运用辅助装置进行多支血管不停跳冠脉搭桥术

目的:探讨应用辅助装置进行多支血管冠状动脉搭桥术的效果。方法:2003年6月-2006年11月本院多支血管病变冠心病患者35例,利用心尖吸引器辅助吸引上提心尖或左室侧壁,应用心脏吸引装置辅助下行冠状动脉搭桥术。结果:术中患者侧壁及下壁靶血管显露良好,术野改善,血压平稳,无严重心律失常发生。结论:对于多支血管病变(尤其是心脏较大)的冠心病患者,运用心脏吸引辅助装置进行冠状动脉搭桥术,可显著改善侧壁和下壁冠状动脉的显露,保证稳定的血流动力学和心脏跳动下靶血管的准确切开和良好吻合。     

非体外循环下冠状动脉搭桥术的麻醉管理

目的分析非体外循环下冠状动脉搭桥术OPCABG血流动力学的变化,探讨OPCABG的麻醉管理。方法择期行OPCABG的冠心病患者120例,年龄48～76岁,射血分数平均（0．53±0．32）,术前放置漂浮导管,监测血液动力学变化,分别在开胸前（T0）、吻合前降支（T1）、吻合回旋支（T2）、吻合对角支（L）、吻合右冠状动脉（T4）、心脏恢复原位置后（L）分别记录MAP、HR、CVP、PCWP、CI、CO、Sv02、SVRI、PVRI、LVSWI、RVSWI。结果吻合前降支时CI、LVSWI下降,PVRI增高,SvO2正常。吻合回旋支、对角支、右冠状动脉时,CI、CO、LVSWI、RVSWI、SvO2明显下降（P〈0．01）,而HR、CVP、PCWP、PVRI增高（P〈0．05）。结论术者翻动心脏可导致明显血流动力学变化,动作要轻,采取必要的心血管功能支持,避免发生严重低血压和心率失常。     

Assays for complement activation

Complement is a major biologic mediation system that functions in host defense against microorganisms and other pathogens and also aids in the elimination of damaged and abnormal cells. This is accomplished by its ability to mediate the destruction of pathogens and altered cells directly through cytolytic and cytotoxic properties, as well as indirectly by its ability to augment the actions of various effector cells, which in turn destroy or inactivate these substances. Its second major action in vivo is the production of an acute inflammatory response that, by altering blood-vessel permeability, contracting smooth muscles, and promoting an influx of leukocytes, aids in the localization of the injurious process responsible for complement activation and retards its spread and dissemination throughout the body. The actions of the activated complement system upon pathogens and altered cells, as well as its phlogistic properties, are the direct consequence of the actions of complement protein-protein complexes, enzymes, peptides, and cleavage products on the activator, on biologic membranes, and on various effector and other tissue cells. Complement activation is a frequent phenomenon in infectious diseases, autoimmune diseases, and many other conditions having an inflammatory component. Because of the importance of this system in contributing to the resolution of the disease process, monitoring of the status of the system in patients is frequently indicated. Monitoring of the complement status is also appropriate in numerous other diseases, such as those with an inflammatory component, in which complement activation occurs secondarily but in which it is frequently responsible for confining the injurious process and aiding in its resolution. A number of techniques are available to assess the status of the complement system in samples obtained from patients. Among these are a group of newer tests that specifically detect complement activation. They quantitate activation-dependent complement cleavage products, antigenic changes, or protein-protein complexes. These tests are quantitative, highly sensitive, and extremely specific; furthermore, most can be employed with samples obtained from patients. Because all of the biologic actions of the complement system require complement activation, such newer activation-specific assays permit the precise evaluation of the status of this system in human diseases. Further extension of their use to additional patients and other disease complexes will undoubtedly increase the understanding of the biologic importance of the complement system in human disease processes.     

Proinflammatory cytokines and complement activation in salvaged blood from abdominal aortic aneurism surgery and total hip replacement surgery

BACKGROUND: Levels of proinflammatory mediators in unwashed salvaged blood from abdominal aortic aneurism (AAA) surgery are unknown. We hypothesized that there are higher levels of these mediators in unwashed blood salvaged in AAA surgery compared to hip replacement surgery. STUDY DESIGN AND METHODS: Ten patients scheduled for AAA surgery (Group A) and 10 patients for total hip replacement surgery (Group H) were included. Blood samples from the autotransfusion set were obtained during surgery and arterial samples before, during, and 6 hours after surgery. Determination of interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor‐α, activated complement 3 (C3a), and high‐sensitivity C‐reactive protein (CRP) were performed. Salvaged blood was not retransfused. RESULTS: Levels (median [range]) of IL‐8 in blood in the salvage system were higher in Group A versus Group H (215.3 [22.5‐697.2] vs. 35.3 [16.7‐66.6] pg/mL; p = 0.002). Higher levels of IL‐6 were also seen in Group A versus Group H (60.0 [52.6‐62.2] vs. 42.34 [19.4‐62.2] pg/mL; p = 0.049). Levels of IL‐6 in blood sampled during surgery were approximately fivefold higher in Group A versus Group H (p = 0.023), whereas approximately 70% higher levels of C3a were observed in Group H versus Group A (p = 0.021). Postoperative concentrations of IL‐1β (p = 0.002), IL‐6 (p = 0.001), and IL‐8 (0.005) were higher in Group A versus Group H. CONCLUSION: Salvaged blood in AAA surgery contains substantially higher levels of proinflammatory mediators compared to blood in total hip replacement surgery.     

