体外循环手术中C3、C4的检测意义

目的 了解体外循环(CPB)手术对病人血浆中C3、C4的影响。方法 用透射比浊法测定行心脏瓣膜置换术前后病人血浆中C3、C4浓度,并进行比较。结果 术前与术后血浆中C3、C4差异有显著性(P<0.05),血浆中C3、C4降低的谷值在CPB末。结论 CPB导致术后早期大量补体激活,易引起全身性炎症反应综合征(SIRS),减少补体激活程度可降低炎症反应强度。     

C3a、C5a、MDA、SOD表达在婴幼儿体外循环心肌损伤中作用

目的探讨婴幼儿体外循环(CPB)术后心肌损害机理及预防方法。方法 20例行CPB手术的先天性心脏病患儿分别在CPB转流前、CPB转流结束后20 min(简称术后20 min)、术后2 h、术后6 h、术后12 h测定动脉血浆补体3a(C3a)、补体5a(C5a)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)、超氧化物歧化酶(SOD)、肌酸激酶同工酶(CK-MB)、肌酸激酶(CK)、肌钙蛋白(cTnI)及乳酸脱氢酶(LDH)浓度。结果与CPB转流前比较,术后20 min及2、6、12 h血浆C3a、C5a浓度降低(P<0.05),血浆CK、LDH浓度升高(P<0.05);术后20 min、2 h血浆IL-6浓度逐渐增高(P<0.05),术后6、12 h逐渐下降,但仍高于CPB转流前(P<0.05);血浆TNF-α浓度术后20 min增高(P<0.05),术后2 h开始逐渐下降;血浆CK-MB术后2 h升高(P<0.05),术后6、12 h逐渐下降,但仍高于CPB转流前(P<0.05);术后2 h血浆cTnI升高(P<0.05);血浆MDA浓度术后20 min和2 h降低(P<0.05),术后6 h明显增高(P<0.05),术后12 h降低(P<0.05);血浆SOD浓度术后2、6、12 h明显降低(P<0.05)。结论婴幼儿CPB术后12 h心肌功能明显受损,其机理可能与CPB术后再灌注损伤补体激活及氧自由基释放导致心肌及内皮损伤有关。     

急性脑梗死诱发全身炎症反应综合征患者血清C-反应蛋白和补体C3、C4水平变化

目的 探讨血清C-反应蛋白(CRP)和补体C3、C4在急性脑梗死(ACI)诱发全身炎症反应综合征(SIRS)发生中的作用.方法 应用全自动免疫比浊定量分析法分别测定52例ACI致SIRS患者(SIRS组)、50例急性单纯ACI患者(SACI组)及46例正常对照组血清CRP和补体C3、C4含量.结果 血清CRP和补体C3、C4含量在3组间比较,差异均具有统计学意义(F值分别为720.6、580.8和94.1,P均<0.01).SIRS组血清CRP水平高于SACI组(P<0.01),血清补体C3、C4均低于SACI组(P均<0.01).血清CRP含量随符合SIRS诊断标准数目的 增多而升高(t=7.69,P<0.01),补体C3、C4含量则随符合SIRS诊断标准数目的 增多而下降(t值分别为10.68和10.53,P均<0.01).结论 ACI进展为SIRS后,血清CRP明显升高,补体C3、C4明显下降,血清CRP和补体C3、C4可作为判断病情进展为SIRS的一项指标.     

新生儿交换输血术对新生儿血清补体C3、C4的影响

目的:通过对新生儿高胆红素血症(简称高胆)患儿进行交换输血治疗的前后分别测定血清补体C3、C4,评估高胆患儿的补体系统免疫状态和换血后的变化情况,了解交换输血术对新生儿血清补体的影响。方法:对62例新生儿高胆患儿进行交换输血治疗,治疗的前后分别测定血中补体(C3、C4),并将高胆患儿依据病因分成ABO溶血病组、Rh溶血病组、脓毒症组、其他组4组进行分析。结果:(1)换血术前:补体C3、C4的水平各组比较差异无统计学意义。(2)换血术后:补体C3:脓毒症组的水平较其他3组高,差异均有统计学意义,其余3组间比较差异无统计学意义;补体C4:各组间的水平比较差异无统计学意义。(3)换血术后与术前比较:C3:各组均数在换血术后均有升高,但只有ABO溶血病组术后的改变差异有统计学意义;C4:ABO、Rh溶血病组较术前稍升高,其余两组稍降低,各组间差值比较差异无统计学意义;术后较术前各组变化值比较差异无统计学意义。结论:(1)新生儿高胆患儿血中补体C3、C4水平无明显差异,但水平偏低;(2)换血术能提升脓毒症患儿血中补体C3的水平,有助于免疫力增强;(3)换血术对补体C4的影响较小;(4)换血术对高胆新生儿补体免疫系统是有益的、安全的。     

