Regulation of local availability of active tissue-type plasminogen activator in vivo in man.

Free, biologically active tissue-type plasminogen activator (tPA) is the main initiator of intravascular fibrinolysis, but little is known about the regulation of active tPA on the organ level. The aim was to investigate if the local availability of active tPA on the organ level depends on the local release rate of tPA or the arterial input of tPA and plasminogen activator inhibitor type 1 (PAI-1). Also, we wanted to evaluate if plasma levels predict capacity for endothelial release of fibrinolytic proteins. Invasive perfused-forearm studies were performed in 96 healthy subjects. Local release rates of fibrinolytic proteins were assessed at baseline and during endothelial stimulation. Stimulation by methacholine and desmopressin induced a 6- and 12-fold increase in total tPA release rates, respectively. With increasing local release rates of tPA a gradually closer correlation emerged between the total tPA secretion and the forearm output of active tPA (from r = 0.102, ns to r = 0.85, P < 0.0001). Forearm availability of active tPA was not related to arterial input of either tPA or PAI-1. Release rates and plasma levels of tPA were not correlated. Baseline release rates of active tPA increased to noon. The major determinant for the local availability of active tPA is the capacity of the endothelium to release tPA rather than the arterial input of PAI-1 or tPA. Despite a molar excess of PAI-1, the majority of tPA released during stimulation does not undergo local inactivation. The capacity to release tPA locally cannot be predicted from its plasma concentration.     

缺血性脑卒中患者血纤溶活性变化规律的研究

目的 研究脑梗死组和非脑梗死组患者急性期,亚急性期和恢复期组织型纤溶酶原激活物（tPA）,纤溶酶原激活物抑制物-1（PAI-1）的变化规律.方法 135例脑梗死组患者于发病96h内,病后14d、3月、6月、9月分别采血,77例非脑梗死组患者先采血一次,然后分别在第一次采血后14d、3月、6月、9月采血.结果 脑梗死急性期tPA含量明显升高,PAI-1的含量明显升高.恢复期脑梗死即发病后3月,6月,9月tPA的含量比急性期明显降低,且脑梗死后时间越长tPA含量越低,恢复期脑梗死PAI-1的含量比急性期明显降低.结论 在缺血性卒中的患者,高tPA含量提示纤溶活性的降低.高PAI-1代表纤溶抑制增强.     

The plasminogen activator system modulates sympathetic nerve function

Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA-null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P<0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)-null mice released much more NE (i.e., a 275% increase; P<0.05). Furthermore, vasa deferentia from t-PA-null mice were hyporesponsive to EFS (P<0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1-null mice were much more responsive (P<0.05). Coronary NE overflow from hearts subjected to ischemia/reperfusion was much smaller in t-PA-null than in WT control mice (P<0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P<0.05) in t-PA-null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.     

气腹及腹腔镜手术对腹膜影响的临床研究

目的探讨腹腔镜与开腹手术中腹膜纤维蛋白溶酶的变化。方法在腹腔镜与开腹手术前、手术后立即、分别测量腹膜组织中组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)浓度及t-PA活性。结果腹膜组织中t-PA浓度在腹腔镜手术和传统腹部手术2组术中均下降,但在传统腹部手术组下降更显著(P<0.05)。而腹膜组织中PAI-1水平在腹腔镜手术组术前较高(P<0.05),PAI-1浓度在传统腹部手术组术中明显升高,但在手术后,2组PAI-1浓度无显著差异。t-PA活性在2组术前、术后均无明显差异,但术中2组均显著下降(P<0.05)。结论本次临床研究结果表明:腹腔镜手术和传统腹部手术对腹膜的影响是相似的,腹腔镜手术中最初的腹膜组织中PAI-1浓度的升高由CO2气腹造成并影响腹膜组织的修复。     

