高原肺水肿患者血浆纤溶系统变化及卡托普利的影响

目的　观察高原肺水肿 (HAPE)患者血浆纤溶系统的变化及卡托普利对其的影响 ,探讨其发病机制。方法　 72例高原肺水肿患者分为卡托普利组 (35例 )和常规组 (37例 ) ,并以 2 0名健康志愿者作为对照。所有患者治疗前、后均测定血浆组织型纤溶酶原激活物 (tPA)及纤溶酶原激活物抑制物 (PAI 1)的活性。结果　血浆tPA含量卡托普利组 (A组 )治疗前、后分别为 (0 4 0± 0 14 )× 10 3 IU/L、(0 5 8± 0 13)× 10 3 IU/L ,常规组 (B组 )治疗前、后分别为 (0 39± 0 19)× 10 3 IU/L、(0 4 9± 0 16 )×10 3 IU/L ,正常对照组 (C组 )为 (0 5 9± 0 17)× 10 3 IU/L ;A、B两组治疗前、后比较差异均有显著性(P <0 0 1、<0 0 5 ) ;血浆PAI 1含量A组治疗前、后分别为 (6 6± 1 8)× 10 3 AU/L、(4 9± 1 5 )×10 3 AU/L ,B组治疗前、后分别为 (6 6± 1 6 )× 10 3 AU/L、(5 8± 1 7)× 10 3 AU/L ,C组为 (4 9± 1 3)×10 3 AU/L。A、B两组治疗前、后比较差异均有显著性 (P <0 0 1、 <0 0 5 )。结论　HAPE患者纤溶系统呈失衡性改变 ,卡托普利有恢复其平衡的治疗作用。     

普伐他汀对不稳定性心绞痛患者血管内皮功能的影响

目的　探讨普伐他汀对不稳定性心绞痛 (UA)患者血管内皮依赖性舒张功能和纤溶系统的影响。方法　采用高分辨超声技术 ,将 42例 AU患者按随机编码分为普伐他汀组和对照组 ,观察降脂治疗前后血管内皮依赖性舒张功能和血浆纤溶酶原激活物 (t PA)及其抑制物 (PAI)活性。结果　普伐他汀组与对照组和治疗前比较 ,血流介导的肱动脉舒张百分率显著增加 ,(9.5± 3.2 ) %和 (5.0± 2 .2 ) %、(4.2± 2 .0 ) % (均 P<0 .0 1 )。血浆 t PA活性增强 ,(0 .48± 0 .1 7) IU/ml和 (0 .352± 2 .0 ) IU/ml、(0 .2 75± 0 .1 5) IU/ml(P<0 .0 1 ) ;血浆 PAI活性减弱 (0 .350± 0 .1 0 5) AU/ml和 (0 .450± 0 .1 2 ) AU/ml、(0 .52 5± 0 .2 5) AU/ml(均 P<0 .0 5)。线性相关分析显示 :血流介导的肱动脉舒张百分率及血浆纤溶活性改变与血脂的降低无关。结论　普伐他汀能改善 UA时受损的血管内皮依赖性舒张功能和血浆纤溶活性。     

老年冠心病患者纤溶酶原激活抑制剂的变化

目的探讨老年人冠心病与纤溶酶原激活抑制剂（PAI）的关系。方法测定了93例老年冠心病患者的PAI和组织型纤溶酶原激活剂（t-PA）活性、胆固醇和甘油三酯的血浆水平,并与健康对照组比较。结果冠心病组的PAI活性〔（810±360）AU/L〕明显高于健康对照组〔（640±300）AU/L,P＜0.01〕;冠心病组的t-PA活性〔（390±140）IU/L〕明显低于对照组的水平〔（490±240）IU/L,P＜0.05〕。结论老年人PAI活性的增高和t-PA活性的降低可能参与了冠心病的发病机制。     

