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)

Platelet thrombus formation occurs at sites of severe arterial narrowing where shear stress is elevated. Shear stress appears to induce platelet aggregation in vitro by means of initiation of von Willebrand factor binding to platelet glycoprotein Ib. Recent in vitro studies have demonstrated that aurintricarboxylic acid can inhibit shear stress-induced platelet aggregation. This effect is mediated by aurintricarboxylic acid binding to von Willebrand factor; this binding results in inhibition of von Willebrand factor interaction with glycoprotein Ib. In this study, we examined the effect of aurintricarboxylic acid on platelet-dependent cyclic flow reductions (CFRs) in a canine coronary stenosis model. In dose-response experiments, six animals received 4 mg/kg aurintricarboxylic acid by bolus infusion, followed by 1 mg/kg every 10 minutes. Total inhibition of CFRs was observed in all animals after 6.7 mg/kg aurintricarboxylic acid; CFRs could not be reinitiated by the thromboxane A2 analogue U46619. Continuous infusion of epinephrine (0.4 micrograms/kg/min) caused CFRs to return; however, 3.7 mg/kg additional aurintricarboxylic acid again induced total inhibition of CFRs. In addition, five animals received a bolus infusion of 10 mg/kg aurintricarboxylic acid, which caused total inhibition of CFRs. The average area of stenosis in the constricted vessels was 83%, and shear stress at the site of constriction averaged 350 dynes/cm2. Aurintricarboxylic acid did not alter hemodynamics, thrombin time, platelet count, or ADP/epinephrine-induced platelet aggregation. These data indicate that platelet glycoprotein Ib-von Willebrand factor interactions are important during coronary occlusion and that aurintricarboxylic acid can inhibit coronary thrombosis associated with coronary constriction.
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PMID:Aurintricarboxylic acid in a canine model of coronary artery thrombosis. 230 18

To determine if inhibition of leukocyte adhesion and aggregation could improve postischemic ventricular dysfunction ("stunning"), a monoclonal antibody (904) that binds to the adhesion-promoting Mo1 glycoprotein on the cell surface of leukocytes was administered intravenously (0.5 mg/kg) to open-chest dogs before a 15-minute coronary occlusion. Ultrasonic crystals placed in ischemic and control myocardium were used to measure systolic wall thickening during a 15-minute occlusion of the left anterior descending artery and for 3 hours after reperfusion. Myocardial blood flow was measured with tracer-labeled microspheres before occlusion, after 10 minutes of occlusion, 3 minutes of reperfusion, and at 1 and 3 hours after reperfusion. Six animals receiving anti-Mo1 antibody had antibody excess demonstrated with immunofluorescence techniques at 5 minutes and 3 hours of reperfusion; this finding indicated saturation of binding sites. Five animals served as controls and received an antibody (murine immunoglobulin G) that does not influence neutrophils. The two groups did not differ hemodynamically during ischemia and reperfusion. Risk areas and myocardial blood flow were also not significantly different between the two groups. The main parameter used to define regional myocardial stunning, percentage systolic wall thickening in the ischemic/reperfused area, did not differ significantly between the two groups. Specimens from nonischemic myocardium were compared with ischemic specimens for myeloperoxidase content. There were no significant differences within or between groups. These data indicate that the anti-Mo1 monoclonal antibody (904) is not effective in improving the profound myocardial dysfunction that persists for 3 hours of reperfusion after 15 minutes of ischemia.
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PMID:F(ab')2 fragments of anti-Mo1 (904) monoclonal antibodies do not prevent myocardial stunning. 255 27

Scanning electron microscopy and transmission electron microscopy were used together with tannic acid and ruthenium-red staining to examine connective tissue damage caused by acute myocardial ischemia for 20, 40 and 120 min in pig hearts. The microsphere blood flow technique revealed that blood flow was approximately 0.02 ml/min/g in inner, middle and outer thirds of the ischemic zone. After 20 min of occlusion of the left anterior descending coronary artery, the collagen network and microfilaments became irregularly arranged. After 40 min of occlusion, ruthenium-red positive glycoprotein material around the collagen fibrils and elastin began to disappear. After 2 h occlusion, the collagen fibrils and microfilaments had separated from the basement membrane. Collagen fibrils, elastic fibers, and microfilaments were broken down and were found in decreased quantities. These results have revealed that the connective tissue remains intact during the first 20 min of coronary occlusion despite zero blood flow and mild cellular changes but does undergo prominent alterations after 40 min of occlusion.
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PMID:Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study. 687 83

The risk of acute coronary occlusion following percutaneous transluminal coronary angioplasty (PTCA) has remained high despite the traditional use of heparin and aspirin. Interest has focused on newer strategies for preventing intracoronary thrombus formation, which is an important mechanism of abrupt vessel closure. Pretreatment with thrombolytic agents has failed vigorous testing in double-blind trials. Retrospective and observational studies have indicated that pretreatment with intravenous heparin is of benefit in patients with unstable symptoms, but prolonged infusion after angioplasty increases bleeding complications without improving outcomes. Subcutaneous heparin may be safer, but has not proved more effective. Oral dipyridamole has shown no advantage over aspirin, although there is evidence to suggest a benefit when given intravenously. Direct thrombin inhibitors (such as hirudin and hirulog) are associated with fewer early complications compared with heparin, but have yielded no apparent long-term benefit. The use of the antiplatelet drug ticlopidine is increasing, although long-term data are lacking. A great deal of recent interest has focused on newer antiplatelet agents, particularly the glycoprotein IIB/IIIa receptor inhibitor c7E3 Fab. In a large-scale trial, c7E3 significantly reduced the 30-day rate of mortality and cardiac events, and these benefits were maintained at 6 mo. This drug, unlike other antiplatelet agents, inhibits the final common pathway of platelet aggregation, which influences not only acute closure but has lasting effects for at least 6 mo. This may reflect a reduction in restenosis, although this remains to be proven. This article gives a brief overview of the pharmacologic agents available for the prophylaxis and treatment of acute ischemic complications of PTCA.
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PMID:Pharmacologic prevention of acute ischemic complications of coronary angioplasty. 936 95

