Moore F D, Warner K G, Assousa S, Valeri C R, Khuri S F
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
Ann Surg. 1988 Jul;208(1):95-103. doi: 10.1097/00000658-198807000-00014.
Complement activation was examined prospectively in 100 cardiopulmonary bypass (CPB) patients. Plasma C3a desArg (C3a) increased (cannulation: 234 +/- 33 ng/mL; 20 minutes on CPB: 622 +/- 51; 2 hours after CPB: 1143 +/- 109, p less than 0.0001). C3a at 2 hours was higher in the 13 patients requiring mechanical ventilation for longer than 1 day (1023 +/- 274) than in the 67 without respiratory complication (568 +/- 45, p less than 0.004). Five more patients were studied for neutrophil activation to confirm that a biologic effect of complement activation occurs during CPB; in these five patients C3a increased to 317% of baseline after 10 minutes on CPB with a corresponding rise in neutrophil cell surface receptors for the complement opsonin C3b (as measured by indirect immunofluorescence) to 168% (p less than 0.05). Both increases were sustained at 30 minutes. Temperature, dilution, and heparin were studied as variables relevant to CPB. Exposure of normal neutrophils to C5a in vitro caused an increase in C3b receptors which was dependent on temperature (0 specific fluorescence at 0 C, 30 at 25 C, 180 at 30 C, and 275 at 37 C). Generation of C3a and C5a in normal serum by zymosan was also temperature-dependent (ng/mL C5a generated: 0.7 at 25 C, 200 at 30 C, and 897 at 37 C; ng/mL C3a generated: 546 at 25 C, 10,872 at 30 C, and 65,667 at 37 C). Serum dilution to 33% decreased ng/mL C5a generated in the same system from 200 to 76 with no effect on C3a. Addition of heparin to 20 U/mL decreased ng/mL C3a generated from 10,872 to 913 and C5a from 200 to 8. Thus, hypothermia, dilution, and heparin protect CPB patients from complement activation by reducing both generation of C3a/C5a and the subsequent cellular response of neutrophil activation.
对100例体外循环（CPB）患者的补体激活情况进行了前瞻性研究。血浆C3a去精氨酸（C3a）水平升高（插管时：234±33 ng/mL；CPB开始20分钟时：622±51 ng/mL；CPB结束2小时后：1143±109 ng/mL，p<0.0001）。在13例需要机械通气超过1天的患者中，CPB结束2小时时的C3a水平（1023±274 ng/mL）高于67例无呼吸并发症患者（568±45 ng/mL，p<0.004）。另外对5例患者进行了中性粒细胞激活研究，以证实CPB期间补体激活会产生生物学效应；在这5例患者中，CPB开始10分钟后C3a增加至基线的317%，同时补体调理素C3b的中性粒细胞细胞表面受体相应增加至168%（通过间接免疫荧光法测定，p<0.05）。两种增加在30分钟时均持续存在。研究了温度、稀释和肝素作为与CPB相关的变量。体外将正常中性粒细胞暴露于C5a会导致C3b受体增加，这取决于温度（0℃时特异性荧光为0，25℃时为30，30℃时为180，37℃时为275）。酵母聚糖在正常血清中产生C3a和C5a也取决于温度（产生的C5a ng/mL：25℃时为0.7，30℃时为200，37℃时为897；产生的C3a ng/mL：25℃时为546，30℃时为10872，37℃时为65667）。将血清稀释至33%可使同一系统中产生的C5a ng/mL从200降至76，而对C3a无影响。加入20 U/mL肝素可使产生的C3a ng/mL从10872降至913，C5a从200降至8。因此，低温、稀释和肝素通过减少C3a/C5a的产生以及随后中性粒细胞激活的细胞反应，保护CPB患者免受补体激活。
