Effect of low-dose methyl prednisolone on serum cytokine levels following extracorporeal circulation.

The systemic inflammatory response to cardiopulmonary bypass (CPB) is associated with increased production of cytokines.This systemic inflammatory response characterized by the activation of interleukin-6 (IL-6) and interleukin-8 (IL-8) during and after CPB is well documented. A prospective, randomized, double-blind study was performed so as to understand the effects of low-dose methyl prednisolone sodium succinate (MPSS) on the circulating levels of serum cytokines and clinical outcome. Twenty patients were randomly divided into two groups on the basis of the administration of low-dose (1 mg/kg) MPSS (n = 10) and placebo (n = 10) into the pump prime solution. All patients were scheduled to undergo a primary elective coronary artery bypass grafting operation. Patients receiving concurrent corticosteroids, salicylates, dipyridamol or anticoagulants were excluded from the study. Other exclusion criteria were concurrent chronic obstructive pulmonary disease, chronic renal failure, insulin-dependent diabetes, congestive cardiac failure, peptic ulcer history, prior cardiac operations, recent (in a one-month period) myocardial infarction and steroid dependency. Mild systemic hypothermia (30-32 degrees C, rectal) was assured during the CPB. Four blood samples were drawn from the radial artery catheter immediately before starting CPB (T1), following protamine administration (T2) and at 24 (T3) and 48 h (T4) after completion of CPB. In each sample, creatine kinase-myocardial band (CK-MB), white blood cell (WBC), IL-6 and IL-8 levels were measured. IL-6 and IL-8 concentrations were measured by enzyme immunoassay and enzyme-linked immunoabsorbant assay methods. Serum IL-6 T2 and serum IL-6 T3 levels were significantly higher than IL-6 T1 levels in both groups (p < 0.001) and (p < 0.01), and there was no significant elevation in serum IL-8 levels in either group. Serum IL-6 levels were significantly higher in the placebo group than in the MPSS group at T3 (p < 0.009). There was no significant difference in CK-MB T1 levels between the groups. Although there was no significant difference between CK-MB T1 and T2 levels in the MPSS group, the CK-MB T2 and CK-MB T3 levels were significantly higher than T1 levels in the placebo group (p < 0.001) and (p < 0.05). There was significant elevation of WBC levels at T2 and T3 in both groups without notable difference between the groups (p < 0.05). This study has shown that low-dose MPSS suppresses CPB-induced inflammatory response. Further clinical studies (on larger and higher risk groups) may reveal more information on relations between morbidity and cytokine levels which may have some predictive value on clinical outcome following CPB.     

Cytokine responses and myocardial injury in coronary artery bypass grafting

OBJECTIVE: Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery, and it may contribute to postoperative complications and even multiple organ dysfunction. We here compared the cytokine responses and the degree of myocardial injury after coronary artery bypass grafting with or without cardiopulmonary bypass. METHODS: Nine patients underwent off-pump revascularization and 13 with cardiopulmonary bypass. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-10 were measured before anesthesia induction, and 5 min, 1, 4, and 20 h after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were also measured after the operation. RESULTS: Levels of TNF-alpha were low in both groups. A delayed elevation of IL-6 was noted in the off-pump group. IL-8 and IL-10 levels were significantly higher in the CPB than in the off-pump patients after reperfusion (p=0.006 and 0.001 respectively). Postoperative CK-MB levels were significantly higher in the CPB than in the off-pump group (p=0.001). Cytokine levels correlated with CK-MB values. CONCLUSION: The results indicated that off-pump revascularization was associated with reduced cytokine responses and less severe myocardial injury. The degree of myocardial injury, as defined by CK-MB release, correlated with cytokine release. Intervention designed to reduce cytokine responses in cardiac surgery may be advantageous for patients with severe comorbidity.     

