Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty fish was included for 7 months into diet of 11 male patients with early stages of ischemic heart disease. Effects of this diet modification on serum fatty acids, lipids and some variables of hemostasis were studied. After control period, patients ate 120-160 g/day of canned Pacific sardine (about 5 g omega-3 polyunsaturated fatty acids) per day. Two patients refused to participate after 2 months and 1 was lost for follow-up. After 7 months of diet, the proportion of eicosapentaenoic acid (EPA) in blood lipids increased from 0.67 + 0.26 to 4.7 + 1.5% (p < 0.015) and of docosahexaenoic acid (DHA) from 2.3 + 1.1 to 4.3 + 1.1% (p < 0.015). Ratio of EPA to arachidonic acid (AA) rose from 0.1 + 0.02 to 0.9 + 0.4 (p < 0.015). Mean serum triglyceride concentration fell after first month from 179.5 + 79.0 to 99.1 + 30.0 mg/dl (p < 0.015) and remained at this level throughout the study. No significant changes were observed in serum total and high-density lipoprotein cholesterol. Plasma activities of tissue-type plasminogen activator inhibitor, contents of plasminogen, alpha 2-antiplasmin, antithrombin III and protein C also did not change. Plasma fibrinogen moderately decreased. Its decrease became statistically significant at month 5 (from 3.8 + 0.5 to 3.0 + 0.7, p = 0.021). Thus, the regimen used in this study led to a substantial and steady increase in plasma EPA, DHA and EPA/AA ratio. This was accompanied by sustained decrease in plasma triglycerides. There were no profibrinolytic changes in the parameters studied.
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PMID:[The effect of the long-term use of a diet enriched with omega-3 polyunsaturated fatty acids on the fatty acid composition, fibrinolytic system indices and lipid spectrum of the blood in patients with ischemic heart disease]. 813 73

This report reviews the major haemostatic deviations associated with the evolution of ischaemic heart disease (IHD) and also such deviations, which might be of importance for the evolution of the acute ischaemic heart syndrome. It is demonstrated that deviation in the t-PA/PAI-1 system indicate endothelial cell dysfunction in patients with IHD. Different factors which have the capability to induce such an endothelial cell dysfunction are proposed, i.e. hyperinsulinemia, mediators of chronic disease phase response, and thrombin. Finally, the intimate interrelation between coagulation and fibrinolysis in patients with IHD is discussed. The experimental and clinical studies reviewed provide good evidence that the endothelial cell response of t-PA and PAI-1 is coupled and that there is an intimate interrelation between generation of thrombin and production/release of t-PA and PAI-1 in IHD patients.
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PMID:The fibrinolysis and coagulation systems in ischaemic heart disease. Risk markers and their relation to metabolic dysfunction of the arterial intima. 822 71

Defective fibrinolysis may constitute a risk for the development of myocardial infarction in patients with ischaemic heart disease. We studied prospectively the factor XII-dependent plasminogen proactivator system in 49 survivors of an acute myocardial infarction. Blood samples were collected 8 weeks after hospital discharge. The factor XII-dependent fibrinolytic activity in the specimens was determined on fibrin plates after complete immuno-inhibition of the urokinase-like and the t-PA related fibrinolytic systems. During the subsequent follow-up period of 2.4 years, 10 patients developed recurrent myocardial infarction, whereas the remaining 39 patients did not. The reinfarction group of patients had a significantly lower median factor XII-dependent fibrinolytic activity (24.9 blood activating units (BAU).ml-1) than the patients without a relapse (41.9 BAU.ml-1, P < 0.02). Plasma concentrations of factor XII did not deviate significantly between the groups (P > 0.05), whereas the median plasma concentrations of prekallikrein was slightly lower in the reinfarction group (90%) than in the non-reinfarction group of patients (105%, P < 0.02). These observations point to an association between a depressed factor XII-dependent fibrinolytic activity and an enhanced risk of reinfarction in patients with a previous episode of acute myocardial infarction.
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PMID:Depression of factor XII-dependent fibrinolytic activity in survivors of acute myocardial infarction at risk of reinfarction. 832 6

