Partrick D A, Moore E E, Fullerton D A, Barnett C C, Meldrum D R, Silliman C C
Department of Surgery, Denver Health Medical Center, Denver, Colorado 80204, USA.
J Surg Res. 1999 Sep;86(1):42-9. doi: 10.1006/jsre.1999.5702.
Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response syndrome (SIRS) and these patients are recognized to be at increased risk for delayed infectious complications. We have documented that circulating neutrophils (PMNs) from patients manifesting SIRS have evidence of early postinjury priming for cytotoxicity. Consequently, we hypothesized that CPB would result in early postoperative PMN hyperresponsiveness (priming).
Six patients (mean age 50 +/- 2.9 years) who underwent CPB for CABG had sequential blood samples obtained perioperatively. PMNs were isolated and superoxide anion (O(-)(2)) generation (nmol O(-)(2)/3.75 x 10(5) PMNs/min) was measured by reduction of cytochrome c after exposure to fMLP, C5a, or PMA; elastase release (% total PMN elastase content) was measured by cleavage of AAPV-pNA after exposure to fMLP or C5a.
PMNs were activated for increased elastase release 6 h after initiation of CPB. Significant PMN priming for O(-)(2) production was discovered at 3, 6, and 12 h following CPB and for elastase release at 3 and 6 h after CPB. At 2 to 3 days after CPB, O(-)(2) generation was significantly less than that of the preoperative control. Neutrophil primability with PAF was detected at 6 h after CPB. A similar defect in PAF-primable O(-)(2) production was seen 2 and 3 days post-CPB. Direct PMN interrogation with the receptor-independent activator PMA revealed loss of integrity of the NADPH oxidase at 2 and 3 days following CPB.
A vulnerable window exists between 3 and 12 h after CPB when PMNs are primed for enhanced cytotoxicity via O(-)(2) production and elastase release. Paradoxically, PMN oxidase integrity becomes deficient 48 h post-CPB, while protease degranulation remains intact. These events render the bypass patient at risk for multiple organ failure via both early PMN-mediated tissue injury and delayed infectious complications.
体外循环（CPB）与全身炎症反应综合征（SIRS）相关，并且这些患者被认为发生延迟性感染并发症的风险增加。我们已证明，表现出SIRS的患者循环中的中性粒细胞（PMN）有损伤后早期细胞毒性启动的证据。因此，我们推测CPB会导致术后早期PMN反应性增高（启动）。
6例（平均年龄50±2.9岁）因冠状动脉旁路移植术（CABG）接受CPB的患者在围手术期接受了序贯血样采集。分离出PMN，并在暴露于fMLP、C5a或PMA后通过细胞色素c还原法测量超氧阴离子（O₂⁻）生成量（nmol O₂⁻/3.75×10⁵ PMN/分钟）；在暴露于fMLP或C5a后通过AAPV-pNA裂解测量弹性蛋白酶释放量（占总PMN弹性蛋白酶含量的百分比）。
CPB开始后6小时，PMN被激活，弹性蛋白酶释放增加。在CPB后3、6和12小时发现PMN对O₂⁻生成有显著启动作用，在CPB后3和6小时对弹性蛋白酶释放有显著启动作用。在CPB后2至3天，O₂⁻生成显著低于术前对照。在CPB后6小时检测到PMN对血小板活化因子（PAF）的启动能力。在CPB后2天和3天观察到PAF启动的O₂⁻生成有类似缺陷。用不依赖受体的激活剂PMA直接检测PMN发现，CPB后2天和3天NADPH氧化酶的完整性丧失。
CPB后3至12小时存在一个易损期，此时PMN通过O₂⁻生成和弹性蛋白酶释放被启动以增强细胞毒性。矛盾的是，CPB后48小时PMN氧化酶完整性受损，而蛋白酶脱颗粒仍保持完整。这些事件使接受旁路手术的患者因早期PMN介导的组织损伤和延迟性感染并发症而面临多器官功能衰竭的风险。
