Augmenting O-GlcNAcylation, an Intrinsic Cardiovascular Stress Adaption, to Prevent Low Cardiac Output Syndrome in Mocel of Pediatric Cardiac Surgery

Lay Summary: The ultimate goal of my work is to reduce morbidity and mortality after congenital heart surgery. Basic scientists identified an important mechanism of the body’s natural response to abnormal stresses similar to those encountered from cardiac surgery. The technical term for this process is O-GlcNAcylation and it involves the rapid, simultaneous modifications of multiple proteins that then change the function of an organ such as the heart. Increasing O-GlcNAcylation with medications improves the recovery of organs to abnormal stressors; however this has never been evaluated in conditions similar to cardiopulmonary bypass in children.

 

We hypothesize that increasing O-GlcNAc levels will improve post-operative cardiac function and hemodynamics. In my project for Saving Tiny Hearts Foundation, we were able to test a pharmaceutical strategy to increase O-GlcNAcylation in order to see whether this improved cardiac function in our piglet model of pediatric heart surgery. Our studies showed a beneficial effect on cardiac function after cardiopulmonary bypass by increasing O-GlcNAc levels. Additional experiments are necessary before we can trial this intervention in children and infants.