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

Dual-site murine antibody-based immunoassays are commonly used in clinical laboratories to quantitate the MB isoenzyme of creatine kinase (CK-MB). Because the serum level of CK-MB is a relatively specific and sensitive indicator of myocardial ischemic damage, accurate quantitation is essential for a correct diagnosis. Heterophile antibodies (eg, human anti-murine antibodies) can interfere with these assays, however, and produce erroneous results. A subpopulation of 19 surgical patients with colorectal carcinoma who had received injections of an 125I-labeled murine monoclonal antibody directed against a tumor-associated glycoprotein was studied. Serum specimens from eight patients (42%) showed a marked increase in the level of CK-MB and normal total CK concentrations. The increased concentrations of CK-MB, which were attributed to interference by human antimurine antibodies, were substantially reduced in these specimens after a heterophile blocking reagent was added. However, this reagent did not significantly alter the serum level of CK-MB in patients who had clinical evidence of acute myocardial ischemia.
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PMID:Heterophilic antibodies produce spuriously elevated concentrations of the MB isoenzyme of creatine kinase in a selected patient population. 912 61

Formation of platelet-rich thrombus superimposed on ruptured atherosclerotic plaque has been implicated in the development of myocardial ischemia and its clinical manifestations. The platelet glycoprotein (GP) IIb-IIIa receptor is the final common pathway leading to platelet aggregation and thrombus formation. GP IIb-IIIa is therefore a logical therapeutic target for management of acute ischemic coronary syndromes and prevention of the ischemic complications of percutaneous coronary procedures. Of the pharmaceutical agents under development, the chimeric monoclonal antibody abciximab (ReoPro) and the cyclic peptide eptifibatide (INTEGRILIN) are the most studied. IMPACT II (Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis), the phase III evaluation of eptifibatide in patients undergoing percutaneous coronary intervention, demonstrated the effectiveness and safety of this GP IIb-IIIa receptor inhibitor in reducing the acute adverse outcomes of invasive management of ischemic heart disease. GP IIb-IIIa receptor blockade provides an effective strategy for prevention of ischemic complications related to angioplasty in patients with coronary artery disease.
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PMID:Impact of eptifibatide on early ischemic events in acute ischemic coronary syndromes: a review of the IMPACT II trial. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis. 929 Dec 42

In unstable angina, there are data to suggest a substantial risk of recurrent ischemia, infarction, and death when early angiography and/or revascularization have been deferred. Conversely, it has been suggested that early angiography and revascularization are more dangerous than deferred procedures. Critical review of the literature, however, suggests that there is no specific risk inherent in early intervention, but rather that patients who cannot wait are at higher risk anyway. The most valuable data on the comparison of an "early invasive" and a "conservative" strategy in unstable angina come from the Thrombolysis in Myocardial Ischemia (TIMI) IIIB study. The results show no major difference in outcome between groups (despite a high intervention rate in the conservative group), but a shorter hospital stay, lower drug use, and fewer rehospitalizations in the group treated according to the early invasive strategy. These results have been interpreted as favoring early intervention, due to the potential for a shorter hospital stay (a major determinant of cost in many countries) because of the possibility of achieving complete diagnosis and treatment within several days of admission, with good results. In addition, since the inception of the TIMI IIIB study, there have been major improvements in the field of angioplasty, such as the increased use of stents and the availability of safe and effective glycoprotein (GP) IIb-IIIa inhibitors. Thus, the pathophysiology, the excellent results of early intervention, and the recent improvements in angioplasty and its medical and pharmacologic environment, provide a strong rationale for early intervention.
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PMID:Revascularization of patients with unstable coronary artery disease: the case for early intervention. 929 70

Previous studies show that infusion of hibernating woodchuck albumin (HWA) induces hibernation in summer-active ground squirrels and results in profound behavioral and physiological depression in primates. These effects are reversed by the administration of opiate antagonists, suggesting that the putative hibernation induction trigger (HIT) may act through opioid receptors. We have demonstrated that both HIT-containing plasma and the synthetic alpha opioid D-Ala2-D-Leu5-enkephalin (DADLE), which mimics the activity of HIT in hibernators, extend tissue survival time of a multi-organ autoperfusion system by 3-fold. In this study we present the first data showing biological activity with a much more highly purified plasma fraction from hibernating woodchucks, identified as the hibernation-related factor (HRF). Both the HRF and DADLE show opiate-like contractile inhibition in the mouse vas deferens (Mvd) bioassay. We also have preliminary evidence in an isolated rabbit heart preparation indicating that the HRF and DADLE act similarly to restore left ventricular function following global myocardial ischemia. Furthermore, we have partially sequenced an alpha 1-glycoprotein-like 88 kDa hibernation-related protein (p88 HRP) present in this fraction, which may prove to be the blood-borne HIT molecule.
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PMID:Isolation and partial characterization of an opioid-like 88 kDa hibernation-related protein. 978 70

