A novel surgical toxicological-free model of diaphragmatic hernia in fetal rats

Autor(es)

Sbragia, Lourenco ^{[1, 2]} ; Oria, Marc ^{[1, 3]} ; Scorletti, Federico ^[1] ; Romero Lopez, Maria del Mar ^{[1, 4]} ; Schmidt, Augusto F. ^[5] ; Levy, Brittany ^[1] ; Peiro, Jose L. ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Cincinnati Childrens Hosp Med Ctr CCHMC, Div Pediat Gen & Thorac Surg, Ctr Fetal & Placental Research, Cincinnati, OH 45229 - USA

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Lab Expt Fetal Surg, Div Pediat Surg, Ribeirao Preto, SP - Brazil

^[3] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 - USA

^[4] Cincinnati Childrens Hosp Med Ctr, Div Neonatol, Perinatal Inst, Cincinnati, OH 45229 - USA

^[5] Univ Miami, Miller Sch Med, Div Neonatol, Miami, FL 33136 - USA

• Tipo de documento: Artigo Científico
• Fonte: Pediatric Research; AUG 2021.
• Citações Web of Science: 0

Resumo

BACKGROUND: Teratogen-induced congenital diaphragmatic hernia (CDH) rat models are commonly used to study the pathophysiology. We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced effects on the lung development. METHODS: Fetal DH was surgically created on fetuses at E18.5 and harvested at E21.5 in rats. Four groups were evaluated (n = 16): control (CONT), control exposed to Nitrofen (CONT NIT), DH surgically created (DH SURG), and CDH Nitrofen (CDH NIT). Body weight, total lung weights, and their ratio (BW, TLW, and TLBR) were compared. Air space (AS), parenchyma (PA), total protein, and DNA contents were measured to verify lung hypoplasia. Medial wall thickness (MWT) of pulmonary arterioles was also analyzed. RESULTS: DH SURG showed significant hypoplasia (decreased in total protein and DNA) vs CONT (p < 0.05); DH SURG vs CDH NIT were similar in TLW and TLBR. DH SURG has less AS than CONT (p < 0.05) and similar PA compared to CONT NIT and CDH NIT, MWT were similarly increased in CONT NIT, DH SURG, and CDH NIT. CONCLUSIONS: This novel surgical model generates fetal lung hypoplasia contributing to the study of the mechanical compression effect on fetal lung development in DH. Impact There is a critical need to develop a surgical model in rat to complement the findings of the well-known Nitrofen-induced CDH model. This experimental study is pioneer and can help to understand better the CDH pathophysiological changes caused by herniated abdominal viscera compression against the lung during the final stage of gestation in CDH fetuses, and also to develop more efficient treatments in near future. (AU)

• Processo FAPESP: 14/02519-6 - Avaliação da contratilidade miocárdica e da função miocítica de neonatos de coelhos com hérnia diafragmática congênita criada cirurgicamente
• Beneficiário: Lourenço Sbragia Neto
• Modalidade de apoio: Bolsas no Exterior - Pesquisa