体外与非体外循环冠状动脉旁路移植术围术期炎症细胞因子与肌钙蛋白的变化及意义

目的探讨体外与非体外循环下行冠状动脉旁路移植术(CABG)对患者围术期炎性反应及心肌损伤的影响。方法60例行择期CABG患者，随机分成体外循环下行CABG组(CCABG组，30例)和非体外循环下行CABG组(OPCABG组，30例)，分别于术前和术后2、8、24、48h抽取中心静脉血，检测白细胞介素-6(IL-6)、IL-8、肿瘤坏死因子-α(TNF-α)、肌酸激酶同工酶(CK—MB)、肌钙蛋白I(cTnI)等，并记录术后早期的各项临床指标。结果CCABG组术后早期IL-6、IL-8、TNF—α、CK—MB及cTnI均明显高于术前及OPCABG组，OPCABG组患者手术过程中大部分指标无明显变化。结论与CCABG组相比，OPCABG组患者全身炎性反应及心肌损伤程度均明显减轻。     

The cerebroprotective effects of pentoxifylline and aprotinin during cardiopulmonary bypass in dogs

OBJECTIVE: The purpose of this study was to investigate the cerebroprotective effects of pentoxifylline (PNX) and aprotinin in dogs using cardiopulmonary bypass (CPB). MATERIALS AND METHODS: Eighteen clinically healthy dogs were divided into three groups: Group 1 (control, n = 6), Group 2 (PNX, n = 6), and Group 3 (aprotinin, n = 6). PNX was administered at a dose of 300 mg/day in Group 2 three days before the operation and during the operation. Half a million IU aprotinin were added to the prime solution and 500,000 IU were transfused via a central venous jugular catheter preoperatively in Group 3. Blood samples were taken from the central jugular vein before and after CPB and interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and S100beta protein were measured. Gliosis was investigated histopathologically in cerebral cortex biopsy samples under light microscopy. RESULTS: The preoperative results of IL-6, TNF-alpha, and S100beta protein values were found to be significantly higher (p < 0.001) when compared with postoperative values. This significant difference was observed in the same parameters between Groups 1 and 2, and 1 and 3 (p < 0.001). There was no significant difference between Groups 2 and 3. Comparison between pre- and postoperative levels of IL-6 and TNF-alpha for Group 2 and Group 3 revealed statistically significant differences (p < 0.001), whereas S100beta protein levels did not. Histopathological examinations showed significant differences between the control group and PNX and aprotinin, and between aprotinin and PNX groups (p < 0.001). CONCLUSION: PNX and aprotinin might be useful in order to reduce postoperative cerebral damage in patients undergoing cardiac surgery with CPB.     

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。     

注射用复合辅酶预处理对心脏病人非心脏手术的心肌钙蛋白与心肌酶学的影响

目的 观察注射用复合辅酶（贝科能）对心脏病人非心脏手术围手术期的心肌酶谱和心肌钙蛋白的变化,从而研究贝科能的心脏保护作用。方法30例心脏病人非心脏手术即全麻下行单纯胆囊切除术的病人,美国麻醉医师协会（ASA）分级Ⅱ-Ⅲ级,随机双盲分成A、B两组,分别静滴贝科能和生理盐水,然后常规诱导。监测心电图（ECG）,心率（HR）,血压（BP）。分别于入室后（T0）,手术开始1h（T1）,术后8h（T2）,术后24h（T3）采集血液2．5ml,定量测定心肌钙蛋白T（cTnI）,及肌酸激酶（CK）和肌酸激酶同工酶（CK—MB）。结果 A组病人cTnI、CK及CK—MB在术后8h及术后24h结果与入室后结果对比均增高（P〈0．05）有显著差异。B组病人cTnI、CK及CK—MB在术后1h,术后8h及术后4h与入室后结果对比均增高（P〈0．05）,有显著差异,其中cTnI在术后8h及24h的结果与入室后对比有非常显著差异（P〈0．01）。与A组病人对比,术后1 h、8 h及24 h的cTnI与A组比较有非常显著差异（P〈0．01）,CK及CK—MB与A组比较有显著差异（P〈0．05）。结论 贝科能能减轻心肌损害,降低心脏病人术后心肌缺血以致心血管意外的发生率,在围术期应用有一定的临床意义。     

