Left Ventricular Cardiac Dysfunction in the Diaphragmatic Hernia Fetus: Fetal Phenotypic Improvement Is Seen with Tracheal Occlusion

Abstract

Background: Recent reports in the care of congenital diaphragmatic hernia (DH) patients focus on the role of decreased left ventricular cardiac output after birth. However, little is known about cardiac function while fetal physiology is still in effect, and even less is understood about the effect of fetal tracheal occlusion (TO) on the left ventricle (LV). Methods: DH were surgically created in fetal sheep at gestational age 70-76 days. Fetuses were cesarean delivered at ∼120 days gestational age, cannulated via the umbilical vein and arteries, and placed on the Extrauterine Environment for Neonatal Development (EXTEND) device. The TO device was applied for ten days, followed by a four-day recovery period of non-occlusion. Results: In the Normal group, the mean right ventricle (RV) to LV Ratio was 1.41 (Std Err 0.0098, 95% CI 1.39-1.43) on day 0 of the experiment and remained stable at 1.39 on Day 14 (Std Err 0.01, 95% CI 1.93-2.22). In the DH group, the RV to LV Ratio was mildly elevated from Day 0, at 1.47 (Std Err 0.28, 95% CI 1.08-1.82), and increased to 2.08 (Std Err 0.07, 95% CI 1.93-2.22) by Day 11 of the study. In DH with TO, the RV to LV Ratio mimicked that of the Normal group. Once TO was released, the RV to LV Ratio began to increase. Combined cardiac output (CO) was lower in the DH group. RVCO was equivalent in both groups. While LVCO remained constant in the Normal and TO groups, it dropped rapidly in the DH group (Prob>F 0.000). Conclusion: Here we demonstrate that LV dysfunction is present during fetal development in a lamb model of severe DH, and is improved by TO treatment in the EXTEND environment.RV to LV Ratio in Fetal Lambs on EXTENDIn DH with TO, the RV to LV Ratio mimicked that of the Normal group. Once TO was released, the RV to LV Ratio began to increase. Here, you see an increase in the RV to LV ratio with balloon release. As a result of the balloon release, the RV to LV ratio begins to drift from the normal animal baseline towards the untreated DH phenotype.