Mathematical studies of complement activation

Kinetic studies of complement activation were followed by hemolytic assay. Mathematical analysis shows that the curve is composed of two exponents: the first one, which occurs during a short span of time, represents the classical pathway, the second the alternative pathway. We were therefore able to foretell the respective participation of each activator used: inulin, zymosan, and aggregated immunoglobulins.     

Antibody-independent complement activation by myelin via the classical complement pathway

Murine or rabbit whole brain homogenates were shown to activate human complement via the classical pathway by an antibody-independent reaction. This activity required Ca++ ions. Anticomplementary activity in fractionated murine brain was found to reside in the myelin fraction and in purified myelin. It was absent, however, both from highly purified myelin basic protein (MBP) and from the MBP-free residue. Because purified MBP is a monomer and this protein exists in brain tissue largely as a dimer, the ability of the cross-linked form of MBP to activate complement was investigated. MBP, dimerized with difluorodinitrobenzene, was highly anticomplementary. The murine brain, inactive when taken from the newborn mouse, was shown to first acquire the capacity to activate complement at 7 d after birth. This finding is consistent with the report that the synthesis of myelin protein has been shown to be initiated in murine brain 8 d after birth. Complement activation by MBP could play an important role in the pathological changes observed in neurological disorders.     

术前急性自体血小板分离对心脏手术患者血小板活化功能的影响

目的探讨术前急性自体血小板分离对心脏手术患者不同阶段血小板活化状态及活化功能的影响。方法40名体外循环心血管外科手术患者,随机分为2组,每组20例。Ⅰ组:急性等容血液稀释(ANH)联合自体富血小板血浆(APRP)回输及术中自体血回收;Ⅱ组:ANH联合术中自体血回收,不进行APRP采集分离。于诱导前(T1)、采血后10min(T2)、自体血回输前10min(T3)、回输后10min(T4)、术后24h(T5)各时点测定Plt、血小板在静息状态及ADP激活后活化指标CD62P、PAC-1的表达量,并测定APRP分离初期和回输前CD62P、PAC-1的表达量,术后出血量及异体输血量。结果T4、T5时点PltⅠ组明显高于Ⅱ组对应时点(P<0.05),术后出血量及异体血输注量Ⅰ组明显减少。APRP分离和保存期间没有进一步激活血小板功能。结论术前急性等容血液稀释联合富血小板血浆回输更有效地保护血液,急性自体血小板分离不会进一步激活血小板。     

Immunoadsorption therapy and complement activation.

Complement activation was studied in six patients treated with immunoadsorption columns Ig-ADSOPAK for myasthenia gravis. Mean therapy duration was 18.6 months (range 4-28 months). Prior and after each procedure, concentrations of C3 and C4 were examined, hemolytic activity of complement by a classic pathway (CH50) was determined, as well as terminal complement complex (TCC). After each immunoadsorption procedure, a decrease of C3 and C4 was noted (median 21.19% and 19.68%, respectively). The CH50 and TCC follow-up showed statistically significant complement activation. Median of TCC accrual was 60.21% and median of CH50 decrease was 23.24%. No clinical manifestations of complement activation were present. With increasing number of procedures a marked decrease of TCC activation was observed in five patients, which was statistically significant in three of them (p < 0.05). This finding may indicate an immunomodulating effect of long-term adsorption therapy. With increasing number of procedures, an inhibition in complement system reactivity occurs. This result, however, has to be confirmed on a larger group of patients.     

Platelet activation leads to activation and propagation of the complement system

Inflammation and thrombosis are two responses that are linked through a number of mechanisms, one of them being the complement system. Various proteins of the complement system interact specifically with platelets, which, in turn, activates them and promotes thrombosis. In this paper, we show that the converse is also true: activated platelets can activate the complement system. As assessed by flow cytometry and immunoblotting, C3 deposition increased on the platelet surface upon cell activation with different agonists. Activation of the complement system proceeded to its final stages, which was marked by the increased generation of the anaphylotoxin C3a and the C5b-9 complex. We identified P-selectin as a C3b-binding protein, and confirmed by surface plasmon resonance binding that these two proteins interact specifically with a dissociation constant of 1 microM. Using heterologous cells expressing P-selectin, we found that P-selectin alone is sufficient to activate the complement system, marked by increases in C3b deposition, C3a generation, and C5b-9 formation. In summary, we have found that platelets are capable of activating the complement system, and have identified P-selectin as a receptor for C3b capable of initiating complement activation. These findings point out an additional mechanism by which inflammation may localize to sites of vascular injury and thrombosis.     

Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery

The kinetics of C-reactive protein (CRP) were studied prospectively in 30 children (aged 21 days – 16 years) undergoing open heart surgery. CRP was related to the kinetics of total haemolytic complement, complement C3a and postoperative complications. Two (7%) patients died and ten (33%) had postoperative complications. The patients with complications were younger (p<0.035), underwent longer perfusions (p<0.001) and had longer aortic cross-clamping times (p<0.003). The mean peak CRP level after surgery (108 mg/l) was reached, on the average, in 43 h. No statistical difference in CRP concentrations was found between the complication and non-complication groups. Extensive complement activation was seen in every patient. CRP did not reflect the magnitude of complement activation induced by cardiopulmonary bypass. The patient sample was too small to draw reliable conclusions about the value of CRP in detecting postoperative complications after open heart surgery in children.     

Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation

In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the membrane complement inhibitors decay accelerating factor (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells, and all were significantly more effective (up to 20-fold) than corresponding untargeted inhibitors at protecting target cells from complement. CR2 fusion proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2 fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition.     

Robotic cardiac surgery

The health care climate is evolving due to influences of new technology, and robotic surgery has become a part of many surgical procedures and specialties. Incorporation of robotic procedures in cardiac surgery has several recognized benefits for patient outcomes, including a smaller incision, decrease in pain, and shorter hospital stay. Increased use of robotics will influence how nurses educate and care for their patients and the types of health care options that will be offered to patients in the future. AORN J 77 (Jan 2003) 182-186.     

Biocompatibility and pathways of initial complement pathway activation with Phisio- and PMEA-coated cardiopulmonary bypass circuits during open-heart surgery

A randomized open-heart surgery study comprising 30 patients was undertaken to compare the biocompatibility of Phisio-(phosphorylcholine) and PMEA-(poly-2-methoxyethyl acrylate) coated cardiopulmonary bypass (CPB) circuits and to assess the initial complement pathway activation during open-heart surgery. Blood samples were obtained at five time points, from the start of surgery to 24 hours postoperatively. The following analyses were performed: haemoglobin, lactate dehydrogenase, leukocyte and platelet counts, myeloperoxidase and neutrophil-activating peptide-2, thrombin-anti-thrombin complexes, syndecan-1 and the complement activation products C1rs-C1-inhibitor complexes, C4bc, C3bc, C3bBbP and the terminal complement complex (TCC). No significant inter-group difference was found in any parameters, except for the concentration of TCC which was moderately lower in the PMEA group at termination of CPB. Complement activation during open-heart surgery was mainly mediated through the alternative pathway. In conclusion, PMEA- and Phisio-coated circuits displayed similar biocompatibility with respect to inflammatory and haemostatic responses during and after open-heart surgery.     

Continual low-level activation of the classical complement pathway

There is evidence that the classical complement pathway may be activated via a "C1-tickover" mechanism, analogous to the C3-tickover of the alternative pathway. We have quantitated and characterized this pathway of complement activation. Analysis of freshly collected mouse and human plasma revealed that spontaneous C3 activation rapidly occurred with the generation of C3 fragments in the plasma. By the use of complement- and Ig-deficient mice it was found that C1q, C4, C2, and plasma Ig were all required for this spontaneous C3 activation, with the alternative complement pathway further amplifying C3 fragment generation. Study of plasma from a human with C1q deficiency before and after therapeutic C1q infusion confirmed the existence of a similar pathway for complement activation in humans. Elevated levels of plasma C3 were detected in mice deficient in complement components required for activation of either the classical or alternative complement pathways, supporting the hypothesis that there is continuous complement activation and C3 consumption through both these pathways in vivo. Blood stasis was found to stimulate C3 activation by classical pathway tick-over. This antigen-independent mechanism for classical pathway activation may augment activation of the complement system at sites of inflammation and infarction.     

Assessment of complement activation during membrane-based plasmapheresis procedures

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.     

Targeted and restricted complement activation on acrosome-reacted spermatozoa

A specific hypoglycosylated isoform of the complement regulator membrane cofactor protein (MCP; CD46) is expressed on the inner acrosomal membrane (IAM) of spermatozoa. This membrane is exposed after the acrosome reaction, an exocytosis event that occurs upon contact with the zona pellucida. We initiated this investigation to assess MCP's regulatory function in situ on spermatozoa. Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. This pattern is consistent with engagement of the classical pathway followed by amplification through the alternative pathway. C3b deposition was targeted to the IAM, where it was cleaved to C3bi. Factor H, and not MCP, was the cofactor responsible for C3b cleavage. We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. In addition, we speculate that this "targeted and restricted" form of complement activation on host cells is a common strategy to handle modified self.