Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusion often reveals eccentric stenoses with irregular borders, suggesting ruptured atherosclerotic plaques and thrombosis, as documented by angioscopy and at autopsy. We have studied these processes in an ex vivo perfusion chamber, an in vivo swine model, and in human subjects. Our results, and those of other investigators, suggest that specific local risk factors at the time of plaque disruption influence the degree of thrombogenicity and, therefore, the various clinical syndromes. These risk factors can be divided into 2 groups: local vessel wall-related factors, and local (focal action) systemic factors. These risk factors include the following: 1) Rheological factors. It has been demonstrated that the more severe the stenotic lesion after plaque rupture, the higher the local shear rate with enhanced platelet deposition and thrombus formation; platelet deposition and thrombosis are particularly likely if the rupture includes the apex of the stenotic plaque, because of the high shear rate induced. 2) Degree of plaque damage. Plaque rupture produces a rough surface and stimulates an occlusive thrombus, which is enhanced depending on the degree of damage or amount of collagen type I and macrophage-dependent tissue factor exposed. 3) Residual thrombus. After spontaneous or pharmacological reperfusion, the surface of the residual thrombus is very thrombogenic and may contribute to reocclusion; this is partially due to thrombin bound to fibrin in the original thrombus. 4) Systemic factors. There is clinical and experimental evidence to suggest that 3 systemic factors at the time of plaque rupture may enhance thrombogenicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vessel wall-related risk factors in acute vascular events. 172 11

Oxygen free radicals induce de novo synthesis of tissue factor (TF), the initiator of the extrinsic pathway of coagulation, within the coronary vasculature during postischemic reperfusion. In the present study we wanted to assess whether TF expression might cause myocardial injury during postischemic reperfusion. Anesthetized rabbits underwent 30 min of coronary occlusion followed by 5.5 h of reperfusion. At reperfusion the animals received 1) saline (n = 8), 2) human recombinant, active site-blocked activated factor VII (FVIIai, 1 mg/kg, n = 8), or 3) human recombinant activated FVII (FVIIa, 1 mg/kg, n = 8). FVIIai binds to TF as native FVII, but with the active site blocked it inhibits TF procoagulant activity. The area at risk of infarction (AR), the infarct size (IS), and the no-reflow area (NR) were determined at the end of the experiment. FVIIai resulted in a significant reduction in IS and NR with respect to control animals (28.1 +/- 11.3 and 11.1 +/- 6.1% of AR vs. 59.8 +/- 12.8 and 24.4 +/- 2.7% of AR, respectively, P < 0.01), whereas FVIIa resulted in a significant increase in IS and NR to 80.1 +/- 13. 1 and 61.9 +/- 13.8% of AR, respectively (P < 0.01). In conclusion, TF-mediated activation of the extrinsic coagulation pathway makes an important contribution to myocardial injury during postischemic reperfusion.
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PMID:Recombinant human, active site-blocked factor VIIa reduces infarct size and no-reflow phenomenon in rabbits. 1077 28

Patients with unstable angina have an increased activation of the coagulation system. Aspirin and ticlopidine given in combination may potentiate each other by the combination of different action mechanisms and may reduce the risk of coronary occlusion and clinical instability. Plasma tissue factor (TF) levels collected into the stenotic coronary artery may be an index of TF expression within the vasculature. In 160 patients undergoing angioplasty for a 81+/-5% coronary lesion, we measured TF in blood samples collected from a vein and from the coronary ostium. Immediately after and 10 minutes after the dilation procedures the samples were withdrawn also beyond the lesion. Heparin 150 U/kg was given as an anticoagulant. All patients were pretreated with 250 mg/day of aspirin. One hundred twenty patients were randomly assigned to receive 24, 48, or 72 hours of ticlopidine treatment (250 mg/twice daily). TF levels did not increase during angioplasty but there was a significantly higher TF expression in unstable than in stable patients, irrespective of the invasiveness of debulking procedures. When ticlopidine was given for 72 hours, TF levels were similar to normal laboratory values both in stable and unstable patients. This combined antiplatelet pretreatment may be of benefit in unstable angina patients, with a favorable cost/benefit ratio.
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PMID:Effect of aspirin and ticlopidine on plasma tissue factor levels in stable and unstable angina pectoris. 1107 61