应用磷酸肌酸对体外循环患者体液免疫功能的影响

目的　观察外源性磷酸肌酸 (CP)对体外循环 (CPB)患者体液免疫功能的影响。方法　CPB患者均选用冠脉搭桥 (CABG)的围术期患者。将 2 8例CABG患者分为CP组 17例 ,对照组 11例。CP组于术前、后各用CP 3～ 7天 ,每天 2g静脉滴注 ,术中将CP加入心脏停搏液中 ;对照组术前、中、后均不用CP。观察两组患者术前 1周、麻醉诱导后、术中阻断升主动脉后 5min、35min、6 5min、6 5min、术毕、术后 2 4h、术后 1周补体 (C3、C4 )及免疫球蛋白 (IgA、IgG、IgE、IgM)的变化。结果　两组患者补体C3、C4及 4种免疫球蛋白的变化曲线相似 ,在术前 1周、麻醉诱导后、术中阻断升主动脉后 5min、35min、6 5min、术毕、术后 2 4h两组间均无明显差别 ,而术后 1周结果显示CP组补体C3、C4及免疫球蛋白IgG、IgM均明显低于对照组 (P <0 .0 5 )。结论　外源性磷酸肌酸用于CPB患者围术前 ,可以营养细胞 ,保护细胞膜的稳定性 ,使补体和免疫球蛋白不会因手术损伤而应激性增高 ,保护体液免疫功能 ,减少炎症 ,有利于术后患者康复。其机制可能是通过清除ADP实现的     

体外循环围术期对超敏C-反应蛋白及补体变化监测的临床价值

体外循环（CPB）心脏手术过程中易引起心肌细胞的损害，诱发机体炎症反应。局部炎症反应一旦扩大则易导致全身炎性反应综合征，从而继发脓毒血症，致使重要脏器功能不全，甚至多系统器官功能衰竭。超敏C-反应蛋白（hs—CRP）具有高度的敏感性，是急性炎症反应的一种特异性标志物，能有效监测心血管疾病的危险及组织损害。补体G3、C4是人体血液中的一种具有酶活性的糖蛋白，可反映机体补体水平，从而显示机体免疫功能状态。作者自2004年11月至2007年4月对本院CPB心脏手术患者围术期血清hs—CRP及补体G3、C4水平作动态检测，以探究其在CPB围术期患者监护及预后判断中的意义。     

阿尔茨海默病患者血浆同型半胱氨酸及血清C反应蛋白、补体C3测定及其意义

目的检测并分析阿尔茨海默病(AD)血浆同型半胱氨酸、血清C反应蛋白及补体C3浓度变化。方法检测30例AD患者(AD组)与30例健康老年人(对照组)的血清C反应蛋白、补体C3、血浆同型半胱氨酸浓度。结果 AD组与对照组患者血清补体C3浓度分别为(637.25±189.13)、(596.98±174.33)mg/L,差异无统计学意义(P>0.05);C反应蛋白分别为(16.78±3.54)、(5.40±1.89)mg/L,差异有统计学意义(P<0.01);血浆同型半胱氨酸分别为(49.84±1.45)、(30.89±1.58)μmol/L,差异有统计学意义(P<0.01)。结论血浆同型半胱氨酸;血清C反应蛋白浓度可作为AD诊断的参考指标之一。     

心血管支架置入与血清补体C3的变化

补体系统是由35种广泛存在于血清、组织液和细胞膜表面具有酶活性的蛋白质组成的反应系统,在机体抗感染第一线防御中起重要作用.补体异常活化也参与许多炎症性疾病的发生和发展,补体的激活有3条途径,即经典途径、旁路途径和凝集素途径.心血管支架置入后,冠状动脉粥样硬化性心脏病患者血管内皮有不同程度损伤,血清补体C3/可以进入动脉管壁,损伤深层的动脉细胞,使动脉壁的通透性增强,并释放血管壁结构抗原成分,诱导抗体产生,使固定免疫复合物形成,进而诱发血小板在此聚集、黏附或引起该处脂质沉积.尽管心血管支架置入后患者体液免疫亢进,但抵御外来微生物的能力减弱,从而刺激机体产生更多的C3进行自我保护,使炎症进一步加重,循环复合物增多,激活补体系统,进一步导致血管内皮损伤加剧.提示C3在缺缸性心血管疾病的发生、发展中起非常重要的作用,是缺血性心血管疾病一个很好的标志物,同时也是心血管支架置入后再狭窄和血栓形成的重要原因之一.     

