UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic diabetes is often associated with cardiomyopathy, which may result, in part, from defects in cardiac muscle proteins. We investigated whether a 20-wk porcine model of diabetic dyslipidemia (DD) would impair in vivo myocardial function and yield alterations in cardiac myofibrillar proteins and whether endurance exercise training would improve these changes. Myocardial function was depressed in anesthetized DD pigs (n = 12) compared with sedentary controls (C; n = 13) as evidenced by an approximately 30% decrease in left ventricular fractional shortening and an approximately 35% decrease in +dP/dt measured by noninvasive echocardiography and direct cardiac catheterization, respectively. This depression in myocardial function was improved with chronic exercise as treadmill-trained DD pigs (DDX) (n = 13) had significantly greater fractional shortening and +dP/dt than DD animals. Interestingly, the isoform expression pattern of the myofibrillar regulatory protein, cardiac troponin T (cTnT), was significantly shifted from cTnT1 toward cTnT2 and cTnT3 in DD pigs. Furthermore, this change in cTnT isoform expression pattern was prevented in DDX pigs. Finally, there was a decrease in baseline levels of cAMP-dependent protein kinase-induced phosphorylation of the myofibrillar proteins troponin I and myosin-binding protein-C in DD animals. Overall, these results indicate that 20 wk of DD lead to myocardial dysfunction coincident with significant alterations in myofibrillar proteins, both of which are prevented with endurance exercise training, implying that changes in myofibrillar proteins may contribute, at least in part, to cardiac dysfunction associated with diabetic cardiomyopathy.
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PMID:Exercise improves impaired ventricular function and alterations of cardiac myofibrillar proteins in diabetic dyslipidemic pigs. 1546 90

We tested the hypothesis that activation of Rho-A-dependent kinase (ROCK-II) alters cardiac myofilament response to Ca2+ by mechanisms involving phosphorylation of thin filament proteins. We determined effects of a constitutively active form of ROCK-II on ATPase activity and tension development in detergent-extracted (skinned) fiber bundles isolated from mouse left ventricular papillary muscles. ROCK-II induced a depression in maximum ATPase rate and tension, which was associated with phosphorylation of troponin T (TnT), troponin I (TnI), and myosin-binding protein C (C-protein). This effect of ROCK-II was retained in fiber bundles isolated from transgenic (TG) mice in which phosphorylation sites (S14, S15, and S19) of myosin light chain 2 were mutated to alanine. Moreover, exchange of ROCK-II-phosphorylated Tn complex with the native Tn complex in the fiber bundles resulted in inhibition of maximal Ca2+ activation of tension and ATPase activity. Mass spectrometric analysis demonstrated that ROCK-II phosphorylated cardiac TnI (cTnI) at S23, S24, and T144 and cardiac TnT (cTnT) at S278 and T287. An important role for these cTnT sites is indicated by results demonstrating that ROCK-II induced a depression in tension and ATPase activity in skinned fiber bundles from a TG model in which cTnI is replaced by slow skeletal TnI, which lacks S23 and S24 and in which T144 is replaced by proline. Our data provide the first evidence that ROCK-II phosphorylation of the Tn complex, most likely at cTnT, has an important role in functional effects of signaling through the Rho-A pathway.
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PMID:Functional effects of rho-kinase-dependent phosphorylation of specific sites on cardiac troponin. 1577 59

The authors describe otherwise healthy 69-year-old man admitted to the hospital with supraventricular tachycardia (193/min) accompanied by chest pain and marked ST depression on ECG. Sinus rhythm was restored after verapamil (5 mg i.v.) administration. Symptoms resolved and ECG returned to normal. However, elevation of troponin I level (1.2 ng/ml) was observed a few hours later. Echocardiography as well as coronary angiogram were normal. In electrophysiologic study typical AVNRT was diagnosed and successful ablation of the slow pathway was performed. The authors present a review of current literature on myocardial ischaemia due to supraventricular tachycardia despite normal coronary arteries. In conclusion authors suggest that elevated troponin levels may reflect subendocardial ischaemia and should prompt RF ablation of underlying arrhythmia.
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PMID:[Supraventricular tachycardia as a cause of elevated troponin I in a patient with normal coronary arteries]. 1612 86

