Abstract
BackgroundExtracellular adenine nucleotides contribute to ischemia-reperfusion injury following infant cardiopulmonary bypass (CPB), whereas conversion to adenosine may be protective. Alkaline phosphatase (AP), a key enzyme responsible for this conversion, decreases after infant CPB. Indirect evidence suggests that soluble CD73 may simultaneously increase and partially offset this loss of AP. We sought to measure CD73 levels in infants undergoing CPB and determine its association with adenosine production capacity and postoperative support requirements.MethodsA prospective cohort study of infants ≤120 days of age undergoing CPB. CD73 was measured before CPB and during rewarming. Multivariable modeling evaluated the contributions of CD73/AP to adenosine production capacity and postoperative support requirements.ResultsSerum samples from 85 subjects were analyzed. The median CD73 concentration increased following CPB (95.2 vs. 179.8 ng/ml; P<0.0001). Rewarming CD73 was independently inversely associated with vasoactive inotropic support (P<0.005) and length of intensive care unit stay (P<0.005). Combined AP activity and CD73 concentration predicted adenosine production capacity (P<0.0001).ConclusionsSerum CD73 increases following infant CPB. Low rewarming CD73 is independently associated with increased postoperative support requirements. CD73 and AP together predict serum adenosine production capacity and may represent potential therapeutic targets to clear extracellular adenine nucleotides and improve outcomes following infant CPB.