Grant: CIHR Fellowship

Persistent pulmonary hypertension of the newborn (PPHN) is a rare but life-threatening condition that affects full term babies. When the fetus is in the womb the requirement for oxygen is met by the mother. Normally at birth, the blood vessels in the lungs widen (dilate) to let blood in and obtain oxygen. However, in PPHN patients the vessels in the lung do not widen. This can be caused by a difficult birth in which the baby does not receive enough oxygen, or an infection. As a result the right side of the heart, responsible for pumping blood to the lungs, needs to work harder causing damage to the heart that reduces the amount of blood it pumps (termed contractile dysfunction). Contractile dysfunction is the main reason that patients with PPHN do not survive. Current treatments involve increasing oxygen levels in the blood. While these treatments deliver adequate oxygen to various organs (brain, liver etc.), the heart still becomes damaged and stops contracting properly in many patients. One reason for contractile dysfunction is that the heart does not produce enough energy. Similar to how a car uses an engine to convert gas to energy, tissues in the body use mitochondria to convert food (sugar, fat) to energy. In the heart, a complex molecule called cardiolipin (CL) is a structural component of mitochondria. When levels of CL are reduced, the mitochondria does not produce enough energy for the heart. Although it is known that CL levels are reduced in PPHN, no one has determined whether restoring the level of CL in the heart prevents the progression to heart failure. Using sophisticated and innovative approaches such as an exciting new method for delivering genes to cardiac tissue of live neonatal pigs with PPHN, we will shed light on whether increasing CL levels in the heart is a viable approach to improve the cardiac function in PPHN and thus increase patient survival.