无症状性脑梗死患者血清炎性因子和纤溶及抗纤溶活性的变化

目的观察无症状性脑梗死(silent cerebral infarction,SCI)患者血清炎性因子和纤溶及抗纤溶活性的变化。方法选择SCI患者53例(SCI组)和健康体检者55例(对照组),分别检测血清高敏C反应蛋白(hs-CRP)、血浆纤溶酶原活性(PLG:A)、纤溶酶活性(PLM:A)、组织型纤溶酶原激活物(t-PA)活性、D-二聚体(D-D)含量、_2α-纤溶酶抑制剂(α_2-PI)和纤溶酶原激活物抑制剂(PAI)活性。结果 SCI组hs-CRP水平明显高于对照组[(15.36±4.30)mg/L vs (10.26±2.61)mg/L,P<0.01],SCI组PLM:A、t-PA和D-D含量均明显低于对照组[(35.84±10.23)% vs (68.74±18.41)%,(0.11±0.01)U/ml vs (0.49±0.12)U/mL(0.36±0.14)mg/L vs (0.68±0.16)mg/L,P<0.01)],SCI组PLG:A与对照组比较差异无统计学意义(P>0.05),SCI组α_2-PI活性和PAI活性明显高于对照组[(128.46±23.75)% vs (96.36±19.34)%,(0.86±0.22)AU/ml vs (0.48±0.10)AU/ml.P<0.01]。结论炎症过程和纤溶及抗纤溶系统的功能失调与SCl的形成有关。     

不稳定型心绞痛患者纤溶活性及内皮功能的变化

目的观察不稳定型心绞痛患者血浆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)、假性血友病因子(vWF)水平的变化,进一步明确纤溶活性和内皮功能在不稳定型心绞痛中的作用,并探讨其临床意义。方法选择40例不稳定型心绞痛患者和30例健康志愿者,均取早晨空腹静脉血,用发色底物法测定血浆t-PA和PAI-1的活性,用酶联免疫吸附双抗体夹心法测其血浆中vWF的含量。结果(1)不稳定型心绞痛组的t-PA活性明显低于对照组(0.2±0.11IU/ml∶0.4±0.09IU/ml,P<0.05),而PAI-1活性则较对照组增高(0.9±0.32AU/ml∶0.53±0.30AU/ml,P<0.05),vWF含量较对照组明显增高［(565±80.5)%∶(80±55.6)%,P<0.001］;(2)PAI-1活性与vWF的含量呈正相关;(3)PAI-1活性、vWF含量均与甘油三酯水平呈正相关。结论纤溶活性降低、血管内皮受损使不稳定型心绞痛患者易发生冠状动脉痉挛及血栓形成。     

急性心肌梗死时血管内皮功能的变化及福辛普利的干预作用

目的 :观察急性心肌梗死早期应用血管紧张素转换酶抑制剂治疗对血管内皮依赖性舒张功能和血浆纤溶平衡的影响。方法 :采用高分辨超声技术和发色底物显示法 ,检测 3 4例急性心肌梗死患者和 3 0例无冠心病患者 (对照组 )肱动脉内皮依赖性舒张功能和血浆组织型纤溶酶原激活物 (t PA)及其抑制物 (PAI)。应用随机编码将 3 4例急性心肌梗死患者分为福辛普利组和常规治疗组 ,治疗 8周后复测其肱动脉内皮依赖性舒张功能和血浆t PA和PAI活性。结果 :急性心肌梗死患者肱动脉内皮依赖性舒张功能 (3 8± 2 3 ) %较对照组 (9 5± 3 2 ) %明显降低 ,血浆t PA活性显著降低和PAI活性明显增加 ,有非常显著性差异 (P均 <0 0 1)。福辛普利治疗 8周后 ,肱动脉内皮依赖性舒张功能(9 45± 3 2 0 ) %与治疗前基础水平 [(3 5 2± 2 70 ) % ,P <0 0 1]、常规治疗后 [(4 60± 2 80 ) % ,P <0 0 5 ]相比有显著改善 ;血浆纤溶活性也有明显改善 (t PA :0 49± 0 2 0IU /mlvs 0 2 8± 0 15IU /ml,P <0 0 1和 0 3 2± 0 15IU/ml,P <0 0 5 ;PAI :0 3 6± 0 12AU /mlvs .0 5 3± 0 2 5AU/ml,P <0 0 1和 0 45± 0 0 9AU /ml,P <0 0 5 ) ,均有显著性差异。结论 :急性心肌梗死患者内皮依赖性舒张功能明显减退 ;血     

运动负荷对不稳定性心绞痛患者纤溶活性影响的研究

对20例健康受试者和25例不稳定性心绞痛患者进行运动负荷前、后组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制剂(PAI-1)活性的测定.结果发现运动前静息时,两组t-PA活性无显著差异,而PAI-1活性不稳定性心绞痛组明显高于对照组;运动后,不稳定性心绞痛组t-PA活性显著低于对照组(0.96±0.45IU/ml对1.89±0.68IU/ml,P<0.01),PAI-1活性下降幅度小于对照组(12.0%对31.9%),使其PAI-1活性仍显著高于对照组(8.20±2.28AU/ml对4.21±0.68AU/ml,P<0.01).提示不稳定性心绞痛患者不论是静息,还是在运动负荷激发后,均存在着纤溶活性的下降.     

