A Reductive Metabolic Switch Protects Infants with Transposition of Great Arteries Undergoing Atrial Septostomy against Oxidative Stress

Transposition of the great arteries (TGA) is one of the most common cyanotic congenital heart diseases requiring neonatal surgical intervention. Parallel circulations that result in impaired cerebral oxygen delivery already in utero may lead to brain damage and long-term neurodevelopmental delay. Balloon atrial septostomy (BAS) is often employed to mix deoxygenated and oxygenated blood at the atrial level. However, BAS causes a sudden increase in arterial blood oxygenation and oxidative stress. We studied changes in oxygen saturation as well as metabolic profiles of plasma samples from nine newborn infants suffering from TGA before and until 48 h after undergoing BAS. The plasma metabolome clearly changed over time and alterations of four metabolic pathways, including the pentose phosphate pathway, were linked to changes in the cerebral tissue oxygen extraction. In contrast, no changes in levels of lipid peroxidation biomarkers over time were observed. These observations suggest that metabolic adaptations buffer the free radical burst triggered by re-oxygenation, thereby avoiding structural damage at the macromolecular level. This study enhances our understanding of the complex response of infants with TGA to changes in oxygenation induced by BAS.