心肌声学造影评价实验性顿抑心肌的微血管功能改变

目的 探讨心肌顿抑时心肌微血管功能改变以及静脉心肌学造影方法的价值。方法 制备左前降支冠脉（ＬＡＤ）不同阻断时间后再 灌注犬心肌凶模型,在不同观察时间点静脉注射含全氟丙烷声振白蛋白微泡造影剂,采用二次谐波成像和间歇发剂技术行心肌声学造影（ＭＣＥ）。由主动脉根部分别注射乙酰胆碱（ＡＣＨ）和硝酸甘油（ＮＧ）后重复ＭＣＥ并计算用药后,前二维超声上所示心肌灰阶峰值（ＰＶＩ）和峰值比值（ＰＶＩＲ）。结果（地     

先天性纤溶酶原激活物抑制剂-1缺乏症的诊断研究

目的　诊断 1例先天性纤溶酶原激活物抑制剂 1(PAI 1)缺乏症患者并研究其基因异常。方法　用发色底物法、酶联免疫吸附实验测定组织型纤溶酶原激活物 (tPA)、α2 纤溶酶抑制剂因子(α2 PI )与PAI 1的活性和 (或 )抗原 ,PCR法与DNA测序分析患者的基因异常 ,用限制性内切酶PshAⅠ对患者和 6 0名正常人PCR产物酶切以排除基因多态性。结果　患者优球蛋白溶解时间 (ELT) 70min ,血浆中加入生理浓度的PAI 1(5 0ng ml)后ELT延长至 12 0min ,PAI 1活性 0 .0 4AU ml,PAI 1抗原 5 .6ng ml,α2 PI活性、F活性及tPA抗原和活性均正常。PCR测序证实患者PAI 1基因外显子 2第 4 3位核苷酸G→A杂合性改变 ,导致信号肽第 15位的丙氨酸突变为苏氨酸。酶切鉴定排除了多态性。结论　报道国内首例PAI 1缺乏症患者 ,其基因改变可能为复合杂合子 ,其中之一为Ala15Thr,该突变为一种国际上尚未报道的新的基因突变。     

老龄大鼠脑缺血-再灌注微血管基底膜损伤变化及与纤溶酶原激活系的关系

目的研究老龄大鼠脑缺血一再灌注（I／R）不同时期微血管基底膜损伤与纤溶酶原激活系的关系。方法采用大脑中动脉阻塞（MCAO）线栓法制备大鼠局灶性脑I／R模型，将大鼠分为青年假手术组、老龄假手术组、青年模型组和老龄模型组，其中模型组又分为I3h，I／R6、12、24、72和144h各时间点组。采用免疫组化、酶谱与反向酶谱分析等方法测定各脑微血管结构、基底膜Ⅳ型胶原、层连蛋白（LN）和纤溶酶原激活系的变化。结果与青年假手术组比较，老龄假手术组Ⅳ型胶原、LN表达增强。随着I／R时间的延长，老龄与青年大鼠基底膜成分Ⅳ型胶原和LN表达递减；组织型纤溶酶原激活剂（t-PA）、尿激酶型纤溶酶原激活剂（u-PA）、纤溶酶原激活物抑制剂（PAI-1）表达水平呈先增强后降低的趋势。与青年模型组相同时间点比较，老龄模型组Ⅳ型胶原（I3h、I／R6h、I／R12h）、LN（I3h、I／R6h～24h）、t-PA（I／R6h～24h）、u-PA（I／R12h～144h）表达增强，PAI-1（I／R12h、I／R24h）表达降低，差异均有显著性。另外，PAI-1的反向酶谱分析比较，量的变化与免疫表达规律基本一致。结论随着增龄，大鼠脑微血管基底膜成分Ⅳ型胶原、LN增加。在脑I／R微血管基底膜损伤方面，老龄大鼠较青年严重，其损伤的特点与纤溶酶原激活系变化有关。     

