Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rat experiments during brain ischemia (30-min carotid artery occlusion), ethomersol administered intraperitoneally in a dose of 50 mg/kg before occlusion or at the end of ischemia eliminated postischemic hypoperfusion. The effect of the drug was due to its spasmolytic and antiaggregatory activities. An analysis of the vasodilating action of ethomersol revealed its capacity to block potential-dependent calcium channels and partially intracellular calcium mobilization when the adrenergic and serotoninergic receptors were activated. The antiaggregatory activity of the drug appeared as inhibited platelet aggregation, which was induced by ADP, serotonin, arachidonic acid, thrombin, and as enhanced antiaggregatory activity of the vascular wall.
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PMID:[The mechanisms of the ethomersol correction of postischemic hypoperfusion]. 145 75

Coronary angioplasty is an effective treatment for subgroups of patients with unstable angina. The procedure has a high initial success rate but there is an increased risk of major complications resulting from a higher incidence of acute closure presumably related to additional injury of the underlying plaque with augmented platelet and clotting activity, and ensuing spasm. Newer agents that inhibit platelet aggregation or thrombin may provide a safer use of coronary angioplasty in patients with unstable angina. Coronary angioplasty is indicated if a stenosis, technically suitable for dilation, is found to be responsible for the unstable state. The decision in favor of coronary angioplasty in patients with single-vessel disease is easy to make. Patients with left main stem disease or severe multivessel disease should primarily be scheduled for bypass surgery. In the presence of other multivessel disease, uncertainty remains. However, in selected patients with multivessel disease, one might prefer dilation of the ischemia-related vessel "the culprit vessel" only, rather than total revascularization by multiple dilatations or bypass surgery, since this can be performed faster and thus shorten the hospital stay. Thrombolytic treatment in the management of patients with unstable angina may be indicated in patients with pre-existing intracoronary thrombi or when procedural acute closure occurs associated with intracoronary thrombus formation.
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PMID:Coronary angioplasty for unstable angina. 154 49

The influence of a disturbed hemostasis as one of the causes of retinal vein occlusions is still controversial. We investigated the functional state of the coagulation system in 16 patients, 7 with a nonischemic and 9 with an ischemic retinal vein occlusion, with an enzyme-linked immunosorbent assay for the determination of thrombin-antithrombin III complex (TAT). Patients with a history of thromboembolic disease, raised blood pressure and/or badly managed diabetes mellitus were excluded from the investigations. In healthy individuals the plasma concentration is 1.45 ng/ml +/- 0.4 (mean value +/- SD), ranging from 1.0 to 4.1 ng/ml. In our patients we measured TAT concentrations ranging from 2.0 to 48.0 ng/ml. In 2 of 7 plasma samples from patients with nonischemic retinal vein occlusion (2.1-6.3 ng/ml, mean = 3.3, SE +/- 0.6) and in 6 of 9 in ischemic retinal vein occlusion (2.0-48.0, mean = 13.2, SE +/- 5.1) TAT concentrations were found to be increased. These data indicate that disturbed hemostasis may be involved in retinal vein occlusion, especially that caused by ischemia. Furthermore, TAT may be useful in differentiating ischemic from nonischemic retinal vein occlusion.
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PMID:[Thrombin-antithrombin III complex. Cause of venous vascular occlusion of the retina]. 158 96

We report a case of unstable angina in an active phase of polymyositis. A 51 year-old man was admitted with a diagnosis of polymyositis and unstable angina with ST elevation on prolonged rest chest pain. Rest anginal attack which had been refractory to conventional antianginal medications was controlled by high dose of glucocorticosteroid. Electrocardiography revealed multifocal premature ventricular contraction. Since silent ischemia on exercise persisted, percutaneous transluminal coronary angioplasty (PTCA) was performed on a stenotic lesion in the left anterior descending artery. Since there was recurrent anginal attack, re-PTCA was carried out at the same site. He was discharged in a good condition. This case is considered to be associated with cardiac involvement of polymyositis because of ventricular arrhythmia, persistent increased serum levels of CPK-MB, and the marked benefits of corticosteroid against unstable angina. In addition, clinical manifestations, coronary arteriographic findings, and increased plasma levels of thrombin-antithrombin III complex suggest that cardiac involvement in polymyositis accelerates intracoronary thrombus formation and/or coronary spasm.
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PMID:[A case of unstable angina pectoris associated with an active phase of polymyositis]. 158 49