大鼠心肌缺血再灌注IL-10的变化及强的松龙干预

目的探讨缺血再灌注中白介素10(IL-10)的变化及甲基强的松龙对其影响,为临床缺血再灌注损伤的诊治提供实验依据。方法将大鼠随机分成缺血再灌注(对照组)、甲基强的松龙治疗组2组,每组内再随机分成缺血0.5h、再灌注0.5h及再灌注2h3个亚组。在心肌缺血前用甲基强的松龙对药物组大鼠预处理。分别测定缺血0.5h、再灌注0.5h及2h血清IL-10、CK-MB的水平。结果(1)对照组与药物组自缺血0.5h、再灌注0.5h至2hIL-10呈逐渐升高趋势,具有显著性差异,两两比较具统计学意义(P<0.05);各时段内,药物组较对照组明显升高,具有显著性差异(再灌注0.5hP<0.05;再灌注2hP<0.01)。(2)对照组与药物组CK-MB在缺血0.5h出现升高,再灌注2h明显升高,具有显著性差异(对照组T=14.609,P<0.01;药物组T=55.707,P<0.05),两两比较具统计学意义(P<0.05);相同时段内,与对照组相比较,药物组CK-MB升高延迟,在心肌缺血0.5h略有降低,但无统计学意义(P>0.05);在再灌注2h降低,呈显著性差异(P<0.05)。结论甲基强的松龙可促进内源性IL-10大量释放,减少心肌缺血再灌注损伤,发挥保护作用。     

The intraoperative effect of pentoxifylline on the inflammatory process and leukocytes in cardiac surgery patients undergoing cardiopulmonary bypass

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of organ dysfunction after cardiopulmonary bypass (CPB). The aim of this study was to investigate whether pentoxifylline (PTX) has effects on the inflammatory process and leukocytes in cardiac surgery patients undergoing CPB. MATERIAL AND METHODS: A double-blind, prospective, randomized, placebo-controlled study was undertaken to assess the effect of PTX on leukocyte counts, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) levels in 60 patients undergoing CPB for elective coronary artery bypass grafting. In 30 patients, 200 mg of PTX was added to 500 mL NaCl and perfused for 180 min after induction of anaesthesia and also 100 mg of PTX was added to the warm cardioplegic solution; another 30 patients received saline solution as placebo. RESULTS: All measurements were performed before PTX infusion (T0), after induction of anaesthesia (T1), 30 min after weaning from CPB (T2), and 6 hours (T3) and 24 hours postoperatively (T4). PTX did not change the percentage of eosinophils, basophils, neutrophils, monocytes, or lymphocytes, or CRP levels. In the control group, however, total leukocyte count and IL-6 level at T3 and T4 period were significantly higher than the study group. The progressive increment in TNF-alpha level observed at each period was also significantly prominent in the control group. CONCLUSION: CPB-related whole body inflammatory response could be partially inhibited by intraoperative PTX administration. This effect of PTX would be helpful in preventing the well-known complications of CPB-induced systemic inflammation.     

