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We examined the relation between oxidative stress and cardiac events in patients with acute myocardial infarction (AMI). There is now increasing evidence that reactive oxygen species cause reperfusion injury to the previously ischemic myocardium after reperfusion. We measured urinary biopyrrin/creatinine levels, an oxidative stress marker, in 41 patients with AMI, 34 patients with stable angina pectoris (SAP), and 29 control subjects. In the patients with AMI, urine samples were taken before, at 4 and 24 hours, and at 1 and 2 weeks after reperfusion therapy. Of these 41 patients with AMI, 38 received reperfusion therapy, and the urinary biopyrrin/creatinine levels (micromol/g.creatinine) before reperfusion were significantly higher than those of the other 2 groups (AMI 4.24 +/- 0.49, SAP 2.45 +/- 0.15, control subjects 2.31 +/- 0.16; p = 0.0003 vs AMI). The onset of reperfusion significantly increased the levels of urinary biopyrrins/creatinine, and this time course was mapped out, peaking at 4 hours (8.21 +/- 0.96 vs 4.24 +/- 0.49 before, p = 0.0001), and decreasing to control levels between 24 hours and 7 days. The peak levels of urinary biopyrrins/creatinine were higher in the positive cardiac event group than in the negative cardiac event group (11.89 +/- 1.77 vs 7.57 +/- 1.00 micromol/g.creatinine, p = 0.029). These findings add further evidence that oxidative stress contributes to the complications of reperfusion injury, and suggest that urinary assessment of biopyrrins may be useful in predicting subsequent cardiac events after reperfusion in AMI.

Plasminogen activator inhibitor (PAI) is a marker of recurrence of myocardial infarction. Diabetes mellitus is also an important risk factor of coronary artery disease, including myocardial infarction and angina pectoris.We examined baseline plasma PAI activity levels, clinical variables, and angiographic findings and assessed them as prospective values for subsequent coronary events, such as sudden death, nonfatal myocardial infarction and coronary revascularization by percutaneous transluminal coronary angioplasty or coronary artery bypass surgery during the follow-up period.We conducted a prospective study for 4 years of 249 consecutive patients admitted with angina pectoris. Blood samples for PAI were drawn at discharge.In the multivariate Cox proportional hazard model, PAI activity and diabetes mellitus were significant and independent risk factors (the risk increased by 10% in those with a higher PAI concentration and by 70% in diabetic patients). Event-free survival was reduced by higher PAI activity (or = 8.4 IU/mL) and the presence of diabetes. The patients with higher PAI activity and diabetes had a 4.2-fold risk in comparison with the patients with lower PAI activity and no diabetes. However, patients with lower PAI activity were less likely to have coronary events even when they had diabetes.Higher PAI activity and diabetes predict subsequent coronary events in patients with angina pectoris. Diabetes has less prognostic value for subsequent coronary events in patients with lower PAI activity.

Background and Purpose: Super-selective thrombolytic therapy (STT) has only been applied in patients with brain embolism associated with known abnormalities such as atrial fibrillation in Japan. The purpose of this study is to report our experience with this therapy for acute phase atherothrombotic brain ischemia (TBI) to prevent from infarction. We compare the results of our study in patients with TBI with those of the same treatment in patients with embolic brain ischemia (EBI). Methods: STT consisted of intraarterial delivery of urokinase (UK) as the thrombolytic agent to the site of occlusion in 21 patients (10 patients with TBI and 11 with EBI). The maximum dose of UK used was 240, 000 IU. Immediate or rescue percutaneous transluminal angioplasty (PTA) was subsequently performed when recanalization failed or post-STT stenosis was >90%. The rates of successful recanalization, improvement of symptoms, required PTA, and occurrence of acute bleeding, and the total dose of UK, were compared between the two groups. Results: STT resulted in successful recanalization in all patients of both groups. The proportions of patients showing improvement of symptoms, required PTA, and those who developed acute bleeding, and the average dose of UK, were 90 and 73%, 10 and 9%, 10 and 18%, 114, 000 and 131, 000 IU in TBI and EBI groups, respectively. There were no significance differences in the above parameters between the two groups. Conclusions: The results of our STT showed high rate of improvement for TBI as well as EBI. We believe this STT will be a rather safe and recommendable treatment for the acute phase of TBI, as the catheters are improving continuously.