补体激活经典途径在胸外科病人手术前后的变化

[目的]探讨胸外科病人术后早期体内补体激活经典途径的活化状态,为临床治疗与护理提供理论依据。[方法]选择2013年1月—2013年7月我院收治的胸外科手术病人108例,分别在术前、术后24h和术后48h抽取病人血液标本,应用ELISA法检测血清中C反应蛋白、补体C3及C4浓度,采用t检验比较C反应蛋白、补体C3及C4在手术前后的变化。[结果]补体C3、C4术后24h浓度下降(P0.05),而术后48h又回升至与术前同一水平(P0.05)。C反应蛋白术后血清浓度持续升高,术后24h和48h均高于术前浓度(P0.05)。[结论]补体激活经典途径中C3、C4位于C反应蛋白下游,受C反应蛋白激活而发挥重要的免疫功能,胸外科手术后24hC反应蛋白升高,C3、C4下降,术后48hC3、C4恢复至术前水平,应在术后24h~48h加强病人的感染预防措施。     

补体C3、C4在家犬脑出血模型中的变化

目的:研究家犬脑出血(ICH)模型补体C3、C4与血肿周围脑水肿的关系。方法:30只家犬随机分为正常对照组、影像组和血肿组3组各10只。正常对照组不予任何处理,影像组和血肿组采用立体定向自体血脑内注入法制备ICH模型。正常对照组和影像组分别于术后6 h、24 h、72 h、5 d、7 d检测外周静脉血C3、C4含量,各时间点行头颅CT扫描并计算水肿比值。血肿组分别于术后6 h、24 h、72 h、5 d、7 d检测血肿液C3、C4含量。各时间点采用Purdy PD评分标准评估神经功能缺损。结果:影像组和血肿组外周血、血肿液补体C3、C4含量术后6 h开始升高,72 h达高峰,之后逐渐下降。影像组、血肿组与正常对照组比较,术后6 h外周血C4差异无统计学意义(P>0.05),其余同时间点两两比较差异均有统计学意义(P<0.05)。ICH后Purdy PD评分即有所下降,72 h下降为最低,之后逐渐升高。结论:ICH后补体C3、C4激活可能参与血肿周围脑水肿形成和继发性脑损害的病理过程。     

Effect of cardiopulmonary bypass on plasma fibronectin, IgG, and C3

The effect of cardiopulmonary bypass operations on the concentration of plasma fibronectin, IgG, and C3 was studied in 28 patients. During cardiopulmonary bypass operations, plasma IgG, and C3 decreased to about 45 percent of their preoperative concentrations, probably as a result of hemodilution and blood loss. On the average, plasma fibronectin decreased significantly more (p less than 0.002), to 32 percent of its preoperative concentration, probably as a result of hemodilution, blood loss, and consumption. We assumed that consumption of fibronectin occurred when its concentration decreased more than the concentrations of IgG and C3. Interestingly, consumption of fibronectin during bypass operations was not demonstrated in seven of the 28 patients who did not require blood products within the 24-hour period after operation. We suggest that consumption, rather than dilution, of plasma fibronectin might be clinically important. A significant (p less than 0.002) negative correlation was observed between the length of the bypass and the concentration of plasma fibronectin during this 24-hour period. We also studied the rate of regeneration of fibronectin, IgG, and C3 in 12 of these patients. The concentrations of fibronectin and C3 were normal by the fifth postoperative day. The rate of regeneration of IgG, however, was slower than that of fibronectin and C3.     