Differential regulation of MMP-2, TIMP-2 and IL-6 in valve replacement versus CABG patients

BACKGROUND: Extracellular matrix degradation may play an important role in left ventricular (LV) remodeling. It has been reported that matrix metalloproteinase-2 (MMP-2) is activated under mechanical stress conditions. Therefore, we examined the release of MMP-2, its inhibitor and interleukin-6 (IL-6), which affects MMPs, in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Arterial blood samples were obtained from 20 patients undergoing cardiac surgery and six patients with descending aortic replacement (as noncardiac control) with CPB. Samples were assayed for plasma MMP-2, tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and IL-6 concentration. RESULTS: Plasma MMP-2 concentrations in the valvular disease patients were greater than in other patients (p < 0.05) and correlated with the LV mass (r=0.810, p < 0.0001) prior to the operation. Plasma MMP-2 concentrations decreased during CPB and gradually recovered to the baseline levels after CPB. Plasma TIMP-2 concentrations increased significantly during and after CPB in a biphasic manner. Plasma IL-6 concentrations also increased significantly during CPB (p < 0.05 versus baseline levels). CONCLUSION: Plasma MMP-2 concentrations reflect the state of the left ventricle, and changes in plasma MMP-2 and TIMP-2 concentrations during CPB may play an important role in LV remodeling after cardiac surgery.     

不同剂量乌司他丁对体外循环患者炎症反应及呼吸功能的影响

目的 研究不同剂量乌司他丁在体外循环(CPB)心脏直视手术中对肺损伤的保护作用机制.方法 采用前瞻性随机对照研究方法,选择42例心脏瓣膜置换术患者,随机分为对照组、乌司他丁8 kU/kg组(U1组)及乌司他丁12 kU/kg组(U2组),3组分别于麻醉诱导后术前(T1)及停止CPB 1 h(T2)、4 h(T3)、24 h(T4)取静脉血,检测血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10的浓度;同时测定动脉血气,对比观察氧合指数(PaO_2/FiO_2)及呼吸指数(RI).结果 ①3组患者T1时血浆TNF-α、IL-6和IL-10比较差异均无统计学意义(P均>0.05),T2～4时则均显著升高(P<0.05或P<0.01).与对照组比较,U1、U2组T2～4时血浆TNF-α、IL-6浓度降低,IL-10浓度升高,且U2组变化较U1组明显(P<0.05或P<0.01).②3组患者T1时PaO_2/FiO_2、RI比较差异均无统计学意义(P均>0.05),T2～4时则出现PaO_2/FiO_2减少、RI值增大(P<0.05或P<0.01).与对照组比较,U1、U2组T2～4时PaO_2/FiO_2增大、RI值减小,且U2组变化较U1组更为显著(P<0.05或P<0.01).结论 在CPB过程中,乌司他丁能明显抑制促炎因子TNF-α、IL-6的产生,上调抗炎因子IL-10的释放,减轻肺损伤,改善CPB术后肺功能,并呈剂量-效应关系.     

甲泼尼龙对心肺复苏后患者血清细胞因子的影响

目的 探讨甲泼尼龙对心肺复苏后患者血清细胞因子表达的影响.方法 将2005年5月至2007年5月上海市闸北区中心医院心肺复苏恢复自主循环(ROSC)30例患者,经心电监护或心电图证实院内心跳呼吸骤停,即刻心肺复苏恢复自主循环、生存≥48 h、年龄≥18岁患者;入选病例排除因各种疾病终末期、晚期肿瘤、自然死亡因素所致心跳呼吸停止者,及发病前一周内伴有各种感染、休克、严重创伤者.随机分为A组(甲泼尼龙组,n=14):复苏后加用甲泼尼龙每日3 mg/kg,分两次静脉滴注,连续3 d;B组(对照组,n=16):采用常规心肺复苏治疗.两组患者原发病因基本相仿.ELISA法检测两组心肺复苏即刻、ROSC后24 h、48 h、72 h、7 d的血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)水平.资料数据采用SPSS11.5版统计软件进行分析处理,计量资料以均数±标准差(-x±s)表示,两组各不同时间点计量资料两两比较采用成组t检验,两组心肺复苏后SIRS患病率和病死率采用Chi-square test,以P＜0.05为差异有统计学意义.结果 两组心跳骤停至心肺复苏恢复自主循环平均间期[(8.9±4.6)min,(9.6±5.0)min]及心肺复苏即刻血清TNF-α、IL-1β、IL-6、IL-8、IL-10水平差异无统计学意义(P＞0.05).与B组比较,A组ROSC后24 h、48 h血清TNF-α、IL-1β、IL-6、IL-8水平明显降低(P＜0.05～0.01),ROSC后72 h A组血清IL-8水平(114.33±149.72)仍低于B组(332.09±277.45)(P＜0.05),ROSC后7 d两组血清各细胞因子水平差异无统计学意义(P＞0.05).血清IL-10水平两组在不同时间点差异均无统计学意义(P＞0.05).结论 早期应用甲泼尼龙可降低心肺复苏后患者血清TNF-α、IL-1β、IL-6、IL-8释放,对复苏患者有保护作用.     