It has been suggested that unstable angina at rest, like acute myocardial infarction, might be associated with a thrombotic process. In order to study the hypothesis that myocardial ischemia during exercise could also be associated with an activation of blood coagulation and/or fibrinolysis, we investigated the presence of plasma markers of a prethrombotic or thrombotic state (thrombin-antithrombin III complexes TAT, prothrombin fragment F1 + 2, and D-dimers DD) in 100 consecutive patients with confirmed or suspected coronary artery disease during ergometric test with myocardial thallium-201 scintigraphy. Symptoms and scintigrams allowed to define three groups of patients: those showing no ischemia (n = 79) and those with symptomatic (n = 8) or silent myocardial ischemia (n = 13). Before exercise, DD and TAT levels were not significantly different among the three groups. On the other hand, the F1 + 2 levels were slightly albeit significantly higher in the patients without ischemia than in the patients with symptomatic or silent ischemia. After exercise, no significant difference was found between the three groups. Exercise induced a significant and parallel increase in both the TAT and the F1 + 2 levels (but not of the DD levels) in the three groups. Thus, our study does not support the hypothesis that myocardial ischemia, silent or symptomatic, is associated with an activation of plasma coagulation and fibrinolysis that can be distinguished from the exercise-induced thrombin generation.
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PMID:Effects of exercise test on plasma markers of an activation of coagulation and/or fibrinolysis in patients with symptomatic or silent myocardial ischemia. 160 40

We examined the effect of coronary thrombolysis by recombinant tissue-plasminogen activator (rtPA) on infarct size using a thrombin-induced thrombosis model of open-chest anesthetized dog. Occlusive thrombus was induced by injection of thrombin (100 U) in the left anterior descending coronary artery (LAD). The intravenous infusion of rtPA (10 micrograms/kg/min) was started at 30 min (30 min-ischemia group) or at 60 min (60 min-ischemia group) after the formation of thrombus, and was continued for 30 min. Spontaneous thrombolysis was not observed in the 360 min-ischemia (vehicle-treated) group. Intravenous infusion of rtPA elicited thrombolysis within 30 min in all the dogs except in one in the 60 min-ischemia group. The infarct size was significantly reduced by rtPA-induced thrombolysis. The shorter the duration of the ischemia, the longer the effect of the drug, and the infarct size after thrombolysis was smaller in the 30 min-ischemia group than in the 60 min-ischemia group. Ischemia-induced changes in ST-segment of electrocardiogram (ECG) were significantly ameliorated after thrombolysis in both 60 min- and 30 min-ischemia group. These results suggest that early reperfusion of coronary thrombosis by rtPA is beneficial to the ischemic myocardium.
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PMID:Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium. 160 39

The effects of combined thromboxane synthetase inhibition and thromboxane receptor antagonism (TSI/TRA) were studied in conscious and in anesthetized canine models of sudden cardiac death. Administration of the TSI/TRA, R68070 10 mg/kg intravenously (i.v.), decreased thrombin-stimulated thromboxane synthesis and significantly antagonized platelet aggregation in response to the thromboxane-mimetic U46,619. In the conscious canine model, R68070 did not change ventricular refractoriness, did not prevent induction of ventricular arrhythmias by programmed electrical stimulation, and failed to prevent development of spontaneous ventricular fibrillation (VF) in response to ischemia produced at a site remote from the area of previous myocardial infarction (R68070 mortality = 70%, vehicle = 100%, p = NS). In the anesthetized canine model, R68070 prevented development of ischemia in 7 of 11 animals and reduced mortality significantly (R68070 27% and vehicle 73%; p = 0.038). R68070 inhibited thrombus formation in both models (R68070 conscious 7.0 +/- 2.6 mg and vehicle conscious 15 +/- 7.6 mg, p = NS; R68070 anesthetized 5.9 +/- 1.9 mg and vehicle anesthetized 17.7 +/- 4.3 mg; p less than 0.05). The results suggest that inhibition of thromboxane-dependent activity during acute recovery from infarction was able to protect the myocardium from developing ischemia in response to current-mediated intimal damage in a noninfarct-related artery. In the subacute phase of recovery from infarction, when the underlying myocardial substrate is susceptible to electrical derangement induced by transient ischemia, thromboxane inhibition in itself was unable to prevent ischemia-induced sudden cardiac death. Although R68070 may delay onset of ischemia due to thrombotic occlusion of the coronary artery, there does not appear to be an antiarrhythmic/antifibrillatory action to be derived from interfering with the synthesis or receptor-mediated action of thromboxane. Furthermore, R68070 does not alter the electrophysiologic properties of the heart which would result in an antiarrhythmic or antifibrillatory action.
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PMID:Effects of combined thromboxane synthetase inhibition/thromboxane receptor antagonism in two models of sudden cardiac death in the canine: limited role for thromboxane. 169 68

