心肺复苏后血浆可溶性选择素及基质金属蛋白酶-9测定的临床意义

目的探讨心肺复苏(CPR)后是否会出现血浆可溶性P-选择素(sP-选择素)、E-选择素(sE-选择素)及基质金属蛋白酶-9(MMP-9)增高,并评价其临床意义.方法对CPR后存活≥48 h的82例患者于CPR后次日取血标本测定血浆sP-选择素、sE-选择素及MMP-9;按是否发生全身炎症反应综合征(SIRS)及脓毒症而进行分组;并选择65例非危重病患者作为对照.结果 CPR后SIRS发生率为68.3%(56/82例),SIRS组患者血浆sP-选择素水平明显高于非SIRS组患者及对照组(P均<0.01), SIRS组与非SIRS组血浆Se-选择素和MMP-9水平虽无明显差异(P>0.05),但却均高于对照组(P均<0.01).CPR后1周内43.9%(36/82例)的患者发展为脓毒症,脓毒症组患者血浆sP-选择素水平明显高于无脓毒症组患者(P<0.05),两组血浆sE-选择素和MMP-9水平无明显差异(P>0.05).CPR后死亡患者的血浆sE-选择素和MMP-9水平显著高于存活患者(P均<0.01),但两组的血浆sP-选择素水平无明显差异(P<0.05).结论 SIRS是CPR后一种常见的非特异性反应,对预后几乎无明显影响;血浆sP-选择素水平可能帮助识别脓毒症高危患者,而血浆sE-选择素和MMP-9水平可能有助于CPR后不良预后的判断.     

急性冠脉综合征患者血清P选择素及基质金属蛋白酶-9水平监测的意义

目的探讨急性冠脉综合征（ACS）患者血清P选择素及基质金属蛋白酶-9（MMP-9）水平及其临床意义。方法选取40例临床确诊的ACS患者,15例稳定心绞痛（SA）和15名健康对照者,采用酶联免疫吸附试验（ELISA）测定P选择素及MMP-9水平。结果ACS患者外周血清P选择素、MMP-9水平均高于SA组及对照组（P〈0．01）;ACS患者治疗后P选择素、MMP-9水平均低于治疗前（P〈0．01）。结论血清P选择素、MMP-9浓度升高与ACS的发生存在密切的关系,血清P选择素、MMP-9浓度升高可以作为ACS发生的预测指标。     

急性冠脉综合征患者血清P选择素及基质金属蛋白酶-9水平监测的意义

目的探讨急性冠脉综合征(ACS)患者血清P选择素及基质金属蛋白酶-9(MMP-9)水平及其临床意义。方法选取40例临床确诊的ACS患者,15例稳定心绞痛(SA)和15名健康对照者,采用酶联免疫吸附试验(ELISA)测定P选择素及MMP-9水平。结果ACS患者外周血清P选择素、MMP-9水平均高于SA组及对照组(P<0.01);ACS患者治疗后P选择素、MMP-9水平均低于治疗前(P<0.01)。结论血清P选择素、MMP-9浓度升高与ACS的发生存在密切的关系,血清P选择素、MMP-9浓度升高可以作为ACS发生的预测指标。     

缬沙坦对原发性高血压患者血清P-选择素和基质金属蛋白酶-9水平的影响

目的:观察原发性高血压患者应用缬沙坦治疗前、后血清P-选择素和基质金属蛋白酶-9浓度水平的变化,为原发性高血压患者动脉粥样硬化的防治提供新的实验依据和临床思路。方法:轻、中度原发性高血压患者40例与健康体检者40例(对照组),用ELISA法分别检测其血清P-选择素和基质金属蛋白酶-9的水平。40例高血压病患者进行8周的药物治疗,并观察对上述指标及血压的影响。结果:(1)与对照组比较,高血压患者血清P-选择素及基质金属蛋白酶-9的浓度均增高,差异有统计学意义(P<0.0l)。(2)治疗8周后,高血压患者血清中P-选择素和基质金属蛋白酶-9的浓度均较前下降(P<0.05)。(3)原发性高血压患者血清P-选择素和基质金属蛋白酶-9的Pearson相关系数为0.443,P=0.007(双侧),呈正相关;收缩压、舒张压与血清P-选择素和基质金属蛋白酶-9浓度之间均无线性相关。结论:(1)轻、中度原发性高血压患者血清P-选择素和基质金属蛋白酶-9浓度水平显著增高,二者呈正相关,提示可能存在动脉粥样硬化的发生、发展。(2)缬沙坦可降低轻、中度原发性高血压患者血清P-选择素及基质金属蛋白酶-9水平,这可能是血管紧张素Ⅱ受体阻...     