丹参注射液对缺血再灌注损伤心肌保护作用

目的研究丹参注射液对风湿性二尖瓣膜置换术病人缺血再灌注损伤心肌的保护作用。方法选取体外循环风湿性二尖瓣膜置换术病人60例,随机分为冶疗组(Ⅰ组,n=30例)、对照组(Ⅱ组,n=30例),两组灌注方法及体外循环方法相同。冶疗组病人于手术开始前、升主动脉开放后静注丹参注射液0.2 mL/kg,对照组给予等容量的平平衡盐溶液。于手术开始前(T0)、心肺转流(CPB)后30 min(T1)、复灌后15 min(T2)、6小时(T3)、12小时(T4)、24小时(T5)共6个时点取颈内静脉血检测磷酸肌酸激酶(CK)、磷酸肌酸激酶同功酶(CK-MB)、乳酸脱氢酶(LDH)、肌钙蛋白(CTnI)的水平及丙二醛(MDA)、超氧化物歧化酶(SOD)的水平;记录两组体外循环时间、主动脉阻断时间,以及体外循环后血管活性药物的用量。观察心脏大血管开放后,心脏自动复跳率,室性心律失常发生率。结果Ⅰ组CK、CK-MB、LDH、CTnI、MDA水平心脏复灌后明显低于Ⅱ组,而I组术后SOD水平要高于Ⅱ组;Ⅰ组心律失常发生率、除颤次数明显低于Ⅱ组;术后Ⅰ组心功能恢复优于Ⅱ组;血管活性药物使用量Ⅰ组低于Ⅱ组。结论丹参注射液对二尖瓣膜置换术病人心肌缺血再灌注损伤具有明显的保护作用。     

Prostaglandin E1 reduces myocardial reperfusion injury by inhibiting proinflammatory cytokines production during cardiac surgery

OBJECTIVE: To determine the influence of prostaglandin E1 (PGE1) on the cytokine balance and myocardial protection during cardiac surgery. DESIGN: Prospective, randomized, nonblinded study. SETTING: University hospital. PATIENTS: A total of 19 patients on cardiopulmonary bypass undergoing cardiac surgery. INTERVENTIONS: According to randomized sequence, the patients received PGE1 (0.02 approximately 0.05 microg x kg(-1) x min(-1)) from the beginning of surgery to the end of study (PGE1 group, n = 11) or nothing (control group, n = 8). MEASUREMENTS AND MAIN RESULTS: Interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor I (sTNF RI), and soluble tumor necrosis factor receptor II (sTNF RII) were measured by enzyme-linked immunosorbent assays. Troponin-T and isoenzyme of creatine kinase with muscle and brain subunits (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption spectrophotometry method, respectively. Serum IL-6 and IL-8 concentrations in both groups increased significantly from 60 mins after declamping the aorta compared with preoperative value (p < .001), However, the increases were greater in the control group than in the PGE1 group (p < .01). Serum IL-10, IL-1ra, sTNF RI, and sTNF RII concentrations increased significantly from 60 mins after declamping the aorta compared with preoperative values in two groups (p < .001, respectively). There were no differences between the two groups. Serum troponin T and CK-MB concentrations increased significantly in the two groups from 60 mins after declamping the aorta (p < .001), but these increases were greater in the control group than in the PGE1 group (p < .01). IL-6 and IL-8 levels correlated with CK-MB concentration (r2 = 0.49, r2 = 0.36; p > .001 respectively). CONCLUSIONS: PGE1 suppressed the production of IL-6 and IL-8 but not IL-10, IL-1ra, sTNF RI, or sTNF RII. The change in the balance between pro-and anti-inflammatory cytokines may be one of the most important cytoprotective mechanisms of PGE1.     

