Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial infarction is linked to atherosclerosis, yet the sequence leading from silent coronary atherosclerosis to acute myocardial infarction has remained unclear. Here we show that hypercholesterolemic apolipoprotein E-/- low density lipoprotein receptor-/- mice develop not only coronary atherosclerosis but also myocardial infarction. Exposure of mice to mental stress or hypoxia led to acute ischemia, which, in a large proportion of the mice, was followed by electrocardiographic changes, leakage of troponin T, and loss of dehydrogenase from the myocardium, all indicative of acute myocardial infarction. Apoptotic death of cardiomyocytes was followed by inflammation and fibrosis in the heart. All these pathological changes could be prevented by a blocker of the endothelin type A receptor. Thus, stress elicits myocardial infarction through endothelin receptor signaling in coronary atherosclerosis caused by hypercholesterolemia.
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PMID:Myocardial infarction mediated by endothelin receptor signaling in hypercholesterolemic mice. 1035 14

Non-ST-elevation myocardial infarction is usually indistinguishable from unstable angina at the initial presentation. The diagnosis is made subsequently when cardiac enzymes are found to be elevated either at admission or within 18 hours. Our understanding of the pathophysiology of acute coronary syndromes has advanced dramatically, and coupled with this understanding has been the introduction of new antiplatelet and antithrombotic treatments. The best way to integrate these treatments into percutaneous revascularization procedures has not yet been defined. In general, patients with non-ST-elevation myocardial infarction should be treated in the same way as those with unstable angina. Patients should be risk profiled at admission and subsequently according to clinical features, electrocardiographic findings, results of laboratory tests including measurement of troponins, and response to therapy. They should also be monitored carefully for signs of ischemia. Patients at low risk with a normal electrocardiogram and normal troponin T or I levels should be assessed for early discharge and outpatient assessment with exercise or pharmacological testing for inducible ischemia. Patients at intermediate risk should be treated with aspirin, unfractionated or low-molecular-weight heparin and, if unfractionated heparin is chosen, an adjunctive IIb/IIIa receptor antagonist. Patients at high risk should be treated with the same therapies and considered for expeditious angiography and revascularization as appropriate. A long-term secondary prevention strategy should be implemented.
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PMID:Optimal treatment of patients with acute coronary syndromes and non-ST-elevation myocardial infarction. 1042 68

Analysis of cardiac troponin T and I have been shown to be effective in detecting minor myocardial injury in cardiac patients who present with acute coronary syndromes (ACS). Determination of minor myocardial injury is significant, as these patients have a higher short-term morbidity and mortality than other unstable angina patients with normal concentrations for these markers. In this report, two theories are given as to why cardiac troponin is superior to other markers such as CK-MB for risk stratification. The 'low cut-off concentration model' is based on the fact that troponin is not increased in patients with skeletal muscle disease or injury, resulting in low baseline concentrations of the cardiac isoforms in the absence of active cardiac disease. This enables the use of low decision limits. Troponin also has a higher myocardial tissue content relative to CK-MB, thereby also increasing its clinical sensitivity to irreversible injury. In the 'reversible ischemia model', cytoplasmic free troponin T and I leak across the membrane of myocytes as the result of reduced coronary blood flow. Jeopardized myocardial tissue can recover with acute recanalization. Support for this model comes from clinical observations and animal studies.
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PMID:Release of cardiac troponin in acute coronary syndromes: ischemia or necrosis? 1045 Dec 43