The present study addresses the potential effects of pacing-induced myocardial ischemia on the secretion of coagulant and fibrinolytic factors within the coronary circulation. In 6 patients undergoing programmed ventricular stimulation with repeated induction of clinical ventricular tachycardia, the coronary release of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) capacity, von Willebrand factor antigen (WF:Ag), and prostacyclin (6-keto-PGF 1a) was measured. Blood samples were collected simultaneously from the ascending aorta and the coronary sinus at baseline and immediately after the induction of ventricular tachycardia. The occurrence of pacing-induced myocardial ischemia was established by myocardial net lactate production. Myocardial ischemia was induced in every patient by repeated pacing trials. Pacing-induced ischemia did not affect the coronary release of any of the above factors. Consequently, there was no alteration of transcardiac gradients of thrombin-antithrombin complexes and D-dimer. The present results indicate that pacing-induced myocardial ischemia does not affect the release of coagulant and fibrinolytic endothelial factors or prostacyclin into the coronary circulation.
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PMID:Pacing-induced myocardial ischemia does not affect the endothelial release of coagulant and fibrinolytic factors into the coronary circulation. 170 56

Myocardial ischemia inhibits endothelium-dependent relaxation stimulated by the coagulant peptide, thrombin. To investigate whether activation of endogenous thrombin contributed to this reduction in relaxant sensitivity, the effects of pretreatment of dogs with the coumarin anticoagulant, brodifacoum, were studied. Experiments were performed in both normal coronary vasculature and coronary vasculature exposed to 90 min of myocardial ischemia, with or without 60 min of subsequent reperfusion. Ischemia was induced in the left anterior descending artery (LAD); nonischemic vessels from the left circumflex (LCX) artery of the same animals were used as control. Thrombin caused dose-dependent relaxation in isolated LCX preconstricted with prostaglandin F2 alpha (Emax of 89.1 +/- 2.33%). Relaxation was reduced by 90 min of ischemia (Emax of 27.5 +/- 8.0%; p less than 0.05), and further reduced after subsequent reperfusion (Emax of 8.7 +/- 8.7%). However, maximum relaxations to acetylcholine, calcimycin, and isoproterenol were unchanged after ischemia (Emax greater than 90% in all groups). Brodifacoum had no effect on thrombin-induced relaxation in control vessels (Emax of 83.0 +/- 3.5%), or on relaxation in response to acetylcholine, calcimycin, or isoproterenol (Emax greater than 90%). In contrast, brodifacoum markedly reduced thrombin-induced relaxation after ischemia (Emax of 3.3 +/- 3.3%; p less than 0.05) yet significantly preserved the relaxant response to thrombin after ischemia and reperfusion (Emax of 36.6 +/- 4.3%). Infusion of the thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), during ischemia and reperfusion also preserved in part the relaxant response induced by thrombin (Emax of 30.0 +/- 5.1%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of thrombin-induced endothelium-dependent relaxation after coronary ischemia in the dog: possible role of the coagulation cascade. 171 94

The interaction of platelets with the vessel wall plays an important pathophysiological role in coronary artery disease. While in healthy blood vessels platelets remain inactivated and do not adhere or aggregate, an augmented interaction occurs in coronary artery disease. Due to their strategic anatomical position between the circulating blood and the media of the vascular wall, endothelial cells play an important regulatory role. Indeed, after endothelial denudation, massive platelet adhesion and aggregation at the vessel wall occurs. Platelet-derived substances lead to vasoconstriction and in the long run also to proliferative changes of the vascular wall. Besides other substances, endothelial cells release vasoactive mediators such as endothelium-derived nitric oxide (NO), prostacyclin and endothelin. In healthy human arteries, aggregating platelets cause endothelium-dependent relaxations in spite of the liberation of serotonin and thromboxane A2 and through the luminally released NO also induce a feedback inhibition of the platelets. In contrast, in arteries without endothelium, a marked vasoconstriction (due to thromboxane A2 and serotonin) is noted. Endothelin may also play a role in platelet-vessel wall interaction, since thrombin and transforming growth factor beta (a platelet-derived product) stimulate the production of this potent vasoconstrictor. Oxidized low-density lipoproteins inhibit the relase of NO and thereby activate the platelet-vessel wall interaction. In atherosclerosis even more pronounced dysfunctions of the endothelium occur, which lead to vasoconstriction, ischemia and thrombus formation in patients with coronary artery disease.
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PMID:[Thrombocyte-vascular wall interaction and coronary heart disease]. 176


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