全身炎症反应综合征患者血浆E-选择素变化及意义

目的观察全身炎症反应综合征(SIRS)患者血浆中可溶性E-选择素(sE-selectin)在疾病不同程度分组中的差别及与感染存在的相关性.方法符合SIBS诊断标准的病人60例,入院后做可疑感染分泌物、排泄物等细菌培养,同时肘静脉穿刺取血进行可溶性E-选择素定量测定和APACHE-Ⅱ评分.根据疾病严重程度分为三组轻度SIRS组、重度SIRS组和休克组.再根据细菌培养结果分为脓毒症组和非脓毒症组.并设对照组.结果轻度SIRS组、重度SIRS组、休克组可溶性E-选择素含量与对照组比较有显著差异(P＜0.01);重度SIRS组和休克组可溶性E-选择素含量与轻度SIRS组比较有显著差异(P＜0.01);而重度SIRS组和休克组无明显差异(P＞0.05).APACHE-Ⅱ评分在三组的组间比较中均有显著差异.脓毒症组和非脓毒症组可溶性E-选择素含量比较有显著性差异(P＜0.01),两组与对照组比较均有显著差异(P＜0.01).结论可溶性E-选择素可作为判断SIRS患者疾病的严重程度和预后指标,也可作为区分脓毒症和非脓毒症SIRS的参考指标.     

基质金属蛋白酶-9与肾脏疾病关系的研究进展

基础研究表明，非肿瘤性肾脏疾病的病理改变实质均是细胞外基质（extra cellular matrix，ECM）在肾小球和肾间质中异常堆积的结果。ECM沉积发生机制复杂，其中基质金属蛋白酶（matrix metallo proteinases，MMPs）及其组织抑制因子（tissue inhibitors ofmetalloproteinases，TIMPs）的功能紊乱在ECM转换过程中起关健作用。MMP-9是基质金属蛋白酶家族中的重要成员之一，因其作用底物广泛，表达细胞众多，在国内外研究中备受重视。现将其与肾脏疾病关系的研究进展综述如下。     

体外循环全身炎性反应与基质金属蛋白酶-9的关系

多数心血管手术在体外循环（cardiopulmonary bypass，CPB）下进行，CPB时血液与人工材料表面直接接触和非生理性灌注以及手术麻醉本身均可触发全身炎性反应综合征（systemic inflammatory response syndrome，SIRS），其过程涉及多种体液因子和细胞。近年来发现基质金属蛋白酶（matrix metalloproteinases，MMPs）在机体炎症反应过程中起一定作用并逐渐引起人们的重视。     

非小细胞肺癌血清基质金属蛋白酶-9水平与转移及预后的关系

目的探讨非小细胞肺癌患者血清基质金属蛋白酶-9水平与转移及预后的关系。方法采用酶联免疫吸附试验（ELISA）检测67例肺癌患者血清MMP-9水平。结果肺癌组血清MMP-9水平显著高于正常对照组;有淋巴结转移组显著高于无淋巴结转移组;Ⅲ期、Ⅳ期组显著高于Ⅰ＋Ⅱ期组;生存期小于12个月组血清MMP-9水平显著高于生存期大于12个月组。结论血清MMP-9水平测定可作为肺癌转移和预后的重要指标。     

