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: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, cardiac troponins have attracted great interest as a marker for myocardial injury. However, there are limited data on strategies for use of creatine kinase (CK)-MB and troponin I (cTnI) in clinical practice. We sought to develop a testing strategy using prospectively collected clinical data including serial CK-MB and cTnI levels from 1,051 patients aged > or = 30 years admitted to a teaching hospital for acute chest pain. Diagnostic performance was evaluated for peak values of CK-MB and cTnI obtained during the first 24 hours for the combined end point of acute myocardial infarction and/or major cardiac events within 72 hours. The overall diagnostic accuracy was similar for both cardiac markers alone, and for the combination of cTnI and CK-MB (receiver-operating characteristic curve 0.84, 0.86, and 0.87, respectively). In the multivariate analysis, models including cardiac markers showed that both CK-MB and cTnI added information to clinical data to predict the combined end point, but cTnI added significantly less. Using recursive partitioning analysis, we developed a strategy that would restrict routine cTnI use to patients with normal CK-MB results and findings on the electrocardiogram consistent with ischemia. This strategy would divide patients with suspected myocardial ischemia into 4 groups with risks for the combined end point of 4%, 13%, 26%, and 85%. Thus, cTnI adds information to CK-MB mass and clinical data for predicting major cardiac events, but this contribution is mainly in patients with evidence of myocardial ischemia on their electrocardiograms.
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PMID:A proposed strategy for utilization of creatine kinase-MB and troponin I in the evaluation of acute chest pain. 1021 79

The purpose of this study is to investigate the effects of ischemic preconditioning on myocardial protection and to compare this method to K(+) crystalloid cardioplegia. Langendorff perfused isolated working rat hearts were used in the following groups. After 20 min of stabilisation, 30 hearts were divided into three groups. In group I (control, n=10), hearts were arrested with cold (+4 degrees C) Krebs-Henseleit (K-H) solution, in group II (cardioplegia, n=10) hearts were arrested with cold K(+) cardioplegia solution, and in group III (preconditioning, n=10) hearts were subjected to 5 min normothermic ischemia followed by 5 min reperfusion then arrested with cold K-H solution. All hearts were subjected to 30 min of global ischemia (24 degrees C) and 40 min of reperfusion. Hemodynamic measurements were performed with a left ventricular latex balloon using a data acquisition system. Creatine kinase (CK-MB) washout and Troponin I (cTnI) levels were determined from the coronary effluents. There was no significant difference among the three groups in any of the parameters (hemodynamic and biochemical) measured at the end of stabilisation period. During reperfusion, functional recovery and coronary flow were significantly improved in K(+) cardioplegia and preconditioned groups compared with control group. CK-MB washout and cTnI levels were significantly lower in groups II and III compared with group I at the reperfusion. However no significant difference was observed between K(+) cardioplegia and preconditioned groups among biochemical and hemodynamic parameters and coronary flow at the post-ischemic period. In conclusion, ischemic preconditioning is as effective as K(+) cardioplegia on myocardial protection and recovery of myocardial function during reperfusion.
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PMID:The effectiveness of ischemic preconditioning on myocardial protection and comparison with K(+) cardioplegia. 1099 2