Unstable angina and non--Q-wave myocardial infarction (MI) are at the center of the spectrum of myocardial ischemia, which ranges from stable angina to acute Q-wave MI. In addition to clinical evaluation, cardiac specific markers such as troponin T or I can assist in early diagnosis, triage, and risk stratification. Antithrombotic therapy with aspirin and heparin have been shown to improve the outcome of patients with acute ischemic syndromes. Thrombolytic therapy does not appear to be beneficial in these syndromes. Antiischemic therapy remains an important component of the overall therapy. A strategy of early coronary angiography and revascularization leads to a similar long-term outcome as compared with a more conservative strategy of revascularization for recurrent ischemia, but the early invasive strategy is more expeditious as a large number of conservatively treated patients have recurrent ischemia. At present, many new antithrombotic agents are under active investigation, with the hope that they will lead to further improvement in the clinical outcome of patients with acute ischemic syndromes.
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PMID:Optimizing the Treatment of Unstable Angina. 1060 25

Coronary artery disease is highly prevalent in patients with end-stage renal disease, and accounts for much of their observed morbidity and mortality. Despite this, diagnosing myocardial disease in this population remains problematic, because many patients present with abnormal baseline electrocardiograms, frequently compounded by silent or atypical symptoms. Conventionally used enzymatic markers of cardiac injury have not resolved this dilemma because of their poor specificity in end-stage renal disease. In particular, nonspecific elevations in creatinine kinase-muscle brain enzyme, a widely accepted marker of cardiac injury, have been consistently observed in the absence of other demonstrable evidence for cardiac injury. Recently, the cardiac troponins (troponin I and troponin T) have emerged as more sensitive markers for cardiac ischemia, facilitating rapid bedside diagnosis and early risk stratification. Unfortunately, cardiac troponin T shows poor specificity in end-stage renal disease, possibly because of variable expression in extracardiac tissues. On the other hand, troponin I consistently maintains a high sensitivity and specificity, and is the most sensitive marker for ischemic heart disease in this patient population.
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PMID:Current markers of myocardial ischemia and their validity in end-stage renal disease. 1063 Aug 19

It is still uncertain to what extent PTCA contributes to a rise of the myocardial ischemic marker troponin T. The purpose of this study was to determine the release of troponin T in patients with unstable and stable angina pectoris pre- and post-PTCA. Serial troponin T measurements were performed in 66 patients with unstable angina (group A) and 55 patients with stable angina pectoris (group B) pre-PTCA and 4, 8 and 24 hours post-PTCA. In group A, 39 (59%) patients with unstable angina pectoris showed pathologic troponin T concentrations (troponin T > or = 0.1 ng/ml); in 27 (41%) patients already pre-PTCA the troponin T was elevated beyond the normal values. Medians of troponin T rose from initially 0.045 ng/ml pre-PTCA to a maximum of 0.21 ng/ml 8 hours post PTCA. In group B medians of troponin T were at all times within normal limits; there was no rise in the observation interval. Using the Chi-square test there were statistically significant differences between group A and B regarding the troponin T values pre- and post-PTCA. In group A medians of total creatine kinase ranging between 24 U/L and 30 U/L were to all times within normal limits. Also in group B medians of total creatine kinase were always within normal limits. Statistically significant differences between the two groups could not be shown. Our study could show a difference in the periinterventional course of the ischemic marker troponin T in patients with unstable and stable angina pectoris. The data indicate a PTCA induced reversible ischemia of the cardiac muscle cell with additional release of the cytoplasmatic bound part of troponin T in patients with unstable angina pectoris. Troponin T also appears to be a more sensitive marker of very short myocardial ischemia than creatine kinase.
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PMID:[Release of troponin T following PTCA in patients with unstable and stable angina pectoris]. 1064 59