纤溶酶原激活物及其抑制剂-1的血浆含量测定在急性肺血栓栓塞症中的意义

目的探讨在急性肺血栓栓塞症(APE)发病中的组织型纤溶酶原激活物(tPA)及其抑制剂-1(PAI-1)的血浆含量、作用及其该病诊断中的意义。方法,对44例APE患者和56例健康正常对照者应用酶联免疫吸附双抗体夹心法(ELISA法)定量测定血浆tPA和PAI-1抗原水平。结果与正常对照组(tPA含量为11．05ng／ml和PAI-1含量为61．31ng／m1)相比,APE组的IPA含量(33．88ng／ml)和PAI-1含量(111．50ng／ml)较高,两组间差异有显著性。在急性肺血栓栓塞症的疾病诊断中,tPA和PAI-1的血浆含量合理诊断截断点分别为21．7ng／ml和79．4ng／ml.结论急性肺血栓栓塞症的发病是由于PAI-1抗原产生和释放增多,而非tPA抗原释放或产生不足所致．tPA和PAI-1抗原血浆含量测定在APE的疾病诊断中具有要意义。     

The regulation by fibrinogen and fibrin of tissue plasminogen activator kinetics and inhibition by plasminogen activator inhibitor 1

BACKGROUND: Tissue plasminogen activator (tPA) is unusual in the coagulation and fibrinolysis cascades in that it is produced as an active single-chain enzyme (sctPA) rather than a zymogen. Two chain tPA (tctPA) is produced by plasmin but there are conflicting reports in the literature on the behaviour of sc- and tctPA and little work on inhibition by the specific inhibitor plasminogen activator inhibitor-1 (PAI-1) under physiological conditions. OBJECTIVES: To perform a systematic study on the kinetics of sctPA and tctPA as plasminogen activators and targets for PAI-1. METHODS: Detailed kinetic studies were performed in solution and in the presence of template stimulators, fibrinogen and fibrin, including native fibrin and partially digested fibrin. Numerical simulation techniques were utilized to cope with the challenges of investigating kinetics of activation and inhibition in the presence of fibrin(ogen). RESULTS: Enzyme efficiency (k(cat)/K(m)) was higher for tctPA than sctPA in solution with chromogenic substrate (3-fold) and plasminogen (7-fold) but in the presence of templates, such as fibrinogen and native or cleaved fibrin, the difference disappeared. sctPA was more susceptible to PAI-1 in buffer solution and in the presence of fibrinogen; however, in the presence of fibrin, PAI-1 inhibited more slowly and there was no difference between sc and tctPA. CONCLUSIONS: Fibrinogen and fibrin modulate the activity of tPA differently in regard to their activation of plasminogen and inhibition by PAI-1. Fibrinogen and fibrin stimulate tPA activity against plasminogen but fibrin protects tPA from PAI-1 to promote fibrinolysis.     

Measurement of different forms of tissue plasminogen activator in plasma

BACKGROUND: We evaluated assays to measure both total tissue plasminogen activator (tPA) and the three principle forms of tPA in plasma: active tPA, tPA complexed with plasminogen activator inhibitor type 1 (PAI-1), and tPA complexed with C1-inhibitor. METHODS: Active tPA was measured by use of an indirect amidolytic assay and immunofunctional assays. tPA/PAI-1, tPA/C1-inhibitor, and total tPA antigen were measured by use of microtiter plates coated with anti-tPA antibodies and, respectively, anti-PAI-1, anti-C1-inhibitor, and anti-tPA antibodies conjugated to peroxidase. RESULTS: The immunofunctional tPA assay detected 1 U/L (0.001 U/mL) tPA and recovered 108% +/- 12% of active tPA added to samples containing high (mean, 60 000 IU/L) PAI-1 activities vs a detection limit of 10 U/L (0.01 U/mL) and 13% +/- 25% recovery for the indirect amidolytic tPA activity assay. For measurement of tPA/PAI-1 complex, polyclonal anti-PAI-1 conjugates recovered 112% +/- 20% of the expected tPA/PAI-1 vs recovery of only 38% +/- 16% when monoclonal anti-PAI-1 conjugates were used. Of three methods tested, two total tPA antigen assays correlated well (r(2) = 0.85) and showed recoveries near 100%, whereas the third method showed lower correlations, higher intercepts, and falsely high recovery. A single anti-tPA capture antibody that performed the best in the individual assay evaluations was used to measure the different forms of tPA in 22 samples with a range of tPA and PAI-1 values. The sum of the molar concentrations of active tPA, tPA/PAI-1, and tPA/C1-inhibitor using the optimized methods was equal to 94% +/- 7% of measured total tPA. CONCLUSION: Optimized assays based on a single anti-tPA capture antibody can be used to accurately measure the major forms of tPA in plasma.     

