Beatrix Leffingwell
Research Mentor(s): Alvaro Rojas-Peña
Mentor Department: Department of Surgery-Transplantation
Authors: Beatrix Leffingwell, Caitlin Bocks, Sarah King, Joseph Church, Alvaro Rojas-Peña
Session: Session 1 (9:00am – 9:50am)
Presentation Type: Poster 46
Abstract
Introduction: Congenital diaphragmatic hernias (CDH) affect one in 2,500 newborns annually and can lead to pulmonary hypoplasia (PH) and pulmonary hypertension (PHT), both of which can be fatal. Treatment for CDH involves surgery to repair the defect, and sometimes the use of extracorporeal membrane oxygenation (ECMO) to bypass the diseased lungs prior surgical repair. Despite being sometimes effective, severe CDH is still associated with high mortality and morbidity rates. This study aims to establish a reliable ovine model of CDH to advance treatment options for affected human infants. Methods: Twenty (20) ewes were bred with the intent of performing fetal surgery at 64-76 days gestation to surgically create diaphragmatic hernias in the fetuses. Surgery was conducted under general anesthesia using standard surgical tools and sterile techniques. Laparotomy and hysterotomy were performed on the ewes to expose the fetuses. A left-sided thoracotomy was performed on the fetus and a small piece of the diaphragm was excised to create a defect to then pull the stomach into the chest cavity. After operation, ewes were closely monitored until their delivery date at almost full-term (term = 145 days). Lambs were delivered by cesarean section. The effectiveness of the diaphragmatic defect creation was assessed through transuterine ultrasound and confirmed by post-mortem necropsy. Results: Of the twenty ewes who underwent creation surgery, 5 (25%) aborted post-surgery. Ten ewes are still pregnant with ultimate plans to deliver. Four of the successful pregnancies had single babies. One ewe had twins, one of which was left untouched during creation surgery and was born with healthy lungs as a control. Four out of the five (80%) lambs that underwent hernia creations had grossly noticeable lung damage seen on necropsy. We found that hernias persisted until delivery in 4 fetuses, with stomach, spleen and intestine found in the chest cavity. There was noticeable lung hypoplasia, and lung adhesions to the chest wall and other organs. Conclusion: In this study, we developed an ovine model for CDH by surgically creating a diaphragm defect in fetal lambs halfway through gestation. Post-delivery inspection revealed that the hernia persists throughout gestation, negatively affecting lung development and leading to PH. This large animal model is crucial for developing novel therapies for newborns with PH and pulmonary hypertension PHT secondary to CDH, facilitating research into new therapeutic approaches, including ECMO support.