E-selectin, also known as endothelial cell leukocyte adhesion molecule-1, is a member of the selectin family of adhesion molecules and is expressed on vascular endothelial cells in inflammatory reactions. The induction of surface E-selectin expression by endothelial cells is considered a marker of activation.We examined the plasma soluble E-selectin (sE-selectin) level in 41 patients within 6 hours after the onset of acute myocardial infarction (AMI) and in 37 patients with stable exertional angina and 27 control patients. Blood samples were obtained on admission, after reperfusion therapy, and at 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 3 days, 5 days, 1 week, and 2 weeks after admission in the AMI group. In this group, 21 patients had a history of prodromal unstable angina before infarction and 20 had sudden onset of infarction. The plasma sE-selectin level (ng/mL) on admission was higher in the AMI group than in the stable exertional angina group and control group (38.5 +/- 3.1 vs 28.5 +/- 1.5, P.01, 26.0 +/- 1.8, P.01, respectively). In addition, plasma sE-selectin levels were higher in the patients with AMI with prodromal unstable angina than in those with a sudden onset of infarction on admission (44.7 +/- 5.4 vs 32.0 +/- 2.1, P.05). The plasma sE-selectin level decreased slowly during the chronic phase both in patients with AMI with prodromal unstable angina (from 44.7 +/- 5.4 to 33.8 +/- 3.4, P.01) and those with a sudden onset of infarction (from 32.0 +/- 2.1 to 24.9 +/- 2.4, P.01).These results suggest that an increase of sE-selectin may reflect enhanced endothelial cell activation in patients with AMI. The higher sE-selectin level in patients with AMI with prodromal unstable angina may have been associated with repeated episodes of myocardial ischemia and reperfusion.

Plasminogen activator inhibitor activity was higher in 18 patients with multivessel spasm than in 20 patients with 1-vessel spasm and in 22 control patients. Tissue plasminogen activator antigen was also higher in patients with multivessel spasm than in those with 1-vessel spasm and control patients. The increased plasminogen activator inhibitor activity in patients with multivessel spasm indicates that the fibrinolytic system is more impaired in such patients than in those with 1-vessel coronary spasm; this may be related to the higher incidence of refractory angina during hospitalization and cardiac events during the follow-up period.

Tissue factor (TF) initiates the extrinsic pathway of blood coagulation by acting as a cofactor for Factor VII. Inhibition of the Factor VIIa–TF complex is mediated by the tissue factor pathway inhibitor (TFPI), which is a serine protease inhibitor with three Kunitz-type domains. The localization of TF and TFPI protein has been examined immunohistochemically in various atherosclerotic lesions of coronary arteries from 22 autopsy cases and their messenger RNA expression has been confirmed by reverse transcription-polymerase chain reaction. Four types of atherosclerotic lesion (types I, II, III, and IV) were classified according to the method described by Stary et al. TF and TFPI were localized in endothelial cells, macrophages, macrophage-derived foam cells, and smooth muscle cells in the intimal lesions, medial smooth muscle cells, and endothelial cells of the microvessels in the adventitia. Immunohistochemical double staining revealed the co-localization of TF and TFPI in the endothelial cells and macrophages in four types of atherosclerotic lesions. In type III and IV lesions, the number of TF- and TFPI-positive cells was increased, accompanied by extracellular localization of TF and TFPI in the lipid core of atherosclerotic plaques. Fibrin deposition was found around TF- and TFPI-positive macrophages and in the lipid core of atherosclerotic plaques. TF and TFPI messenger RNA were detected more frequently in coronary arteries with type III and IV lesions than in those with type I and II lesions. The co-localization of TF and TFPI was demonstrated in various atherosclerotic lesions of coronary arteries and was shown to be intimately related to fibrin deposition in advanced atherosclerotic plaques. The co-localization of TF and TFPI may thus be closely associated with thrombogenicity in atherosclerotic lesions of coronary arteries. Copyright © 1999 John Wiley & Sons, Ltd.