Plasminogen and plasmin activity in patients with coronary artery disease

OBJECTIVE: While coronary artery disease (CAD) is associated with disturbances of the plasma fibrinolytic system, the nature of these disturbances is not fully defined. Fibrinolysis is regulated by plasmin, whose production is mediated by plasminogen activator conversion of plasminogen (Plg) to plasmin. The cascade is modulated by feedback loops that include Plg activator inhibitor 1 (PAI-1). Molecular interactions with Plg kringle domains play an important role in regulating plasmin production and its modulation of fibrinolysis. We hypothesized that interactions of tissue plasminogen activator (tPA) with Plg kringle domains regulates plasmin levels in patients with stable CAD. METHODS: Plasma was collected from patients (n = 33) with an angiographically significant CAD and controls (n = 18) with angiographically established normal or minimally diseased arteries. Plasmin activity, tPA activity, and plasma levels of Plg, PAI-1, uPA, and tPA were determined. RESULTS: CAD patients had 1.7-fold greater plasmin activity (P = 0.02) that correlated with 1.5-fold higher tPA activity when compared to controls. Epitope mapping of Plg domains showed Plg differences in epitope exposure between the two groups. Plasma from CAD patients had 50% less (P < 0.001) detectable kringle 4 and 48% less (P = 0.007) detectable kringles 1-3. CONCLUSIONS: Based on detectable differences in Plg, we conclude that in patients with stable CAD, Plg complexed with tPA exists in a conformation that enables increased tPA activity and Plg conversion to plasmin.     

阻塞性睡眠呼吸暂停低通气综合征患者血管内皮细胞及纤溶系统功能变化

目的：探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血管内皮细胞及纤溶系统功能变化。方法：根据多导睡眠呼吸监测仪监测结果，选择年龄、性别、体重指数(BMI)无明显差异的OSAHS患者52例和健康者48例。以Clauss法测定纤维蛋白原(Fg)，以发色底物法测定组织纤溶酶原激活物活性(tPA：A)、纤溶酶原激活物抑制物-1活性(PAI-1：A)，以酶联免疫法测von Willebrand因子含量(vWF)、组织纤溶酶原激活物含量(tPA：Ag)、纤溶酶原含量(PLg：Ag)和纤溶酶原激活物抑制物-1含量(PAI-1：Ag)。结果：与对照组比较，(3SAHS组vWF、Fg、PAI-1：A、PAI-1：Ag水平明显升高，PLg：Ag、tPA：Ag含量明显降低，tPA：A无明显变化。结论：OSAHS患者血管内皮细胞功能受损，纤溶系统功能降低。     

Adhesion molecules in different treatments of acute myocardial infarction

Background  

Tissue damage after ischemia and reperfusion involves leukocyte endothelial interactions mediated by cell adhesion molecules. This study was designed to determine the time course of soluble adhesion molecules in patients with acute myocardial infarction after attempted reperfusion by thrombolysis with tissue plasminogen activator (tPA) or streptokinase (SK), or percutaneous transluminal coronary angioplasty (PTCA).     

