Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis.

BACKGROUND: The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model. METHODS: Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used. RESULTS: In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls. CONCLUSIONS: Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.

Abdominal wall incision with or without exteriorization of bowel: results from a fetal lamb model for the embryogenesis of gastroschisis.

INTRODUCTION: The embryogenesis of gastroschisis is not completely understood. The aim of our study was to evaluate the impact of a simple abdominal wall defect versus a defect including eviscerated intestine or omentum for the development of gastroschisis in a fetal lamb model. MATERIAL AND METHODS: At mid-gestation (day 77) an abdominal wall defect was fetoscopically created with three different approaches in 19 German blackhead sheep. The intestine was eviscerated in 7 fetuses (group 1). The peritoneum was incised and a patch of the omentum pulled through the incision in 5 fetuses (group 2). In 7 fetuses (group 3) the skin and rectus muscle were incised until the peritoneum was visible. In this group, no abdominal contents were exteriorized and the peritoneum was left intact. A second fetoscopic procedure was performed 21 days later, assessing the condition and extension of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. RESULTS: The second fetoscopy acting as a control for the creation of gastroschisis demonstrated eviscerated and inflamed intestine in all 3 groups. The amount of eviscerated intestine did not appear to depend on the size of the defect nor on its duration. DISCUSSION: It appears that a simple incision of the abdominal wall with intact peritoneum is sufficient for the development of gastroschisis in a fetal sheep model. This finding may improve the understanding of the etiology of gastroschisis.

Fetoscopic management of gastroschisis in a lamb model.

BACKGROUND: Gastroschisis is a malformation consisting of an abdominal wall defect with eviscerated bowel. Its standard treatment is postnatal repositioning or temporary prosthetic bag placement. The aim of our study is to evaluate the feasibility of its fetoscopic management in a lamb model. METHODS: At mid-gestation (day 75), gastroschisis was created in eight German blackhead sheep. A second fetoscopic procedure was performed on day 105, assessing the viability, extension, and potential for repositioning of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. RESULTS: In six fetuses gastroschisis could be successfully created and assessed with fetoscopy. Two fetuses were lost due to technical complications. Primary repair by repositioning the intestine into the abdomen was not possible because it grew into an inflammatory conglomerate too large for the small fetal abdominal cavity. CONCLUSIONS: Although technically demanding, we were able to produce and reassess six cases of gastroschisis by fetoscopy. As primary repositioning appears unfavorable, fetoscopic prosthetic bag placement may become an alternative.

Prediction of volume responsiveness using pleth variability index in patients undergoing cardiac surgery after cardiopulmonary bypass.

BACKGROUND: The pleth variability index (PVI) is derived from analysis of the plethysmographic curve and is considered to be a noninvasive parameter for prediction of volume responsiveness. The aim of our prospective clinical study was to evaluate if volume responsiveness can be predicted by PVI in patients undergoing cardiac surgery after cardiopulmonary bypass. METHODS: Eighteen patients were prospectively studied. Directly after cardiac surgery, PVI, stroke volume variation (SVV), and cardiac index (CI) were recorded. Colloid infusion (4 ml/kg body weight) was used for volume loading, and volume responsiveness was defined as increase of CI more than 10 %. RESULTS: SVV and PVI measures were found to be highly correlated at r = 0.80 (p < 0.001). Receiver operating characteristics curve (ROC) analysis resulted in an area under the curve of 0.87 for SVV and 0.95 for PVI, which values did not differ statistically significant from each other (p > 0.05). The optimal threshold value given by ROC analysis was ≥11 % for SVV with a sensitivity and specificity of 100 % and 72.2 %. For PVI, optimal threshold value was ≥16 % with a sensitivity and specificity of 100 % and 88.9 %. Positive and negative predictive values estimating an increase of CI ≥10 % for SVV were 44.4 % and 100 % and 66.7 % and 100 % for PVI. CONCLUSIONS: For consideration of fluid responsiveness PVI is as accurate as SVV in patients after cardiopulmonary bypass. Methodological limitations such as instable cardiac rhythm after cardiopulmonary bypass and right- or left ventricular impairment seem to be responsible for low specificity and positive predictive values in both parameters PVI and SVV.