It has been suggested that active inflammation plays an important role in the pathogenesis of acute coronary syndromes, including unstable angina. Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial cells for adherence of the activated polymorphonuclear leukocytes. Recently, it has been demonstrated that the soluble form of ICAM-1 has been detected in human serum and has been increased in many other inflammatory or autoimmune disorders. To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma soluble ICAM-1 (sICAM-1) levels in coronary circulation. The plasma sICAM-1 levels in the coronary sinus and aortic root were simultaneously examined in 20 patients with unstable angina, 19 patients with stable exertional angina, and 16 control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter) both in the coronary sinus and aortic root were significantly higher (p0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (217+/-14 vs 126+/-8; 120+/-10 in the coronary sinus, 202+/-13 vs 125+/-9; 123+/-10 in the aortic root). Furthermore, the mean value was higher in the coronary sinus than in the aortic root in patients with unstable angina. There were no significant differences in the values between in the coronary sinus and aortic root in patients with stable exertional angina and control subjects. Thus, sICAM-1 release is increased, especially in coronary circulation in unstable angina.

Tissue factor pathway inhibitor (TFPI) is known to inhibit the initial reaction in the tissue factor-mediated coagulation pathway. We measured plasma free-form TFPI antigen levels and monitored 24-h Holter recordings at 06.00, 14.00 and 22.00 h in 15 patients with coronary spastic angina, 13 patients with stable exertional angina, and 11 control subjects. There was a significant circadian variation in plasma free-form TFPI antigen levels in patients with coronary spastic angina (25.8±2.0 ng/ml at 06.00 h, 21.1 ±1.6 ng/ml at 14.00 h, 20.2±1.4 ng/ml at 22.00 h; p

We have reported that the plasma levels of plasma fibrinopeptide A and plasminogen activator inhibitor activity increase in patients with unstable angina and acute myocardial infarction. Tissue factor (TF) is a low-molecular-weight glycoprotein that binds to and acts on essential cofactor VII, and the resulting complex activates factors IX and X, initiating the coagulation cascade. We measured plasma TF antigen levels in 21 patients with unstable angina (on admission and after treatment), 27 patients with stable exertional angina, and 27 control subjects. The 3 groups were matched for age, gender, and other clinical variables. The plasma TF antigen levels were higher in the unstable angina group than in the stable exertional angina and control groups (240 +/- 75 vs 184 +/- 46 and 177 +/- 37 pg/ml, p0.01). There were no significant differences in the plasma TF antigen levels between the stable exertional angina and the control groups. Furthermore, the plasma TF antigen levels were reexamined after treatment in the 21 patients with unstable angina. The mean level in these 21 patients decreased after 2 weeks of treatment (from 240 +/- 75 to 206 +/- 57 pg/ml, p0.01). This study suggests that the plasma TF antigen levels correlate with disease activity in patients with unstable angina. The increased plasma TF antigen levels in patients with unstable angina may reflect intravascular procoagulant activity.

Intercellular adhesion molecule-1 (ICAM-1) is a major ligand for 2 members of the CD18 family of leukocyte integrin adhesion molecules and mediates adhesion between leukocytes and stimulated endothelial cells. We examined plasma soluble ICAM-1 (sICAM-1) levels in 30 patients with acute myocardial infarction (AMI) within 6 h of symptom onset, 21 patients with unstable angina (UA), 35 patients with stable exertional angina (SEA) and 21 control subjects. Plasma sICAM-1 levels (ng/ml) were significantly higher in both the acute and chronic phases of AMI and in the UA group than in the SEA and the control groups (195 +/- 14, 198 +/- 16 in the acute and chronic phases of AMI, 188 +/- 11 in the UA group vs 142 +/- 7 in the SEA group, 141 +/- 10 in the control group, p < 0.01). Plasma sICAM-1 levels were significantly higher in AMI patients when preceded by unstable angina than when not preceded by unstable angina at any point over the time course except 1 week after admission (p < 0.01 vs admission, 12 h, 2 days, 3 days, 5 days, 2 weeks, 3 weeks. p < 0.05 vs 24 h). These results suggest that the increase in sICAM-1 is associated with repeated episodes of myocardial ischemia and reperfusion not leading to myocardial necrosis. The increase in sICAM-1 may play an important role as an inflammatory component in the pathogenesis of the ischemic myocardium.

In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated acute myocardial infarction, it was established that the baseline plasma tissue factor antigen level was significantly higher in patients with myocardial infarction than in control subjects, and enalapril therapy significantly reduced the elevated plasma tissue factor antigen level. This may be associated with the reduction in the risk of coronary thrombosis seen with the use of angiotensin-converting enzyme inhibitors.

