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)

The aim of this study was to define the use of a new cardiac troponin I (cTnI) assay for emergency patients with chest pain and no specific electrocardiographic changes consistent with the presence of ischemia. Patients (n = 106) admitted in Emergency/Cardiology Departments for chest pain and suspicion of acute coronary syndrome (ACS) were randomized into two diagnosis groups (ACS or non-ACS) by two independent cardiologists. cTnI measurements were performed at admission, and 6 hours and 12 hours later with a new generation assay (Access AccuTnI, Beckman Coulter). Using an upper reference limit of 0.04 microg/l, 27 patients had a cTnI elevation not related to the final diagnosis of ischemia; the positive predictive value (PPV) was 67% with specificity 48%. The decisional value was re-defined and set at 0.16 microg/l, a concentration corresponding to the 99th percentile of the non-ACS patient group. Precision (coefficient of variation) was 8% at this level, PPV 97% and specificity 98%. This new decisional value is now used in our institution and could be included in standard care guidelines to improve the management of patients presenting chest pain in emergency departments.
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PMID:Emergency department triage of patients with acute chest pain: definition of cardiac troponin I decisional value to manage patients without electrocardiographic evidence of ischemia. 1520 94

The general anesthetic propofol has been shown to be cardioprotective. However, its benefits when used in cardioplegia during cardiac surgery have not been demonstrated. In this study, we investigated the effects of propofol on metabolic stress, cardiac function, and injury in a clinically relevant model of normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest. Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60-min aortic cross-clamped period. Propofol was continuously infused for the duration of CPB and was therefore present in blood cardioplegia. Myocardial biopsies were collected before, at the end of cardioplegic arrest, and 20 mins after the release of the aortic cross-clamp. Hemodynamic parameters were monitored and blood samples collected for cardiac troponin I measurements. Propofol infusion during CPB and before ischemia did not alter cardiac function or myocardial metabolism. Propofol treatment attenuated the changes in myocardial tissue levels of adenine nucleotides, lactate, and amino acids during ischemia and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced measurable hemodynamic dysfunction after cardioplegic arrest when compared to untreated controls. In conclusion, propofol protects the heart from ischemia-reperfusion injury in a clinically relevant experimental model. Propofol may therefore be a useful adjunct to cardioplegic solutions as well as being an appropriate anesthetic for cardiac surgery.
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PMID:Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass. 1595 71

Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.
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PMID:Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction. 1602 65

All novel markers of myocardial ischemia (ischemia-modified albumin, choline, unbound free fatty acids) lack cardiac specificity. Therefore, for the specific detection of myocardial ischemia selective blood sampling from an inserted coronary sinus catheter is needed, which limits the applicability of these markers in most clinical routine settings. In addition, the superiority of these novel markers over the calculation of myocardial lactate production, the current criterion standard for the laboratory diagnosis of myocardial ischemia, has not been demonstrated so far, and even comparative data is frequently lacking. Further the superiority of these new candidate markers over lactate determination for the diagnosis of myocardial ischemia in peripherally drawn blood samples has not been demonstrated either, and these novel parameters appear not to be a breakthrough for laboratory diagnosis of myocardial ischemia during or after percutaneous coronary interventions or coronary artery bypass grafting. The determination of cardiac troponin I or troponin T is the current criterion standard for the laboratory diagnosis of myocardial damage due to their higher sensitivities and specificities compared to creatine kinase isoenzyme MB. According to current knowledge, troponin increases in peripherally drawn blood samples must be regarded as an indicator of myocardial necrosis which, however, may be limited, only detectable by troponin and may be missed by creatine kinase isoenzyme MB determination. After on-pump coronary artery bypass grafting the generally applied troponin discriminator limits are not valid as there is limited, inevitable cardiac tissue damage occurring during the surgical procedure. Therefore, troponins are significantly increased after reperfusion of the arrested heart over values seen before bypass and also in patients without complications. Perioperative myocardial infarctions can be reliably identified by their characteristic troponin time courses, and both peak concentrations and time of peak values are diagnostic criteria. Troponin release is lower in off-pump compared to on-pump bypass surgery. Despite the controversy over the significance of troponin elevations after clinically uncomplicated and successful procedures, it is tempting to postulate that less myocardial damage as detected by troponin release is beneficial for the patient. After elective percutaneous coronary interventions, only troponin increases >8-fold the upper reference limit were associated with increased mortality in long-term follow-up.
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PMID:Markers for perioperative myocardial ischemia: what both interventional cardiologists and cardiac surgeons need to know. 1609 33

Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of transgenic mice seems critical. Due to technical difficulty associated with performing cardiac IP in mice, we developed an in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion. This technique has the major advantage of eliminating the necessity of intermittently occluding the coronary artery with a knotted suture. To systematically evaluate this model, we first demonstrated correlation of ischemia times (10-60 min) with infarct sizes [3.5 +/- 1.3 to 42 +/- 5.2% area at risk (AAR), Evan's blue/triphenyltetrazolium chloride staining]. IP (4 x 5 min) and cold ischemia (27 degrees C) reduced infarct size by 69 +/- 6.7% and 84 +/- 4.2%, respectively (n = 6, P < 0.01). In contrast, lower numbers of IP cycles did not alter infarct size. However, infarct sizes were distinctively different in mice from different genetic backgrounds. In addition to infarct staining, we tested cardiac troponin I (cTnI) as marker of myocardial infarction in this model. In fact, plasma levels of cTnI were significantly lower in IP-treated mice and closely correlated with infarct sizes (R(2) = 0.8). To demonstrate transcriptional consequences of cardiac IP, we isolated total RNA from the AAR and showed repression of the equilibrative nucleoside transporters 1-4 by IP in this model. Taken together, this study demonstrates highly reproducible infarct sizes and cardiac protection by IP, thus minimizing the variability associated with knot-based coronary occlusion models. Further studies on cardiac IP using transgenic mice may consider this technique.
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PMID:Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice. 1676 32

The use of biochemical markers in the diagnosis and management of patients with acute coronary syndrome has increased continually in recent decades. The development of highly sensitive and cardiac-specific troponin assays has changed the view on diagnosis of myocardial infarction and also extended the role of biochemical markers of necrosis into risk stratification and guidance for treatment. The consensus definition of myocardial infarction places increased emphasis on cardiac marker testing, with cardiac troponin replacing creatine kinase MB as the "gold standard" for diagnosis of myocardial infarction. Along with advances in the use of more cardiac-specific markers of myocardial necrosis, biochemical markers that are involved in the progression of atherosclerotic plaques to the vulnerable state or that signal the presence of vulnerable plaques have recently been identified. These markers have variable abilities to predict the risk of an individual for acute coronary syndrome. The aim of this review is to provide an overview of the well-established markers of myocardial necrosis, with a special focus on cardiac troponin I, together with a summary of some of the potential future markers of inflammation, plaque instability, and ischemia.
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PMID:Present and future biochemical markers for detection of acute coronary syndrome. 1704 39

It has been shown that glutamine protects the heart from ischemia/reperfusion (I/R) injury; however, the mechanisms underlying this protection have not been identified. Glutamine:fructose-6-phosphate amidotransferase (GFAT) regulates the entry of glucose into the hexosamine biosynthesis pathway (HBP), and activation of this pathway has been shown to be cardioprotective. Glutamine is required for metabolism of glucose via GFAT; therefore, the goal of this study was to determine whether glutamine cardioprotection could be attributed to increased flux through the HBP and elevated levels of O-linked N-acetylglucosamine (O-GlcNAc) on proteins. Hearts from male rats were isolated and perfused with Krebs-Henseliet buffer containing 5 mM glucose, and global, no-flow ischemia was induced for 20 min followed by 60 min of reperfusion. Thirty-minute pre-treatment with 2.5 mM glutamine significantly improved functional recovery (RPP: 15.6+/-5.7% vs. 59.4+/-6.1%; p<0.05) and decreased cardiac troponin I release (25.4+/-3.0 vs. 4.7+/-1.9 ng/ml; p<0.05) during reperfusion. This protection was associated with a significant increase in the levels of protein O-GlcNAc and ATP. Pre-treatment with 80 muM azaserine, an inhibitor of GFAT, completely reversed the protection seen with glutamine and prevented the increase in protein O-GlcNAc. O-GlcNAc transferase (OGT) catalyzes the formation of O-GlcNAc, and inhibition of OGT with 5 mM alloxan also reversed the protection associated with glutamine. These data support the hypothesis that in the ex vivo perfused heart glutamine cardioprotection is due, at least in part, to enhanced flux through the HBP and increased protein O-GlcNAc levels.
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PMID:Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels. 1706 47