Ischemic cardiac manifestations have been reported in a various percentage of patients with anti-phospholipid antibodies. As concerns the relationship between anti-beta2 glycoprotein I antibodies (anti-beta2-GPI) and ischemic heart disease (IHD), it was investigated in only one coronary primary prevention study. We investigated the prevalence of anti-beta2-GPI in a well characterized group of patients with different clinical manifestation of IHD. Sera from 37 patients (mean age 62.7 +/- 9.9) with IHD (20 with unstable angina-UA and 17 with effort angina-EA) and from 40 healthy subjects, matched for age and sex, were tested for the presence of IgG and IgM anti-beta2-GPI using an ELISA technique. Eleven/37 patients (29.7%) resulted positive for anti-beta2-GPI. A positivity for IgG anti-beta2-GPI was found in 10 patients, 1 patient was positive for IgM and 1 for both isotypes. The prevalence of anti-beta2-GPI in the control group resulted significantly lower (2.5%; p < 0.005) than in patients with IHD. Positivity for anti-beta2-GPI was found in 9/20 (45%) patients with UA and only in 2/17 patients (11.8%) with EA (p = 0.0365). IgG anti-beta2-GPI levels (median 7.7U/ml, range 2.6-24.1) were significantly higher in patients with UA compared to patients with EA (median 4.6 U/ml, range 2.3-11.5; p = 0.02) and controls (median 3.15 U/ml, range 2.3-9.0; p < 0.0001); also IgM levels resulted higher in patients with unstable angina. A positivity for anti-beta2-GPI was observed in 4/13 patients (30.8%) with a previous myocardial infarction (MI) and in 7/24 (29.2%) patients without a previous MI. Our findings suggest that anti-beta2-GPI could represent an expression of the T-cell activation detectable in patients with unstable angina. The lack of a significant difference in the prevalence of these antibodies in patients with or without a previous MI suggests that anti-beta2-GPI are not induced by tissue necrosis.
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PMID:High prevalence of anti-beta2 glycoprotein I antibodies in patients with ischemic heart disease. 1043 22

Acute coronary syndromes (ACS) are the major cause of mortality and morbidity in Western countries. The primary pathophysiologic mechanism of ACS involves the formation of thrombus in coronary arteries in response to spontaneous or intervention-induced endothelial damage. This leads to myocardial ischemia. The final common pathway to the coronary thrombosis underlying ACS involves the aggregation of platelets mediated by the binding of soluble fibrinogen to the platelet receptor glycoprotein (GP) IIb-IIIa. Several GP IIb-IIIa inhibitors have been developed that promise greater antithrombotic potential than aspirin and heparin alone. Over the past 2 years, 4 major trials involving more than 18,000 patients have evaluated the therapeutic potential of 3 small-molecule, intravenous GP IIb-IIIa inhibitors as a component of first-line management of unstable angina or non-ST-segment elevation myocardial infarction. Results of these studies show that administration of a GP IIb-IIIa inhibitor in combination with aspirin and heparin provides a significant reduction in mortality and morbidity rates compared with aspirin plus heparin alone. Recent approvals of 2 GP IIb-IIIa inhibitors, the peptide eptifibatide and the peptidomimetic tirofiban, mark the beginning of a new era in the management of non-ST-segment elevation ACS.
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PMID:Overview of clinical trials of glycoprotein IIb-IIIa inhibitors in acute coronary syndromes. 1050 33

