ENDOTHELIAL-DEPENDENT VASCULAR REACTIVITY AFTER CARDIOPULMONARY BYPASS IS ASSOCIATED WITH UNIQUE METABOLOMIC SIGNATURES.

ABSTRACT

ABSTRACT Cardiopulmonary bypass (CPB), an extracorporeal method necessary for the surgical correction of complex congenital heart defects, incites significant inflammation that affects vascular function. These changes are associated with alterations in cellular metabolism that promote energy production to deal with this stress. Utilizing laser Doppler perfusion monitoring coupled with iontophoresis in patients undergoing corrective heart surgery, we hypothesized that temporal, untargeted metabolomics could be performed to assess the link between metabolism and vascular function. Globally, we found 2,404 unique features in the plasma of patients undergoing CPB. Metabolites related to arginine biosynthesis were the most altered by CPB. Correlation of metabolic profiles with endothelial-dependent (acetylcholine [ACh]) or endothelial-independent (sodium nitroprusside [SNP]) vascular reactivity identified purine metabolism being most consistently associated with either vascular response. Concerning ACh-mediated responses, acetylcarnitine levels were most strongly associated, while glutamine levels were associated with both ACh and SNP responsiveness. These data provide insight into the metabolic landscape of children undergoing CPB for corrective heart surgery and provide detail into how these metabolites relate to physiological aberrations in vascular function.