Rapid, efficient, and accurate evaluation of chest pain patients in the emergency department optimizes patient care from public health, economic, and liability perspectives. To evaluate the performance of an accelerated critical pathway for patients with suspected coronary ischemia that utilizes clinical history, electrocardiographic findings, and triple cardiac marker testing (cardiac troponin I [cTnI], myoglobin, and creatine kinase-MB [CK-MB]), we performed an observational study of a chest pain critical pathway in the setting of a large Emergency Department at the Veterans Affairs Medical Center in 1,285 consecutive patients with signs and symptoms of cardiac ischemia. The accelerated critical pathway for chest pain evaluation was analyzed for: (1) accuracy in triaging of patients within 90 minutes of presentation, (2) sensitivity, specificity, positive predictive value, and negative predictive value of cTnI, myoglobin, and CK-MB in diagnosing acute myocardial infarction (MI) within 90 minutes, and (3) impact on Coronary Care Unit (CCU) admissions. All MIs were diagnosed within 90 minutes of presentation (sensitivity 100%, specificity 94%, positive predictive value 47%, negative predictive value 100%). CCU admissions decreased by 40%. Ninety percent of patients with negative cardiac markers and a negative electrocardiogram at 90 minutes were discharged home with 1 patient returning with an MI (0.2%) within the next 30 days. Thus, a simple, inexpensive, yet aggressive critical pathway that utilizes high-risk features from clinical history, electrocardiographic changes, and rapid point-of-care testing of 3 cardiac markers allows for accurate triaging of chest pain patients within 90 minutes of presenting to the emergency department.
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PMID:Ninety-minute accelerated critical pathway for chest pain evaluation. 1156 82

The purpose of this study was to test the hypothesis that myocardial ischemia-reperfusion (I/R) is accompanied by an early burst in calpain activity, resulting in decreased calpastatin activity and an increased calpain/calpastatin ratio, thereby promoting increased protein release. To determine the possibility of a 'calpain burst' impacting cardiac calpastatin inhibitory activity, rat hearts were subjected (Langendorff) to either 45 or 60 min of ischemia followed by 30 min of reperfusion with and without pre-administration (s.c.) of a cysteine protease inhibitor (E-64c). Myocardial function, calpain activities (casein release assay), calpastatin inhibitory activity and release of CK, LDH, cTnI and cTnT were determined (n = 8 for all groups). No detectable changes in calpain activities were observed following I/R with and without E-64c (p > 0.05). Both I/R conditions reduced calpastatin activity (p < 0.05) while E-64c pre-treatment was without effect, implicating a non-proteolytic event underlying the calpastatin changes. A similar result was noted for calpain-calpastatin ratios and the release of all marker proteins (p < 0.05). In regard to cardiac function, E-64c resulted in transient improvements (15 min) for left ventricular developed pressure (LVDP) and rate of pressure development (p < 0.05). E-64c had no effect on end diastolic pressure (LVEDP) or coronary pressure (CP) during I/R. These findings demonstrate that restricting the putative early burst in calpain activity, suggested for I/R, by pre-treatment of rats with E-64c does not prevent downregulation of calpastatin inhibitory activity and/or protein release despite a transient improvement in cardiac function. It is concluded that increases in calpain isoform activities are not a primary feature of l/R changes, although the role of calpastatin downregulation remains to be elucidated.
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PMID:Calpain, calpastatin activities and ratios during myocardial ischemia-reperfusion. 1248 22

The physiopathological mechanisms resulting in increased left ventricular pressures in acute cardiac failure with normal systolic function are not well understood. Although coronary artery disease is commonly associated with acute episodes, the diagnostic value of troponin I measurement and the prevalence of ischaemia as the predisposing factor are not known. Twenty coronary patients (mean age 77 +/- 9 years) in acute cardiac failure with left ventricular ejection fractions of 50% or over and without angina, were studied retrospectively. The diagnostic value of troponin I (cTnI, AxSYM, method) was assessed by comparing with a control group of 16 acute cardiac failure patients without coronary disease. The frequency of hypertension and diabetes in the coronary group was 50 and 45% respectively. At the time of investigation, the pulmonary capillary and systemic arterial pressures were comparable in the coronary patients irrespective of the cTnl value. At threshold levels of 0.5 microgram/l, cTnl had a specificity of 100% and confirmed ischaemia in 60% of the coronary patients. Ischaemia was the commonest predisposing factor for increased cardiac pressures. Over a 268 +/- 101 days follow-up period, half the coronary patients were readmitted for acute cardiac failure and a third of them died. The authors conclude that silent ischaemia is a common predisposing factor for acute cardiac failure in coronary patients with normal systolic function and troponin I measurement is a useful diagnostic help.
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PMID:[Silent ischemia and acute cardiac insufficiency with normal systolic function: diagnostic value of troponin I measurement]. 1457 38