Recent studies suggest that plasminogen activator inhibitor (PAI-1) may be a risk factor for recurrent myocardial infarction. We measured PAI-1 activity and antigen and tissue-type plasminogen activator (t-PA) antigen in 35 (20 nondiabetic and 15 diabetic) subjects with no clinical or electrocardiographic evidence of ischemic heart disease and in 74 (50 nondiabetic and 24 diabetic subjects) who had survived a myocardial infarction in the preceding 6-24 months. Levels of PAI-1 activity (18.7 +/- 5.6 versus 12.0 +/- 3.8 arbitrary units [AU] per milliliter, p = 0.001) and t-PA antigen (7.0 +/- 1.9 versus 4.6 +/- 2.0 ng/mL, p = 0.001) were significantly higher in diabetic compared with nondiabetic control subjects. Survivors of myocardial infarction had higher levels of PAI-1 activity and antigen and t-PA antigen than control subjects, and the diabetic survivors had higher levels of PAI-1 activity (25.3 +/- 6.7 versus 20.1 +/- 7.1 AU/mL, p = 0.004) and t-PA antigen (10.6 +/- 4.3 versus 8.4 +/- 3.3 ng/mL, p = 0.03) than the nondiabetic survivors. No difference in PAI-1 antigen levels was found between the diabetic subjects and either the nondiabetic control subjects or survivors of myocardial infarction. After venous occlusion in control subjects, there was a significant increase in PAI-1 antigen (mean 26.7%, range 14.1-58.1% in nondiabetics and mean 25.2%, range 6.2-39.7% in diabetics) and t-PA antigen (mean 78.3%, range 13.6-186.2% for nondiabetic and mean 40.7%, range 17.5-76.2% for diabetic subjects), but in the survivors of myocardial infarction, no significant effect of venous occlusion was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activator inhibitor activity in diabetic and nondiabetic survivors of myocardial infarction. 844 45

An increased risk of ischemic heart disease in men with the Lewis blood group phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-) phenotype is a genetic marker of the insulin resistance syndrome. To examine whether Le(a-b-) confers the insulin resistance syndrome, we studied a random sample of unrelated healthy young white men and women living in Copenhagen (n = 380, 18 to 32 years). All individuals had their insulin sensitivity estimated using Bergman's minimal model (intravenous glucose in combination with tolbutamide) and systolic blood pressure (SBP) was measured with a London School of Hygiene Sphygmomanometer. A number of anthropometric measurements including body mass index (BMI, kilograms/meters squared) and biochemical characteristics were performed. The Lewis blood group typing was carried out on erythrocytes. Twenty-one men had the Le(a-b-) phenotype. Compared to all other men (N = 165), the Le(a-b-) men had a significantly higher SBP (6 mm Hg, P = .0024). They also had higher values of BMI (8%, P = .016), total body fat mass (25%, P = .015), fasting values of serum insulin (32%, P = .006), serum C-peptide (20%, P = .029), and plasma glucose (8%, P = .003). The fasting values of serum lipids, plasminogen activator inhibitor (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, and insulin sensitivity did not differ between Le(a-b-) men and men with other Lewis phenotypes. Altogether 194 women participated in the study of which 21 women had the Le(a-b-) phenotype. Except for a lower PAI-1 activity (45%, P = .044), no values differed between Le(a-b-) women and women with other Lewis phenotypes. The women were also stratified according to use of oral contraceptives. Le(a-b-) women using oral contraceptives (N = 8) had a significantly lower plasma level of fasting PAI-1 activity (P = .029) and t-PA antigen (P = .004) compared to women using oral contraceptives without the Le(a-b-) phenotype (N = 42). Our data support the hypothesis that Le(a-b-) men exhibit features of the insulin resistance syndrome, including higher levels of BMI, SBP, and fasting levels of serum insulin and plasma glucose. In young women no signs of the insulin resistance syndrome were found in subjects with the Le(a-b-) phenotype.
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PMID:Lewis phenotypes and the insulin resistance syndrome in young healthy white men and women. 855 28

Plasma levels of tissue type plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen (Fg), thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), renin activity (PRA) and angiotensin II (ANGII) were assayed in 18 patients with coronary heart disease and 11 healthy subjects before and after submaximal treadmill exercise test according to "Bruce programme". All patients showed significant (> or = 50%) stenosis of at least one branch of the coronary arteries in coronary angiography and normal levels of serum trinitroglycerin. Drugs of dipyridamole, heparin, warfarin and aspirin were not administered to the patients two weeks before the test. The results were as follows: (1) Plasma PAI activity and Fg levels in 12 patients with positive test were remarkablly higher than in the remaining 6 subjects with negative test in the CHD group and in the control before and after exercise. Plasma tPA antigen changed in a reverse way. (2) Plasma levels of TXB2, PRA and ANGII in the positive test subgroup of CHD were higher than in the negative test subgroup and in the control after exercise, but differences of the parameters among the three groups were insignificant before exercise. The study suggests that defectiveness of fibrinolytic system in CHD patients was shown mainly as disorder of tPA-PAI equilibrium and that decreased fibrinolytic activity and increased PAI in exercise-induced myocardial ischemia have relations with activation of platelets and renin-angiotensin system.
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PMID:[Clinical significance of fibrinolytic system defectiveness in exercise induced myocardial ischemia and its mechanism]. 856 12

