Early neonatal echocardiographic findings in an experimental rabbit model of congenital diaphragmatic hernia

Abstract

This study aimed to demonstrate that congenital diaphragmatic hernia (CDH) results in vascular abnormalities that are directly associated with the severity of pulmonary hypoplasia and hypertension. These events increase right ventricle (RV) afterload and may adversely affect disease management and patient survival. Our objective was to investigate cardiac function, specifically right ventricular changes, immediately after birth and relate them to myocardial histological findings in a CDH model. Pregnant New Zealand rabbits underwent the surgical procedure at 25 days of gestation (n=14). CDH was created in one fetus per horn (n=16), and the other fetuses were used as controls (n=20). At term (30 days), fetuses were removed, immediately dried and weighed before undergoing four-parameter echocardiography. The lungs and the heart were removed, weighed, and histologically analyzed. CDH animals had smaller total lung weight (P<0.005), left lung weight (P<0.005), and lung-to-body ratio (P<0.005). Echocardiography revealed a smaller left-to-right ventricle ratio (LV/RV, P<0.005) and larger diastolic right ventricle size (DRVS, P<0.007). Histologic analysis revealed a larger number of myocytes undergoing mitotic division (186 vs 132, P<0.05) in CDH hearts. Immediate RV dilation of CDH hearts is related to myocyte mitosis increase. This information may aid the design of future strategies to address pulmonary hypertension in CDH.

Abnormal Shape and Size of the Cardiac Ventricles Are Associated with a Higher Risk of Neonatal Death in Fetuses with Isolated Left Congenital Diaphragmatic Hernia

“…In agreement with our results, in a systematic review, Crawford et al reported that a small LV before 24 weeks of gestation and ventricular disproportion in the third trimester of pregnancy were associated with a significant risk of neonatal mortality in fetuses with left-sided CDH [32]. Manso et al reported an experimental model showing differences in RV diastolic size and LV/RV ratio in fetuses with CDH, as compared to healthy controls [33]. We were not able to see differences in cardiac function; however, other authors reported reduced systolic and diastolic performance in the RV in fetuses with CDH receiving ECLS (extracorporeal life support or extracorporeal membrane oxygenation) after birth [34,35].…”

Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

“…129 Manso et al performed postnatal echocardiography on rabbit neonates with CDH, and reported a larger diastolic right ventricle size and an increased number of myocytes undergoing mitotic division, indicating that cardiac alterations occur in utero in this model. 130…”