The aim of this study is to investigate the molecular events associated with the deleterious effects of acidosis on the contractile properties of cardiac muscle as in the ischemia of heart failure. We have conducted a study of the effects of increasing acidity on the Ca(2+) induced conformational changes of pyrene labelled cardiac troponin C (PIA-cTnC) in isolation and in complex with porcine cardiac or chicken pectoral skeletal muscle TnI and/or TnT. The pyrene label has been shown to serve as a useful fluorescence reporter group for conformational and interaction events of the N-terminal regulatory domain of TnC with only minimal fluorescence changes associated with C-terminal domain. Results obtained show that the significant decreases at pH 6.0 of site II Ca(2+) affinity of PIA-cTnC when complexed as a binary complex with either cTnI or cTnT are significantly reduced when cTnI is replaced with sTnI or cTnT with sTnT. However, this effect is appreciably diminished when the cTnI and cTnT in the ternary complex are replaced by sTnI and sTnT. The smaller effects in the ternary complex of replacing both cTnI and cTnT by their skeletal counterparts on depressing the Ca(2+) affinity from pH 7.0 to 6.0 arise from TnI replacement. Thus, changes in TnC conformation resulting from isoform-specific interactions with TnI and TnT could be an integral part of the effect of pH on myofilament Ca(2+)sensitivity.
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PMID:Differential pH effect on calcium-induced conformational changes of cardiac troponin C complexed with cardiac and fast skeletal isoforms of troponin I and troponin T. 1563 9

Calpain-1 is a ubiquitous intracellular Ca2+-activated protease, which has been implicated in the pathogenesis of reversible myocardial depression (i.e. myocardial stunning) that follows ischemia and reperfusion via myofibrillar protein degradation. However, the target proteins of this degradative process in the human myocardium have not yet been identified. In order to compare the levels of Calpain-1 susceptibility within a set of human myofibrillar proteins (titin, alpha-fodrin, desmin, troponin T (cTnT), troponin I (cTnI) and alpha-actinin), crude left ventricular tissue homogenates were incubated for 0.5, 15, 30, 60 or 120 min in the presence of Calpain-1 (1 U or 5 U). Differences in the kinetics and extents of protein degradation were subsequently evaluated by using silver-stained SDS-polyacrylamide gels and Western immunoblot analyses. These assays revealed myofibrillar proteins with high (titin and alpha-fodrin), moderate (desmin and cTnT), or low (cTnI and alpha-actinin) relative Calpain-1 susceptibilities. The level of phosphorylation of cTnI did not explain its relatively low Calpain-1 susceptibility. Moreover, the molecular mass distributions of the truncated alpha-fodrin, desmin and cTnI fragments resulting from Ca2+-dependent autoproteolysis exhibited marked similarities with those of their Calpain-1-clipped products. These in vitro results shed light on a number of structural (titin, alpha-fodrin, desmin and alpha-actinin) and regulatory (cTnT and cTnI) proteins within the contractile apparatus as potential targets of Calpain-1. Their degradation may contribute to the development of postischemic stunning in the human myocardium.
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PMID:Calpain-1-sensitive myofibrillar proteins of the human myocardium. 1618 82

Recent studies highlighted the 'obesity paradox' after revascularization, suggesting a 'cardioprotective' effect of obesity. We assessed the association of BMI and regional wall motion score (RWMS) and peak CK and cTnI values (markers of infarct size) and 30-day survival among consecutive first ST-segment-elevation myocardial infarction patients who underwent successful primary PCI. Of the 164 patients, we found no difference in infarct size among the different groups, BMI < or = 25 kg/m2, 25 < BMI < or = 30 kg/m2, and BMI > 30 kg/m2, and no association between BMI as continuous variable and these variables. Thirty-day death rates were not statistically different among the three groups (10, 5, 2%, respectively, P = 0.83). Increased BMI does not confer any protective effect on the heart during acute ischemia.
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PMID:Is increased body mass index associated with a cardioprotective effect after ST-segment-elevation myocardial infarction? 1688 73

