Department of Pediatrics, University of Colorado, Aurora, Colorado.
Department of Biostatistics, University of Colorado, Aurora, Colorado.
Pediatr Res. 2018 Apr;83(4):858-865. doi: 10.1038/pr.2017.325. Epub 2018 Jan 17.
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.
细胞外腺嘌呤核苷酸会导致婴儿体外循环（CPB）后的缺血再灌注损伤，而转化为腺苷可能具有保护作用。碱性磷酸酶（AP）是负责这种转化的关键酶，在婴儿 CPB 后会减少。间接证据表明，可溶性 CD73 可能同时增加并部分抵消 AP 的这种损失。我们试图测量接受 CPB 的婴儿的 CD73 水平，并确定其与腺苷产生能力和术后支持需求的关系。
这是一项对≤120 天龄接受 CPB 的婴儿进行的前瞻性队列研究。CPB 前和复温期间测量 CD73。多变量模型评估了 CD73/AP 对腺苷产生能力和术后支持需求的贡献。
对 85 名受试者的血清样本进行了分析。CPB 后血清 CD73 浓度中位数升高（95.2 与 179.8ng/ml；P<0.0001）。复温时的 CD73 与血管活性正性肌力支持（P<0.005）和重症监护病房停留时间（P<0.005）独立呈负相关。AP 活性和 CD73 浓度的组合预测了腺苷的产生能力（P<0.0001）。
婴儿 CPB 后血清 CD73 增加。复温时的 CD73 较低与术后支持需求增加独立相关。CD73 和 AP 共同预测血清腺苷的产生能力，可能代表清除细胞外腺嘌呤核苷酸并改善婴儿 CPB 后结果的潜在治疗靶点。
