Cardiac ketone metabolism in newborns with congenital heart defects

Program Type (Grant): Graduate Studentship Award
Applicant Name: Persad, Kaya
Competition Cycle: 2022-04
Start Date: 2022-09-01
End Date: 2023-05-31
Supervisor Name: Lopaschuk, Gary D.
Institutional Sponsor: Medicine & Dentistry-Pediatrics
Supervisor Faculty / Department: Medicine & Dentistry-Pediatrics
WCHRI Funder: SCHF
External Funder: CIHR - CGS M
Total WCHRI Funding Commitment: $36,000.00

Approximately 500 babies are born in Alberta each year with problems regarding the structure/function of their heart (congenital heart defects- CHD). In fact, 4.2% of all newborn deaths are due to CHD, with half of these deaths occurring within the first year of life. Surgery is often employed as a treatment for CHD. We have previously shown that there are significant changes in how the heart uses energy once a baby is born. Disruptions to these changes in energy metabolism of the heart can lead to heart failure. Cardiac hypertrophy, where the heart muscle thickens and impedes cardiac blood flow, can cause issues in the hearts ability to deal with the stress of surgery. This can further disrupt the energy metabolic changes of the developing heart, with the heart maintaining a fetal like metabolic profile. These changes make the heart less efficient in its ability to produce energy for use. The current proposal aims to understand the role that ketones, a potential energy source for the heart, have in the maturation of energy metabolism following birth and how this may be influenced under conditions of cardiac hypertrophy due to CHD. Infant surgical heart tissue, with or without cardiac hypertrophy due to CHD, will be analyzed. Target proteins involved in ketone metabolism will be identified and measured. We will directly study energy metabolism of cardiac cells under fetal like conditions (growing cells) and newborn conditions (maturing cells). The results of this study will be important in understanding how energy metabolism develops in the newborn heart. The data from my study would be invaluable in improving patient care of newborns that are born with heart defects.