经胸廓内动脉置泵对急性心肌缺血犬t-PA和PAI的影响

目的　通过建立经胸廓内动脉置泵治疗犬急性心肌缺血的动物模型 ,观察介入组和对照组组织型纤溶酶原激活物及其抑制物 ( t PA、PAI)的变化。方法　 6 0条健康杂种犬 ,随机分为介入组和对照组 ,每组 30条。在静脉麻醉下开胸 ,结扎左冠状动脉前降支 ,建立急性心肌缺血动物模型。介入组分离胸廓内动脉后远端结扎 ,在近端置管 ,外接输液加压泵 ,通过胸廓内动脉加压滴注硝酸甘油 ;对照组通过外周静脉滴注硝酸甘油。于冠状动脉结扎前、结扎后 0 .5 h、以及给予硝酸甘油 2 h和 6 h后股静脉采血测定 t PA和 PAI。结果　在冠状动脉结扎后 0 .5 h两组 t PA均升高 ,对照组在 2 h和 6 h逐渐下降 ,而介入组无明显变化 ;两组在结扎后 6 h差异有统计学意义 ( P<0 .0 5 )。冠状动脉结扎后两组 PAI逐渐上升 ,对照组在结扎后 6 h最高 ,而介入组在结扎后 2 h最高 ;两组 PAI在结扎后 6 h差异有统计学意义 ( P<0 .0 5 )。结论　经胸廓内动脉置泵介入治疗犬急性心肌缺血可促进血管内皮释放 t PA、抑制 PAI分泌 ,对纤溶平衡有一定的调节作用     

d-dimer predicts major bleeding,cardiovascular events and all-cause mortality during warfarin treatment

ObjectivesPrevious studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of d-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.Design and methodsIn a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for d-dimer, tPA, and tPA/PAI-1 complex.ResultsIn multivariate Cox regression analysis, high levels of d-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01–1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05–1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06–1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.ConclusionWe conclude that high levels of d-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment.     

Thrombin upregulates production of plasminogen activator inhibitor type 1 in human peritoneal mesothelial cells.

OBJECTIVE: To determine the influence of thrombin, which is generated intraperitoneally during peritoneal dialysis, on the synthesis of fibrinolytic system components in human peritoneal mesothelial cells (HMC). METHODS: Confluently grown HMC, isolated from the omental tissue, were used in the experiments. Conditioned media were obtained by incubating cells with serum-free M199 containing the appropriate concentration of the test compound. Tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) antigen concentrations were measured by ELISA. Northern blot analysis was conducted for mRNA expression experiments. To test thrombin specificity, we used the thrombin inhibitor hirudin. The protein kinase C (PKC) inhibitor Ro 31-8220 was inserted to examine whether the effect of thrombin depends on PKC activity. RESULTS: Thrombin increased PAI-1 antigen in the conditioned media of HMC in a time- and concentration-dependent manner. After 24 hours incubation, PAI-1 levels increased from 350+/-30 ng/10(5) cells in control conditions to 620+/-30 ng/10(5) cells in HMC exposed to 5 U/mL thrombin (n = 8, p < 0.05). In contrast, there was no effect of thrombin on tPA antigen levels. An increase of PAI-1 mRNA expression was also observed by Northern blot hybridization. Hirudin (10 U/mL) inhibited the thrombin-induced increase in PAI-1 synthesis. In addition, a complete inhibition of the stimulating effect of thrombin on PAI-1 synthesis was obtained by blocking PKC activity with Ro 31-8220 (3 micromol/L). CONCLUSIONS: Thrombin increases PAI-1 synthesis in HMC via a PKC-dependent mechanism.Thereby the synthesis of tPA is not affected. Thus, thrombin may not only promote fibrin formation in the peritoneal cavity, but may also inhibit fibrin degradation by release of free PAI-1 from HMC.     

The effect of body build, diet and endocrine factors on the extrinsic fibrinolytic system in healthy young women

In this study, the importance of anthropometric, nutritional and endocrine variables on the plasma concentrations of tissue plasminogen activator antigen (tPA) and plasminogen activator inhibitor (PAI-l) were investigated. Tissue plasminogen activator concentration and PAI-l activity in plasma were studied in 24 healthy young women after diet periods which caused depletion or filling of hepatic glycogen stores. Plasminogen activator inhibitor levels in the glycogen-depleted state and the glycogen-repleted state were positively correlated, as were also tPA levels. In fasting subjects with repleted glycogen stores, tPA values correlated with fasting insulin concentration and blood pressures. In fasting subjects depleted of glycogen stores, PAI-l correlated with tPA, plasma insulin, triglycerides, and waist-to-hip girth ratio; triglycerides and waist-to-hip girth ratio also correlated with tPA. Over a 4-h period following intake of a test-meal, the glucose and insulin responses were not correlated with the fibrinolytic variables. Multivariate regression analysis suggested that waist-to-hip girth ratio and diastolic blood pressure were independently associated with tPA concentrations both in subjects with depleted and repleted glycogen stores. Thus, both constitutional factors such as anthropometric variables and blood pressure, and nutritional status of the subjects may be related to tPA and PAI- levels in plasma. This should be taken into account in clinical studies on fibrinolysis.     