Platelet-mediated coronary thrombosis is the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute ischemic complications of percutaneous coronary intervention (PCI). The final common pathway of platelet aggregation that leads to thrombotic occlusion of coronary arteries involves cross-linking of receptor glycoprotein (GP) IIb-IIIa on adjacent platelets by adhesive plasma proteins, primarily fibrinogen. Clinical trials of several GP IIb-IIIa inhibitors have demonstrated an unequivocal clinical benefit of this potent antithrombotic therapy in patients with ACS as well as in those undergoing PCI. Nevertheless, a significant number of patients with ischemic heart disease may still be expected to require elective or emergency coronary artery bypass graft (CABG) after treatment with GP IIb-IIIa inhibitors. In the emergency CABG setting, complications and platelet blockade with GP IIb-IIIa inhibitors may further enhance the already heightened risk of bleeding as compared with elective procedures. This issue became apparent in the first large clinical trial of the GP IIb-IIIa inhibitor abciximab (c7E3 Fab, ReoPro((R)); Centocor, Malvern, Pa, and Eli Lilly and Co, Indianapolis, Ind) in patients undergoing high-risk PCI. In this study, mortality rates and bleeding complications were increased among patients undergoing emergency CABG after treatment with a bolus plus infusion of abciximab. Subsequent clinical experience also suggests that the potential for bleeding complications related to emergency CABG may be increased in patients treated with abciximab, particularly if the drug is discontinued within 6 hours of the operation. Higher bleeding risk with abciximab is a result of its prolonged antiplatelet effect, which is in contrast to the readily reversible platelet blockade provided by more recently developed small-molecule GP IIb-IIIa inhibitors such as the peptide eptifibatide (Integrilin((R)); COR Therapeutics, South San Francisco, Calif, and Key Pharmaceuticals, Kenilworth, NJ) and the nonpeptide tirofiban HCl (MK-383, Aggrastat((R)); Merck & Co, Whitehouse Station, NJ). Therefore, among patients requiring CABG after treatment with GP IIb-IIIa inhibitors, eptifibatide and tirofiban may be associated with fewer bleeding episodes than is abciximab. With recent approval of eptifibatide for patients with ACS and those scheduled for PCI and of tirofiban for patients with ACS, the number of patients receiving GP IIb-IIIa inhibitor therapy who subsequently undergo CABG is expected to increase significantly. Strategies for improved management of bleeding complications in these patients, including the choice of a GP IIb-IIIa inhibitor, are clearly needed and are discussed in detail.
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PMID:Safety of glycoprotein IIb-IIIa inhibitors: A heart surgeon's perspective. 1050 36

The purpose of this manuscript is to review the available antagonists of platelet glycoprotein (GP) IIb/IIIa. The critical role of platelet aggregation in the pathogenesis of acute coronary syndromes of unstable angina and non-Q-wave myocardial infarction, as well as in mediating abrupt vessel closure and periprocedural infarction after percutaneous coronary interventions, has been recognised recently. Platelet aggregation is mediated through expression of activated GP IIb/IIIa and its subsequent binding to circulating fibrinogen. Inhibition of this interaction with one of 3 commercially available agents has been demonstrated to reduce ischaemic complications of coronary intervention and to reduce the rates of death and myocardial infarction in patients with acute coronary syndromes. Differential pharmacological characteristics of the drugs abciximab, tirofiban and eptifibatide are described and the trials which have defined their role in the management of ischaemic heart disease are reviewed.
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PMID:GP IIb/IIIa antagonists. Clinical experience and potential uses in cardiology. 1056 65

Ischemic mechanisms in pa2000Mar;58(1)1-10 studied for more than 150 years. Antiplatelet agents did show benefit in secondary prevention. Aspirin is the most common antiaggregant in clinical use today. However, the benefit produced by the "best" antiplatelet regimen in stroke prevention is lower than 40%. The adherence of circulating platelets to the subendothelium is mediated by glycoprotein (GP) residing on the cell's surface. GPIIb/IIIa is the most important platelet membrane receptor that mediates the process of platelet aggregation, and thrombus formation. Thus, new drugs that block the GPIIb/IIIa receptor have recently emerged. Clinical trials using these agents have shown effectiveness in acute coronary syndromes. However, the absence of studies in cerebrovascular disease and the potential hemorrhagic complications questioned their use in stroke prevention. We review the clinical trials using the new GPIIb/IIIa agents in myocardial ischemia, and consider the potential implications for cerebrovascular disease.
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PMID:Arteriosclerosis and the promise of GPIIb/IIIa inhibitors in stroke. 1077 Aug 59

Cardiomyopathy is a multifactorial disease, and the dystrophin-glycoprotein complex has been implicated in the pathogenesis of both hereditary and acquired forms of the disease. Using mouse models of cardiomyopathy made by ablating genes for components of the sarcoglycan complex, we show that long-term treatment with verapamil, a calcium channel blocker with vasodilator properties, can alleviate the severe cardiomyopathic phenotype, restoring normal serum levels for cardiac troponin I and normal cardiac muscle morphology. Interruption of verapamil treatment leads again to vascular dysfunction and acute myocardial necrosis, indicating that predilection for cardiomyopathy is a continuing process. In contrast, verapamil did not prevent cardiac muscle pathology in dystrophin-deficient mdx mice, which neither show a disruption of the sarcoglycan complex in vascular smooth muscle nor vascular dysfunction. Hence, our data strongly suggest that pharmacological intervention with verapamil merits investigation as a potential therapeutic option not only for patients with sarcoglycan mutations, but also for patients with idiopathic cardiomyopathy associated with myocardial ischemia not related to atherosclerotic coronary artery disease.
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PMID:Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex. 1116 Jan 28


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