Utilising cardiopulmonary bypass for cancer surgery. Malignancy-induced protein C deficiency and thrombophilia

Cardiopulmonary bypass has evolved over the last 30 years. It is an important tool for the cardiac surgeon today and also has applications in non-cardiac operations such as surgery to extract tumours. Such patients undergoing surgery for cancer may be at an increased risk of a thromboembolic event post surgery, due to disturbances in the normal clotting pathway leading to hypercoagulability. One such disturbance is malignancy-induced Protein C deficiency. A deficiency of Protein C can cause hypercoagulabitity. Recent studies have examined cardiopulmonary bypass and inherited Protein C deficiency. However, surgery for cancer patients with a malignancy-induced Protein C deficiency involving cardiopulmonary bypass has not been reported. Surgery using CPB in these patients may result in increased morbidity and mortality. The objective of this article is to review the literature in order to discuss the occurrence, the aetiology and possible management of cancer patients with malignancy-induced Protein C deficiencies that require cardiopulmonary bypass for their surgery.     

Adsorption of anaphylatoxins from the plasma of systemic lupus erythematosus patients using dextran sulfate cellulose columns

Complement-derived anaphylatoxin may be one of the causes of vascular injury and an indicator of activity in systemic lupus erythematosus (SLE). The present study examines the effectiveness of dextran sulfate (DS) column immunoadsorption treatment to remove anaphylatoxins (C3a, C4a, and C5a) from the blood of patients with SLE. Seven SLE patients were subjected to immunoadsorption using DS-bound cellulose columns (Selesorb®, Kaneka). Blood samples were taken both before and after the immunoadsorption session. Specimens were also obtained from both the inlets and outlets of the DS columns every 1,000 ml of treated plasma volume. The DS columns removed anaphylatoxins C3a and C4a from the separated plasma (from 775 ± 334 ng/ml to 640 ± 252 ng/ml, and from 1,303 ± 847 ng/ml to 619 ± 578 ng/ml, respectively) during the clinical anti-DNA apheresis procedure. In these study, the C5a levels in the circulating plasma of SLE patients were not elevated. To confirm whether DS-bound cellulose beads adsorbs anaphylatoxins in vitro, zymosan-activated plasma (ZAP) containing high levels of anaphylatoxins was incubated with DS-bound cellulose beads. The levels of C3a, C4a and C5a in the ZAP significantly decreased by mixing with DS-bound cellulose beads (P < 0.05). Nevertheless, C3a and C4a in the peripheral blood were not significantly decreased after the immunoadsorption, suggesting that these anaphylatoxins bypass the DS columns in apheresis and return to the patient via the cell-rich fraction. J. Clin. Apheresis 13:108–113, 1998. © 1998 Wiley-Liss, Inc.     

Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation.

Complement activation contributes to the systemic inflammatory response induced by cardiopulmonary bypass. At the cellular level, cardiopulmonary bypass activates leukocytes and platelets; however the contribution of early (3a) versus late (C5a, soluble C5b-9) complement components to this activation is unclear. We used a model of simulated extracorporeal circulation that activates complement (C3a, C5a, and C5b-9 formation), platelets (increased percentages of P-selectin-positive platelets and leukocyte-platelet conjugates), and neutrophils (upregulated CD11b expression). to specifically target complement activation in this model, we added a blocking mAb directed at the human C5 complement component and assessed its effect on complement and cellular activation. Compared with a control mAB, the anti-human C5 mAb profoundly inhibited C5a and soluble C5b-9 generation and serum complement hemolytic activity but had no effect on C3a generation. Additionally, the anti-human C5 mAb significantly inhibited neutrophil CD11b upregulation and abolished the increase in P-selectin-positive platelets and leukocyte-platelet conjugate formation compared to experiments performed with the control mAb. This suggests that the terminal components C5a and C5b-9, but not C3a, directly contribute to platelet and neutrophil activation during extracorporeal circulation. Furthermore, these data identify the C5 component as a site for therapeutic intervention in cardiopulmonary bypass.     

肺动脉灌注肺保护液对体外循环相关性炎症反应影响的实验研究

目的探讨肺动脉灌注低温肺保护液对体外循环相关性炎症反应的影响。方法将20只杂种犬随机分为对照组和实验组。实验组在阻断升主动脉后经肺动脉灌注低温肺保护液,对照组则行常规体外循环、不灌注肺保护液,分别于诱导前(T1),转流1h(T2),停机1h(T3),停机2h(T4)抽取动脉血,测定血浆肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)浓度。结果两组实验犬血浆TNF-α、IL-6和IL-10的浓度,在T2-T4各时点与体外循环前比较均明显增加(P0.05);T2-T4时点实验组血浆TNF-α和IL-6浓度明显低于对照组(P0.01),IL-10浓度明显高于对照组(P0.05)。结论体外循环期间经肺动脉灌注低温肺保护液可抑制体外循环过程中促炎细胞因子TNF-α和IL-6的释放,促进抗炎细胞因子IL-10的释放,从而减轻体外循环引起的全身炎症反应。     