The early release of cardiac markers is influenced by a variety of factors, the most important influence being their intracellular compartmentation. In contrast to the release of cytosolic proteins, the release of structurally bound proteins requires both a leaky plasma membrane and a dissociation or degradation of the subcellular structure, which is a slower process. Another major impact is the susceptibility to the degradation by cytosolic proteases, such as the calpains. The lysosomes are stable within the first 3-4 hours after onset of ischemia, and, therefore, their enzymes are not involved in the early degradation of structurally bound proteins. Troponin I and troponin T are substrates of micro-calpain. Current experimental as well as clinical results suggest that the molecular mass seems to be of minor importance for the pattern of appearance of myocardial proteins in blood after myocardial infarction. However, within the family of molecules with a certain intracellular compartmentation, the molecular mass is an influence on the appearance in blood, because heavier molecules diffuse at a slower rate, and particularly smaller molecules, such as myoglobin, may enter the vascular system to an even larger extent directly via the microvascular endothelium. The higher the concentration gradient of a marker between the cardiomyocytes and the interstitial space, the faster a parameter will translocate from sarcoplasma to the interstitial space as soon as the plasma membrane permeability is increased. Another influence is local blood and lymphatic flow. Recent experimental studies showed that reperfusion causes a true acceleration of cellular protein leakage by an acute manifestation of plasmalemmal disruptions and not just an enhanced wash out. Marker protein time-courses after myocardial damage are also markedly influenced by their disappearance rate from blood. Most proteins appear to be catabolized in organs with a high metabolic rate, such as liver, pancreas, kidneys, and the reticuloendothelial system. Smaller molecules, such as myoglobin, also pass the glomerular membranes of the kidneys and are reabsorbed and subsequently metabolized in tubular epithelial cells.
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PMID:Tissue release of cardiac markers: from physiology to clinical applications. 1072 15

Limitations of creatine kinase-MB (CK-MB) have led to alternative biochemical markers, including troponin T (TnT), to detect myocardial necrosis. Limited data are available regarding the predictive value of this new marker in patients with chest pain of uncertain etiology. Therefore, we prospectively compared CK-MB and TnT in a broad population with suspected acute coronary syndromes, including those admitted to a short-stay chest pain unit. CK-MB, quantitative TnT levels, and a rapid bedside assay were performed at 0, 4, 8, and 16 hours. Adverse events, including infarction, recurrent ischemia, coronary surgery, need for catheterization and/or intervention, stroke, congestive heart failure, or death, were identified by chart review and by follow-up phone call at 6 months. Of 707 patients, 104 were excluded for creatinine >2 mg/dl or incomplete data, leaving a total cohort of 603 patients. Coronary Care Unit admissions were 18%, intermediate care admissions were 14%, telemetry admissions is 21%, and admissions to 24-hour short-stay area were 47%. TnT (at 0.1 ng/ml) and CK-MB were positive in a similar proportion of patients (20.4% and 19.7%, respectively); however, the patients identified by TnT and CK-MB were not identical. In-hospital adverse events occurred in 37.1% with no differences in positive predictive value for the markers (p = NS). If CK-MB and TnT were negative, the early adverse event rate was 27%. No cardiac marker was positive by 16 hours in 54.9% of patients with an adverse event. Six-month follow-up was obtained in 576 of the 603 patients (95.5%). One hundred fifty-five late adverse events occurred in 134 patients (23.3%) at an average of 3.3+/-2.5 months after discharge. If both markers were negative, the late event rate was 20.2% and did not increase in patients with positive CK-MB or TnT >0.2 ng/ml. However, the late event rate was substantially higher (52.9%) in those with intermediate TnT levels of 0.1 to 0.2 ng/ml (p = 0.002). Thus, TnT is a suitable alternative to CK-MB in patients with suspected acute coronary syndromes. The rapid bedside assay is comparable to quantitative TnT and may enable early diagnosis and triage. A negative cardiac marker value (TnT or CK-MB) does not necessarily confer a low risk of complication in patients presenting with acute chest pain to an emergency department.
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PMID:Comparison of troponin T versus creatine kinase-MB in suspected acute coronary syndromes. 1072 44