舒芬太尼对非体外循环冠状动脉旁路移植术的心肌保护

目的：研究在行非体外循环冠状动脉旁路移植术（OPCABG）时,舒芬太尼对心肌的保护作用。方法：择期行OPCABG的患者60例,年龄52—75岁,ASAⅡ或Ⅲ级,随机分为舒芬太尼组和芬太尼组,每组30例。舒芬太尼组用舒芬太尼1μg/kg,芬太尼组用芬太尼10μg／kg进行麻醉诱导,分别于切皮、劈胸骨、钳夹主动脉侧壁、关胸前追加舒芬太尼每次0．8μg／b（舒芬太尼组）或芬太尼每次8μg／kg（芬太尼组）维持麻醉。于麻醉诱导前（T0）、桥血管吻合结束（T1）、手术结束即刻（T2）、术毕8、16和24h（T3-5）,采集桡动脉血10m1分离血清,用酶联免疫法分别测定两组患者血清IL-15、IL．10、CK-MB、心肌肌钙蛋白I（cTnI）水平及超氧化物歧化酶（SOD）活性。结果：与芬太尼组比较,舒芬太尼组血清cTnI水平在T4．。时显著降低（P〈0．05）,IL-6水平在T1．4时降低（P〈0．05）,IL-10在T1-4时升高（P〈0．05）,SOD活性在T1-3时升高（P〈0．05）。结论：舒芬太尼对OPCABG的心肌具有保护作用,其机制可能与抗炎、清除自由基、减少氧化应激等有关。     

Reduction of blood coagulation and monocyte-platelet interaction following the use of a minimal extracorporeal circulation system (Synergy) in coronary artery bypass grafting (CABG)

Cardiovascular surgery with cardiopulmonary bypass (CPB) induces activation of blood coagulation and systemic inflammation involved in post-operative complications. Our study evaluated the impact of the minimal extracorporeal circulation (mini-CPB) system (Synergy, Sorin Group) on these functional aspects. Twenty patients were randomly assigned to standard CPB (n = 10) or to Synergy (n = 10). Platelet expression of PAC-1, and monocyte/granulocyte-platelet conjugates were evaluated by flow cytometry. A leukocyte-platelet adhesion index was calculated after cell number normalization. ELISAs were performed to measure IL-6 and TNF-alpha, thrombin-antithrombin III complexes (TAT), prothrombin fragments (F1+2), beta-thromboglobulin (beta-TG) and sP-selectin (sCD62P). Blood samples were drawn at the time of anesthesia (T1), at the end of CPB (T2), and at 4 (T3) and 24 hours (T4) after weaning from CPB. All patients were similar for clinical characteristics. When compared to standard CPB, the Synergy showed lower levels of the monocyte-platelet adhesion index at T2 (0.023 +/- 0.005 vs 0.063 +/- 0.013, P = 0.0092) and T4 (0.031 +/- 0.003 vs 0.055 +/- 0.005, P = 0.0017), TAT complexes at T2 (27.175 +/- 5.967 vs 86.592 +/- 5.415, P = 0.0005) and T3 (26.977 +/- 2.468 vs 45.146 +/- 4.365, P = 0.0041), F1+2 fragments at T2 (2.222 +/- 0.226 vs 4.249 +/- 0.292, P = 0.0009), and sP-selectin at T3 (115.17 +/- 19.623 vs 169.554 +/- 19.709, P = 0.0703) and T4 (108.542 +/- 6.429 vs 140.799 +/- 14.771, P = 0.0833). In summary, the Synergy exhibited a lower post-operative activation of blood coagulation, together with a reduced interaction between circulating monocytes and platelets.     