心房颤动的低纤溶状态

目的 :研究心房颤动 (房颤 )的纤溶系统改变及其临床意义。方法 :采用发色底物法测定 30例房颤患者(其中冠心病 14例 ,风湿性心脏病 16例 )和 2 5例正常人血浆组织型纤溶酶原激活剂活性 ( t- PA∶ a)和纤溶酶原激活剂抑制物活性 ( PAI∶ a) ;并测定血浆纤维蛋白原 ( Fg)浓度、凝血酶原时间 ( PT)和部分凝血活酶时间( APTT)。结果 :房颤患者与正常人相比 ,血浆 t- PA∶ a降低〔( 340 .0± 70 .0 )对 ( 480 .0± 5 0 .0 ) IU /L ,P <0 .0 1)〕;PAI∶ a升高〔( 90 0 .0± 80 .0 )对 ( 6 90 .0± 5 0 .0 ) AU/L,P <0 .0 1〕;PAI∶ a/t- PA∶ a比值增高〔( 2 .87±0 .89)对 ( 1.49± 0 .2 9) ,P <0 .0 1〕,而 Fg、PT、APTT无显著性差异 ( P >0 .0 5 )。风湿性心脏病房颤与冠心病房颤之间血浆 t- PA∶ a,PAI∶ a,PAI∶ a/t- PA∶ a比值及 PT、APTT均无显著性差异 ( P>0 .0 5 ) ,但前组血浆 Fg浓度较后组低〔( 2 .5 9± 0 .6 9)对 ( 3.35± 1.0 4) g/L,P <0 .0 5〕。结论 :房颤患者血浆存在低纤溶状态 ,表现为 PAI活性增加 ,t- PA活性降低。房颤的低纤溶状态可能与其高发血栓栓塞并发症有关     

脑梗死急性期患者凝血与纤溶指标的改变及降纤酶的疗效

目的 :研究脑梗死急性期患者纤溶、凝血指标的变化及降纤酶的疗效。方法 :测定 38例脑梗死急性期 (<3天 )患者降纤酶治疗前、后的血浆纤维蛋白原 (Fbg)、α2 抗纤溶酶 (α2 - PI)、血浆组织型纤溶酶原激活物 (t- PA)及其抑制物 (PAI- 1)和 D-二聚体 (D- D)的变化。结果 :脑梗死急性期患者血浆 Fbg、α2 - PI、 PAI- 1、 D- D水平分别为 4.32± 1.7g/ L、 (15 4.39± 34 .86 ) %、 0 .2 6± 0 .1IU/ m l、 1.12± 0 .32 AU/ ml和 1.34± 1.18mg/ L,明显升高 ,较正常对照组有显著差异 P<0 .0 1) ,t- PA水平下降非常显著 (P<0 .0 0 1)。降纤酶治疗后 Fbg、α2 - PI、 PAI- 1、 D- D水平显著下降 (P<0 .0 5～ P<0 .0 0 1) ,t- PA水平升高非常显著 (P<0 .0 0 1)。结论 :降纤酶有良好降纤、溶纤作用 ,对脑梗死急性期患者有显著疗效。     

纤溶酶原激活抑制物活性与冠心病发病关系

目的 :探讨纤溶酶原激活抑制物 (PAI)与冠心病 (CHD)发病的关系。方法 :用免疫化学方法观察测定 145例CHD患者和 130例健康对照者的血浆PAI、纤溶酶原激活物 (PA)活性和胆固醇、甘油三酯 (TG)的血清水平。结果 :CHD组的PAI/PA比值 (1.83± 0 .5 2 )明显高于对照组 [(1.17± 0 .48) ,P <0 .0 5 ],PAI与TG具有显著相关性 (r =0 .45 ,P <0 .0 5 )。结论 :PAI与TG相关性在CHD发生、发展过程中具有重要作用。     