幽门螺杆菌感染与不同胃粘膜病变中基质金属蛋白酶-9表达的关系

目的　探讨基质金属蛋白酶9(MMP 9)在胃癌及不同胃粘膜病变发生过程中的表达,及其与幽门螺杆菌的相互作用。方法　选择2 0 9例病例,包括慢性胃炎2 0例、肠上皮化生18例、轻度不典型增生4 1例、中重度不典型增生76例及胃癌5 4例;HP检测采用Giemsa染色、快速尿素酶试验或14 C尿素呼气试验;SP法检测MMP 9的表达。结果　慢性胃炎粘膜组未见MMP 9表达,肠上皮化生粘膜组MMP 9阳性率为4 4 .4 % ,轻度不典型增生粘膜组MMP 9阳性率为4 8.9% ,中、重度不典型增生粘膜组MMP 9阳性率为71.1% ,胃癌组MMP 9阳性率为83.3% ,明显高于慢性胃炎粘膜组(P <0 .0 1) ,高于不典型增生粘膜组(P <0 .0 1)。MMP 9在不典型增生及胃癌的HP阳性组中的表达率明显高于HP阴性组(P <0 .0 5 )。结论　MMP 9在胃癌中有较高的阳性率,与HP感染密切相关,可作为诊断胃癌的一个参考指标。     

辛伐他汀对冠心病患者基质金属蛋白酶-9和C-反应蛋白的影响

目的 :观察辛伐他汀治疗稳定型心绞痛 ( SAP)、急性冠脉综合征 ( ACS)患者 4周后基质金属蛋白酶 - 9( MMP- 9)和 C-反应蛋白 ( CRP)的变化 ,以了解辛伐他汀治疗对斑块稳定性的影响。方法 :将 30例 SAP和 30例 ACS患者分为他汀治疗组和常规治疗组 ,测定治疗前后 MMP- 9和 CRP水平。结果 :经辛伐他汀治疗后 ,治疗组 MMP- 9和 CRP水平明显降低 ,与治疗前比较有统计学差异 ( P<0 .0 0 1)。结论 :辛伐他汀治疗可明显减轻炎症因子 MMP- 9和 CRP水平 ,可能有利于动脉粥样硬化斑块的稳定     

Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation

OBJECTIVE: Elevated cytokine levels have been reported after ischemia/reperfusion injury and might cause a systemic inflammatory response syndrome (SIRS) after successful cardiopulmonary resuscitation (CPR). It is unknown whether patients with SIRS after CPR exhibit higher levels of soluble adhesion molecules than patients without SIRS and whether SIRS or elevation of adhesion molecules is associated with outcome after CPR. We analyzed the relationships among various CPR-related variables, plasma levels of E- and P-selectin, the occurrence of SIRS after CPR, and the development of sepsis and outcome. DESIGN: Prospective, controlled study. SETTING: Intensive care unit at a university hospital. PATIENTS: A total of 25 patients on the second day after successful CPR and 7 non-critically ill control patients. INTERVENTIONS: Blood sampling for determination of plasma levels of soluble (s) E- and P-selectin. MEASUREMENTS AND MAIN RESULTS: SIRS was a frequent finding after CPR (66% of all patients) unrelated to time until return of spontaneous circulation (SIRS, 17+/-13 mins; no SIRS, 19+/-16 mins; p = .761), epinephrine dose (SIRS, 4+/-5 mg; no SIRS, 5+/-6 mg; p = .906), or serum lactate level after CPR (SIRS, 8.6+/-2.6 mmol/L; no SIRS, 8.7+/-4.0 mmol/L; p = .174). sP-selectin levels were higher in patients with SIRS (291.7+/-227.4 ng/mL) compared with patients without SIRS (113.4+/-88.4 ng/mL; p = .018) or with non-critically ill patients (116.9+/-33.4 ng/mL; p = .031). Compared with non-critically ill control patients (42.8+/-19.4 ng/mL), sE-selectin levels were higher in patients with (96.2+/-47.3 ng/mL; p = .023) and without SIRS (99.5+/-65.7 ng/mL; p = .030). sP-selectin was higher in patients developing sepsis within 1 wk after CPR (n = 9) than in patients without sepsis (350.2+/-233.4 ng/mL vs. 158.5+/-157.8 ng/mL; p = .022) and sE-selectin levels were higher in nonsurvivors (n = 5) than in survivors (144.2+/-62.4 ng/mL vs. 85.7+/-45.3 ng/mL; p = .025) whereas SIRS was unrelated to the development of sepsis (p = .4) and unrelated to survival (p = .4). CONCLUSIONS: SIRS is an unspecific finding after CPR with only minor impact on outcome. Determination of sP- and sE-selectin early after CPR might help to identify patients at a high risk for sepsis or for an adverse outcome, respectively.     

