Seghaye M C, Duchateau J, Grabitz R G, Faymonville M L, Messmer B J, Buro-Rathsmann K, von Bernuth G
Department of Pediatric Cardiology, Hôpital St. Pierre, Brussels, Belgium.
J Thorac Cardiovasc Surg. 1993 Dec;106(6):978-87.
Twenty-nine children 3 months to 17 years of age undergoing operations for congenital heart disease were included in this prospective study. Complement activation, activation of the plasma contact system, leukocytes, leukocyte elastase release, and C-reactive protein were studied during and after cardiopulmonary bypass for the first postoperative week and related to multiple system organ failure occurring in eight (27.5%) of the 29 children. During cardiopulmonary bypass complement activation via the alternative pathway as indicated by significant conversion of C3 (expressed by C3d/C3) and abnormally high C5a values at the end of cardiopulmonary bypass without consumption of C4 was shown in all children. At the end of cardiopulmonary bypass, C3 conversion was significantly higher in the eight patients with multiple system organ failure than in the others (p < 0.05), whereas no difference in C5a level was shown. All children had a significant increase in leukocyte count directly after protamine administration (p < 0.0001) and elastase release during cardiopulmonary bypass that was significantly higher in patients with multiple system organ failure than in those without (p < 0.05). Consumption of prekallikrein as an indicator of activation of the Hageman system was not detectable during cardiopulmonary bypass in any child. After cardiopulmonary bypass, in patients without multiple system organ failure, C3d/C3 decreased and reached preoperative values within the first postoperative week, whereas, in patients with multiple system organ failure, C3d/C3 increased further, reaching a maximal value on the third postoperative day. In comparison with patients without multiple system organ failure, patients with multiple system organ failure showed a severe decrease of C4 (with minimal values on the third postoperative day), suggesting consumption by activation of the classic pathway of the complement system or a hepatic synthesis deficiency. Prekallikrein values were also significantly lower in patients with multiple system organ failure than in the others, with a maximal difference on the third postoperative day (p < 0.005). C-reactive protein was significantly lower in patients with multiple system organ failure than in the others for the first 2 postoperative days (p < 0.05), probably because of severe hepatic failure in patients with multiple system organ failure. This study demonstrates that, in children, cardiopulmonary bypass induces complement activation principally via the alternative pathway. It suggests a relationship between complement activation and multiple system organ failure observed in the postoperative period. Furthermore, it points out the role of multiple system organ failure itself on the C3 conversion and on the synthesis of the markers of the inflammatory response in children after heart operations.
本前瞻性研究纳入了29例年龄在3个月至17岁之间接受先天性心脏病手术的儿童。在体外循环期间及术后第一周，对补体激活、血浆接触系统激活、白细胞、白细胞弹性蛋白酶释放及C反应蛋白进行了研究，并与29例儿童中8例（27.5%）发生的多系统器官衰竭相关。在体外循环期间，所有儿童均显示通过替代途径激活补体，表现为C3显著转化（以C3d/C3表示），且体外循环结束时C5a值异常升高而C4未消耗。体外循环结束时，8例发生多系统器官衰竭的患者C3转化率显著高于其他患者（p<0.05），而C5a水平无差异。所有儿童在给予鱼精蛋白后白细胞计数均显著增加（p<0.0001），且体外循环期间弹性蛋白酶释放量在发生多系统器官衰竭的患者中显著高于未发生者（p<0.05）。在任何儿童的体外循环期间均未检测到作为Hageman系统激活指标的前激肽释放酶消耗。体外循环后，未发生多系统器官衰竭的患者C3d/C3降低，并在术后第一周内恢复至术前值，而发生多系统器官衰竭的患者C3d/C3进一步升高，在术后第三天达到最大值。与未发生多系统器官衰竭的患者相比，发生多系统器官衰竭的患者C4严重降低（术后第三天降至最低值），提示补体系统经典途径激活导致消耗或肝脏合成不足。发生多系统器官衰竭的患者前激肽释放酶值也显著低于其他患者，术后第三天差异最大（p<0.005）。术后前两天，发生多系统器官衰竭的患者C反应蛋白显著低于其他患者（p<0.05），可能是因为发生多系统器官衰竭的患者存在严重肝功能衰竭。本研究表明，在儿童中，体外循环主要通过替代途径诱导补体激活。提示补体激活与术后观察到的多系统器官衰竭之间存在关联。此外，还指出了多系统器官衰竭本身对儿童心脏手术后C3转化及炎症反应标志物合成的作用。