氯沙坦对原发性高血压患者纤溶功能的影响

目的观察氯沙坦对原发性高血压(EH)患者纤溶功能的影响。方法观察34例EH患者应用氯沙坦治疗4周后收缩压(SBP)、舒张压(DBP)、心率、血浆组织型纤溶酶原激活物(t-PA)、内皮细胞型纤溶酶原激活物抑制剂(PAI-1)水平的变化,并与30例健康人作比较。结果治疗前EH患者血浆t-PA水平明显低于对照组,而PAI-1水平明显高于对照组(均P<0.01)。氯沙坦治疗4周后,血压明显下降,心率无明显变化,血浆t-PA水平增加,但无统计学意义,而PAI-1水平明显降低,t-PA/PAI-1比值升高(均P<0.01)。结论EH患者存在着内源性纤溶功能紊乱,氯沙坦可以改善EH患者的纤溶功能。     

培哚普利对慢性心力衰竭患者血浆t-PA和PAI-1水平的影响

目的评价培哚普利对慢性心力衰竭(CHF)患者血浆组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制物-1(PAI-1)水平的影响。方法采用酶联免疫吸附法测定60例CHF患者(CHF组)及20例健康人(正常对照组)血浆t-PA、PAI-1水平。CHF组患者又随机均分为常规治疗亚组和培哚普利亚组。培哚普利亚组在常规治疗基础上加用培哚普利2~4mg,每日1次。所有CHF患者治疗2周后复测血浆t-PA、PAI-1水平。结果CHF患者血浆t-PA、PAI-1水平比正常对照组明显增高(P<0.01)。治疗后,培哚普利亚组血浆PAI-1水平比常规治疗亚组明显降低(P<0.01),血浆t-PA水平比常规治疗亚组明显升高(P<0.01)。结论培哚普利不仅可降低PAI-1水平,而且可升高t-PA水平,改善内源性纤溶功能。     

Maximal endothelial tissue plasminogen activator release is not impaired in patients with acute coronary syndromes before heparin treatment.

Procoagulant and fibrinolytic disturbances are described in patients with acute coronary syndromes (ACS), but whether defective maximal tissue plasminogen activator (t-PA) release from the endothelium is also present is still controversial. Previous studies did not take into consideration the contribution of heparin, which strongly affects fibrinolysis. Accordingly, in this study, we measured maximal t-PA release in patients with ACS before, during, and after heparin treatment. Maximal t-PA release was measured by the venous occlusion test in 38 hospitalized patients with confirmed ACS (18 acute myocardial infarctions and 20 unstable anginas) before starting heparin, during heparin treatment, and 4 and 12 h after discontinuation. Plasma plasminogen activator inhibitor type 1 (PAI-1), D-dimer and prothrombin fragment F1 + 2 were also measured. Eighteen age-matched subjects with no evidence of coronary disease were used as controls. At admission, patients showed significantly higher plasma levels of t-PA, PAI-1, and F1 + 2 than controls. Before heparin, maximal t-PA release was similar in patients and controls. Heparin treatment was associated with a significant increase of plasma t-PA, while it did not affect maximal t-PA release. Coagulative and fibrinolytic disturbances are present in patients with ACS, but these do not include maximal t-PA release. Among our patients, maximal t-PA release appears stable over time and is not affected by heparin treatment.     

Behaviour of tissue plasminogen activator, plasminogen activator inhibitor 1 and their complex in various disease states.

Plasma levels of tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen and t-PA/PAI-1 complex were measured in plasmas from 18 healthy subjects and 75 patients with various diseases (28 patients with haematological malignancies, 20 with thrombotic diseases, five with infectious diseases, four with liver diseases, ten with bleeding disorders and eight miscellaneous conditions). In addition, we studied ten patients with bleeding disorders after DDAVP infusion and 18 healthy subjects after venous occlusion. Plasma levels of t-PA antigen, PAI-1 antigen and t-PA/PAI-1 complex were increased in the patients compared with the healthy subjects. t-PA/PAI-1 complex levels correlated well with t-PA antigen levels and molar concentrations of t-PA antigen were similar to those of the t-PA/PAI-1 complex. Venous occlusion induced an increase in both t-PA antigen and PAI-1 antigen and the molar concentration of the t-PA/PAI-1 complex was equivalent to that of t-PA antigen. Following DDAVP infusion, the levels of t-PA antigen and t-PA/PAI-1 complex increased but PAI-1 antigen levels decreased, and the increase of t-PA antigen was greater than that of t-PA/PAI-1 complex. These findings indicate that PAI-1 antigen exceeds t-PA antigen in healthy subjects and in patients with various diseases. We conclude that part of the t-PA/PAI-1 complex is rapidly cleared from the circulation and that free t-PA increases after DDAVP infusion.     