兔心肺复苏后全身炎症反应综合征的动态变化

目的 探讨心搏骤停心肺复苏后全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)的变化规律,为临床防治提供理论依据。方法 将日本大耳白兔40只随机（随机数字法）分为假手术组和心搏骤停4,5,6 min组,每组10只。假手术组仅进行麻醉和逆行气管插管、动脉血压监测,不进行气管夹闭窒息;心搏骤停组采用气管夹闭窒息法致使心脏骤停,分别于心搏骤停后4,5,6 min进行复苏,分别在0,24,48,72,96,120 h6个时点观察动物生理参数,取血样测定炎性因子肿瘤坏死因子-α(TNF-α)、C-反应蛋白(C-reactive protein, CRP)和白细胞的水平。多时点资料比较采用重复测定方差分析。结果 复苏组心肺复苏后24h均呈现SIRS,TNF-α,CRP的表达明显升高,与心搏骤停前基础值相比差异具有统计学意义(P＜0.01)。心搏骤停4 min复苏组,SIRS水平以24～48 h较高,于复苏后72 h基本消失。心搏骤停5,6 min组,SIRS水平以24 ～72 h较高,持续至复苏后96h。结论心搏骤停4 min,SIRS较轻,容易恢复。心搏骤停5 min以上,SIRS严重。心搏骤停复苏后血清TNF-α是反映SIRS程度的敏感指标,可作为SIRS的辅助诊断指标,并指导临床早期诊断、早期治疗。     

Plasminogen activator inhibitor type 1 and outcome after successful cardiopulmonary resuscitation

OBJECTIVE: Patients after successful cardiopulmonary resuscitation have been shown to exhibit elevated plasma concentrations of plasminogen activator inhibitor (PAI) type 1, the main circulating antifibrinolytic protein. It has been suggested that elevations in PAI-1 contribute to cerebral no-reflow after successful cardiopulmonary resuscitation. We analyzed whether PAI-1 concentrations might predict cerebral outcome after cardiopulmonary resuscitation. DESIGN: Prospective, controlled study. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty-five patients after successful cardiopulmonary resuscitation and 35 control patients who were not critically ill. INTERVENTIONS: Blood sampling for determination of plasma concentrations of active and total PAI-1 antigen. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of total and active PAI-1 antigen on the second day after successful cardiopulmonary resuscitation were significantly higher in patients after cardiopulmonary resuscitation than in controls (p <.0001) and were unrelated to duration of cardiopulmonary resuscitation. Both active and total PAI-1 antigen were higher in patients who developed acute renal failure after cardiopulmonary resuscitation. Patients with an unfavorable cerebral outcome after cardiopulmonary resuscitation had higher total PAI-1 antigen concentrations compared with patients with good outcome after cardiopulmonary resuscitation (p =.026). We identified 180 ng/mL as the best cutoff value for total PAI-1 antigen with respect to cerebral outcome (chi-square 11.8, p =.001). In a logistic regression analysis, only systemic inflammatory response syndrome (p =.028), acute renal failure after cardiopulmonary resuscitation (p =.017), and cardiopulmonary resuscitation duration >15 mins (p =.042) were significantly and independently associated with cerebral outcome after cardiopulmonary resuscitation. Total PAI-1 antigen reached only borderline significance (p =.058) but nevertheless slightly improved the correct prediction of cerebral outcome after cardiopulmonary resuscitation. CONCLUSIONS: Acute renal failure after cardiopulmonary resuscitation, systemic inflammatory response syndrome, and cardiopulmonary resuscitation duration are better predictors of cerebral outcome after cardiopulmonary resuscitation than PAI-1 antigen, but determination of total PAI-1 antigen nevertheless might improve the early prediction of cerebral outcome after cardiopulmonary resuscitation. Whether elevated PAI-1 concentrations, possibly via prothrombogenic/antifibrinolytic effects, contribute causally to cerebral no-reflow and acute renal failure after cardiopulmonary resuscitation remains to be clarified.     