While the role of the ubiquitin-proteasome system (UPS) in regulating cellular processes continues to expand, the elucidation of its role in cardiac disease is just beginning. The UPS regulates pivotal processes at all levels of cardiac biology: from membrane-associated ion channels and receptors to downstream signaling intermediates and transcription factors. Moreover, the role of the UPS in maintaining cardiac protein quality control is emerging, as exemplified by its multiple interactions with the cardiac sarcomere and role in familial cardiomyopathies. The diversity of UPS regulation lies in E3 ligases, which specifically recognize targets and direct the ubiquitination process. In the context of disease, E3 ligase expression affects the severity of disease in both ischemia reperfusion injury and cardiac hypertrophy in vivo by modulating signaling intermediates. In ischemia-reperfusion injury, the activities of CHIP and MDM2 (both with E3 ligase activity) profoundly affect apoptosis regulation and severity of disease. In cardiac hypertrophy, Atrogin1 and MuRF1 attenuate cardiac hypertrophy by interacting with calcineurin and PKCepsilon, respectively. Additionally, MuRF1 and MDM2 interact with sarcomeric proteins (cTnI and Tcap, respectively) which may prove to be mechanisms by which hypertrophy is attenuated or protein quality modulated. All of these exciting new findings, however, must be taken in the context of disease regulation of the UPS components themselves. Key UPS components (e.g. ubiquitin, E1, E2, E3, proteasome) are themselves transcriptionally regulated in cardiac disease. Our understanding of the precise nature by which the UPS regulates key biological functions in cardiac disease has just begun.
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PMID:Into the heart: the emerging role of the ubiquitin-proteasome system. 1694 2

With the introduction of biomarkers like troponin I (cTnI), our ability to identify and quantify myocardial infarction in the postoperative period has been greatly enhanced. Even small elevations of cTnI should be considered as a myocardial infarction. Small increases in cTnI postoperatively have indeed been found to be associated with worse short and long-term outcomes, the higher the cTnI level the worse the outcome. Studies undertaken in the 1980s when postoperative myocardial infarction (PMI) was detected by means of electrocardiogram recordings every 12 hours following operation suggested that this complication occurred on the second or third postoperative day. More recent studies where postoperative myocardial necrosis has been detected by repeated troponin dosages have revealed that, in fact, postoperative myocardial infarction appears much earlier between 12 and 32 hour after the end of surgery. Two types of PMI were identified based on intense troponin surveillance. They stem from two different major pathophysiological mechanisms. One seems to be related to plaque-vulnerability, while the other may be due to the effects of prolonged ischemia. The postoperative period should be regarded as a vulnerable period' that acts synergistically with both plaque and patient vulnerabilities in the development of PMI. Monitoring troponin levels in the postoperative period following surgery enables the identification of patients with myocardial damage and the institution of early aggressive intervention (e.g., intensive beta blockers therapy, adequate analgesia, correction of anemia) in order to prevent the evolution of PMI during this golden period' that lasts about two days. In patients that are prone to develop PMI, and especially in those who are prone to develop PMI related to plaque rupture, prevention can be achieved by better preoperative identification of the vulnerable plaque, and by a better plaque stabilization, either metabolically (e.g., statins) or by actual coronary stenting. Further understanding of the mechanisms underlying PMI, as well as their early identification, may contribute to the reduction of the incidence of PMI and its associated morality in the future.
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PMID:Postoperative myocardial infarction: pathophysiology, new diagnostic criteria, prevention. 1723 64


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