Alterations in the fibrinolytic system components during acute myocardial infarction

The purpose of this study was to evaluate the changes in tissue-plasminogen activator (t-PA), plasminogen activator inhibitor - type 1 (PAI-1) and D-dimer (DD) antigen plasma levels in acute myocardial infarction (AMI) patients after thrombolytic therapy with two different thrombolytic agents, rt-PA or acetyl-streptokinase and to find out any correlation between the plasma t-PA, PAI-1 and DD levels with the infarct size as it is estimated from the peak of serum CPK levels. The plasma antigen levels of t-PA, PAI-1 and DD were measured by the enzyme immunoassay method (Stago), in 57 consecutive patients (M = 46, F = 11, mean age 55.6 +/- 8.8 years) and in 25 normal subjects (M = 18, F = 7, mean age 54.0 +/- 5.5 years). In 47 out of the 57 patients who were treated successfully with 100 mg of rt-PA (26 patients) or with 1.5 MU 21 of acetyl-streptokinase, as well as in 10 patients who were not treated, samples were obtained again 4 and 24 hours after the end of thrombolytic therapy or admission, respectively. During the acute phase of myocardial infarction the t-PA, PAI-1 and DD antigen plasma levels were significantly higher than in healthy people. There were no significant changes in the t-PA, PAI-1 and DD plasma levels of the patients who were not treated with a thrombolytic agent. We found a significant elevation of t-PA (p < 0.001), PAI-1 (p < 0.05) and DD (p < 0.001) after 4 hours in comparison with the baseline (at presentation, before therapy). After 24 hours the t-PA and DD plasma levels remained significantly higher (p < 0.001) while the PAI-1 plasma levels returned to the pre-therapy levels. There were no significantly different changes in the t-PA, PAI-1 and DD plasma levels of either group of patients, treated with rt-PA or acetyl-streptokinase while the t-PA and PAI-1 levels were positively correlated with infarct size as estimated from peak serum CPK levels.     

The effects of rosiglitazone treatment on the fibrinolytic system in patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.     

Effects of perindopril treatment on hemostatic function in patients with essential hypertension in relation to angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms

BACKGROUND AND AIM: An imbalance in the hemostatic system is a frequent finding in untreated essential hypertension (HT), and it has been shown that treatment with angiotensin converting entyme (ACE) inhibitors improves hemostatic function. In order to elucidate the role of genetic factors, we studied hemostasis in patients with untreated and treated HT and correlated the results with ACE I/D and plasminogen activator enhibitor-1 (PAI-1) 4G/5G gene polymorphisms. METHODS AND RESULTS: Forty-three males with HT (mean age 31.7 +/- 6.8 years) were compared with 34 age and gender-matched controls. All of the patients were treated with perindopril (4 mg/day) and, after one and six months of therapy, their levels of plasma fibrinogen (Fb), t-PA antigen, PAI-1 antigen, von Willebrand factor (vWF), ACE activity and blood pressure were measured. ACE and PAI-1 genotypes were identified by means of the polymerase chain reaction on DNA isolated from peripheral blood lymphocytes. Untreated patients had significantly higher levels of Fb, PAI-1 (p < 0.01) and t-PA (p < 0.05) regardless of their ACE or PAI-1 genotypes. Perindopril reduced blood pressure regardless of ACE or PAI-1 genotype (p < 0.001). ACE II homozygotes showed the greatest decrease in ACE activity (p < 0.01) and a significant reduction in Fb levels (p < 0.05) after just one month of treatment. Analysis of the group as a whole revealed an increase in t-PA antigen levels after six months of treatment, regardless of ACE or PAI-1 genotype (p < 0.01). CONCLUSIONS: Our results show that essential hypertension predisposes to the procoagulant state characterized by hyperfibrinogenemia and hypofibrinolysis. Perindopril reduced fibrinogen levels in ACE II homozygotes due to its more potent inhibitory action on the renin-angiotensin system in such patients. It improved fibrinolysis by increasing t-PA levels regardless of ACE and PAI-1 genotype.     

