Cardiothoracic Surgery and Cardiovascular Medicine Units, Imperial College Healthcare NHS Trust, Imperial College London, London, UK.
Eur J Cardiothorac Surg. 2010 Jun;37(6):1360-6. doi: 10.1016/j.ejcts.2009.12.043. Epub 2010 Feb 12.
Circulating monocytes may counter systemic pro-inflammatory and haemolytic insults through the expression and shedding of the haemoglobin scavenger receptor (CD163). This prospective study aims to assess the effects of coronary artery bypass grafting with and without cardiopulmonary bypass (CPB) on haemoglobin scavenging and anti-inflammatory monocyte behaviour.
Forty consecutive patients underwent coronary surgery using CPB (n=20) and off-pump (n=20) techniques. Peri-operative blood samples were taken until the fifth day following surgery and statistical comparison performed to baseline using group- and subject-based analysis. Monocyte receptor expression and plasma concentrations of anti-inflammatory molecules were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively.
Monocyte CD163 expression was significantly elevated post-operatively in both surgical groups with (p=0.001) and without CPB (p=0.000) at 24-48h. By contrast, shed CD163 (p=0.02) and haemoglobin-haptoglobin complexes (p=0.000) in plasma were only significantly elevated in the on-pump group at 2-4h. Subject-based analysis demonstrated that CPB is an independent predictor of monocyte CD163 (p=0.002) and plasma sCD163 (p=0.01) concentration adjusting for the measurement timing. Significant downregulation of the monocyte major histocompatibility complex II receptor was observed in both surgical groups, whereas lipopolysaccharide receptor (CD14) expression only declined following on-pump surgery. The anti-inflammatory cytokine interleukin (IL)-10 was elevated post-operatively in both surgical groups peaking earlier in the on-pump group (2h) versus off-pump group (4h). The immunoregulatory IL-6 cytokine was significantly upregulated at 4h in both groups.
Coronary artery bypass surgery induces monocyte-associated anti-inflammatory and immunoregulatory responses. There was no significant difference in haemolysis although the effect on monocyte CD163 and plasma sCD163 concentration was significantly different between the two groups. Compensation for varying pro-inflammatory and haemolytic insults may explain the differences observed. Therapeutic strategies for inducing such desirable circulating monocytes may potentially improve surgical outcome and patient recovery.
循环中的单核细胞可能通过表达和释放血红蛋白清除受体（CD163）来对抗全身的促炎和溶血性损伤。本前瞻性研究旨在评估体外循环（CPB）和非体外循环（CPB）冠状动脉旁路移植术对血红蛋白清除和抗炎性单核细胞行为的影响。
40 例连续患者接受 CPB（n=20）和非 CPB（n=20）冠状动脉手术。在手术后直到第 5 天采集围手术期血液样本，并使用基于组和基于个体的分析与基线进行统计比较。通过流式细胞术和酶联免疫吸附试验分别测量单核细胞受体表达和血浆抗炎分子浓度。
两组手术后单核细胞 CD163 表达均显著升高，CPB 组（p=0.001）和无 CPB 组（p=0.000）在 24-48 小时。相比之下，仅在 CPB 组中，在 2-4 小时时，血浆中脱落的 CD163（p=0.02）和血红蛋白-触珠蛋白复合物（p=0.000）显著升高。基于个体的分析表明，CPB 是单核细胞 CD163（p=0.002）和血浆 sCD163（p=0.01）浓度的独立预测因子，调整了测量时间。两组均观察到单核细胞主要组织相容性复合体 II 受体的显著下调，而 LPS 受体（CD14）的表达仅在 CPB 手术后下降。两组手术后抗炎细胞因子白细胞介素（IL）-10 升高，CPB 组更早（2 小时），而非 CPB 组（4 小时）升高。两组均在 4 小时时，免疫调节细胞因子 IL-6 显著上调。
冠状动脉旁路手术诱导单核细胞相关抗炎和免疫调节反应。尽管两组之间在溶血方面没有显著差异，但对单核细胞 CD163 和血浆 sCD163 浓度的影响有显著差异。可能是由于补偿了不同的促炎和溶血损伤，从而解释了观察到的差异。诱导这种理想的循环单核细胞的治疗策略可能会改善手术结果和患者的恢复。
