Centre for Critical Illness Research, Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada.
J Cardiothorac Vasc Anesth. 2013 Feb;27(1):35-40. doi: 10.1053/j.jvca.2012.09.004.
The purpose of this study was to evaluate the mechanisms of cardiopulmonary bypass (CPB)-induced dysregulation between thrombin and its regulatory anticoagulant activated protein C (APC).
A prospective observational cohort study.
A tertiary care university hospital and associated research laboratory.
Twenty patients undergoing elective coronary artery bypass surgery with (n = 10) or without CPB (n = 10).
Blood samples were collected at 7 time points: preinduction; after heparin; 1 hour after the institution of CPB (or the completion of distal anastomoses in off-CPB group); after protamine; and at 0, 4, and 18 hours in the Intensive care unit (ICU). Samples were analyzed for prothrombin fragments (F1+2), thrombin-antithrombin complexes, protein C (PC), APC, soluble thrombomodulin (sTM), and soluble endothelial protein C receptor (sEPCR).
F1+2 levels increased significantly 1 hour after the initiation of CPB in comparison with baseline (2.7 ± 0.5 v 0.5 ± 0.2 nmol/L, p < 0.001) (mean ± standard deviation) and remained elevated until 4 hours after ICU admission (p < 0.001). In contrast, APC levels did not show any significant changes over time in either group. sEPCR, sTM, and PC levels did not change during CPB although sEPCR decreased significantly after the termination of CPB compared with baseline in the CPB group.
Exposure to CPB is associated with a distinct thrombin surge that continues postoperatively for 4 hours. The impaired ability to generate APC reflects a complex process that is not associated with increased levels of sEPCR and thrombomodulin during CPB. Further studies are required to evaluate the regulation of the host APC response in cardiac surgery.
本研究旨在评估体外循环（CPB）引起的凝血酶与其调节性抗凝蛋白 C（APC）之间失调的机制。
前瞻性观察队列研究。
三级护理大学医院及相关研究实验室。
20 例择期行冠状动脉旁路移植术的患者，其中 10 例接受 CPB（CPB 组），10 例不接受 CPB（非 CPB 组）。
在 7 个时间点采集血样：诱导前；肝素后；CPB 开始后 1 小时（或非 CPB 组完成远端吻合后）；鱼精蛋白后；ICU 中 0、4 和 18 小时。分析样本中的凝血酶原片段（F1+2）、凝血酶-抗凝血酶复合物、蛋白 C（PC）、APC、可溶性血栓调节蛋白（sTM）和可溶性内皮蛋白 C 受体（sEPCR）。
与基线相比，CPB 开始后 1 小时 F1+2 水平显著升高（2.7±0.5比 0.5±0.2 nmol/L，p<0.001），并持续升高至 ICU 入院后 4 小时（p<0.001）。相比之下，两组 APC 水平在整个过程中均无明显变化。虽然 CPB 组 CPB 终止后 sEPCR 与基线相比显著降低，但 sEPCR、sTM 和 PC 水平在 CPB 期间并未发生变化。
暴露于 CPB 会导致明显的凝血酶激增，这种激增会持续到术后 4 小时。APC 生成能力受损反映了一个复杂的过程，与 CPB 期间 sEPCR 和血栓调节蛋白水平升高无关。需要进一步研究来评估心脏手术中宿主 APC 反应的调节。