BACKGROUND Lipoprotein (a) [Lp(a)] is an independent risk factor for coronary artery disease and niceritrol (a prodrug of nicotinic acid) is known to reduce Lp(a) levels. Patients with coronary artery disease often have impairment of the fibrinolytic system. METHODS To elucidate the effect of niceritrol on fibrinolysis and Lp(a) levels, we examined plasminogen activator inhibitor (PAI) activity, tissue-type plasminogen activator (t-PA) antigen, and serum Lp(a) levels before and after administration of niceritrol to coronary artery disease patients with high baseline Lp(a) levels (> or = 20 mg/dl). Niceritrol was administered to 26 patients for 12 weeks at 750 mg/day. Fasting blood samples were obtained at 0800 h from each patient before treatment, after administration of niceritrol for 12 weeks and 4 weeks after the discontinuation of therapy. RESULTS There were significant reductions in PAI activity (9.9 +/- 1.8 compared with 5.4 +/- 1.6 IU/ml, P < 0.01), t-PA antigen levels (10.0 +/- 0.5 compared with 8.8 +/- 0.6 ng/ml, P < 0.05), and Lp(a) levels (49.3 +/- 5.9 compared with 42.5 +/- 5.4 mg/dl, P < 0.01) after 12 weeks of niceritrol administration. Four weeks after the discontinuation of niceritrol treatment, all these parameters returned to baseline. CONCLUSIONS This study demonstrated that niceritrol administration decreases PAI activity and t-PA antigen levels together with Lp(a) levels in patients with coronary artery disease. These observations suggest that niceritrol administration may tend to normalize fibrinolysis in such patients.

Background: Treatment with an angiotensin-con verting enzyme (ACE) inhibitor in patients with myocardial infarction has been shown to modify endogenous fibrinolysis. Hypothesis: We investigated the effects of the ACE inhibitor imidapril on endogenous fibrinolysis in association with the serum ACE activity. Methods: In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated myocardial infarction, 15 patients received imidapril (5 mg daily) (imidapril group) and another 15 received placebo therapy (placebo group) for 4 weeks. Blood sampling was performed before the start of administration and on Days 3, 7, and 28 after the start of administration. Serum ACE activity and plasma fibrinolytic variables [plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor type 1 (PAI-1) antigen level, and tissue type plasminogen activator (TPA) antigen level] were measured. Results: There was no difference between the imidapril and placebo groups in serum ACE activity or plasma fibrinolytic variables before administration. Serum ACE activity decreased significantly on Days 3, 7, and 28 in the imidapril group. The decrease of PAI activity and PAI-1 antigen levels was significantly less on Days 7 and 28, but not on Day 3. The TPA antigen level in the imidapril group was unchanged. None of the parameters in the placebo group was changed. Conclusion: The ACE inhibitor imidapril modified fibrinolysis, but the effects occurred after the inhibition of serum ACE activity.

Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, and *Department of BiologicalResponses, Institute for Virus Research, Kyoto University, Kyoto, JapanSummaryBackground and hypothesis:Thioredoxin is an importantbiomarker for oxidative stress. We investigated whether thiore-doxin levels were elevated in patients with acute myocardialinfarction (AMI) and were associated with the results of coro-nary reperfusion.Methods: The present study determined plasma thioredox-in levels in 51 patients with AMI, 30 patients with stable exer-tional angina (SEA), and 30 patients with chest pain syndrome(CPS). Plasma sampling was performed on admission, at 12 h,1 week, 2 weeks, and 4 weeks in patients with AMI, and afteradmission in patients with SEA and CPS.Results: Plasma thioredoxin levels on admission were high-er in patients with AMI than in those with SEA and CPS. Plas-ma thioredoxin levels in patients with AMI were decreased in12 h without further change thereafter. However, thioredoxinlevels in patients with AMI remained higher than in those withSEA. In multivariate analysis, higher levels of thioredoxin onadmission were a risk factor for failure in emergent reperfusiontherapy in patients with AMI independent of other factors.Conclusion: Plasma thioredoxin levels are elevated in pa-tients with AMI, and higher thioredoxin levels may predictsubsequent failed coronary reperfusion therapy in patientswith AMI.Key words: acute myocardial infarction, reperfusion, oxida-tive stress, thioredoxinIntroductionOxidative stress is believed to play an important role incoronary artery disease.

