The Jonker Lab is thrilled to announce that we’ve been awarded an R01 grant to study the growth and function of the fetal heart using a sheep model hypoplastic left heart syndrome (HLHS). In this model, the left ventricle doesn’t contribute to fetal cardiac output because it is not allowed to fill via the left atrium.
Sometimes, the left ventricle fails to grow properly in the fetus. The presence of the arterial shunt between the pulmonary artery and the aorta in the fetus allows the right ventricle to take over all cardiac output to the fetal body and placenta. This adaptation is possible because the placenta oxygenates the fetal blood. However, after birth, everything changes. The infant must begin breathing, and the right ventricle is tasked with pumping blood to the lungs, while the left ventricle should pump blood to the body. In HLHS, however, the left ventricle is absent, so it cannot pump blood to the body. When the arterial shunt closes, the infant will not survive without intervention. A series of palliative surgeries is necessary, starting in the newborn period, to allow the infant to live.
One remaining mystery is how the right ventricle adapts and functions during fetal life when it has to compensate for the underdeveloped left ventricle. How does the loss of the left ventricular output affect the overall loading and performance of the right ventricle? How do circulating hormones influence growth and maturation of the cardiac myocytes? And perhaps most importantly, could increasing the number of myocytes help the right ventricle become more resilient to the demands placed on it?
We’re excited to explore these questions and more as we dive into our experiments in “Regulation of cardiomyocyte growth in a fetal ovine model of reduced left ventricular filling.” This research has the potential to deepen our understanding of how the fetal heart compensates during development and help guide future treatments for infants with HLHS.