火器伤烟雾吸入致吸入性肺损伤细胞因子的变化及与多器官功能损害的关系

目的 观察火器伤烟雾吸入致重度吸入性肺损伤后支气管肺泡灌洗液（BALF）中致炎、抗炎细胞因子含量变化，及其在多器官功能损害中的作用。方法复制火器伤致大鼠重度吸入性肺损伤模型。观察大鼠伤后2、4、6、8、12和24h肺湿重／干重比，BALF中白蛋白、乳酸脱氢酶（LDH）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、IL-4的含量，外周血丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、血尿素氮（BUN）、血肌酐（SCr）、肌酸激酶同工酶（CK-MB）含量，并与正常对照组比较。结果大鼠肺湿重／干重比、BALF中白蛋白及LDH含量随时间的延长而增加；TNF-α在损伤后即增加，2h达高峰；IL-6损伤后4h明显增加，且伤后4～24h保持较高浓度；IL-4于伤后6～8h下降。外周血ALT、AST、BUN、SCr、CK-MB伤后持续增加。结论细胞因子可能是介导多器官功能损害的直接介质。多器官功能损害可能由TNF-α触发，随后引起细胞因子的级联反应，致炎因子IL-6的持续高表达和抑炎因子IL-4后期失控加剧了MOF的发展。     

Effects of polyenylphosphatidylcholine on cytokines,nitrite/nitrate levels,antioxidant activity and lipid peroxidation in rats with sepsis

OBJECTIVES: To determine the effect of pretreatment with polyenylphosphatidylcholine (lecithin, PPC) on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, total nitrite/nitrate (NOx), and tissue levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in septic rats. DESIGN: Prospective, randomized, controlled animal study. SETTING: University laboratory. SUBJECTS: Forty-five Spraque-Dawley rats were divided into three groups: group C, sham-operated; group S, sepsis; and group P, sepsis pretreated with PPC. INTERVENTIONS: Rats were made septic by cecal ligation and puncture (CLP). Group P rats were treated with PPC (100 mg/day orally) for 10 days before sepsis. Twenty-four hours later CLP, plasma concentrations of TNF-alpha, IL-6 and IL-10 and plasma levels of NOx were measured. SOD and MDA were determined in liver, lung and heart homogenates. MEASUREMENTS AND MAIN RESULTS: All rats in group P survived during the 24-h observation time after CLP, whereas survival rate in group S was 66.7% (10/15; P<0.05). PPC significantly reduced plasma levels of TNF-alpha (P=0.006), IL-6 (P=0.007), IL-10 (P=0.016), NOx (P<0.001), and tissue levels of MDA (P<0.001) in group P with respect to in group S. Tissue levels of SOD significantly increased in group P when compared with group S (P<0.001). CONCLUSIONS: These results show that PPC pretreatment exerts cumulative effects in decreasing the levels of cytokines, NOx, and tissue MDA concentrations, with a concomitant increase in survival in septic rats. Lecithin therapy may be a useful adjuvant therapy in controlling of the excessive production of the inflammatory cytokines in patients with severe sepsis. DESCRIPTOR: SIRS/sepsis, experimental studies.     