Stents are indicated in the prevention and treatment of coronary occlusion and restenosis following percutaneous transluminal coronary angioplasty. ReoPro (abciximab) is a chimeric monoclonal antibody interfering with the IIb-IIIa glycoprotein platelet receptor. Its efficacy in preventing ischaemic events after coronary angioplasty was evaluated in the EPIC, EPILOG and CAPTURE studies. In these studies, 525 (9.6 per cent) patients were treated with coronary angioplasty and stent. Amongst them, 388 were in a bail-out situation (73.4 per cent). Results showed a significant reduction in the principal criterion (death, myocardial infarction, revascularization procedures) occurrence at 30 days (60.3 per cent; p < 0.001) and at 6 months (23.7 per cent; p = 0.043) and good safety. The greatest reduction was observed in the bail-out situation. Its efficacy must be confirmed by specific studies including health economy data in order to define the place of such an association amongst future therapies.
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PMID:[Abciximab in the treatment of acute coronary syndromes by angioplasty and stents]. 980 3

The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12 dyne/cm2), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.
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PMID:AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes. 1019 12

Reperfusion injury after coronary occlusion is in part mediated by leukocyte activation and adhesion. Platelets may interact with polymorphonuclear granulocytes (PMNs), causing aggravated reperfusion injury. We studied whether c7E3Fab, a chimeric Fab fragment blocking platelet glycoprotein (GP) IIb/IIIa, decreases PMN-platelet-dependent myocardial dysfunction after ischemia. Isolated guinea pig hearts (n=5 per group) perfused at a constant flow of 5 mL/min were subjected to ischemia (15 minutes, 37 degrees C) and reperfusion. Human PMNs (10x10(6) cells, 3 mL), platelets (400x10(6), 3 mL), and fibrinogen (1 mg/mL) were infused for 3 minutes after 2 minutes of reperfusion, with or without c7E3Fab. Flow cytometry detected GPIIb/IIIa (platelets) and MAC-1 (aMbeta2, PMNs) as well as coaggregates of both in the effluent, whereas double-fluorescence microscopy visualized intracoronary PMN-platelet coaggregates. Postischemic recovery of pressure-volume work (12-cm H(2)O preload and 60-mm Hg afterload) was defined as the ratio of postischemic to preischemic external heart work (mean+/-SEM). c7E3Fab reduced platelet GPIIb/IIIa detection to 10% of controls, blocked a transcoronary MAC-1 increase (+25% without versus -23% with c7E3Fab), and inhibited PMN-platelet coaggregation in the effluent (49+/-12% without versus 17+/-2% with c7E3Fab) as well as in the hearts themselves (5.0+/-0.7/cm(2) without versus 1.2+/-0.3/cm(2) surface area with c7E3Fab). Postischemic recovery of external heart work (83+/-5% in cell-free hearts) declined to 46+/-4% after postischemic PMN-platelet infusion, but not in the presence of c7E3Fab (74+/-11%) or LPM19c (71+/-6%). We conclude that c7E3Fab inhibits formation of PMN-platelet aggregates during myocardial reperfusion, an effect that protects against PMN-platelet-dependent stunning.
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PMID:c7E3Fab reduces postischemic leukocyte-thrombocyte interaction mediated by fibrinogen. Implications for myocardial reperfusion injury. 1103 Dec 8

Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRgamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRgamma-deficient (FcRgamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcRgamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRgamma(-/-) mice than in the FcRgamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRgamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.
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PMID:Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury. 1624 61

The treatment and therapy of acute myocardial infarction has substantially improved during the past decades. After thrombotic coronary occlusion had been identified as the underlying cause of myocardial infarction, thrombolysis emerged as the standard therapy. The development of more and more effective thrombolytic therapies and optimization of adjunctive antithrombotic therapies resulted in improved clinical outcomes and decreased mortality rates of acute myocardial infarction patients. Optimization of percutaneous coronary intervention (PCI) techniques including implantation of coronary stents shifted the therapeutic approach from thrombolysis toward acute mechanical reperfusion. The safety and efficacy profile of PCI has been made possible by the development of potent antiplatelet agents such as clopidogrel and glycoprotein (GP) IIb/IIIa antagonists. For the future therapy of acute myocardial infarction the following goals will be important to consider: (1) are there ways to increase the percentage of patients reaching out for medical support when suffering from acute myocardial infarction?, (2) what strategies will be useful to shorten coronary reperfusion time?, (3) are there means to protect affected myocardium from ischemic damage?, and (4) can necrotic myocardium be reconstituted functionally? Potential approaches such as improved public information, combination of thrombolytic and interventional therapy to accelerate coronary reperfusion, pharmacological protection of myocardium by modulation of myocardial metabolism or protection from reperfusion damage as well as progenitor cell therapy are discussed in this overview.
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PMID:[Future developments in the therapy of acute ST segment elevation myocardial infarction]. 1633 65