We investigated changes in vascular reactivity to endothelin (ET) and local release of ET-like immunoreactivity (ET-LI) induced by myocardial ischemia and reperfusion in a pig model of coronary thrombosis and thrombolysis and studied the possible mechanisms producing the changed vascular reactivity to ET-1. We induced coronary thrombosis by inserting a copper coil into the left anterior descending coronary artery (LAD) and achieved thrombolysis with tissue plasminogen activator (t-PA). Vascular reactivity to ET-1 in the nonischemic and ischemic/reperfused LAD diagonal branches was evaluated in vitro. ET-LI was analyzed in plasma from the great cardiac vein and aorta for estimation of local release. The vasoconstrictor response to ET-1 was enhanced twofold (p < 0.01) in the ischemic/reperfused arteries as compared with the nonischemic arteries. The vasoconstriction induced by the ETB receptor agonist [Ala 1,3,11,15] ET-1 or serotonin was not significantly affected by ischemia/reperfusion. The ETA receptor antagonist BQ-123 reversed the ET-1-induced vascular contraction to a similar degree in ischemic/reperfused and control arteries. The ET-1-induced vasoconstriction of control arteries was not affected by inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NNA) or cyclooxygenase with indomethacin. During reperfusion, the myocardial venoarterial plasma concentration difference of ET-LI and blood flow increased, resulting in an increased overflow of ET-LI. Our results demonstrate that coronary thrombosis and thrombolysis evokes enhanced local release of ET-LI during the reperfusion period and increases the vasoconstrictor effects of ET-1 through a mechanism related to ETA receptor activation but unrelated to altered endothelial function. These changes may play a role in the development of ischemic/reperfusion injury and no-reflow phenomenon.
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PMID:Myocardial release of endothelin (ET) and enhanced ET(A) receptor-mediated coronary vasoconstriction after coronary thrombosis and thrombolysis in pigs. 863 92

This study assesses the effects of invasive procedures, hemostatic and clinical variables, and doses of recombinant tissue plasminogen activator (t-PA) on hemorrhagic events in the thrombolysis in myocardial ischemia (TIMI), phase 1B clinical trial (n = 1,425). Patients seen within 24 hours of the onset of ischemic chest pain at rest were randomized using a 2 x 2 factorial design for comparison of: (1) t-PA versus placebo as initial therapy, and (2) an early invasive (coronary arteriography with percutaneous angioplasty, if feasible) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients received conventional medication for acute ischemic syndromes, including heparin, aspirin, beta blockers, nitrates, and calcium antagonists. The total dose of t-PA or placebo was 0.8 mg/kg, up to a maximum dose of 80 mg. In patients treated with t-PA, major and minor hemorrhagic events were more common than among those assigned to placebo (p < 0.001). Patients assigned to the invasive strategy arm had a higher hemorrhagic event rate than the noninvasive strategy, although the difference was not significant (p = 0.026). Patients > 75 years of age had higher intracranial hemorrhage rates than those < 75 years of age (6.7% vs 0.2%, respectively, p = 0.01). Major hemorrhagic events were more common in patients with higher heparin levels (p < 0.001), higher peak D-dimer levels (p = 0.007), and lower nadir fibrinogen levels (p = 0.005). Thus, increased morbidity due to hemorrhagic complications is associated with the use of t-PA, increased age, and selected hemostatic measures. Comparison to TIMI II demonstrates a significant association between the dose of t-PA and hemorrhagic complications.
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PMID:Hemorrhagic events during therapy with recombinant tissue plasminogen activator, heparin, and aspirin for unstable angina (Thrombolysis in Myocardial Ischemia, phase IIIB trial). 905 37

Angiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type I Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.
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PMID:Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells. 924 56

The initial step in atherosclerosis is the rapid targeting of monocytes to the sites of inflammation and endothelial injury. Serum levels of intercellular adhesion molecule-1 were found to be increased in ischaemic heart disease patients and polymorphisms in the E-selectin gene were associated with accelerated atherosclerosis in young (age < 40 years) patients, further suggesting a role of inflammation in atherosclerosis. Cholesterol loading in macrophages was found to induce interleukin-8 expression, suggesting an association between foam cell formation and beta 2-integrin-dependent adhesion of leukocytes. Enhanced endothelium-platelet interaction induced by hypercholesterolaemia is mediated by von Willebrand factor, whereas platelet adhesion to subendothelial matrix is mediated by fibulin-fibrinogen complexes. Activated platelets mediate the homing of leukocytes by interaction with the subendothelial matrix under shear stresses that do not allow neutrophil adhesion. They may also contribute to the oxidative modification of LDL, provide a source of lipids for foam cell generation and contribute to smooth muscle cell proliferation. Oxidized LDL induces tissue factor in macrophages that also provide sites for fibrin polymerization and decreases the anticoagulant activity of endothelium by interfering with thrombomodulin expression and inactivating tissue factor pathway inhibitor. Intravascular fibrinolysis induced by tissue-type plasminogen activator or urokinase may contribute to the initiation of atherosclerosis by inducing P-selectin and platelet activating factor as well as to plaque rupture, either directly or indirectly, by activating metalloproteinases. Plasminogen activator inhibitor-1 inhibits smooth muscle cell migration and, in the presence of vitronectin, promotes the clearance of thrombin by LDL receptor-related protein at sites of endothelial injury.
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PMID:Thrombosis and atherosclerosis. 933 57


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