The cardiac myofilaments are composed of highly ordered arrays of proteins that coordinate cardiac contraction and relaxation in response to the rhythmic waves of [Ca(2+)] during the cardiac cycle. Several cardiac disease states are associated with altered myofilament protein interactions that contribute to cardiac dysfunction. During acute myocardial ischemia, the sensitivity of the myofilaments to activating Ca(2+) is drastically reduced, largely due to the effects of intracellular acidosis on the contractile machinery. Myofilament Ca(2+) sensitivity remains compromised in post-ischemic or "stunned" myocardium even after complete restoration of blood flow and intracellular pH, likely because of covalent modifications of or proteolytic injury to contractile proteins. In contrast, myofilament Ca(2+) sensitivity can be increased in chronic heart failure, owing in part to decreased phosphorylation of troponin I, the inhibitory subunit of the troponin regulatory complex. We highlight, in this paper, the central role of the myofilaments in the pathophysiology of each of these distinct disease entities, with a particular focus on the molecular switch protein troponin I. We also discuss the beneficial effects of a genetically engineered cardiac troponin I, with a histidine button substitution at C-terminal residue 164, for a variety of pathophysiologic conditions, including hypoxia, ischemia, ischemia-reperfusion and chronic heart failure.
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PMID:Tuning cardiac performance in ischemic heart disease and failure by modulating myofilament function. 1739 43

Previous studies demonstrated the protective effects of estrogen administration in models of cardiovascular disease. However, there is a discrepancy between these data and those from the recent clinical trials with hormone replacement therapy in menopausal women. One possible explanation for the divergent results is the addition of progestin to the hormone regimen in the Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study trials. The aim of the present study was to examine the effects of a combination of 17beta-estradiol (E(2), 20 microg) and medroxyprogesterone acetate (MPA, 80 microg) on infarct size in New Zealand White rabbits. Infarct size as a percentage of the area at risk was significantly reduced by administration of E(2) 30 min before induction of myocardial ischemia compared with vehicle (19.5 +/- 3.1 vs. 55.7 +/- 2.6%, P < 0.001). However, E(2) + MPA failed to elicit a reduction in infarct size (52.5 +/- 4.6%), and MPA had no effect (50.8 +/- 2.6%). E(2) also reduced serum levels of cardiac troponin I, immune complex deposition in myocardial tissue, activation of the complement system, and lipid peroxidation. All these effects were reversed by MPA. The results suggest that MPA antagonizes the infarct-sparing effects of E(2), possibly through modulation of the immune response after ischemia and reperfusion.
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PMID:Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory effects of 17beta-estradiol in an in vivo model of myocardial ischemia and reperfusion. 1743 82

Cardiac troponins are important biochemical markers for defining the presence of myocardial injury. However, limitations in troponin testing exist, including the relatively late increase in troponin after onset of ischemia. We therefore evaluated a more sensitive troponin assay for detection of myocardial injury in "early presenters." Discarded serial specimens were obtained from 103 patients who had a negative cardiac troponin I (cTnI) result followed by a positive cTnI result. Results were obtained using our current cTnI method and a new more sensitive assay, TnI-Ultra (Siemens Medical Solutions, Diagnostics Division, Tarrytown, NY). Medical records were reviewed to determine the clinical diagnosis. Precision studies yielded a 10% coefficient of variation at the diagnostic cut points for cTnI (0.10 ng/mL [0.10 microg/L]) and TnI-Ultra (0.04 ng/mL [0.04 microg/L]). TnI-Ultra was positive before cTnI in 66 (64.1%) of 103 cases. We conclude that the more sensitive assay, TnI-Ultra, has better analytic performance and has the potential to detect myocardial injury earlier than the current cTnI assay.
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PMID:Earlier detection of myocardial injury in a preliminary evaluation using a new troponin I assay with improved sensitivity. 1763 63


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