Interactions of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications

To delineate interactions of infused tissue-type plasminogen activator (t-PA) with inhibitors in plasma and their impact on fibrinolytic activity, serial plasma samples from patients with acute myocardial infarction and from normal rabbits given infusions of t-PA were assayed for t-PA antigen, activity of "fast acting" plasminogen activator inhibitor (PAI-1), and the presence and nature of t-PA-inhibitor complexes. In patients, endogenous t-PA circulated predominantly as a 100 kilodalton (kDa) complex with PAI-1, as verified by immunoprecipitation. During infusions, t-PA circulated not only as free t-PA (55 kDa) but also in complexes with PAI-1 (100 kDa), alpha 2-antiplasmin (110 kDa), and C1-esterase inhibitor (170 kDa). After termination of infusions, levels of free t-PA declined, while inhibitor complexes remained prominent. Free PAI-1 activity, assayed spectrophotometrically, was markedly elevated in the 24 hr interval after infusion of t-PA in 47% of patients with infarction. The specific activity of t-PA during infusions was 0.4 IU/ng or greater. However, during the 3 hr interval after infusions in patients, specific activity declined in association with prominence of t-PA complexes, predominantly with PAI-1. Infusions of t-PA in normal rabbits did not result in reactive increases in PAI-1 activity or in the t-PA-PAI-1 complex. After infusions, t-PA was associated predominantly with alpha 2-antiplasmin and C1-esterase inhibitor rather than PAI-1. t-PA inhibitor complexes were seen despite immediate acidification of whole blood, indicating that they were present in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue-type plasminogen activator and its inhibitor (PAI-1) in plasma in cases of non-insulin-dependent diabetes mellitus (NIDDM)

Parameters of fibrinolysis, including plasminogen, alpha 2 plasmin-inhibitor (alpha 2 PI), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigens, and fibrinogen were assayed in 53 patients (28 women and 27 men; mean age: 64 years, age range: 32-87 years) with non-insulin-dependent diabetes mellitus (NIDDM). The control group was similarly aged (mean age: 60.4 years, age range: 38-81). The levels of t-PA and t-PA/PAI-1 ratio of the diabetic group (mean +/- SD; 9.8 +/- 4.3 ng/ml, 0.94 +/- 0.47, respectively) were significantly higher than that of the control group (5.5 +/- 2.5 ng/ml, 0.51 +/- 0.23, respectively). The increased levels of t-PA antigen and t-PA/PAI-1 ratio in diabetics mean that free t-PA has been released. However, there was no significant difference in the level of PAI-1 between the diabetic group (12.9 +/- 6.4 ng/ml) and the control group (12.1 +/- 5.6 ng/ml). Levels of fibrinogen, plasminogen and alpha 2 PI in plasma were not different in the two groups. Duration of the disease, levels of glycosylated hemoglobin, differences in treatment and presense of diabetic nephropathy or retinopathy did not affect the fibrinolytic parameters. The levels of fibrinogen was higher in those with nephropathy than in the diabetics without nephropathy and retinopathy (p less than 0.05). There were no significant differences in the levels of t-PA, t-PA/PAI-1 ratio and PAI-1 between younger (less than 65 years) and older (65 years or more) subjects, in either the control or diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasminogen activator inhibitor 1 and tissue-type plasminogen activator during exercise in patients with coronary artery disease

As depressed fibrinolysis is implicated in the pathogenesis of coronary artery disease, we have studied the activation of fibrinolysis during maximal, symptom-limited exercise in a group of 68 men. After exercise they were divided, according to their coronary angiography and exercise 201Tl emission computed tomography results, into three groups. Group 1: persons with normal exercise 201Tl emission computed tomography results and no underlying diseases who served as controls; group 2: patients with coronary artery disease without exercise-induced myocardial ischemia, and group 3: patients with coronary artery disease with transient, exercise-induced myocardial ischemia. Before and at peak exercise we measured the plasminogen activator activity (PAA) in the euglobulin fraction of plasma by an amidolytic method and the concentrations of tissue plasminogen activator (t-PA), activator-inhibitor complex - plasminogen activator inhibitor 1 (PAI-1) complexed with t-PA - and total PAI-1 by enzyme immunoassay. The concentration of free PAI-1 in plasma was calculated by subtraction of the concentration of activator-inhibitor complex from that of total PAI-1. Under basal conditions, group 3 had significantly higher free and total PAI-1 levels than group 1. There were no statistically significant differences between the three groups in PAA, t-PA, and activator-inhibitor complex levels. At peak exercise, group 1 showed the highest release of t-PA accompanied with highest increases in PAA as well as in activator-inhibitor complex, the proportion of released t-PA antigen not bound to PAI-1 being highest in group 1. Free PAI-1 decreased significantly, but there were no differences between individual groups.(ABSTRACT TRUNCATED AT 250 WORDS)