Risk stratification of patients presenting to the hospital with acute coronary syndrome (ACS) is usually based on ECG assessment, and several clinical and biochemical criteria, which are all intended to identify subjects with more severe disease, who might benefit from aggressive medical or interventional treatment. However, no one widely accepted jeopardy score is available. Our aim was to determine whether the initial ECG, biochemical data and past medical history correlate with the extent of coronary artery disease in patients with ACS thus identifying subjects with severe coronary artery disease (CAD) who may benefit from the early invasive strategy. Patients' data was prospectively collected and retrospectively analysed according to the result of angiography examination. Our cohort consisted of 220 consecutive patients hospitalised due to typical chest pain (> 5 min.) occurring at rest within the last 24 hours. Study group comprised of 115 patients, who were subsequently subjected to coronary angiography Blood for qualitative troponin I test (Cardiac STATus, Spectral Inc., NJ, USA), and other routine biochemistry tests was drawn and ECG was done on admission. Chi-square and Pearson correlation tests were used for statistical analysis, p < 0.05 being considered statistically significant. Stepwise forward regression analysis was used to identify variables predictive of significant coronary artery stenosis. We have identified 65 patients with significant and 5 patients with insignificant multivessel stenosis, 33 patients with significant and 7 patients with insignificant single vessel disease. Five patients had normal coronary arteries. Male sex was significantly more prevalent among patients with coronary artery disease than with normal arteries (71% vs. 40%, p = 0.02). No differences in biochemistry values were seen among the groups. There was a significant difference in the prevalence in ST segment depression (p = 0.03) among these patients and in the incidence of plasma fibrinogen levels of >380 mg% (p = 0.02), those findings being most frequently encountered in significant multi- and single-vessel disease subjects. Hypertension, myocardial infarction more than 10 days ago, history of smoking, hypercholesterolemia and diabetes were independent predictors of the presence of significant stenosis. Assessment of admitting ECG and troponin I together with patients medical history may allow for identification of ACS patients with significant CAD that may benefit from early invasive treatment.
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PMID:[Severity of coronary artery disease in patients with acute coronary syndrome without ST segment elevation]. 1616 13

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

Little is known about the prognostic value of leukocyte count on admission for patients with chest pain. In total, 1,461 patients who presented to the emergency department with non-ST-segment elevation chest pain were studied by clinical history, electrocardiography, serial troponin I determination, and leukocyte count on admission. End points were 1-year mortality and major events (mortality or infarction). Overall patient distribution by quartiles of leukocyte count showed increased mortality (6%, 7%, 6%, and 17%, p = 0.0001) and major events (13%, 13%, 15%, and 24%, p = 0.0001) in the fourth quartile. After adjustment for other risk factors, the fourth quartile cut-off value (>10,000 cells/ml) predicted mortality (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p = 0.0001) but not major events (p = 0.07). When analysis was performed to assess troponin status, in the subgroup with increased troponin (n = 634, 16% mortality), a leukocyte count >10,000 cells/ml was related to mortality (hazard ratio 2.2, 95% confidence interval 1.5 to 3.4, p = 0.0001). However, in the subgroup with normal troponin levels (n = 827, 4.2% mortality), there were no differences in mortality between patients with or without a leukocyte count >10,000 cells/ml (4.4% vs 4.2%, p = 0.8), with survival curves showing a tight overlap (p = 0.9). Further, in the subgroup with normal troponin levels, leukocyte count was not significantly different between patients with or without ST depression (7,969 +/- 2,171 vs 8,108 +/- 2,356 cells/ml, p = 0.6) and was not associated with mortality in patients with ST depression (p = 0.7). In conclusion, leukocyte count on admission is predictive of mortality in patients with chest pain and non-ST-segment elevation myocardial infarction. However, in the absence of myocardial necrosis, leukocyte count lacks prognostic value.
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PMID:Prognostic usefulness of white blood cell count on admission and one-year outcome in patients with non-ST-segment elevation acute chest pain. 1699 67

Our objective in work presented here was to understand the mechanisms by which activated p38alpha MAPK depresses myocardial contractility. To test the hypothesis that activation of p38 MAPK directly influences sarcomeric function, we used transgenic mouse models with hearts in which p38 MAPK was constitutively turned on by an upstream activator (MKK6bE). These hearts demonstrated a significant depression in ejection fraction after induction of the transgene. We also studied hearts of mice expressing a dominant negative p38alpha MAPK. Simultaneous determination of tension and ATPase activity of detergent-skinned fiber bundles from left ventricular papillary muscle demonstrated a significant inhibition of both maximum tension and ATPase activity in the transgenic-MKK6bE hearts. Fibers from hearts expressing dominant negative p38alpha MAPK demonstrated no significant change in tension or ATPase activity. There were no significant changes in phosphorylation level of troponin-T3 and troponin-T4, or myosin light chain 2. However, compared with controls, there was a significant depression in levels of phosphorylation of alpha-tropomyosin and troponin I in fiber bundles from transgenic-MKK6bE hearts, but not from dominant negative p38alpha MAPK hearts. Our experiments also showed that p38alpha MAPK colocalizes with alpha-actinin at the Z-disc and complexes with protein phosphatases (PP2alpha, PP2beta). These data are the first to indicate that chronic activation of p38alpha MAPK directly depresses sarcomeric function in association with decreased phosphorylation of alpha-tropomyosin.
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PMID:p38-MAPK induced dephosphorylation of alpha-tropomyosin is associated with depression of myocardial sarcomeric tension and ATPase activity. 1723 67