Thrombosis and ischaemia are often linked to an atherosclerotic arterial lesion. An inflammatory process implicating leucocytes and inflammation mediators (cytokines) as well as atheroma plaque rupture liberating tissue factor are at the origin of this pathology. Equally, blood platelets play an important role, not only with the formation of platelet aggregates, but also by their procoagulant action resulting from the exposure of membrane phospholipids. Apoptotic cells release procoagulant microparticles from the plaque, favouring thrombogenesis. In this context reperfusion would a priori restore blood flow, but it is also the origin of cytotoxicity due to the sudden release of necrotising factors. Various animal models are used to experimentally reproduce arterial thrombosis either following or not following ischaemia/reperfusion. Among them the model of progressive coronary occlusion by intraluminal electrical stimulation, the model of quasi-instantaneous thrombosis by the introduction of a copper coil, and the model of ischaemia/reperfusion by occlusion of the left descending coronary for 90 minutes followed by reperfusion have been studied more precisely in the dog. In the rat, cerebral ischaemia followed by reperfusion has been provoked with occlusion of the middle cerebral artery. The studies in dogs show that Enoxaparine significantly reduces the formation of coronary thrombus induced progressively by an anodal current and potentiates the action of the tissular activator plasminogen (t-PA) on a recently formed thrombus. At the level of myocardial ischaemia. Enoxaparine reduces the extent of infarction as well as the neutrophil and platelet accumulation in the infarcted zone or in at risk zone. This effect seems to correlate with an anti-inflammatory type action demonstrated elsewhere in vitro with platelet/neutrophil adhesion in the presence of P-Selectin. In all of these studies standard heparin used under the same conditions proves to be inactive. In the ischaemia/reperfusion model in the dog, aspirin has been shown to be ineffective up to a dose of 6 mg/Kg. Enoxaparine is an example of a possible double anti-thrombotic and anti-ischaemic component in the prevention of disorders caused by the thrombosis-ischaemia-reperfusion triad.
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PMID:[Thrombosis and ischemia: experimental data]. 1250 Jun 2

Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality. Since the introduction of drug-eluting stents (DES), most interventional centers have noted stent thrombosis up to 3 years after implantation, a complication rarely seen with bare-metal stents. Some data from large registries and meta-analyses of randomized trials indicate a higher risk for DES thrombosis, whereas others suggest an absence of such a risk. Several factors are associated with an increased risk of stent thrombosis, including the procedure itself (stent malapposition and/or underexpansion, number of implanted stents, stent length, persistent slow coronary blood flow, and dissections), patient and lesion characteristics, stent design, and premature cessation of antiplatelet drugs. Drugs released from DES exert distinct biological effects, such as activation of signal transduction pathways and inhibition of cell proliferation. As a result, although primarily aimed at preventing vascular smooth muscle cell proliferation and migration (ie, key factors in the development of restenosis), they also impair reendothelialization, which leads to delayed arterial healing, and induce tissue factor expression, which results in a prothrombogenic environment. In the same way, polymers used to load these drugs have been associated with DES thrombosis. Finally, DES impair endothelial function of the coronary artery distal to the stent, which potentially promotes the risk of ischemia and coronary occlusion. Although several reports raise the possibility of a substantially higher risk of stent thrombosis in DES, evidence remains inconclusive; as a consequence, both large-scale and long-term clinical trials, as well as further mechanistic studies, are needed. The present review focuses on the pathophysiological mechanisms and pathological findings of stent thrombosis in DES.
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PMID:Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. 1732 55