The early presence of troponin T in serum strongly predicts short-term mortality and myocardial infarction in patients with acute coronary syndromes. We investigated the long-term outcome of the prognostic significance of the troponin T rapid bedside assay (TROPT) and compared this with the quantitative troponin T assay (cTnT enzyme-linked immunosorbent assay), myoglobin and creatine kinase-MB (CK-MB) mass. One hundred sixty-three patients with chest pain and suspected acute coronary syndromes were studied and followed prospectively for 3 years. Serial blood specimens were obtained at admission and at 3, 6, 12, 24, 48, 72, and 96 hours after admission. Patients were classified as having acute myocardial infarction in 99 patients (61%), unstable angina in 34 patients (21%), and no evidence for acute cardiac ischemia in 30 patients (18%). At 3 years, 28 patients (17%) had died of which 25 deaths (15%) were for cardiac reasons. Twenty-one patients (13%) had a nonfatal (recurrent) myocardial infarction. At admission 29% of the patients were TROPT positive (> or = 0.2 microg/L), another 31% became positive within 12 hours, and 39% remained negative. When adjusted for baseline variables, a positive TROPT (any sample 0 to 12 hours) was independently associated with a higher risk of cardiac mortality (RR 4.3, 95% confidence interval [CI] 1.3 to 14.0). Because troponin T stays elevated up to 2 weeks, later TROPT results between 24 and 96 hours remained significantly predictive for mortality. The cTnT enzyme-linked immunosorbent assay (any sample 0 to 12 hours; cutoff > or = 0.2 microg/L) was similarly predictive (RR 2.9, 95% CI 1.0 to 8.6). Early myoglobin results were significantly prognostic for cardiac mortality up to 12 hours after admission (RR 3.7; 95% CI 1.0 to 12.0). In contrast, serial CK-MB mass measurements were not predictive of mortality. Thus, a combination of a baseline TROPT and an additional TROPT 12 hours or later identifies a subgroup of patients at high risk for subsequent mortality and reinfarction, both at short-term but also at long-term.
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PMID:Long-term prognostic value of serial troponin T bedside tests in patients with acute coronary syndromes. 1098 Feb 12

We searched the medical literature for articles containing markers of cardiac ischemia and echocardiography in the evaluation of patients presenting to the emergency department to determine their combined clinical use. Several published articles indicate two-dimensional echocardiography is a useful and cost-effective imaging technique for the evaluation of patients with chest pain in the emergency department. New studies are emerging that evaluate ischemic markers in combination with echocardiography to assess patients presenting to the emergency department with chest pain. We searched the MEDLINE Database for English-language articles published from December 1980 to August 1998 using the key words troponin, echocardiography, myocardial infarction, and emergency. These key words were crossed referenced to determine publications in this area. Pertinent trials and reviews were selected from the database. There were six articles evaluating biochemical markers of ischemia and echocardiography to assess patients presenting with acute coronary syndromes in the emergency department. Very few studies combined the information obtained from novel ischemic markers and echocardiogram analysis to help delineate potential cardiac etiologies of acute coronary syndromes. However, the limited studies available indicate that echocardiography is both sensitive and specific for detecting acute myocardial infarction. The presence of regional wall motion abnormalities increases the chance of in-hospital complications and likelihood of developing congestive heart failure after admission for unstable angina. The combined use of troponin T levels and echocardiographic imaging was a more powerful predictor of adverse events than were isolated results. Myocardial scarring with ventricular wall thinning or aneurysm may allow for rapid diagnosis of 'occult' coronary artery disease in a patient presenting with chest pain who does not have a previous history of a cardiovascular event. Echocardiography may also help identify other cardiovascular causes of chest pain, such as aortic dissection, aortic stenosis, cardiac tamponade, pericarditis, and hypertrophic cardiomyopathy. The clinical use of combining ischemic markers of disease with echocardiographic imaging seems justified given their unique clinical advantages. Future clinical trials are needed to determine whether the combination of novel ischemic markers and echocardiography can provide for a more expedient and accurate diagnosis, resulting in improved patient care and a safe reduction in unnecessary hospitalization.
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PMID:Clinical Use of Ischemic Markers and Echocardiography in the Emergency Department. 1117 40


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