帕瑞昔布钠超前镇痛对下肢缺血—再灌注患者炎性因子的影响

目的:观察帕瑞昔布钠超前镇痛对下肢缺血-再灌注(ischemia-reperfusion,I-R)患者围术期白细胞介素-6(interleukin-6,IL-6)、白细胞介素-8(interleukin-8,IL-8)、肿瘤坏死因子-α(tumor necro-sis factor-α,TNF-α)的影响。方法:将40例单侧膝关节手术患者随机分为帕瑞昔布钠组(P组,n=20)和对照组(C组,n=20)。均采用连续硬膜外麻醉。P组患者于上止血带前10 min静注帕瑞昔布钠40 mg+生理盐水2 ml,C组患者给予生理盐水2 ml。分别于两组患者上止血带前(T1)、手术结束时(T2)、术后6小时(T3)、术后12小时(T4)、术后24小时(T5)抽取静脉血样,测定血浆IL-6、IL-8、TNF-α浓度。结果:与T1时比较,C组在T2、T3、T4时IL-6浓度升高(P<0.05),T3、T4时IL-8浓度升高(P<0.05),T3时TNF浓度升高(P<0.05)。P组在T3时IL-6浓度升高(P<0.05),T4时IL-8浓度升高(P<0.05)。与C组比较,P组在T3时的血浆IL-6浓度和T4时的IL-8浓度显著降低(P<0.05),血浆TNF-α的浓度无明显变化(P>0.05)。结论:帕瑞昔布钠超前镇痛可有效抑制I-R患者围术期炎细胞因子产生。     

氟比洛芬酯保护心肺转流术后急性肺损伤的机制研究

目的探讨氟比洛芬酯对心肺转流术导致急性肺损伤的保护作用。方法30例择期行瓣膜置换术的风湿性心脏病患者分为实验组（15例）和对照组（15例）。在体外循环心肺转流开始后,实验组单次加入氟比洛芬酯2mg／妇于体外循环机中,而对照组给予等量0．9％氯化钠注射液。采用酶联免疫吸附法分别于麻醉诱导（T1）、转流前5min（T2）、转流30min（T3）、主动脉开放后心脏复跳5min（T4）、CPB结束后1h（T5）、CPB结束后5h（T6）检测两组患者的白细胞介素6（IL-6）、IL-10、肿瘤坏死因子仅（TNF-α）和可溶性细胞间黏附分子-1（sICAM-1）,并同时记录肺泡-动脉氧分压差（A-aD02）和呼吸指数（RI）。结果体外循环开始后,两组患者血IL-6、IL-10、TNF-α、sICAM-1及A-aDO2、RI均进行性升高,后逐渐下降,但仍均高于同组T1水平（P均〈0．05）。实验组IL-6、IL-10和slCAM-1水平在T3、T4、T5和T6时段与同时段对照组比较,差异均有统计学意义（P均〈0．05）。与同时段对照组比较,TNF-α水平在T4时段明显增高（P〈0．05）;A-aDO：及RI在T4、T5和T6时段均明显降低（P均〈0．05）。结论氟比洛芬酯能通过抑制IL-6、TNF-α和sICAM-1的产生,促进IL-10的释放,减轻心肺转流术后的急性肺损伤,从而保护并改善术后肺功能。     

Leukocyte filtration in the early reperfusion phase on cardiopulmonary bypass reduces myocardial injury

Improved myocardial protection and cardiopulmonary bypass (CPB) have limited, but not abolished, intraoperative myocardial damage due to surgical reperfusion injury after release of the aortic crossclamp. In this double-blind, randomized study, we evaluated whether short-term leukocyte filtration during reperfusion may further reduce myocardial damage. Thirty-eight patients with coronary artery disease were randomly assigned to CPB with (group I; n = 19) or without leukocyte filtration (group II; n = 19). There was no difference in bypass time or crossclamp time between the groups. No patient in group I required catecholamines, whereas three patients in group II were supported with adrenaline or dobutamine on the first and second postoperative day. In addition, troponin T plasma levels were lower in group I (p < 0.05), whereas other markers for tissue injury (CK, CK-MB, LDH, S-GOT and S100B) did not differ. In conclusion, leukocyte filtration during reperfusion may further improve CPB by reducing myocardial damage.