Adiponectin is a new member of adipocyte derived proteins belonging to the soluble defence collagens.1 Plasma adiponectin concentrations in obese subjects are decreased in spite of an adipose specific expression.1 More interestingly, the patients with chronic coronary artery disease exhibited lower plasma adiponectin concentrations compared to body mass index (BMI) matched control subjects.2 On the other hand, adiponectin accumulates in the vascular subendothelial space when the endothelial barrier is damaged.3 In vitro, adiponectin suppresses the expression of adhesion molecules in the vascular endothelial cells and cytokine production from macrophages.2,4 Therefore, the molecule may be involved in the inflammation and tissue repairing processes. Acute coronary syndrome is often precipitated by acute thrombosis.5 It is commonly accepted that the rupture or the erosion of plaques by the inflammatory process leads to coronary thrombosis and acute myocardial infarction (AMI). The C reactive protein (CRP) concentrations in the acute phase are suggested to reflect pre-existing coronary plaque instability associated with the onset of AMI. The significance of adiponectin in acute coronary syndrome has never been investigated. In the present study, we examined the serial change in plasma adiponectin concentrations and its relation to plasma CRP concentration in …

The left ventricular ejection fraction (LVEF) is one of the major prognostic factors after acute myocardial infarction (AMI) and matrix metalloproteinase-1 (MMP-1) is an enzyme responsible for extracellular collagen degradation and remodeling. The present study investigated whether the concentration of serum MMP-1 was associated with the LVEF after AMI. Blood was sampled on admission, and at 24 h, 3 days, 7 days, 2 weeks and 4 weeks in 24 patients with their first AMI. Left ventriculography was performed 4 weeks after the onset of AMI and the LVEF was calculated by center line method. MMP-1 concentrations were higher at 7 days and at 2 weeks than on admission (p

Vascular endothelial growth factor (VEGF) is a growth factor for vascular endothelial cells in vitro. The present study was designed to determine whether serum VEGF levels increase in patients with acute myocardial infarction (AMI) compared with patients with stable exertional angina and control subjects, and to examine the serial changes of serum VEGF levels in patients with AMI. We examined serum VEGF levels by using antibody prepared from serum immunized with human VEGF121. The serum VEGF level (pg/ml) was higher (p < 0.0001) on admission in the patients with AMI (177 ± 19) than in those with stable exertional angina (61 ± 7) and control subjects (62 ± 6). The serum VEGF level (pg/ml) of the patients with AMI was 177 ± 19 on admission, 125 ± 9 on day 3, 137 ± 11 on day 5, 242 ± 18 at 1 week, and 258 ± 22 at 2 weeks after admission. The value was higher on admission than on day 3 after admission (p = 0.014), the values were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01). Furthermore, there were correlations between peak VEGF levels at 1 week or 2 weeks after admission and peak creatine kinase levels. The increase of VEGF on admission in the patients with AMI may be due to the hypoxia of acute myocardial ischemia. The elevation at 1 week and 2 weeks from the onset may cause the development of collateral circulation in relation to the healing of the infarction site.

An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis.We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period.There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P0.01). The captopril-treated patients showed significantly reduced PAI activity (P0.01), and a concomitant decrease in ACE activity.These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p

This study sought to determine whether early treatment with angiotensin-converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI) is useful for the improvement of fibrinolytic function, as well as left ventricular function. This study was designed to examine the levels of plasma plasminogen activator inhibitor (PAI) activity and serum ACE activity during the course of 2 weeks in 40 patients with AMI within 12 hours after the onset of the symptom and who randomly received early treatment with either the ACE inhibitor imidapril or a placebo (20 patients in the imidapril group and 20 in the placebo group). The levels of serum ACE activity in the imidapril group decreased significantly (p0.01) 8 hours after the administration of imidapril, and the levels 24 hours after administration were significantly lower than those in the placebo group (3.6 +/- 0.6 IU/L vs 7.4 +/- 0.8 IU/L; p0.001). The plasma PAI activity increased gradually to peak levels 16 hours after the administration of imidapril and placebo. The levels in the placebo group decreased gradually but remained high during the study period. On the other hand, the levels of PAI activity in the imidapril group decreased rapidly and those 48 hours after administration were significantly lower than those in the placebo group (7.9 +/- 1.9 IU/ml vs 18.4 +/- 3.5 IU/ml; p0.01). The levels of left ventricular ejection fraction about 2 weeks after admission were significantly higher in the imidapril group than in the placebo group (65.9% +/- 2.5% vs 49.1% +/- 4.4%; p0.01). This study showed that imidapril, an ACE inhibitor, might be useful for the improvement of fibrinolytic function and left ventricular function in the acute phase of myocardial infarction.

Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis, and thrombosis.We examined plasma TF levels in 31 consecutive patients with acute myocardial infarction (AMI) (within 6 hours after the onset of symptoms), 27 patients with stable exertional angina, and 27 control subjects. Ten patients with AMI had a history of unstable angina before infarction, and 21 had a sudden onset of infarction. The plasma TF level was higher in the AMI group than in the stable exertional angina and control groups (240 +/- 112 vs 184 +/- 46 pg/ml [p0.05] vs 177 +/- 37 pg/ml, p0.01, respectively). TF levels were decreased in the chronic phase (2 weeks after admission) compared with the acute phase of infarction (from 240 +/- 112 pg/ml to 222 +/- 97 pg/ml, p0.05). In addition, plasma TF levels were higher in patients with AMI with prodromal unstable angina than in patients with a sudden onset of infarction (300 +/- 169 pg/ml vs 212 +/- 57 pg/ml, p0.05). TF levels were similar in the acute and chronic phases in the patients with AMI with prodromal unstable angina (300 +/- 169 pg/ml vs 290 +/- 136 pg/ml, p = not significant) but were decreased in the chronic phase in the patients with AMI with sudden onset (from 212 +/- 57 pg/ml to 190 +/- 49 pg/ml, p0.05).Increased plasma TF levels in patients with AMI may reflect enhanced intravascular procoagulant activity. The higher TF levels in patients with AMI with prodramol unstable angina may be associated with repeated episodes of myocardial ischemia and reperfusion.

Recent clinical trials have demonstrated that the administration of angiotensin-converting enzyme (ACE) inhibitors to patients with myocardial infarction reduces the incidence of recurrent myocardial infarction. It has also been reported that an elevated level of plasminogen activator inhibitor (PAI) appears to constitute a marker of the risk of recurrent coronary thrombosis. To determine whether the ACE inhibitor captopril reduces plasma PAI inhibitor activity, we measured changes in plasma PAI activity (IU/ml), tissue plasminogen activator (t-PA) antigen (ng/ml), and serum ACE activity (IU/L) in 14 survivors of myocardial infarction receiving captopril therapy (37.5 mg daily) and compared them with the values in 15 placebo-treated patients chosen at random. Blood sampling was performed at 07.00 h. In the captopril-treated group, serum ACE activity decreased significantly, from 14.0 +/- 0.8 to 11.5 +/- 1.2 IU/L 24 h after captopril therapy (p < 0.01), and those of PAI activity and t-PA antigen also decreased significantly-from 11.9 +/- 2.8 to 5.5 +/- 2.2 IU/ml (p < 0.02) and from 9.9 +/- 1.0 to 7.5 +/- 0.9 ng/ml (p < 0.05), respectively 48 h after captopril therapy. However, the levels of ACE activity, PAI activity, and t-PA antigen remained unchanged during the study period in the placebo group. Thus, our data indicate that the administration of captopril to patients with acute myocardial infarction may result in a reduced frequency of recurrent coronary thrombosis by increasing fibrinolytic capacity.

Background The glycoprotein P-selectin is an adhesion molecule involved in the property change of leukocytes at the initiation of the inflammatory process. The purpose of the present study was to determine whether acute myocardial ischemia induced by coronary spasm causes an acute inflammatory response in the coronary circulation. Methods and Results We examined plasma soluble P-selectin levels in the coronary sinus and the aortic root simultaneously in 16 patients with coronary spastic angina before and after left coronary artery spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Ten control patients with chest pain but normal coronary arteries and no coronary spasm also received intracoronary acetylcholine. Plasma soluble P-selectin levels were increased significantly in the coronary sinus (32.8±3.6 to 52.8±5.9 ng/mL, P P P Conclusions Our data indicate that soluble P-selectin is released into the coronary circulation after coronary artery spasm. We conclude that coronary artery spasm may induce the leukocyte adhesion in the coronary circulation and may lead to myocardial damage.