Sepsis is associated with increased production of reactive oxidant species. Oxidative and nitrosative stress can lead to activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP), with subsequent loss of cellular functions. Activation of PARP may dramatically lower the intracellular concentration of its substrate, NAD thus slowing the rate of glycolysis, electron transport and subsequently ATP formation. This process can result in cell dysfunction and cell death. In addition, PARP enhances the expression of various pro-inflammatory mediators, via activation of NF-kappaB, MAP kinase and AP-1 and other signal transduction pathways. Preclinical studies in various rodent and large animal models demonstrate that PARP inhibition or PAR deficiency exerts beneficial effects on the haemodynamic and metabolic alterations associated with septic and haemorrhagic shock. Recent human data also support the role of PARP in septic shock: In a retrospective study in 25 septic patients, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histological analysis of heart showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial criptae. Immunohistochemical staining for poly(ADP-ribose) (PAR), the product of activated PARP was demonstrated in septic hearts. There was a positive correlation between PAR staining and troponin I; and a correlation of PAR staining and LVSSW. Thus, there is significant PARP activation in animal models subjected to circulatory shock, as well as in the hearts of septic patients. Based on the interventional studies in animals and the correlations observed in patients we propose that PARP activation may be, in part responsible for the cardiac depression and haemodynamic failure seen in humans with severe sepsis. Interestingly, recent studies reveal that the protective effects of PARP inhibitors are predominant in male animals, and are not apparent in female animals. Oestrogen, by providing a baseline inhibitory effect on PARP activation, may be partially responsible for this gender difference.
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PMID:Poly (ADP-ribose) polymerase activation and circulatory shock. 1738 Jul 90

A case of 23-years old woman, addicted to alcohol and affected by depression, with functional heart disturbances is described. The heart left ventricle dysfunction developed after alcohol withdrawal. In ECG leads (V2-V6, I, II, aVL) symmetrical, negative T waves were present. Echocardio graphy revealed decreased left ventricle ejection fraction (LVEF=35%) and local abnormal contractility. The cardiomyocytes necrosis markers (CK-MB, troponin I) were negative. After several days the improvement of the heart function was observed (LEVF= 56%, improving of myocardium regional contractility). The rest scintigraphy of the heart (99mTc-MIBI GSPECT) was performed and its results corresponded with echocardiography revelations. The ECG changes improved during three weeks hospitalization, but were not normal on discharge.
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PMID:[Withdrawal syndrome complicated with heart left ventricle dysfunction in young woman addicted to alcohol]. 1772 88

Direct, dose dependent effects of the nose-horned vipers (Vipera ammodytes ammodytes) venom on various parameters of cardiac action in isolated rat hearts were examined. Biochemical (protein content, SDS polyacrylamide gel electrophoresis) and biological (minimum haemorrhagic and necrotizing dose and lethal dose (LD(50))) characterization of the venom was performed before testing. The hearts were infused with venom doses of 30, 90 and 150 microg/mL for 10 min followed by 30 min of wash out period. Left ventricular pressure, coronary flow, heart rate, atrioventricular conduction, myocardial oxygen consumption, incidence and duration of arrhythmias were measured and relative cardiac efficiency was calculated. Cardiac CPK, LDH, AST and troponin I were measured as biochemical markers of myocardial damage. The venom caused dose dependent electrophysiological instability and depression of contractility and coronary flow. Effects on the heart rate were biphasic; transient increase followed by significant slowing of the frequency. Relative cardiac efficiency decreased as oxygen consumption remained high relative to the heart rate-contractility product, indicating purposeless expenditure of oxygen and energy. Effects by the dose of 30 microg/mL were highly reversible while the dose of 90 mug/mL caused damages that were mostly irreversible. The dose of 150 mug/mL induced irreversible asystolic cardiac arrest.
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PMID:Dose dependent effects of standardized nose-horned viper (Vipera ammodytes ammodytes) venom on parameters of cardiac function in isolated rat heart. 1831 64

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