Imbalance between tissue inhibitor of metalloproteinase 1 and matrix metalloproteinase 9 after cardiopulmonary resuscitation

Aims

This study aimed to determine whether (a) there was an imbalance between matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) after cardiopulmonary resuscitation (CPR) in a canine model of prolonged ventricular fibrillation (VF); (b) with the duration of VF, the degree of the imbalance would be greater; and (c) there was a relationship between the level of MMP-9 or TIMP-1 and the cardiac function.

Methods and Results

Ventricular fibrillation was electrically induced in 24 dogs. The animals were randomly divided into 3 groups (sham control, n = 8; 8-minute VF, n = 8; 12-minute VF, n = 8). Echocardiographic measurement and hemodynamic variables were recorded before VF and after return of spontaneous circulation. Tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-9 were analyzed by Western blot and immunohistochemistry. Compared with sham controls, dogs under VF and CPR showed significantly decreased level of TIMP-1 (P < .001), and with the duration of VF, the level of TIMP-1 declined (P < .01). The level of MMP-9 did not achieve statistical significance in the 3 groups (P > .05); however, they were higher in VF and longer duration VF groups. The ratios of TIMP-1/MMP-9 were lower in VF groups (P < .05). There was a negative correlation between TIMP-1 and left atrium dimension and left ventricular diastolic dimensions (r = −0.83 and r = −0.96, respectively; P < .01) and a positive correlation between TIMP-1 and left ventricular ejection fraction (r = 0.85; P < .01).

Conclusions

There was an imbalance between TIMP-1 and MMP-9 after CPR. It may partly contribute to the postresuscitation cardiac dysfunction.     

血浆MMP-9与体外循环炎性反应相关性研究

目的 :探讨体外循环 (CPB)围术期血浆基质金属蛋白酶 9(MMP 9)和细胞因子之间的关系。方法 :选择 3 0例接受CPB的病人 ,分别在CPB开始前、开始后 3 0min、结束时、结束后 2h采集血标本 ,采用酶联免疫吸附分析方法检测血浆MMP 9和TNF α、IL 8、IL 6的浓度。结果 :(1)血浆MMP 9和TNF α、IL 8的浓度在CPB期间呈逐渐升高 ,在CPB结束时达到最高峰值 ,之后呈下降趋势 ,IL 6在CPB结束后仍继续升高。 (2 )围CPB期血浆MMP 9与TNF α、IL 8、IL 6之间均呈明显的正相关性。结论 :CPB期间血浆MMP 9、TNF α、IL 8、IL 6释放均明显增加 ,除IL 6外在CPB结束时达到最高峰值 ,围CPB期细胞因子可以诱导MMP 9的激活和释放 ,同时MMP 9可以通过对细胞因子的正反馈作用而参与CPB过程的炎症反应。     

Cerebral density on CT immediately after a successful resuscitation of cardiopulmonary arrest correlates with outcome