To determine whether plasma sICAM-1 levels increase in the coronary circulation in patients (pts) with unstable angina, we measured plasma sICAM-1 levels in the coronary sinus (CS) and aortic root (Ao) simultaneously in 18 unstable angina pts (UA), 18 stable exertional angina pts (SEA) and 14 control pts (Cont). Unstable angina was defined as worsening effort or rest angina, or both within 1 month of catherization. The three groups were matched for age and gender. The levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. Data are shown below as means ± SE (ng/ml) UA SEA Cont CS 201 ± 16 * # 124 ± 8 119 ± 11 Ao 187 ± 15 * 123 ± 9 118 ± 11 * p l 0.01 vs SEA and Cont # p l 0.01 vs Ao The mean values of CS and Ao were significantly higher in UA than in SEA and in Cont. Furthermore, in UA the mean value was higher in CS than in Ao. There were no significant differences of the mean values of CS and Ao between SEA and Cont. We conclude that sICAM-1 release is increased especially in coronary circulation in UA. ICAM-1 is known to be a major ligand on endothelial cells for adherence of activated leukocyles. These results suggest that activation of leukocytes take place within coronary circulation, further may activate platelet and induce coronary thrombosis in UA

Vitronectin (VN) is an adhesive glycoprotein that promotes cell adhesion and spreading and located in mainly extracellular matrix. VN is also known to regulate the fibrinolytic system by forming complexes with plasminogen activator inhibitor (PAI)-1. To elucidate the serial changes of plasma VN level in association with fibrinolytic capacity in patients with acute myocardial infarction (AMI), we measured plasma levels of VN as well as PAI activity. PAI-5 antigen and tissue plasminogen activator (t-PA)-PAI-1 complexes antigen in 20 consecutive AMI patients. All patients were administered alteplase 0.45 mg/kg intravenously for coronary thrombolysis. Blood sampling was done on admission, 4, 8, 12, 16, 20, 24 and 48 hours; 3, 4, 5, 6 and 7 days after admission. PAl activity. PAI-1 antigen and t-PA-PAI-1 complexes antigen levels were increased 4 hours after admission (p l 0.01 vs admission) and the levels maintained higher level during the first 24 hours. On the other hand, VN levels were increased at 48 hours (p l 0.01 vs admission) and showed a tendency to be high until 7 days. In contrast to the VN level, PAl activity, PAI-1 antigen and t-PA-PAI-1 complexes antigen levels were decreased after 48 hours (p l 0.05 vs 4 hours). We conclude that VN is increased 48 hours after admission with complementary decreasing of PAI-1 in AMI patients. It is possible that VN removes PAI-1 from the circulation to the extracellular matrix where VN exists by forming the complexes. These results suggest that VN may act as a scavenger of PAI-l and playa protective role for the fibrinolytic system in patients with AMI. Download : Download high-res image (114KB) Download : Download full-size image

The presence of intercellular adhesion molecule-1 (ICAM-1) on arterial endothelial cells and on non-endothelial cells has previously demonstrated in human coronary atherosclerotic plaques. We hypothesized that ICAM-1 expression on coronary arteries is increased by mechanical compression of coronary atherosclerotic plaques such as coronary balloon angioplasty. Coronary thrombolysis (intravenous administration of alteplase. 0.45 mg/kg) was done in 31 consecutive patients with acute myocardial infarction (AMI) immediately after admission. Thirteen patients whose coronary arteries were not recanalized completely (below TIMI grade 2) were performed subsequent coronary angioplasty. Blood sampling were done on admission, 2, 4, 8, 12, 24,48, 72 and 96 hours after admission. Plasma levels of soluble ICAM-1 were measured by enzyme-linked immunosorbent assay. Plasma soluble ICAM-1 level was increased significantly in patients with angioplasty (p = 0.03. vs patients without angioplasty) and the level reached a peak 8 hours after admission (116 ± 7% of baseline level). On the other hand. the level was unchanged in patients without angioplasty (99 ± 3% of baseline. 8 hours after admission). Download : Download high-res image (92KB) Download : Download full-size image Conclusion Plasma levels of soluble ICAM-1 are increased after angioplasty in patients with AMI. Mechanical stimulation of coronary atherosclerotic plaques by balloon catheter may induce activation of mononuclear leukocyte or T-lymphocyte in the vessel wall. Cytokines released from the activated leukocyte may amplify the synthesis of ICAM-1 on the endothelium and increase the plasma level of ICAM-1.