The glycocalyx protects erythrocyte-bound tissue-type plasminogen activator from enzymatic inhibition

Coupling tissue-type plasminogen activator (tPA) to carrier red blood cells (RBC) prolongs its intravascular life span and permits its use for thromboprophylaxis. Here, we studied the susceptibility of RBC/tPA to PA inhibitors including plasminogen activator inhibitor-1 (PAI-1) that constrain its activity and may reduce the duration of its effect. Despite lesser spatial and diffusional limitations, soluble tPA was far less effective than RBC/tPA in dissolving clots formed in vitro from blood of wild-type (WT) mice (40 versus 80% lysis at equal doses of tPA). Furthermore, after i.v. injection, soluble tPA lost activity faster in transgenic mice expressing a high level of PAI-1 than in WT mice, whereas the activity of RBC/tPA was unaffected. PAI-1 inactivated soluble tPA at equimolar ratios in vitro, but it had no effect on the amidolytic or fibrinolytic activity of RBC/tPA. RBC/tPA was also more resistant than soluble tPA to in vitro inhibition by other serpins (alpha2-macroglobulin and alpha1-antitrypsin) and pathologically high levels of glucose. However, coupling to RBC did not protect a truncated tPA mutant, Retavase, from plasma inhibitors. Chemical removal of the RBC glycocalyx negated tPA protection from inhibitors: tPA coupled to glycocalyx-stripped RBC bound twice as much 125I-PAI-1 as did tPA coupled to naive RBC, and susceptibility of the bound tPA to inhibition by PAI-1 was restored. Thus, the RBC glycocalyx protects RBC-coupled tPA against inhibition. Resistance to high levels of inhibitors in vivo contributes to the potential utility of RBC/tPA for thromboprophylaxis.     

Effects of hyperbaric oxygen on expression of fibrinolytic factors of human endothelium in a simulated ischaemia/reperfusion situation

Background : Treatment with hyperbaric oxygen (HBO 2 ) is controversial when treating disorders other than decompression sickness. Still, HBO 2 is a treatment modality that has gained recognition in certain situations of ischaemia reperfusion. However, not much is known about its effect on the endothelial cells. Based on earlier studies, the hypothesis was that HBO 2 treatment stimulates the release of fibrinolytic factors. The aim of the study was to investigate the effect of HBO 2 treatment on cultured endothelial cells in a simulated ischaemiareperfusion model. Methods : To mimic the clinical situation during ischaemia reperfusion, endothelial cells were subjected to anoxia for 8 h, followed by reperfusion with either HBO 2 or normobaric air for 1.5 h, and compared with an untreated control that was not exposed to anoxia. Components investigated were the fibrinolytic stimulator tissue plasminogen activator (t-PA), urokinase plasminogen activator (uPA) and the antagonist, plasminogen activator inhibitor type one (PAI-1). Results : Immediately after 8 h of total anoxia and reoxygenation with HBO 2 (for 1.5 h), the mean (SEM) concentrations of t-PA, PAI-1 and uPA were significantly increased compared to the other groups. The difference between the normobaric and control groups, measured at 1.5 h, 6 h and 24 h post-anoxia, persisted throughout the experiment. Conclusion : In this ischaemia-reperfusion model, HBO 2 stimulates the release of fibrinolytic factors. These observations might be relevant in trauma care in preventing thromboses and/or microembolization following ischaemia-reperfusion.