associated bronchopulmonary malformations that are frequently not diagnosed.
Adolescent↗
[Tissue adhesives in closing of fistulas after surgery of esophageal atresia].
AIMS: Recurrent tracheoesophageal fistula is a severe postoperative complication after esophageal atresia repair. Endoscopic obliteration with tissue adhesives has been used as an alternative to reoperation. The aim of this study is to review our experience with such procedure. MATERIAL AND METHODS: The medical records of 415 esophageal atresia patients were retrospectively reviewed in order to analyze the incidence of complications and the outcome of patients in whom tissue adhesives were used to close a recurrent tracheoesophageal fistula. RESULTS: 334 patients underwent an esophageal anastomosis and fistula closure or fistula division alone, 41 (12.3%) of them had recurrent tracheoesophageal fistula. In eight of these patients and one having an H type tracheoesophageal fistula, endoscopic obliteration using tissue adhesives was attempted. None of these nine children cured after this procedure and all required an open procedure for their recurrent tracheoesophageal fistula. CONCLUSIONS: Contrary to some published cases, we have not succeeded with endoscopic obliteration of recurrent tracheoesophageal fistula using tissue adhesives; therefore, we do not recommend this treatment.
Endoscopy↗