PURPOSE: To evaluate whether cerebral CT findings taken immediately after successful resuscitation from cardiopulmonary arrest (CPA) correlate with the outcome or not. MATERIAL AND METHODS: We analyzed retrospectively brain sections with the Housfield unit (CT number). Between May 2001 and March 2004, 16 consecutive patients, who recovered from CPA, were included as subjects in this study. They satisfied all of the following criteria: (a) a helical multislice head CT was performed within 1 h of the return of the spontaneous circulation (ROSC); (b) patients died within 24 h after ROSC, and any patients with trauma or cerebral vascular disease were excluded. The subjects were divided into two groups; those with a cerebral performance category of 1-3 (GR group) and those with a cerebral performance category of 4-5 (VD group). RESULTS: There were no significant differences between the two groups except for age. The average ventricle size on the brain CT showed no significant difference between the two groups. The average CT number of the putamen and cerebral cortex, and the corticomedullary contrast in the GR group were higher than those in the VD group. CONCLUSION: Although the influence of age cannot be disregarded, the CT number of the putamen and cortex, and also the corticomedullary contrast correlated with outcome of hypoxic encephalopathy even when cerebral CT was performed within 1 h after ROSC following CPA.     

One-year survival and neurological outcome after pediatric cardiopulmonary resuscitation

OBJECTIVE: Reported survival after cardiopulmonary resuscitation (CPR) in children varies considerably. We aimed to identify predictors of 1-year survival and to assess long-term neurological status after in- or outpatient CPR. DESIGN: Retrospective review of the medical records and prospective follow-up of CPR survivors. SETTING: Tertiary care pediatric university hospital. PATIENTS AND METHODS: During a 30-month period, 89 in- and outpatients received advanced CPR. Survivors of CPR were prospectively followed-up for 1 year. Neurological outcome was assessed by the Pediatric Cerebral Performance Category scale (PCPC). Variables predicting 1-year survival were identified by multivariable logistic regression analysis. INTERVENTIONS: None. RESULTS: Seventy-one of the 89 patients were successfully resuscitated. During subsequent hospitalization do-not-resuscitate orders were issued in 25 patients. At 1 year, 48 (54%) were alive, including two of the 25 patients with out-of-hospital CPR. All patients died, who required CPR after trauma or near drowning, when CPR began >10 min after arrest or with CPR duration >60 min. Prolonged CPR (21-60 min) was compatible with survival (five of 19). At 1 year, 77% of the survivors had the same PCPC score as prior to CPR. Predictors of survival were location of resuscitation, CPR during peri- or postoperative care, and duration of resuscitation. A clinical score (0-15 points) based on these three items yielded an area under the ROC of 0.93. CONCLUSIONS: Independent determinants of long-term survival of pediatric resuscitation are location of arrest, underlying cause, and duration of CPR. Long-term survivors have little or no change in neurological status.     

Severe endothelial injury and subsequent repair in patients after successful cardiopulmonary resuscitation

Introduction  

Ischemia and reperfusion after cardiopulmonary resuscitation (CPR) induce endothelial activation and systemic inflammatory response, resulting in post-resuscitation disease. In this study we analyzed direct markers of endothelial injury, circulating endothelial cells (CECs) and endothelial microparticles (EMPs), and endothelial progenitor cells (EPCs) as a marker of endothelial repair in patients after CPR.     

Relationship between matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases systems and autoantibody patterns in systemic sclerosis

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis that reflects an imbalance between collagen production and degradation. Matrix metalloproteinases (MMPs) are a family of endopeptidases involved in the remodelling of extracellular matrix (ECM). This activity is controlled by tissue inhibitors of MMP (TIMPs). Aim of this study was the evaluation of MMP-9/TIMP-1 and MMP-2/TIMP-2 systems in patients with SSc. DESIGN AND METHODS: SearchLight Human MMP Array 1 was used to measure MMPs and TIMPs in 32 SSc patients and 32 matched healthy controls. RESULTS: SSc patients showed higher values of both MMP-9 and TIMP-1 in comparison with controls. The patients with anticentromere antibodies (ACA) positivity showed higher values of MMPs and TIMPs in comparison with either controls or the patients with anti-Scl70-positive antibodies. CONCLUSION: Results of this investigation suggest that SSc patients with ACA positivity, after a primary fibrogenetic noxa, react with a more abundant release of MMP/TIMP, whereas patients with anti-Scl70 antibody show a normal response.