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding

OBJECTIVE: Cardiopulmonary bypass is known to result in a reduction in the plasma binding of drugs. The resulting effect on the hepatic clearance of drugs with low extraction is well understood. However, the situation with those that are highly extracted is less clear. Studies were, therefore, undertaken with one such drug, propofol, for which plasma binding was changed during cardiac surgery with cardiopulmonary bypass. METHODS: After induction of anesthesia with midazolam in 19 patients, propofol was infused continuously at a rate of 4 mg. kg(-1). h(-1) during surgery. Propofol's concentration was measured by HPLC in blood samples collected from the radial artery and hepatic vein during surgery at predetermined intervals. The drug's unbound fraction in arterial plasma was estimated via equilibrium dialysis. RESULTS: The total concentration of propofol in blood was unchanged during surgery except shortly after the initiation of cardiopulmonary bypass. By contrast, the fraction of unbound propofol in blood increased by 2-fold during cardiopulmonary bypass and then decreased after the completion of cardiopulmonary bypass. The hepatic extraction ratio of propofol was greater than 0.8 and remained constant throughout surgery. The ratio of propofol concentration in erythrocytes to that in blood increased by 1.6-fold during cardiopulmonary bypass. CONCLUSIONS: During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.     

Protein C -1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis

OBJECTIVE: Protein C contains an A/G polymorphism at position -1641 and a C/T polymorphism at -1654 associated with risk of deep venous thrombosis. We tested the hypothesis that these polymorphisms are associated with altered outcome in patients having severe sepsis, in which protein C is a central molecule. DESIGN: Prospective cohorts, gene-association study. SETTING: Tertiary care medical/surgical intensive care unit. PATIENTS: We first recruited a derivation cohort of patients having severe sepsis (n = 62). A second replication cohort was similarly defined but larger (n = 402). We tested for biological plausibility in a third cohort of post-cardiopulmonary bypass patients (n = 61). INTERVENTIONS: Patients were genotyped at protein C -1641 and -1654. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was survival in cohorts 1 and 2 and postoperative serum interleukin-6 concentration in cohort 3. Severity of individual organ dysfunctions and systemic inflammation were secondary outcome variables. In the first derivation cohort, the protein C -1641 AA genotype was associated with decreased 28-day survival (p < .05). This finding was confirmed in the much larger replication cohort of patients having severe sepsis (p = .028). In addition, the protein C -1641 AA genotype was associated with significantly more organ dysfunction and more clinical evidence of systemic inflammation (p < .05). Furthermore, the -1641 AA genotype was associated with increased serum interleukin-6 at 4 and 24 hrs after cardiopulmonary bypass (p = .024). There was no association of -1654 A/G with phenotype in any cohort. CONCLUSIONS: Protein C -1641 AA genotype is associated with decreased survival, more organ dysfunction, and more systemic inflammation in patients having severe sepsis and with increased interleukin-6 levels after cardiopulmonary bypass surgery.     

Indocyanine green clearance after cardiac surgery: the impact of cardiopulmonary bypass

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven.     

Alterations in anion gap following cardiopulmonary bypass.

OBJECTIVES: To evaluate the changes in the anion gap and their relation to hyperlactatemia and alterations in plasma proteins after cardiopulmonary bypass. DESIGN: Prospective study. SETTING: Cardiothoracic intensive therapy unit. PATIENTS: One hundred eleven consecutive patients after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Data were collected before cardiopulmonary bypass and every 6 hrs for 24 hrs after cardiopulmonary bypass. Results were analyzed for the entire cohort and for hyperlactatemic subgroups. The major finding of this study was that the anion gap decreased significantly at all sampling periods relative to precardiopulmonary bypass values, despite the presence of clinically important hyperlactatemia. No correlation between the decrease in plasma protein concentrations and the decrease in anion gap could be demonstrated. CONCLUSIONS: The decrease in anion gap after cardiopulmonary bypass appears to represent a balance between the influences of increased serum chloride and lactate concentrations and reduced plasma protein concentrations. This analysis demonstrates the limitations of the anion gap in the evaluation of a metabolic acidosis after cardiopulmonary bypass.